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Credentials

Education ?

Medical School Score
Drexel University (1984)
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Awards & Distinctions ?

Awards  
Castle Connolly's Top Doctors™ (2013)
Patients' Choice Award (2010 - 2011)
Compassionate Doctor Recognition (2011)
Appointments
University of Pennsylvania
Clinical Associate Professor of Medicine Director, Echocardiography at Penn Presbyterian Medical Center
Associations
American Board of Internal Medicine

Affiliations ?

Dr. Weiss is affiliated with 25 hospitals.

Hospital Affiliations

Score

Rankings

  • Nazareth Hospital
    Cardiology
    2601 Holme Ave, Philadelphia, PA 19152
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    Top 25%
  • Atlantic City Medical Center-Atlantic Di
    Cardiology
    1925 Pacific Ave, Atlantic City, NJ 08401
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    Top 25%
  • Mercy Fitzgerald Hospital
    Cardiology
    1400 Lansdowne Ave, Darby, PA 19023
    •  
    Top 25%
  • Hospital of the University of PA
    Cardiology
    3400 Spruce St, Philadelphia, PA 19104
    •  
    Top 50%
  • University of PA Medical Center/Presbyterian
    Cardiology
    51 N 39th St, Philadelphia, PA 19104
    •  
    Top 50%
  • Virtua West Jersey Hospital - Voorhees
    Cardiology
    94 Brick Rd, Marlton, NJ 08053
    •  
  • Cooper University Hospital
    Cardiology
    1 Cooper Plz, Camden, NJ 08103
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  • Pennsylvania Hospital University PA Health System
    Cardiology
    800 Spruce St, Philadelphia, PA 19107
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  • Virtua West Jersey Hospital - Marlton
    Cardiology
    94 Brick Rd, Marlton, NJ 08053
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  • Lourdes Medical Center of Burlington County
    Cardiology
    218A Sunset Rd, Willingboro, NJ 08046
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  • Our Lady Of Lourdes Medical Center
    Cardiology
    1600 Haddon Ave, Camden, NJ 08103
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  • Graduate Hospital
    1800 Lombard St, Philadelphia, PA 19146
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  • Cooper Hospital Umc
  • Presbyterian Medical Center Of The University Of Pennsylvania Health System
  • Virtua West Jersey Hospital Marlton
  • Presbyterian Hospital
  • Virtua WJ Hospital Voorhees
  • Virtua Health System West Jersey, Voorhees
  • University of Penn Med Center-Presb Med Group
  • Cooper Hospital/U M C
  • Clinical Practices of the University of Pennsylvania,
  • University Of Pittsburgh Med C, Braddock, Pa
  • Clinical Health Care Associates of New Jersey
  • Virtua-West Jersey Health System
  • Mercy Suburban Hospital
  • Publications & Research

    Dr. Weiss has contributed to 148 publications.
    Title Validation of Plasma Biomarkers in Degenerative Calcific Aortic Stenosis.
    Date September 2010
    Journal The Journal of Surgical Research
    Excerpt

    Calcific aortic stenosis (CAS) is the most common acquired valvular disorder in industrialized countries. This study investigates the correlation of different known biomarkers for CAS as a first step towards the development of a panel of biomarkers that can be used in prognostic staging.

    Title Obscure Gastrointestinal Bleeding in a Patient with Orthotopic Heart Transplantation. Answer to the Clinical Challenges and Images in Gi Question: Image 2: Primary Jejunal B Large Cell Lymphoma.
    Date August 2010
    Journal Gastroenterology
    Title Balloon Catheter Sinusotomy: One-year Follow-up--outcomes and Role in Functional Endoscopic Sinus Surgery.
    Date October 2008
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    OBJECTIVE: The primary objective was to assess the long-term effectiveness of balloon catheter sinusotomy. METHODS: Patients who had sinus ostia dilated with balloon catheters were prospectively evaluated 1 year after surgery with nasal endoscopy, a CT scan, and the Sino-Nasal Outcome Test (SNOT-20). RESULTS: Sixty-six patients (202 sinuses) were examined. One hundred seventy-two of 202 sinus ostia (85%) were endoscopically patent, 1 percent (2/202) were nonpatent, and ostial patency could not be determined by endoscopy in 28 of 202 (14%). In these "indeterminate" sinuses, the CT scans were normal in 13, implying functional patency in 91.6 percent of sinuses (185/202). Sinus CT scan scores were 1.95 at 1 year versus 8.89 at baseline (P < 0.001), and 1-year SNOT-20 scores (0.91) were significantly improved from baseline (2.14, P < 0.0001). CONCLUSION: Balloon catheter sinusotomy results were durable over the study period, showing long-term effectiveness.

    Title Long-term Outcome Analysis of Balloon Catheter Sinusotomy: Two-year Follow-up.
    Date October 2008
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    OBJECTIVE: Assess two-year postoperative clinical outcomes for patients receiving balloon catheter sinusotomy. METHODS: Patients who had sinus ostia dilated with balloon catheters were prospectively evaluated two years after surgery by Sinonasal Outcome Test (SNOT-20) and computed tomographic (CT) scan. RESULTS: Sixty-five patients (195 ballooned sinuses) were followed for two years after surgery, including 34 "balloon-only" patients and 31 "hybrid" patients. SNOT-20 symptom scores were significantly improved from baseline (0.87 vs 2.17 baseline, P < 0.001) and stable compared to six months and one year; this was the case for both balloon-only (1.09 vs 2.09, P < 0.001) and hybrid (0.64 vs 2.26, P < 0.001) patients. Lund-MacKay CT scores were significantly improved from baseline (2.69 vs 9.66, P < 0.001) and stable compared to one year, confirmed for both balloon-only (1.75 vs 5.67, P < 0.015) and hybrid (3.25 vs 12.05, P < 0.001) subsets of patients. A total of 85% of patients reported improvement of their sinus symptoms, with 15% same and 0% worsened. Revision treatment was required in seven of 195 sinuses (3.6%) in six of 65 patients (9.2%). CONCLUSION: Patients who receive balloon catheter sinusotomy in endoscopic sinus surgery have significant improvement in symptoms two years after surgery. Radiographic evidence also confirms resolution of disease after two years. This demonstrates durability of clinical results previously reported at 24 weeks and one year after surgery.

    Title Multicenter Registry of Balloon Catheter Sinusotomy Outcomes for 1,036 Patients.
    Date May 2008
    Journal The Annals of Otology, Rhinology, and Laryngology
    Excerpt

    OBJECTIVES: This study assesses the safety and effectiveness of balloon catheters used as instruments in sinus surgery in a "real-world" multicenter registry of 1,036 patients across 27 US otolaryngology practices. METHODS: Data were collected by standardized chart review with centralized database administration for all consecutive functional endoscopic sinus surgeries that included the use of balloon catheters across the 18-month time period from December 2005 to May 2007. RESULTS: Balloon catheters were used in 3,276 peripheral (maxillary, frontal, and sphenoid) sinuses, for an average of 3.2 sinuses per patient. There were no major adverse events related to the use of balloon catheter instruments. The revision rate was 1.3% of sinuses treated with a balloon catheter after an average follow-up of 40.2 weeks. Sinus symptoms were improved in 95.2%, unchanged in 3.8%, and worse in 1.0% of patients. Postoperative sinus infections were significantly less frequent and less severe compared to infections before surgery. The results were consistent across all patient categories, including balloon-only patients and revision patients. CONCLUSIONS: Use of balloon catheters as instruments in sinus surgery appears to be relatively safe and effective and to improve the patient's quality of life. The results are consistent and generalizable across a wide range of sinusitis patients and physician practices. The complication rates, revision rates, and patient symptom improvement rates all compare favorably with previously reported results of functional endoscopic sinus surgery.

    Title Reference Labs: Who, What, Where, When, and How?
    Date March 2008
    Journal Mlo: Medical Laboratory Observer
    Title Patient and Surgeon Radiation Exposure in Balloon Catheter Sinus Ostial Dilation.
    Date March 2008
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    OBJECTIVE: The aim of this study was to determine the extent of radiation exposure to the patient and the surgeon in balloon catheter dilation. METHODS: Dosimeters were used to record radiation exposure to both patients and surgeons. The mean radiation dose per sinus treated and per patient treated was calculated for each dosimeter location. RESULTS: The mean patient dose (108 sinuses treated in 34 patients), was 0.32 mSv per sinus and 1.02 mSv per patient over the eye and 1.33 mSv per sinus and 4.22 mSv per patient over the temple. The average total fluoroscopy time was 3.6 minutes per patient. The average number of sinuses treated was 3.2. The mean surgeon dose at the chest (254 sinuses in 89 patients) was 0.025 mSv per sinus and 0.072 mSv per patient. The mean surgeon dose at the hand (182 sinuses in 68 patients) was 0.009 mSv per sinus and 0.023 mSv per patient. CONCLUSIONS: The use of fluoroscopy in balloon catheter dilation exposes both the patient and surgeon to very low doses of radiation.

    Title Risk Management and Compliance in Pathology and Laboratory Medicine.
    Date December 2007
    Journal Clinics in Laboratory Medicine
    Excerpt

    Successful and ethical management of a clinical laboratory requires vigilant focus on proper business conduct. A comprehensive risk management program must encompass government standards as provided for financial and marketing practices, including fraud and abuse, antitrust, antikickback, privacy, and security. The program also must incorporate the appropriate reaction to medical malpractice litigation along with considerations of expert testimony.

    Title Coding, Coverage, and Compensation for Pathology and Laboratory Medicine Services.
    Date December 2007
    Journal Clinics in Laboratory Medicine
    Excerpt

    Compensation for pathologist and clinical laboratory services generally depends upon standardized procedural coding systems, the coverage determinations of individual insurance companies, fee schedules that assign reimbursement rates for those services, and contractual compensation arrangements. Procedural coding relies primarily on the American Medical Association's Current Procedural Terminology (CPT) nomenclature. Disease conditions, signs, and symptoms are coded using the International Classification of Diseases, Ninth Revision, Clinical Modification. The single largest health insurance "company" in the United States is the Center for Medicare and Medicaid Services (CMS), and most private insurance companies look to CMS as a model for health services compensation. CMS uses a Physician Fee Schedule and a separate Clinical Laboratory Fee Schedule, whose designs and annual updates differ.

    Title Future Trends.
    Date December 2007
    Journal Clinics in Laboratory Medicine
    Excerpt

    Several current forces have set anticipated future changes in health care in motion, or, at least, have set the stage for change. End-consumer demand increasingly drives the market; as a result, entire businesses are transforming or emerging anew to meet these demands. In general, consumers demand high quality at reasonable cost, to be delivered as fast as possible with minimal inconvenience. The health care consumer takes this expectation further, to include the desire for all helpful information regarding one's health to be made readily available for him/her to make the best decision and minimize morbidity, mortality, misdiagnosis, and inconvenience. This article addresses the impact upon the laboratory by considering four key interrelated dynamics that affect these trends: market, medicine, technology, and information systems.

    Title Training in Laboratory Management and the Mba/md in Laboratory Medicine.
    Date August 2007
    Journal Clinics in Laboratory Medicine
    Excerpt

    The business of medicine requires more than just the knowledge and skills necessary to provide quality patient care. A growing number of opportunities are available for physicians to learn how to better manage the business side of their practices. Today's clinical laboratories, particularly those in health care organizations under pressure to efficiently use limited resources, benefit from having management and leadership specifically trained for these roles.

    Title Safety and Outcomes of Balloon Catheter Sinusotomy: a Multicenter 24-week Analysis in 115 Patients.
    Date August 2007
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    OBJECTIVE: The aim of this study was to further evaluate the safety and effectiveness of balloon catheter devices to dilate obstructed sinus ostia/perform sinusotomy. METHODS: Through a prospective, multicenter evaluation, safety was assessed by rate of adverse events, patency was determined by endoscopic examination, and sinus symptoms were determined by the Sino-Nasal Outcome Test (SNOT 20). RESULTS: At the conclusion of the 24-week analysis, endoscopy determined that the sinusotomy was patent in 80.5% (247 of 307) sinuses and nonpatent in 1.6% (5 of 307), and could not determine ostial patency status in 17.9% (55 of 307). Of the ostia visualized on endoscopy, 98% were patent (247 of 252), while 2% (5 of 252) were considered nonpatent. SNOT 20 scores showed consistent symptomatic improvement over baseline. Revision treatment was required in 3 sinuses (3 of 307 sinuses, 0.98%) in 3 patients (3 of 109 patients, 2.75%). CONCLUSION: Balloon catheter technology appears safe and effective in relieving ostial obstruction. Patients were pleased and indicated that they experienced symptomatic improvement.

    Title Enabling a Community to Dissect an Organism: Overview of the Neurospora Functional Genomics Project.
    Date April 2007
    Journal Advances in Genetics
    Excerpt

    A consortium of investigators is engaged in a functional genomics project centered on the filamentous fungus Neurospora, with an eye to opening up the functional genomic analysis of all the filamentous fungi. The overall goal of the four interdependent projects in this effort is to accomplish functional genomics, annotation, and expression analyses of Neurospora crassa, a filamentous fungus that is an established model for the assemblage of over 250,000 species of non yeast fungi. Building from the completely sequenced 43-Mb Neurospora genome, Project 1 is pursuing the systematic disruption of genes through targeted gene replacements, phenotypic analysis of mutant strains, and their distribution to the scientific community at large. Project 2, through a primary focus in Annotation and Bioinformatics, has developed a platform for electronically capturing community feedback and data about the existing annotation, while building and maintaining a database to capture and display information about phenotypes. Oligonucleotide-based microarrays created in Project 3 are being used to collect baseline expression data for the nearly 11,000 distinguishable transcripts in Neurospora under various conditions of growth and development, and eventually to begin to analyze the global effects of loss of novel genes in strains created by Project 1. cDNA libraries generated in Project 4 document the overall complexity of expressed sequences in Neurospora, including alternative splicing alternative promoters and antisense transcripts. In addition, these studies have driven the assembly of an SNP map presently populated by nearly 300 markers that will greatly accelerate the positional cloning of genes.

    Title A High-throughput Gene Knockout Procedure for Neurospora Reveals Functions for Multiple Transcription Factors.
    Date August 2006
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    The low rate of homologous recombination exhibited by wild-type strains of filamentous fungi has hindered development of high-throughput gene knockout procedures for this group of organisms. In this study, we describe a method for rapidly creating knockout mutants in which we make use of yeast recombinational cloning, Neurospora mutant strains deficient in nonhomologous end-joining DNA repair, custom-written software tools, and robotics. To illustrate our approach, we have created strains bearing deletions of 103 Neurospora genes encoding transcription factors. Characterization of strains during growth and both asexual and sexual development revealed phenotypes for 43% of the deletion mutants, with more than half of these strains possessing multiple defects. Overall, the methodology, which achieves high-throughput gene disruption at an efficiency >90% in this filamentous fungus, promises to be applicable to other eukaryotic organisms that have a low frequency of homologous recombination.

    Title Developmental Expression of Two Forms of Arginase in Neurospora Crassa.
    Date July 2006
    Journal Biochimica Et Biophysica Acta
    Excerpt

    N. crassa has two forms of arginase. The physiological role of multiple arginases is not understood. The two forms were shown to be differentially expressed from a single locus (aga) and both proteins are localized to the cytoplasm. The 36-kDa protein was expressed in minimal and arginine supplemented medium, whereas the 41-kDa form was detected only in the presence of arginine. In this study we examined developmental expression of the two arginase transcripts and proteins in conidia and during conidial germination. Two novel observations are revealed, storage of both arginase proteins in conidia and temporal expression of aga transcripts during early germination. To better understand the role of arginase in conidia and the nature of the temporal expression, we examined the effects of related metabolites, arginine, ornithine, proline, glutamate and glutamine on protein storage and temporal expression. These metabolites were used as supplements or sole nitrogen sources. Storage of arginase protein was detected in all conidial samples examined except when glutamate was used as the nitrogen source. The aga temporal RNA expression early in germination was abolished when arginine related metabolites were used as nitrogen sources. The exception to this result is observed with glutamate where temporal expression was seen when glutamate was the sole nitrogen source and abolished with glutamate supplementation. The temporal expression result supports a unique role for arginase in glutamate accumulation early in germination whereas the protein storage result supports the existence of a novel pathway utilizing arginase for glutamate synthesis in asexual spore development.

    Title Teaching Pediatric Laboratory Medicine to Pathology Residents.
    Date July 2006
    Journal Archives of Pathology & Laboratory Medicine
    Excerpt

    CONTEXT: Laboratory data are essential to the medical care of fetuses, infants, children, and adolescents. However, the performance and interpretation of laboratory tests on specimens from these patients, which may constitute a significant component of the workload in general hospitals and integrated health care systems as well as specialized perinatal or pediatric centers, present unique challenges to the clinical pathologist and the laboratory. Therefore, pathology residents should receive training in pediatric laboratory medicine. OBJECTIVE: Children's Health Improvement through Laboratory Diagnostics, a group of pathologists and laboratory scientists with interest and expertise in pediatric laboratory medicine, convened a task force to develop a list of curriculum topics, key resources, and training experiences in pediatric laboratory medicine for trainees in anatomic and clinical pathology or straight clinical pathology residency programs and in pediatric pathology fellowship programs. DATA SOURCES: Based on the experiences of 11 training programs, we have compiled a comprehensive list of pediatric topics in the areas of clinical chemistry, endocrinology, hematology, urinalysis, coagulation medicine, transfusion medicine, immunology, microbiology and virology, biochemical genetics, cytogenetics and molecular diagnostics, point of care testing, and laboratory management. This report also includes recommendations for training experiences and a list of key texts and other resources in pediatric laboratory medicine. CONCLUSIONS: Clinical pathologists should be trained to meet the laboratory medicine needs of pediatric patients and to assist the clinicians caring for these patients with the selection and interpretation of laboratory studies. This review helps program directors tailor their curricula to more effectively provide this training.

    Title Effectively Managing Your Reference Laboratory Relationship.
    Date February 2004
    Journal Clinical Leadership & Management Review : the Journal of Clma
    Excerpt

    Clinical laboratories use reference laboratories for laboratory services that they, themselves, routinely are unable to provide, often for economic and/or competency-related reasons. Decisions on reference laboratory providers usually are based upon reputation, quality of service, depth of test menu, other value-added services, testing frequency and turnaround time, price, client services support, information technology support, and logistics. The referring laboratory also is faced with the challenge of how to manage physician ordering patterns and their requests for esoteric testing. This is particularly important and problematic in cases of questionable medical necessity, high cost, or both. This article attempts to address this dilemma and how best to manage the utilization of expensive esoteric tests, particularly in the face of little or no reimbursement for these services by payers and health plans.

    Title A Tool to Assess Homebound Status.
    Date January 2004
    Journal Home Healthcare Nurse
    Title Associations Between Anxiety and Marital Adjustment.
    Date January 2003
    Journal The Journal of Psychology
    Excerpt

    Cognitive-behavioral theories of marital functioning and contextual models of close relationships highlight the importance of proximal affect states such as anxiety in couple functioning. Despite these assertions, research examining the role of state anxiety is lacking in the literature on intimate relationships. In this study, the authors examined state anxiety and marital adjustment in a sample of 45 couples. Hierarchical regression analyses indicated that husbands' Time 1 anxiety can predict their own and their wives' subsequent reports of marital adjustment. Wives' Time 1 anxiety did not predict their own or their husbands' subsequent reports of marital adjustment. In this study, the authors focused on the role of husband anxiety in marital adjustment and on implications for further study of the contextual model of close relationships.

    Title Talking with Dr. Ronald L. Weiss, Arup's Senior Vice President. Interview by C. Anne Pontius.
    Date December 2002
    Journal Mlo: Medical Laboratory Observer
    Title Automated Transport and Sorting System in a Large Reference Laboratory: Part 1. Evaluation of Needs and Alternatives and Development of a Plan.
    Date October 2002
    Journal Clinical Chemistry
    Excerpt

    BACKGROUND: Our laboratory, a large, commercial, esoteric reference laboratory, sought some form of total laboratory automation to keep pace with rapid growth of specimen volumes as well as to meet competitive demands for cost reduction and improved turnaround time. METHODS: We conducted a systematic evaluation of our needs, which led to the development of a plan to implement an automated transport and sorting system. We systematically analyzed and studied our specimen containers, test submission requirements and temperatures, and the workflow and movement of people, specimens, and information throughout the laboratory. We performed an intricate timing study that identified bottlenecks in our manual handling processes. We also evaluated various automation options. RESULTS: The automation alternative viewed to best meet our needs was a transport and sorting system from MDS AutoLab. Our comprehensive plan also included a new standardized transport tube; a centralized automated core laboratory for higher volume tests; a new "automation-friendly" software system for order entry, tracking, and process control; a complete reengineering of our order-entry, handling, and tracking processes; and remodeling of our laboratory facility and specimen processing area. CONCLUSIONS: The scope of this project and its potential impact on overall laboratory operations and performance justified the extensive time we invested (nearly 4 years) in a systematic approach to the evaluation, design, and planning of this project.

    Title Automated Transport and Sorting System in a Large Reference Laboratory: Part 2. Implementation of the System and Performance Measures over Three Years.
    Date October 2002
    Journal Clinical Chemistry
    Excerpt

    BACKGROUND: Our laboratory implemented a major automation system in November 1998. A related report describes a 4-year process of evaluation and planning leading to system installation. This report describes the implementation and performance results over 3 years since the system was placed into use. METHODS: Project management software was used to track the project. Turnaround times of our top 500 tests before and after automation were measured. We compared the rate of hiring of employees and the billed unit per employee ratio before and after automation by use of linear regression analysis. Finally, we analyzed the financial contribution of the project through an analysis of return on investment. RESULTS: Since implementation, the volume of work transported and sorted has grown to >15,000 new tubes and >25,000 total tubes per day. Median turnaround time has decreased by an estimated 7 h, and turnaround time at the 95th percentile has decreased by 12 h. Lost specimens have decreased by 58%. A comparison of pre- and post-implementation hiring rates of employees estimated a savings of 33.6 employees, whereas a similar comparison of ratios of billed units per employee estimated a savings of 49.1 employees. Using the higher figure, we estimated that the $4.02 million cost of the project would be paid off approximately 4.9 years subsequent to placing the system into daily use. CONCLUSIONS: The overall automation project implemented in our laboratory has contributed considerably to improvement of key performance measures and has met our original project objectives.

    Title Estimating the Budgetary Impact of Setting the Medicare Clinical Laboratory Fee Schedule at the National Limitation Amount.
    Date July 2002
    Journal American Journal of Clinical Pathology
    Excerpt

    The Institute of Medicine (IOM) of the National Academy of Sciences was commissioned by Congress to study the current system for the payment of diagnostic clinical laboratory services provided to Medicare beneficiaries. The current system was established in 1984 and has grown in complexity and is of diminishing contemporary relevance. The IOM recommended that a single, rational, nationalfee schedule be established and that it be initially based on the National Limitation Amount (NLA) currently mandated as the national fee cap. To estimate the potential budgetary impact of this recommendation, we merged the 1999 Part B Extract and Summary System and the 1999 Clinical Diagnostic Laboratory Fee Schedule (CLFS). By using an estimated 193 million allowed services from this data set and the current mean fee of $9.14 per test, current spending is approximately $1,768 million. The impact of raising the CLFS to the NLA will be approximately $1,792 million, or $9.26 per test. The estimated cumulative budgetary effect, factoring in the current forecast for the Consumer Price Index, is an increase of approximately $993 million over 5 years and $2,359 million over 10 years.

    Title A Tool to Assess Homebound Status.
    Date July 2000
    Journal Home Healthcare Nurse
    Excerpt

    Although this specific instrument focuses solely on helping the home care nurse determine homebound status, this type of instrument can be developed for the other criteria used in assessing a client for Medicare-eligible home care services. For example, a similar instrument can be developed to assess whether a patient meets the criteria for part-time intermittent care or skilled care using the Medicare definitions as a guide to tool development. As we move into a time when there is more scrutiny of home care for compliance to Medicare regulations and increased productivity to assure cost effectiveness, instruments like this are essential for careful documentation that allows the agency to demonstrate accountability. In addition, home care agencies are expecting new home care nurses to know and be able to apply the Medicare regulations after a brief orientation. Instruments like this can shorten the orientation process and provide support for the home care nurse in the field.

    Title Interrelationships Between Microtubules, a Striated Fiber, and the Gametic Mating Structure of Chlamydomonas Reinhardi.
    Date January 2000
    Journal The Journal of Cell Biology
    Excerpt

    The microtubule system associated with the Chlamydomonas reinhardi flagellar apparatus is shown to differ from previous descriptions; two of the four flagellar "roots" possess only two microtubules and are associated with a finely striated fiber. In gametic cells this fiber underlies the gametic mating structure and makes contact with it. Functional interpretations are offered.

    Title Ase/sca Guidelines for Performing a Comprehensive Intraoperative Multiplane Transesophageal Echocardiography Examination: Recommendations of the American Society of Echocardiography Council for Intraoperative Echocardiography and the Society of Cardiovascular Anesthesiologists Task Force for Certification in Perioperative Transesophageal Echocardiography.
    Date November 1999
    Journal Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography
    Title Ase/sca Guidelines for Performing a Comprehensive Intraoperative Multiplane Transesophageal Echocardiography Examination: Recommendations of the American Society of Echocardiography Council for Intraoperative Echocardiography and the Society of Cardiovascular Anesthesiologists Task Force for Certification in Perioperative Transesophageal Echocardiography.
    Date October 1999
    Journal Anesthesia and Analgesia
    Title Integrated Laboratory Networks: Ideas That Work--and Some That Don't.
    Date April 1999
    Journal Mlo: Medical Laboratory Observer
    Title A Mentor-based Laboratory Management Elective for Residents.
    Date February 1999
    Journal American Journal of Clinical Pathology
    Excerpt

    With the evolution of health care delivery systems, laboratories are being viewed as cost centers, and their value is being continually challenged. This requires pathologists to be adequately trained as leaders and managers. New training curricula for pathology residents have been developed, including combined didactic and mentor-based training. At the University of Utah, Salt Lake City, the combination of a large academic pathology department with a wholly owned commercial laboratory has allowed the development of a comprehensive 1-month didactic management course for senior residents. This course is designed to develop a broad-based foundation in laboratory management principles. The reinforcement of many of these principles, however, requires additional hands-on effort. We describe our first experience with this 1-month, theory based-teaching followed by a 3-month "real-world" experience based on a one-on-one mentor relationship between the director of laboratories and a senior resident, who assumed the role of the assistant director of laboratories.

    Title Multiple Forms of Arginase Are Differentially Expressed from a Single Locus in Neurospora Crassa.
    Date December 1998
    Journal The Journal of Biological Chemistry
    Excerpt

    The Neurospora crassa catabolic enzyme, arginase (L-arginine amidinohydrolase, EC 3.5.3.1), exists in multiple forms. Multiple forms of arginase are found in many vertebrates, but this is the only reported example in a microbial organism. The two major forms are structurally similar with subunit sizes of 36 and 41 kDa, respectively. The larger form is produced by mycelia growing in arginine-supplemented medium. Both forms are localized in the cytosol. The structural gene for arginase, aga, has been cloned and sequenced; it contains a 358-codon open reading frame with three in-frame ATGs at the amino terminus. Mutagenesis of these ATGs revealed that the first ATG initiates the 41-kDa protein and the third ATG initiates the 36-kDa protein. Mutation of the second ATG has no effect on translation. Northern analysis demonstrated that a 1.4-kilobase (kb) transcript is synthesized in minimal medium and both a 1.4- and 1.7-kb transcript are produced in arginine-supplemented medium. Primer extension identified the 5' ends of each transcript and demonstrated that the first and third ATG of the open reading frame are the initial AUGs of the 1.7- and 1. 4-kb mRNA, respectively. The results suggest that a basal promoter produces the 1.4-kb transcript and an arginine "activated" promoter is responsible for the 1.7-kb transcript. Tandem promoters are rare in eukaryotic organisms, and they often regulate developmental or tissue-specific gene expression. The possibility that arginase has a role in differentiation in N. crassa is being investigated.

    Title Malignant Transformation of Recurrent Respiratory Papillomatosis Associated with Integrated Human Papillomavirus Type 11 Dna and Mutation of P53.
    Date May 1998
    Journal The Laryngoscope
    Excerpt

    Recurrent respiratory papillomatosis (RRP), usually confined to the nasopharynx, trachea, and larynx, occasionally can progress to extensive bronchopulmonary disease. Most cases of bronchopulmonary and laryngeal papillomatosis are cytologically benign and do not undergo malignant transformation; however, squamous cell carcinoma (SCC) can arise in RRP in the absence of known risk factors such as radiation and smoking. In this study, the authors investigated molecular genetic alterations occurring in a case of metastasizing SCC that arose in long-standing bronchopulmonary papillomatosis. Genomic DNA from tracheal papillomata, tracheobronchial papillomata, SCC of the lung, and a lymph node metastasis was extracted. The physical state of the human papillomavirus type 11 (HPV-11) DNA was investigated by two-dimensional gel electrophoresis. Molecular genetic alterations of the host genome were studied by direct sequencing of polymerase chain reaction-amplified gene fragments and restriction fragment length polymorphism (RFLP) analysis. Episomal and integrated forms of HPV-11 sequences were detected in histologically benign tumors, but only the integrated form of the viral DNA could be found in malignant tissue samples. Molecular genetic studies revealed that an allelic loss of the interferon-beta gene (IFNbeta-1) and an endogenous type of mutation of the p53 antioncogene were found only in the malignant lesions. Mutations were not observed in the ras, neu, or multiple tumor suppressor (MTS1/p16) genes in any specimens. The authors' data indicated that the p53 genetic mutation was associated with integration of HPV-11 in histologically malignant lesions. This association may promote a progressive genetic instability that can lead to the development and clonal expansion of malignant lesions in RRP.

    Title Regional Laboratory Networks.
    Date May 1998
    Journal American Journal of Clinical Pathology
    Title Processing and Function of a Polyprotein Precursor of Two Mitochondrial Proteins in Neurospora Crassa.
    Date May 1998
    Journal The Journal of Biological Chemistry
    Excerpt

    In Neurospora crassa, the mitochondrial arginine biosynthetic enzymes, N-acetylglutamate kinase (AGK) and N-acetyl-gamma-glutamyl-phosphate reductase (AGPR), are generated by processing of a 96-kDa cytosolic polyprotein precursor (pAGK-AGPR). The proximal kinase and distal reductase domains are separated by a short connector region. Substitutions of arginines at positions -2 and -3 upstream of the N terminus of the AGPR domain or replacement of threonine at position +3 in the mature AGPR domain revealed a second processing site at position -20. Substitution of arginine at position -22, in combination with changes at -2 and -3, prevented cleavage of the precursor and identified two proteolytic cleavage sites, Arg-Gly downward arrow Tyr-Leu-Thr at the N terminus of the AGPR domain and Arg-Gly-Tyr downward arrow Ser-Thr located 20 residues upstream. Inhibitors of metal-dependent peptidases blocked proteolytic cleavage at both sites. Amino acid residues required for proteolytic cleavage in the connector were identified, and processing was abolished by mutations changing these residues. The unprocessed AGK-AGPR fusion had both catalytic activities, including feedback inhibition of AGK, and complemented AGK-AGPR- mutants. These results indicate that cleavage of pAGK-AGPR is not required for functioning of these enzymes in the mitochondria.

    Title Characterization of Vacuolar Arginine Uptake and Amino Acid Efflux in Neurospora Crassa Using Cupric Ion to Permeabilize the Plasma Membrane.
    Date March 1998
    Journal Fungal Genetics and Biology : Fg & B
    Excerpt

    Treatment of Neurospora crassa mycelia with cupric ion has been shown to permeabilize the plasma and mitochondrial membranes. Permeabilized mycelia were shown to take up arginine into the vacuoles. Uptake was ATP-independent and appeared to be driven by an existing K+-gradient. The kinetic characteristics of the observed uptake were similar to those observed using vacuolar membrane vesicles: the Km for arginine uptake was found to be 4.2-4.5 mM. Permeabilized mycelia were used to study the regulation of arginine uptake into vacuoles. The results suggest that uptake is relatively indifferent to the contents of the vacuoles and is not affected by growth of mycelia in amino acid-supplemented medium. Efflux of arginine, lysine, and ornithine from vacuoles was also measured using mycelia permeabilized with cupric ion. Arginine release was shown to be specifically enhanced by cytosolic ornithine and/or increases in the vacuolar pool of arginine or ornithine. Lysine efflux was shown be indifferent to the presence of other amino acids. These observations emphasize the importance of vacuolar compartmentation in controlling arginine and ornithine metabolism and suggest that vacuolar compartmentation may play an important role in nitrogen homeostasis of filamentous fungi.

    Title Natural Killer-like T-cell Lymphoma in the Small Intestine of a Child Without Evidence of Enteropathy.
    Date August 1997
    Journal The American Journal of Surgical Pathology
    Excerpt

    A previously healthy 6-year-old boy developed symptoms of small intestinal obstruction and was found to have a large intraabdominal mass. At laparotomy the mass involved the jejunum and adjacent mesenteric lymph nodes, requiring resection. Microscopic and immunohistochemical studies demonstrated a T-cell non-Hodgkin's lymphoma, confirmed by finding clonal T-cell receptor-beta and -gamma gene rearrangements by Southern blot analysis. The immunophenotype of this lymphoma-CD3+CD4-CD8-CD56+TIA-1+ beta F1(-)-suggests that the tumor cells are cytotoxic natural killer (NK)-like T cells, probably of CD3+CD4-CD8- intraepithelial cell origin. Examination of the adjacent and distal small intestinal mucosa failed to show any significant pathologic change. This case was unusual because intestinal lymphomas in children are usually of B-cell origin and most commonly have small noncleaved cell morphology. Childhood intestinal T-cell lymphomas have not been the focus of specific study but appear to be rare. In adults, intestinal T-cell lymphomas often arise in the background of gluten-sensitive enteropathy (celiac disease). In contrast, this child had peripheral T-cell lymphoma, with NK-like T-cell features, in the small intestine with no clinical or histologic evidence of enteropathy.

    Title High Jugular Bulb and Conductive Hearing Loss.
    Date April 1997
    Journal The Laryngoscope
    Excerpt

    A high jugular bulb is often discovered as an incidental finding that is asymptomatic. Conductive hearing loss in association with this anomaly may occur, but has been reported infrequently in the literature. We report five cases of high jugular bulb and associated conductive hearing loss. Mechanisms to explain the conductive hearing loss include contact of the jugular bulb with the tympanic membrane, interference with the ossicular chain, and obstruction of the round window niche. The operative findings, radiographic and audiometric data that support these mechanisms of conductive hearing loss are presented.

    Title Acetylglutamate Synthase from Neurospora Crassa: Structure and Regulation of Expression.
    Date March 1997
    Journal Molecular Microbiology
    Excerpt

    A DNA clone which complemented an arg-14 mutation of Neurospora crassa was isolated by sib selection from a cosmid library (pMOcosX). Southern and restriction-fragment-length polymorphism (RFLP) analysis confirmed that the cloned DNA contained the arg-14 gene. The arg-14 gene was identified as the structural gene for acetylglutamate synthase by immunodepletion of enzyme activity with antibodies prepared against an arg-14 fusion protein and by the thermal instability of acetylglutamate synthase in a temperature-sensitive arg-14 mutant. The fungai acetylglutamate synthase has little sequence homology to its bacterial counterpart, unlike other arginine biosynthetic enzymes. Expression of the arg-14 gene is regulated by cross-pathway control similar to many amino acid biosynthetic genes. However, expression of acetylglutamate synthase occurs throughout the developmental growth cycle, unlike other arginine biosynthetic enzymes.

    Title Nontuberculous Mycobacterial Infection of the Frontal Sinus in a Child.
    Date February 1997
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Title Clear Plastic Cups: a Childhood Choking Hazard.
    Date January 1997
    Journal International Journal of Pediatric Otorhinolaryngology
    Excerpt

    The disposable plastic beverage cup is not usually regarded as hazardous to young children. Certain varieties of these products however, are manufactured from a brittle, clear plastic that easily cracks and fragments. While most conscientious parents keep their children safe from peanuts, balloons, and other known choking hazards, a child can surreptitiously bite a cup edge and aspirate the fragment. We report two cases of foreign body aspiration involving clear plastic cups that went undetected one of which remained 21 months following a negative rigid bronchoscopy. Diagnostic difficulties are related to the transparency and radiolucency of these objects. When suspicious of foreign body aspiration in children, otolaryngologists should inquire about the availability of clear plastic cups in the household and be mindful of the diagnostic pitfalls. Further investigations including CT scanning and repeat bronchoscopy may be helpful in cases of suspected missed foreign bodies. An educational campaign aimed at prevention and placement of product package warning labels should be established.

    Title Prosthetic Heart Valves.
    Date January 1997
    Journal The New England Journal of Medicine
    Title Theophylline and Atrioventricular Block.
    Date September 1996
    Journal Annals of Internal Medicine
    Title Descending Thoracic Aortomyoplasty: a Technique for Clinical Application.
    Date February 1996
    Journal The Annals of Thoracic Surgery
    Excerpt

    BACKGROUND. Descending thoracic aortomyoplasty is a form of skeletal muscle-powered cardiac assistance. Its use in clinical settings has been limited by the ligation of intercostal arteries necessary to complete a circumferential wrap of the aorta with the latissimus dorsi. METHODS. This study assessed the feasibility and the efficacy of aortomyoplasty constructed with a modified latissimus dorsi. A pericardial patch was attached to the latissimus dorsi and divided around the preserved intercostal arteries. Nine alpine goats (37 +/- 2 kg) underwent descending aortomyoplasty using this technique. All intercostal arteries were preserved. After a 6-week recovery period, the animals underwent a 6-week, incremental electrical conditioning program. After 90 postoperative days, animals were examined under anesthesia with the myostimulator on and off. RESULTS: Aortomyoplasty activation resulted in augmentation of mean diastolic aortic pressure by 16.0 +/- 0.9 mm Hg (23%). Significant improvements in cardiac index (40%), stroke volume index (37%), left ventricular stroke work index (49%), and mean arterial pressure (19%) were noted. An intravascular sonographic probe placed in the descending aorta revealed circumferential compression of the aorta during counterpulsation. Mean cross-sectional aortic area was reduced by 51.8%, from 210.1 +/- 7.1 to 108.9 +/- 6.7 mm2 during aortomyoplasty activation (p < 0.05). Histologic analysis confirmed the long-term patency of intercostal arteries. CONCLUSIONS. Descending aortomyoplasty, modified with an interposing patch of pericardium, effectively transfers skeletal muscle force across the aortic wall and assists cardiac function. This technique allows preservation of all aortic branches, and with this novel approach, the clinical utility of aortomyoplasty can now be explored.

    Title The Usefulness of Transesophageal Echocardiography in Diagnosing Cardiac Contusions.
    Date February 1996
    Journal Chest
    Excerpt

    OBJECTIVES: To assess the usefulness of transesophageal echocardiography in diagnosing cardiac contusions in patients with blunt trauma. BACKGROUND: For more than a decade, noninvasive tests, including ECGs, cardiac enzymes, nuclear studies, and transthoracic echocardiography have been utilized in an attempt to identify trauma patients with cardiac injuries. These tests have been imperfect in identifying the patients at high risk for mortality. METHODS: We retrospectively reviewed the charts in 22 patients with transesophageal echocardiographically diagnosed cardiac contusions noting age, race, sex, transthoracic echocardiographic examinations, study quality, and outcome. We also noted the Injury Severity Score, which is a measure of the severity of illness in trauma patients. Higher scores correlate more severe injury and higher mortality. We defined cardiac contusions as presence of wall motion abnormality, including either or both ventricles, in the absence of transmural myocardial infarction on ECG following nonpenetrating chest trauma. RESULTS: Over a 30-month period, 81 transesophageal echocardiographic examinations were performed on trauma patients. Among this group, 22 patients were diagnosed as having cardiac contusions. There were 15 patients with right ventricular contusions, 7 patients with left ventricular contusions, and 2 patients with both ventricles involved. We compared this group with all ICU trauma patients admitted to the hospital during this time period. Overall, the contusion patients had an average Injury Severity Score of 27 and a mortality of 27% compared with the overall trauma group with an Injury Severity Score of 33 and a corresponding mortality of 9% (p < 0.001). Corresponding ECGs were nondiagnostic in 73% of patients with cardiac contusion. There were no complications related to the transesophageal examinations. CONCLUSIONS: Transesophageal echocardiographically diagnosed cardiac contusion in trauma patients carries a high mortality rate. Transesophageal examinations are safe and provide excellent quality images where transthoracic examinations were inadequate. Right ventricular contusions are approximately twice as common as left ventricular contusions.

    Title Cardiac Tamponade Without Pericardial Effusion After Blunt Chest Trauma.
    Date February 1996
    Journal American Heart Journal
    Title Marital Interaction Coding System: Revision and Empirical Evaluation.
    Date September 1995
    Journal Behaviour Research and Therapy
    Excerpt

    Given the vast amount of codeable information in marital interactions, observational coding systems must emphasize particular classes of behavior. The most widely used marital coding scheme, the Marital Interaction Coding System (MICS), like many older behavioral coding systems, emphasizes verbal content over affect. Changes made to the MICS between versions III and IV are described; they were intended to increase the system's use of coded affect and to decrease autodependence in sequential analysis. We used an archival data set of 994 couples' videotaped conflict negotiations coded with the MICS. As intended, the MICS-IV, relative to the MICS-III, was found to have the advantage of capturing more non-verbal affect expressed during marital interactions, which resulted in stronger interactional contingencies (e.g. Wife Blame-->Husband Blame, Husband Facilitation-->Wife Facilitation). The MICS-IV also yielded significantly lower levels of spurious autodependence.

    Title Transition in Quality: from Quality Assurance to Strategic Quality Management.
    Date March 1995
    Journal Clinical Laboratory Management Review : Official Publication of the Clinical Laboratory Management Association / Clma
    Excerpt

    The 1990s and beyond present formidable challenges to health-care providers, including clinical laboratories and pathology departments. However, numerous opportunities lie within these challenges. Discovering these opportunities and exploiting them will be critical success factors for future survival. Quality assurance, continuous quality improvement, and strategic and financial planning are all activities used to a varying extent by clinical laboratories. The cumulative potential benefits to an organization in which these activities are integrated can far exceed their sum as individual components. Coordinating these interdependent processes is the basis for managing strategically. The experience of one organization's efforts to plan and develop such a strategy is presented and discussed.

    Title Improvement in Circulatory and Oxygenation Status by Perflubron Emulsion (oxygent Ht) in a Canine Model of Surgical Hemodilution.
    Date March 1995
    Journal Artificial Cells, Blood Substitutes, and Immobilization Biotechnology
    Excerpt

    To examine the effect of a low dose of Oxygent HT on hemodynamics and oxygen transport variables in a canine model of profound surgical hemodilution, two groups of adult anesthetized splenectomized beagles were hemodiluted with Ringer's solution to Hb 7 g/dL. The treated group received 1 mL/kg Oxygent HT (90% w/v perflubron emulsion [perfluorooctyl bromide], Alliance Pharmaceutical Corp.) and both groups (7 controls and 10 treated) were further hemodiluted using 6% hydroxyethyl starch until cardiorespiratory decompensation occurred. Pulmonary artery catheterization data and oxygen transport variables were recorded at Hb decrements of 1 g/dL breathing room air. There was no difference among groups during initial hemodilution. However, in the Oxygent HT group there was a statistically significant improvement in mean arterial pressure, CVP, cardiac output, PvO2, SvO2, DO2, and pulmonary venous admixture shunt during profound hemodilution to Hb levels of 6, 5, and 4 g/dL. A low dose of Oxygent HT offered benefit in improving hemodynamics and oxygen transport parameters even under air breathing conditions in a model of surgical hemodilution. This effect was most apparent at lower levels of Hb.

    Title Reversible Uridylylation of the Escherichia Coli Pii Signal Transduction Protein Regulates Its Ability to Stimulate the Dephosphorylation of the Transcription Factor Nitrogen Regulator I (nri or Ntrc).
    Date December 1994
    Journal The Journal of Biological Chemistry
    Excerpt

    We have reconstituted the signal transduction system responsible for the negative regulation of the transcription of the Escherichia coli glnA gene, encoding glutamine synthetase, by glutamine. This signal transduction system consists of four proteins: the transcription factor NRI (NtrC), which activates glnA transcription when it is phosphorylated, the kinase/phosphatase protein NRII (NtrB) that directly controls the extent of NRI phosphorylation, the PII signal transduction protein that controls the phosphatase activity of NRII, and the uridylyltransferase/uridylyl-removing (UTase/UR) enzyme that is regulated by glutamine and controls the activity of PII. In the reconstituted system, the removal of uridylyl groups from the PII protein, catalyzed by the UTase/UR protein in the presence of glutamine, resulted in the stimulation of NRI approximately P dephosphorylation. In contrast, the uridylylated form of the PII protein had no discernible effect on NRI phosphorylation. The uridylylation of the trimeric PII protein by the monomeric UTase/UR protein is a non-cooperative reaction in which the partially modified species accumulated and were readily observed. Partially modified PII trimers were partially active in stimulating the dephosphorylation of NRI approximately P. Thus, both the PII-UTase/UR and PII-NRII interactions display the continuous variability characteristic of rheostats as opposed to the binary variability characteristic of toggle switches.

    Title Pseudoinfarction Ecg Pattern Caused by Diaphragmatic Hernia Uniquely Resolved by Transthoracic Echocardiography.
    Date November 1994
    Journal Journal of the American Society of Echocardiography : Official Publication of the American Society of Echocardiography
    Excerpt

    A case of pseudoinfarction electrocardiographic pattern caused by diaphragmatic hernia is presented. The transthoracic echocardiographic examination revealed a large hiatal hernia enhanced by contrast injections below the inferior wall causing paradoxical systolic motion. The location of the hernia simulated a pericardial effusion.

    Title Management of the Thyroid Isthmus in Tracheostomy: a Prospective and Retrospective Study.
    Date November 1994
    Journal Otolaryngology--head and Neck Surgery : Official Journal of American Academy of Otolaryngology-head and Neck Surgery
    Excerpt

    The thyroid isthmus is often encountered while a tracheostomy is being performed. This study details retrospective and prospective comparison of electrocautery division of the isthmus with older techniques. In this study, electrocautery division of the thyroid isthmus during tracheostomy is faster and as safe as other techniques with respect to blood loss, perioperative complications, and airway outcome.

    Title The Pivotal Role of Transesophageal Echocardiography in the Management of Traumatic Thoracic Aortic Rupture with Associated Intra-abdominal Hemorrhage.
    Date July 1994
    Journal Chest
    Excerpt

    Rupture of the thoracic aorta after blunt trauma, particularly when associated with multiple injuries, presents a major problem of resuscitation and management. Transesophageal color Doppler echocardiography (TEE) during laparotomy played a major role in confirming the diagnosis of thoracic aortic rupture in a patient.

    Title Impact of the Incidental Diagnosis of Clinically Unsuspected Central Pulmonary Artery Thromboembolism in Treatment of Critically Ill Patients.
    Date May 1994
    Journal Chest
    Excerpt

    Mortality is high in unrecognized pulmonary embolism (PE), but the diagnosis is difficult to establish, especially in patients with coexisting cardiopulmonary disorders. We describe a group of 14 patients with pulmonary thromboemboli in whom transesophageal echocardiography (TEE) performed for coexisting cardiopulmonary conditions established the clinical diagnosis of PE not suspected prior to TEE. The patients had initial clinical diagnoses of heart failure (eight patients), cardiogenic shock (two patients), atrial septal defect (two patients), aortic dissection (one patient), and pneumonia (one patient). Thirteen patients had risk factors for PE. Transthoracic echocardiography (TTE) demonstrated right heart strain in eight patients but did not visualize PE in any of the patients. The TEE diagnosis of occult central pulmonary artery thromboembolism changed treatment in all 14 patients. Ten of the 14 patients were successfully discharged from the hospital. We conclude that occult central pulmonary artery thromboemboli are not uncommon in patients presenting with acute cardiopulmonary disorders and the presence of risk factors for PE and right heart strain on TTE should alert the physician to suspect PE. If and when TEE is performed in patients with acute cardiopulmonary disorders with risk factors for PE and right heart strain, the physician should evaluate the main pulmonary artery and its branches for central pulmonary artery thromboemboli.

    Title Avoiding a Catastrophe: Use of Transesophageal Echocardiography in Diagnosing Salmonella Aortitis.
    Date May 1994
    Journal American Heart Journal
    Title A Polyprotein Precursor of Two Mitochondrial Enzymes in Neurospora Crassa. Gene Structure and Precursor Processing.
    Date April 1994
    Journal The Journal of Biological Chemistry
    Excerpt

    N-Acetylglutamate kinase (AGK) and N-acetyl-gamma-glutamyl-phosphate reductase (AGPR) function as two separate mitochondrial enzymes, but are encoded by a single nuclear gene in several fungi. The Neurospora crassa arg-6 gene encoding these enzymes has been cloned and sequenced, and the enzymes responsible for processing the polyprotein precursor have been identified. The 871-amino acid precursor contains a normal N-terminal mitochondrial targeting sequence, an internal connecting region (approximately 200 amino acids) upstream of the distal reductase domain, and coding regions with N-terminal amino acid sequences identical with those of purified N-acetylglutamate kinase and N-acetyl-gamma-glutamyl-phosphate reductase. Sequence comparisons of the coding regions indicate high levels of conservation between prokaryotic and fungal proteins. Regions suggesting ancestral relationships to N-acetylglutamate synthase and aspartate beta-semialdehyde dehydrogenase have been identified. Both the N-terminal targeting sequence and the connecting region contain consensus sites for cleavage by the mitochondrial processing peptidase and processing enhancing protein. In vitro processing assays with intact mitochondria, solubilized mitochondria, and purified enzymes have shown that the mitochondrial processing peptidase and processing enhancing protein cleave not only the N-terminal mitochondrial targeting sequence but also process the polyprotein precursor into the two mature enzymes.

    Title Malignant Thymoma. A Complicated Triad of Svc Syndrome, Cardiac Tamponade, and Dic.
    Date April 1994
    Journal Chest
    Excerpt

    A patient presented with multisystem disease due to a very aggressive malignant thymoma. The case was complicated by the triad of cardiac tamponade, superior vena cava (SVC) syndrome, and disseminated intravascular coagulation (DIC). A review of the English literature reveals this to be a unique constellation of clinical symptoms and that DIC was heretofore unreported.

    Title Evaluation of a Noninvasive Hematocrit Monitor: a New Technology.
    Date April 1993
    Journal American Clinical Laboratory
    Title Ornithine Decarboxylase Activity in Tumor and Normal Tissue of Head and Neck Cancer Patients.
    Date September 1992
    Journal The Laryngoscope
    Excerpt

    Tumorigenesis requires increased biosynthesis of polyamines and elevated levels of ornithine decarboxylase, which is the rate-limiting enzyme in the polyamine synthesis pathway. Previous animal studies have noted a marked increase in ornithine decarboxylase after exposure to tumorigenic stimuli and that pretreatment with vitamins A and E provides protection against the carcinogenic action. However, studies of ornithine decarboxylase activity in human oral cavity carcinoma have not been as specific. The goal of this study was to determine whether a specific difference in ornithine decarboxylase activity occurs in tumor versus adjacent normal tissue in head and neck squamous cell carcinoma patients. Ornithine decarboxylase activity was measured in 30 consecutive head and neck cancer patients undergoing surgical therapy. Ornithine decarboxylase levels were found to be significantly elevated in tumor tissue samples when compared to adjacent normal mucosa samples (P less than .004). This finding confirms the previous findings noted in animal models and implies that the protective effects of vitamins A and E will extend to human head and neck cancers.

    Title Arginine Transport in Mitochondria of Neurospora Crassa.
    Date August 1992
    Journal The Journal of Biological Chemistry
    Excerpt

    Transport of arginine into mitochondria of Neurospora crassa has been studied. Arginine transport was found to be saturable (Km = 6.5 mM) and to have a pH optimum of pH 7.5. Mitochondrial arginine transport appeared to be facilitated transport rather than active transport because: (i) the arginine concentration within the mitochondrial matrix after transport was similar to that of the reaction medium, and (ii) uncouplers and substrates of oxidative phosphorylation did not affect the transport rate. The basic amino acids ornithine, lysine, and D-arginine inhibited arginine transport. The arginine transport system could be irreversibly blocked by treating mitochondria with the reactive arginine derivative, N-nitrobenzyloxycarbonyl-arginyl diazomethane.

    Title Pathologic Quiz Case 2. Plexiform Neurofibroma.
    Date August 1992
    Journal Archives of Otolaryngology--head & Neck Surgery
    Title A Clinical Laboratory Management Elective for Pathology Residents.
    Date February 1992
    Journal Archives of Pathology & Laboratory Medicine
    Excerpt

    Many practicing pathologists, particularly those in private settings, function as managers. Their responsibilities may not only involve directing the successful activities of laboratory personnel, but often require a level of accountability to hospital administrators or business managers. Traditional training programs focus on technical competency and devote little time, if any, to preparing their graduates for the management aspects of their careers. In response to this need, a 1-month elective was designed for senior pathology residents at the University of Utah, Salt Lake City. The cumulative experiences of a large academic pathology department and its successful commercial laboratory venture provided a real-world supplement to a curriculum founded in basic business management principles.

    Title Multichamber Gunshot Wounds of the Heart. The Utility of Transesophageal Echocardiography.
    Date February 1992
    Journal Chest
    Excerpt

    A patient had a gunshot wound to the heart involving three cardiac chambers. Conventional echocardiography failed to identify the intracardiac injuries. The utility of transesophageal echocardiography in a patient with cardiac trauma is described.

    Title Diagnosis of Cytomegalovirus Pneumonitis on Bronchoalveolar Lavage Fluid: Comparison of Cytology, Immunofluorescence, and in Situ Hybridization with Viral Isolation.
    Date September 1991
    Journal Diagnostic Cytopathology
    Excerpt

    Forty-three bronchoalveolar lavage (BAL) specimens from 40 immunocompromised patients were studied for the presence of cytomegalovirus (CMV) by rapid diagnostic methods. DNA in situ hybridization, cytology, and immunofluorescence were compared to conventional cell culture. Eleven (25%) of the 43 BAL samples grew CMV in culture. In situ hybridization detected 6 of these 11 for sensitivity, specificity, and predictive values of positive and negative of 55%, 94%, 75%, and 86%, respectively. Cytology had a sensitivity of 73% and specificity of 100%. Six Papanicolaou-stained cytospins were screened cytologically versus one hybridization cytospin, and the higher sensitivity of cytology may reflect this extensive sampling. The immunofluorescent method had a sensitivity equal to that of cytology (73%): however, the specificity (72%) was significantly less than that of either the probe or cytology. These data suggest that although in situ hybridization can be a rapid, useful method for detecting CMV in BAL specimens, cytology appears to be a more sensitive method.

    Title Transesophageal Echocardiographic Diagnosis of Aortic Dissection During Cardiac Surgery.
    Date August 1991
    Journal Anesthesiology
    Title Efficiency Factors and Atp/adp Ratios in Nitrogen-fixing Bacillus Polymyxa and Bacillus Azotofixans.
    Date May 1990
    Journal Journal of Bacteriology
    Excerpt

    The efficiency factor, the number of moles of ATP generated per mole of glucose fermented, was determined in anaerobic, non-carbon-limited N2-fixing cultures of Bacillus polymyxa, Bacillus macerans, Bacillus azotofixans, and Clostridium butyricum through identification and quantitation of the fermentation products by 13C nuclear magnetic resonance spectroscopy and measurement of acetate kinase activities. All three Bacillus species had acetate kinase activities and produced acetate and ethanol as the major fermentation products. The maximum amounts of ATP generated per mole of glucose fermented were 2.70, 2.64, and 2.88 mol in B. polymyxa, B. macerans, and B. azotofixans, respectively, compared with 3.25 mol in C. butyricum. Thus, in the N2-fixing Bacillus species, the efficiency factors are lower than that in C. butyricum. Steady-state ATP/ADP concentration ratios were measured in non-carbon-limited N2-fixing cultures of B. polymyxa and B. azotofixans through separation and quantitation of the adenylates in cell extracts by ion-pair reversed-phase high-performance liquid chromatography. The observed ATP/ADP ratios were 4.5 and 3.8, and estimated energy charges were 0.81 to 0.86 and 0.81 to 0.83, respectively, for B. polymyxa and B. azotofixans. The results suggest that under these growth conditions, the rate of ATP regeneration is adequate to meet the energy requirement for N2 fixation in the Bacillus species, in contrast to N2-fixing Clostridium pasteurianum and Klebsiella pneumoniae, for which substantially lower steady-state ATP/ADP ratios and energy charges have been reported. Implications of the results are discussed in relation to possible differences between Bacillus and Clostridium species in energy requirements for N2 fixation and concomitant ammonia assimilation.

    Title Multilobated B-cell Lymphoma. A Clinicopathologic Study of 24 Cases.
    Date January 1990
    Journal Archives of Pathology & Laboratory Medicine
    Excerpt

    The clinical, histologic, and immunologic features of 24 cases of multilobated B-cell lymphoma are presented and compared with those of previously reported cases. Cases were included in this study when more than 50% of the tumor cells had nuclear multilobation. There were 13 males and 11 females with an age range of 13 to 79 years. A slight predominance of node-based presentations was observed. Seventeen patients (71%) presented with advanced (stage III or IV) disease. Complete remissions were achieved in 13 (59%) of 22 patients, and 14 (58%) of the 24 patients were still alive after a follow-up period ranging from 10 to 124 months. The 1-year survival was 65% (SE = 10%). Relapses occurred in 4 (31%) of 13 patients with complete responses. These observations, together with those previously reported, support the conclusion that the multilobated B-cell variant of non-Hodgkin's lymphoma behaves in a fashion similar to that of the intermediate-grade, diffuse, large-cell non-Hodgkin's lymphomas.

    Title Novel Mechanisms Controlling Arginine Metabolism in Neurospora.
    Date June 1989
    Journal Trends in Biochemical Sciences
    Title Identification of an Arginine Carrier in the Vacuolar Membrane of Neurospora Crassa.
    Date June 1989
    Journal The Journal of Biological Chemistry
    Excerpt

    A number of arginine derivatives were tested for their ability to inhibit arginine uptake into vacuolar membrane vesicles of Neurospora crassa. The guanido side chain and L-configuration were found to be important for recognition by the arginine carrier. Based upon the specificity of recognition, a reactive arginine derivative (N alpha-p-nitrobenzyloxycarbonyl arginyl diazomethane) was synthesized which has an intact guanido side chain and a diazo group at the carboxyl end. The latter decomposes to a reactive carbene group. This derivative inhibited arginine uptake into vacuolar membrane vesicles at low concentrations. Radioactive N alpha-p-nitrobenzyloxycarbonyl arginyl diazomethane was covalently bound to vacuoles. Binding was specific for a single membrane protein with an approximate molecular weight of 40,000, saturable (2 pmol/mg vacuolar membrane protein), and inhibited by 100 mM L-arginine but not by 100 mM L-lysine. The results suggest that this protein is the arginine carrier.

    Title Ammonia Assimilation Pathways in Nitrogen-fixing Clostridium Kluyverii and Clostridium Butyricum.
    Date May 1989
    Journal Journal of Bacteriology
    Excerpt

    Pathways of ammonia assimilation into glutamic acid were investigated in ammonia-grown and N2-fixing Clostridium kluyverii and Clostridium butyricum by measuring the specific activities of glutamate dehydrogenase, glutamine synthetase, and glutamate synthase. C. kluyverii had NADPH-glutamate dehydrogenase with a Km of 12.0 mM for NH4+. The glutamate dehydrogenase pathway played an important role in ammonia assimilation in ammonia-grown cells but was found to play a minor role relative to that of the glutamine synthetase/NADPH-glutamate synthase pathway in nitrogen-fixing cells when the intracellular NH4+ concentration and the low affinity of the enzyme for NH4+ were taken into account. In C. butyricum grown on glucose-salt medium with ammonia or N2 as the nitrogen source, glutamate dehydrogenase activity was undetectable, and the glutamine synthetase/NADH-glutamate synthase pathway was the predominant pathway of ammonia assimilation. Under these growth conditions, C. butyricum also lacked the activity of glucose-6-phosphate dehydrogenase, which catalyzes the regeneration of NADPH from NADP+. However, high activities of glucose-6-phosphate dehydrogenase as well as of NADPH-glutamate dehydrogenase with a Km of 2.8 mM for NH4+ were present in C. butyricum after growth on complex nitrogen and carbon sources. The ammonia-assimilating pathway of N2-fixing C. butyricum, which differs from that of the previously studied Bacillus polymyxa and Bacillus macerans, is discussed in relation to possible effects of the availability of ATP and of NADPH on ammonia-assimilating pathways.

    Title Glutamate Biosynthesis in Bacillus Azotofixans. 15n Nmr and Enzymatic Studies.
    Date March 1988
    Journal The Journal of Biological Chemistry
    Excerpt

    Pathways of ammonia assimilation into glutamic acid in Bacillus azotofixans, a recently characterized nitrogen-fixing species of Bacillus, were investigated through observation by NMR spectroscopy of in vivo incorporation of 15N into glutamine and glutamic acid in the absence and presence of inhibitors of ammonia-assimilating enzymes, in combination with measurements of the specific activities of glutamate dehydrogenase, glutamine synthetase, glutamate synthase, and alanine dehydrogenase. In ammonia-grown cells, both the glutamine synthetase/glutamate synthase and the glutamate dehydrogenase pathways contribute to the assimilation of ammonia into glutamic acid. In nitrate-grown and nitrogen-fixing cells, the glutamine synthetase/glutamate synthase pathway was found to be predominant. NADPH-dependent glutamate dehydrogenase activity was detectable at low levels only in ammonia-grown and glutamate-grown cells. Thus, B. azotofixans differs from Bacillus polymyxa and Bacillus macerans, but resembles other N2-fixing prokaryotes studied previously, as to the pathway of ammonia assimilation during ammonia limitation. Implications of the results for an emerging pattern of ammonia assimilation by alternative pathways among nitrogen-fixing prokaryotes are discussed, as well as the utility of 15N NMR for measuring in vivo glutamate synthase activity in the cell.

    Title Relationship Between Two Major Immunoreactive Forms of Arginase in Neurospora Crassa.
    Date January 1988
    Journal Journal of Bacteriology
    Excerpt

    Two major immunoreactive proteins of Mr 41,700 and 36,100 have been detected in crude mycelial extracts with polyclonal antibodies raised against arginase purified from Neurospora crassa. The latter corresponded to the protein used to obtain the antibodies. Both polypeptides were either missing or present in very low amounts in mutant strains having little or no detectable arginase activity. The relative proportion of the two species was altered in strains containing the nitrogen catabolite regulatory mutation nit-2. Peptide mapping indicated that the two species are very closely related, but several of the peptides which appeared to be identical by staining reacted differently with the antibodies. Both species were produced by in vitro translation of poly(A)+ mRNA, although the larger species was produced to a much smaller extent than was expected from its abundance in vivo. The results suggest the existence of multiple forms of arginase in N. crassa which differ in their response to nitrogen catabolite regulation.

    Title Role of Glutamate Dehydrogenase in Ammonia Assimilation in Nitrogen-fixing Bacillus Macerans.
    Date November 1987
    Journal Journal of Bacteriology
    Excerpt

    Pathways of ammonia assimilation into glutamic acid in Bacillus macerans were investigated by measurements of the specific activities of glutamate dehydrogenase (GDH), glutamine synthetase, and glutamate synthase. In ammonia-rich medium, GDH was the predominant pathway of ammonia assimilation. In nitrogen-fixing cells in which the intracellular NH4+ concentration was 1.4 +/- 0.5 mM, the activity of GDH with a Km of 2.2 mM for NH4+ was found to be severalfold higher than that of glutamate synthase. The result suggests that GDH plays a significant role in the assimilation of NH4+ in N2-fixing B. macerans.

    Title Carboxyl-terminal Sequences Influence the Import of Mitochondrial Protein Precursors in Vivo.
    Date November 1987
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    The large subunit of carbamoyl phosphate synthase A [carbon-dioxide: L-glutamine amido-ligase (ADP-forming, carbamate-phosphorylating), EC 6.3.5.5] from Neurospora crassa is encoded by a nuclear gene but is localized in the mitochondrial matrix. We have utilized N. crassa strains that produce both normal and carboxyl-terminal-truncated forms of carbamoyl phosphate synthase A to ask whether the carboxyl terminus affects import of the carbamoyl phosphate synthase A precursor. We found that carboxyl-terminal-truncated precursors were directed to mitochondria but that they were imported less efficiently than full-length proteins that were synthesized in the same cytoplasm. Our results suggest that effective import of proteins into mitochondria requires appropriate combinations of targeting sequences and three-dimensional structure.

    Title Ammonia Assimilation in Bacillus Polymyxa. 15n Nmr and Enzymatic Studies.
    Date September 1987
    Journal The Journal of Biological Chemistry
    Excerpt

    Pathways of ammonia assimilation into glutamic acid and alanine in Bacillus polymyxa were investigated by 15N NMR spectroscopy in combination with measurements of the specific activities of glutamate dehydrogenase, glutamine synthetase, glutamate synthetase, alanine dehydrogenase, and glutamic-alanine transaminase. Ammonia was found to be assimilated into glutamic acid predominantly by NADPH-dependent glutamate dehydrogenase with a Km of 2.9 mM for NH4+ not only in ammonia-grown cells but also in nitrate-grown and nitrogen-fixing cells in which the intracellular NH4+ concentrations were 11.2, 1.04, and 1.5 mM, respectively. In ammonia-grown cells, the specific activity of alanine dehydrogenase was higher than that of glutamic-alanine transaminase, but the glutamate dehydrogenase/glutamic-alanine transaminase pathway was found to be the major pathway of 15NH4+ assimilation into [15N]alanine. The in vitro specific activities of glutamate dehydrogenase and glutamine synthetase, which represent the rates of synthesis of glutamic acid and glutamine, respectively, in the presence of enzyme-saturating concentrations of substrates and coenzymes are compared with the in vivo rates of biosynthesis of [15N]glutamic acid and [alpha,gamma-15N]glutamine observed by NMR, and implications of the results for factors limiting the rates of their biosynthesis in ammonia- and nitrate-grown cells are discussed.

    Title Purification and Characterization of Arginase from Neurospora Crassa.
    Date June 1987
    Journal The Journal of Biological Chemistry
    Excerpt

    We have purified an enzymatically active form of arginase from a wild-type strain of Neurospora crassa to homogeneity. The enzyme has a subunit molecular weight of 38,300 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The native protein migrated as a hexamer during gel-filtration chromatography with an apparent molecular weight of 266,000. The enzyme exhibited hyperbolic kinetics at pH 9.5 with an apparent Km for arginine of 131 mM. Antiserum was prepared against the purified enzyme and used to demonstrate the existence of three cross-reactive proteins in crude extracts of wild-type N. crassa. One of these proteins corresponded to the purified protein, whereas the other two were of molecular weights 41,700 and 26,800, respectively. Using the same antiserum, we found that rat liver, but not rat kidney, contains immunoreactive material. We also detected two proteins in extracts of Saccharomyces cerevisiae that were weakly cross-reactive with the antiserum. These data provide evidence for the existence of multiple forms of arginase in fungi as well as in mammals.

    Title A Single Precursor Protein for Two Separable Mitochondrial Enzymes in Neurospora Crassa.
    Date June 1987
    Journal The Journal of Biological Chemistry
    Excerpt

    The arg-6 locus of Neurospora crassa encodes two early enzymes of the arginine biosynthetic pathway, acetylglutamate kinase and acetylglutamyl-phosphate reductase. Previous genetic and biochemical analyses of this locus and its products showed that: 1) strains carrying polar nonsense mutations in the acetylglutamate kinase gene lacked both enzyme activities (Davis, R.H., and Weiss, R.L. (1983) Mol. Gen. Genet. 192, 46-50), and 2) the proteins isolated from mitochondria were completely separable (Wandinger-Ness, A., Wolf, E.C., Weiss, R.L., and Davis, R.H. (1985) J. Biol. Chem. 260,5974-5978). These data suggested that the two enzymes were initially synthesized as a single precursor which was subsequently cleaved into two distinct polypeptides. We report here the identification of a high molecular weight protein, synthesized in vitro from isolated N. crassa RNA, that contains sequences corresponding to acetylglutamate kinase as well as acetylglutamyl-phosphate reductase. An analogous precursor was identified in vivo by pulse-labeling experiments. The precursor was similar to other mitochondrial precursors in that its uptake and processing in vivo was rapid and required an intact mitochondrial electrochemical gradient. This represents the first report of a bifunctional protein precursor which gives rise to two mitochondrial enzymes.

    Title Simultaneous Cytomegalovirus and Herpes Simplex Virus Pneumonia.
    Date March 1987
    Journal Archives of Pathology & Laboratory Medicine
    Excerpt

    A 35-year-old patient who underwent renal transplant developed persistent fever, hypoxemia, and diffuse interstitial pulmonary infiltrates one month after allograft implantation. An open lung biopsy specimen demonstrated simultaneous infection with cytomegalovirus and herpes simplex virus type 1. This initially was unsuspected on routine histology, but was confirmed by the demonstration of both viruses with immunofluorescence, as well as the timely recovery in culture of both. The clinical and pathologic implications of an accurate diagnosis of such a simultaneous infection are discussed.

    Title Current Concepts in the Surgical Pathology of Pulmonary Infections.
    Date March 1987
    Journal The American Journal of Surgical Pathology
    Excerpt

    Among patients with pulmonary infections, those who are immunosuppressed and have pulmonary infiltrates continue to be the most numerous coming to biopsy and present the greatest diagnostic challenge to the surgical pathologist. These are the cases in which immunodiagnostic methods and DNA probes are immediately beneficial. Enthusiasm for application of these new methods for the recognition of infectious agents must be tempered by careful clinicopathologic correlation, since more sensitive methods are likely to pick up more bystander organisms and polymicrobial processes. Nevertheless, the development of organism-specific visualization reagents remains one of the most exciting areas in pathology.

    Title Group B Streptococcal Breast Abscess.
    Date January 1987
    Journal Archives of Pathology & Laboratory Medicine
    Excerpt

    A 22-year-old women was admitted to the hospital with a large, tender supraareolar mass of her right breast. Cultures of the purulent aspirate yielded beta-hemolytic group B streptococcus. Surgical incision and drainage, together with therapy with erythromycin ethylsuccinate in this penicillin-allergic patient, resulted in cure. This is the first report, to our knowledge, of group B streptococcus causing human breast abscess.

    Title Control of Arginine Metabolism in Neurospora Crassa. Role of Feedback Inhibition.
    Date September 1986
    Journal The Journal of Biological Chemistry
    Excerpt

    Flux through the arginine biosynthetic pathway of Neurospora crassa was measured under a variety of physiological conditions. Flux persisted, although at a reduced rate, in mutant strains resistant to feedback inhibition even after prolonged growth in the presence of exogenous arginine. Flux reverted to the uninhibited rate more quickly in feedback-resistant strains than in wild type strains upon removal of exogenous arginine. These results rule out enzyme repression as a major factor in controlling arginine biosynthesis. Feedback inhibition was shown to be independent of the size of the mycelial arginine pool or of the cytosolic arginine concentration, suggesting a role for the mitochondrial membrane in controlling the concentration of arginine at the site of inhibition--the mitochondrial matrix. The implications of these results are discussed.

    Title The Properties of Arginine Transport in Vacuolar Membrane Vesicles of Neurospora Crassa.
    Date August 1986
    Journal The Journal of Biological Chemistry
    Excerpt

    We have measured the uptake of arginine into vacuolar membrane vesicles from Neurospora crassa. Arginine transport was found to be dependent on ATP hydrolysis, Mg2+, time, and vesicle protein with transported arginine remaining unmodified after entry into the vesicles. The Mg2+ concentration required for optimal arginine transport varied with the ATP concentration so that maximal transport occurred when the MgATP2- concentration was at a maximum and the concentrations of free ATP and Mg2+ were at a minimum. Arginine transport exhibited Michaelis-Menten kinetics when the arginine concentration was varied (Km = 0.4 mM). In contrast, arginine transport did not follow Michaelis-Menten kinetics when the MgATP2-concentration was varied (S0.5 = 0.12 mM). There was no inhibition of arginine transport when glutamine, ornithine, or lysine were included in the assay mixture. In contrast, arginine transport was inhibited 43% when D-arginine was present at a concentration 16-fold higher than that of L-arginine. Measurements of the internal vesicle volume established that arginine is concentrated 14-fold relative to the external concentration. Arginine transport was inhibited by dicyclohexylcarbodiimide, carbonyl cyanide m-chlorophenyl-hydrazone, and potassium nitrate (an inhibitor of vacuolar ATPase activity). Inhibitors of the plasma membrane or mitochondrial ATPase such as sodium vanadate or sodium azide did not affect arginine transport activity. In addition, arginine transport had a nucleoside triphosphate specificity similar to that of the vacuolar ATPase. These results suggest that arginine transport is dependent on vacuolar ATPase activity and an intact proton channel and proton gradient.

    Title Scheuermann's Dorsal Kyphosis and Spinal Cord Compression: Case Report.
    Date June 1986
    Journal Neurosurgery
    Excerpt

    Although Scheuermann's disease (juvenile dorsal kyphosis) is a common problem of late childhood and adolescence, its potential for neurological complications is not widely appreciated. In rare instances, spinal cord compression appears to be produced by the kyphotic protrusion alone, and we present an example of this unusual problem. Although the results of surgical treatment in this situation cannot be substantiated, anterior spondylotomy and decompression followed by posterior fixation appear to offer the best mechanical relief. Spinal cord compression can also be produced by extradural cysts, with which Scheuermann's disease is frequently associated. Scheuermann's disease also is reported to occur in combination with thoracic disc protrusion, but the coincidence here may be random. Pertinent literature is reviewed.

    Title Effect of Chloramphenicol and Ethidium Bromide on the Level of Ornithine Carbamoyltransferase in Neurospora Crassa.
    Date June 1986
    Journal Journal of Bacteriology
    Excerpt

    The specific activity of the nuclear-gene-encoded, mitochondrial arginine biosynthetic enzyme ornithine carbamoyltransferase (EC 2.1.3.3) in Neurospora crassa was elevated in mycelia treated with chloramphenicol or ethidium bromide. The increase in specific activity was caused by an increase in the number of mature enzyme molecules rather than by the activation of a preexisting enzyme. Chloramphenicol and ethidium bromide appeared to act indirectly via arginine-mediated derepression. However, derepression did not appear to result from a drug-mediated decrease in the arginine pool.

    Title N-acetyl-l-glutamate Synthase of Neurospora Crassa. Characteristics, Localization, Regulation, and Genetic Control.
    Date May 1986
    Journal The Journal of Biological Chemistry
    Excerpt

    N-Acetylglutamate synthase, an early enzyme of the arginine pathway, provides acetylglutamate for ornithine synthesis in the so-called "acetylglutamate cycle." Because acetylglutamate is regenerated as ornithine is formed, the enzyme has only a catalytic or anaplerotic role in the pathway, maintaining "bound" acetyl groups during growth. We have detected this enzyme in crude extracts of Neurospora crassa and have localized it to the mitochondria along with other ornithine biosynthetic enzymes. The enzyme is bound to the mitochondrial membrane. The enzyme has a pH optimum of 9.0 and Km values for glutamate and CoASAc of 6.3 and 1.6 mM, respectively. It is feedback-inhibited by L-arginine (I0.5 = 0.16 mM), and its specific activity is augmented 2-3-fold by arginine starvation of the mycelium. Mutants of the newly recognized arg-14 locus lack activity for the enzyme. Because these mutants are complete auxotrophs, we conclude that N-acetylglutamate synthase is an indispensible enzyme of arginine biosynthesis in N. crassa. This work completes the assignment of enzymes of the arginine pathway of N. crassa to corresponding genetic loci. The membrane localization of the enzyme suggests a novel mechanism by which feedback inhibition might occur across a semipermeable membrane.

    Title Simultaneous Purification of Three Mitochondrial Enzymes. Acetylglutamate Kinase, Acetylglutamyl-phosphate Reductase and Carbamoyl-phosphate Synthetase from Neurospora Crassa.
    Date May 1986
    Journal The Journal of Biological Chemistry
    Excerpt

    The early enzymes of arginine biosynthesis in Neurospora crassa are localized in the mitochondrion and catalyze the conversion of glutamate to citrulline. The final conversion of citrulline to arginine occurs via two enzymatic steps in the cytoplasm. We have devised a method for the isolation and purification of three of the mitochondrial arginine biosynthetic enzymes from a single extract. Acetylglutamate kinase and acetylglutamyl-phosphate reductase (both products of the complex arg-6 locus) were purified to homogeneity and near homogeneity, respectively. The large catalytic subunit of carbamoyl-phosphate synthetase was also purified to homogeneity. The three enzymes were resolved into separate fractions by chromatography on three dye-ligand affinity resins, which are specific for nucleotide binding enzymes and have a high protein binding capacity. High performance liquid chromatography was employed in the final stages of purification and was extremely effective in fractionating both acetylglutamate kinase and acetylglutamyl-phosphate reductase from proteins with very similar properties, which were not removed by other techniques. The purified proteins were used to raise specific antisera against these proteins. Acetylglutamate kinase and acetylglutamyl-phosphate reductase were shown to be immunologically unrelated. This finding suggests that the arg-6 locus encompasses two nonoverlapping cistrons. The antisera raised against carbamoyl-phosphate synthetase has been shown to cross-react with related enzymes in Saccharomyces cerevisiae, Escherichia coli, and rat liver (Ness, S. A., and Weiss, R. L. (1985) J. Biol. Chem. 260, 14355-14362). Acetylglutamate kinase is a regulatory enzyme and has been shown to be feedback-inhibited by arginine. We have determined the submitochondrial localization of acetylglutamate kinase and the second arg-6 product, acetylglutamyl-phosphate reductase. Both enzymes were shown to be soluble matrix enzymes. We discuss the relevance of this finding with respect to possible mechanisms for end product inhibition of a mitochondrial enzyme by a cytoplasmic effector.

    Title Carbamoyl-phosphate Synthetases from Neurospora Crassa. Immunological Relatedness of the Enzymes from Neurospora, Bacteria, Yeast, and Mammals.
    Date December 1985
    Journal The Journal of Biological Chemistry
    Excerpt

    Neurospora crassa contains two carbamoyl-phosphate synthetases: a mitochondrial enzyme (CPS-A) which supplies carbamoyl phosphate for arginine biosynthesis, and a nuclear enzyme whose product is used for the synthesis of pyrimidines. We have prepared antiserum against a highly purified preparation of the large subunit of CPS-A and have used the antiserum to demonstrate that the large subunit is, like most mitochondrially localized proteins, initially synthesized as a higher molecular weight precursor. The CPS-A antiserum cross-reacts with the nuclear enzyme, allowing us to identify the product of the complex N. crassa pyr-3 genetic locus as a protein with a subunit molecular weight of 180,000. Finally, we have found that the CPS-A antiserum also cross-reacts with carbamoyl-phosphate synthetases from bacteria, yeast, and mammals. The immunological relatedness of carbamoyl-phosphate synthetases from such diverse species suggests that the protein sequences required for carbamoyl phosphate production have been highly conserved during the course of evolution.

    Title Fungal Contamination of Balanced Salt Solution.
    Date November 1985
    Journal Journal - American Intra-ocular Implant Society
    Excerpt

    A fungal organism, identified as Ulocladium, was isolated from an unopened 15 ml bottle of balanced salt solution. The authors note the importance of visually inspecting solutions used in ophthalmic surgery.

    Title Multilobated B Cell Lymphomas. A Study of 7 Cases.
    Date August 1985
    Journal Hematological Oncology
    Excerpt

    Seven cases of multilobated lymphomas with B cell surface markers are presented. Clinical, histological, ultrastructural and immunohistochemical features are detailed. These observations serve to underscore the importance of not relying on morphology alone for the phenotypic classification of non-Hodgkin's lymphomas.

    Title Acetylglutamate Kinase-acetylglutamyl-phosphate Reductase Complex of Neurospora Crassa. Evidence for Two Polypeptides.
    Date June 1985
    Journal The Journal of Biological Chemistry
    Excerpt

    Mutations at the arg-6 locus in Neurospora crassa are divided into two complementation groups (A and B) and a third noncomplementing group. There are many suppressible nonsense mutations among mutants in complementation group B and one in the noncomplementing group; no nonsense mutations exist among mutants in complementation group A (Davis, R. H., and Weiss, R. L. (1983) Mol. Gen. Genet. 192, 46-50). We show here that the mutants are defective in either or both of two enzymes of arginine biosynthesis, acetylglutamate kinase and/or acetylglutamyl-phosphate reductase. Mutants in complementation group A lack acetylglutamate kinase, those in complementation group B lack acetylglutamyl-phosphate reductase, and those in the noncomplementing group lack both activities. Mutants in group B also have reduced levels of acetylglutamate kinase. The enzymes from purified mitochondria are readily separable by gel filtration and by Blue A dye affinity chromatography. Acetylglutamate kinase appears to be an octamer with a molecular weight of 400,000, whereas acetylglutamyl-phosphate reductase appears to be a dimer with a molecular weight of 93,000. This suggests that the two activities reside on distinct polypeptides. These results are best accommodated by the following model: the arg-6 locus encodes a single mRNA which is translated into a single polypeptide; the latter is then cleaved post-translationally to yield two physically separable enzymes.

    Title Ornithine Transcarbamylase from Neurospora Crassa: Purification and Properties.
    Date June 1985
    Journal Archives of Biochemistry and Biophysics
    Excerpt

    Ornithine transcarbamylase catalyzes the synthesis of citrulline from carbamyl phosphate and ornithine. This enzyme is involved in the biosynthesis of arginine in many organisms and participates in the urea cycle of mammals. The biosynthetic ornithine transcarbamylase has been purified from the filamentous fungus, Neurospora crassa. It was found to be a homotrimer with an apparent subunit molecular weight of 37,000 and a native molecular weight of about 110,000. Its catalytic activity has a pH optimum of 9.5 and Km's of about 5 and 2.5 mM for the substrates, ornithine and carbamyl phosphate, respectively, at pH 9.5. The Km's and pH optimum are much higher than those of previously characterized enzymes from bacteria, other fungi, and mammals. These unusual kinetic properties may be of significance with regard to the regulation of ornithine transcarbamylase in this organism, especially in the avoidance of a futile ornithine cycle. Polyclonal antibodies were raised against the purified enzyme. These antibodies and antibody raised against purified rat liver ornithine transcarbamylase were used to examine the structural similarities of the enzyme from a number of organisms. Cross-reactivity was observed only for mitochondrial ornithine transcarbamylases of related organisms.

    Title Localization of Concanavalin A Binding Carbohydrate in Chlamydomonas Flagella.
    Date December 1984
    Journal Journal of Cell Science
    Excerpt

    Chlamydomonas flagella are shown to possess two zones of concanavalin A (ConA) binding carbohydrate. The first zone, distinguished by a requirement for a prolonged labelling period for visualization of fluorescein isothiocyanate (FITC)-ConA fluorescence, is localized in the flagellar coat. The second zone is characterized by a rapid FITC- and [125I]ConA labelling subsequent to disruption of the flagellar membrane, but is unaffected by reagents that act only on the flagellar surface coat. Electron microscopy and ferritin-ConA labelling indicate that this subsurface zone is localized between the flagellar membrane and axoneme in the space that we term the flagelloplasm. These results are used to suggest possible functions for ConA binding glycosyl residues in flagella.

    Title Improved Coating and Fixation Methods for Scanning Electron Microscope Autoradiography.
    Date September 1984
    Journal Biology of the Cell / Under the Auspices of the European Cell Biology Organization
    Excerpt

    A simple apparatus for emulsion coating is described. The apparatus is inexpensive and easily assembled in a standard glass shop. Emulsion coating for scanning electron microscope autoradiography with this apparatus consistently yields uniform layers. When used in conjunction with newly described fixation methods, this new approach produces reliable autoradiographs of undamaged specimens.

    Title Distribution of Concanavalin a Binding Carbohydrates During Mating in Chlamydomonas.
    Date September 1984
    Journal Journal of Cell Science
    Excerpt

    Cell surface carbohydrates, detected by fluorescein isothiocyanate/concanavalin A (FITC-ConA), were identified at four locations on gametes of Chlamydomonas reinhardtii. (1) The cell wall: uniform labelling with FITC-ConA was observed; a substantial number of sites were localized in the sodium dodecyl sulphate-insoluble inner wall, which contains the flagellar collars. (2) The periplasm: a crescent-shaped area was visualized with FITC-ConA and localized by ferritin-ConA. We were able to recover autolytic activity on a ConA affinity column from the mating medium of wild-type cells after the release of these periplasmic sites. The cell-wall-less mutant CW15 displays no periplasmic sites and demonstrates a corresponding inability to release autolytic activity after mating for 60 min. A model for wall lysis is presented, which considers the involvement of these sites in the lytic process. (3) The mating structure: during mating a small fluorescent plaque-like site was observed on cells at a location corresponding to the carbohydrate-like zone of the mating type minus mating structure and may indicate the involvement of ConA binding material in gametic cell fusion. (4) Secreted products: following cell fusion zygotes begin to secrete ConA positive material at about 1 1/2 h. After 24 h a ConA positive zygote wall and pellicle appear.

    Title Ultrastructure of the Flagellar Roots in Chlamydomonas Gametes.
    Date September 1984
    Journal Journal of Cell Science
    Excerpt

    The cytoskeleton of Chlamydomonas reinhardtii gametes has been studied by electron microscopy. The microtubular system, consisting of four flagellar roots inserted into the basal apparatus, is shown to include two daughter basal bodies and two striated fibres, newly described in this report. One new fibre associates with the 3-over-1 root and is similar to its counterpart, the striated fibre of the 2-member root. These similar root fibres connect each daughter basal body to the V-shaped microtubular root pair. The other new striated fibre joins the daughter basal body to both flagellar roots and is similar to the proximal striated fibre. In mt+ gametes, the conventional root microtubules make direct contact with the doublet zone of the non-activated mating structure. During activation, doublet zone microfilaments associate with the daughter basal body and the finely striated fibre of the 3-over-1 root. These observations suggest that the cytoskeleton acts as a scaffolding for membrane extension by the mt+ mating structure microfilaments.

    Title Mobilization of Vacuolar Arginine in Neurospora Crassa. Mechanism and Role of Glutamine.
    Date August 1984
    Journal The Journal of Biological Chemistry
    Excerpt

    Nitrogen starvation has been shown to increase the cytosolic arginine concentration and to accelerate protein turnover in mycelia of Neurospora crassa. The cytosolic arginine is derived from a metabolically inactive vacuolar pool. Redistribution of arginine between cytosolic and vacuolar compartments is the result of mobilization of this metabolite in response to nitrogen starvation. Mobilization of arginine (and purines) also occurred in response to glutamine limitation, but arginine accumulated upon proline starvation. These observations indicate that mobilization is a consequence of glutamine limitation rather than a general response to amino acid starvation (or limitation). Analysis of the amino acid pools in mycelia subjected to starvation or limitation suggests that glutamine (or a metabolite derived from glutamine) provides a signal which determines the metabolic fate of vacuolar arginine. The results are consistent with the hypothesis that vacuolar compartmentation provides a readily available store of nitrogen-rich compounds to be utilized during differentiation or under conditions of nutritional stress.

    Title Cloning and Characterization of the Ornithine Carbamoyltransferase Gene from Aspergillus Nidulans.
    Date February 1984
    Journal Gene
    Excerpt

    An Aspergillus nidulans DNA fragment composed of two adjacent SalI subfragments (1.8 and 0.85 kb) that carries an argB gene complementing the yeast arg3 mutation has been isolated from two different gene libraries. Hybridization results and immunological tests indicate that the cloned fragment contains the A. nidulans structural gene coding for ornithine carbamoyltransferase (OTCase). Using the cloned gene as a probe, the specific mRNA was identified. The level of this RNA observed in A. nidulans strains grown under various conditions correlated with the level of the OTCase activity, suggesting transcriptional control of OTCase synthesis. Expression of the cloned gene in Saccharomyces cerevisiae does not depend on its orientation in the vector. In Escherichia coli, the cloned gene does not function; however arg- transformants revert to prototrophy with high frequency possibly due to DNA rearrangements within the recombinant plasmid.

    Title Measurements of Cytoplasmic and Vacuolar Ph in Neurospora Using Nitrogen-15 Nuclear Magnetic Resonance Spectroscopy.
    Date June 1983
    Journal Biochemistry
    Excerpt

    The nitrogen-15 chemical shift of the N1 (tau)-nitrogen of 15N-labeled histidine and the half-height line widths of proton-coupled resonances of the delta- and omega,omega'-nitrogens of 15N-labeled arginine and of the alpha-nitrogens of 15N-labeled alanine and proline were measured in intact mycelia of Neurospora crassa to obtain to estimates of intracellular pH. For intracellular 15N-labeled histidine, the N1 (tau)-nitrogen chemical shift was 200.2 ppm. In vitro measurements showed that the chemical shift was slightly affected by the presence of phosphate, with which the basic amino acids may be associated in vivo. These considerations indicate a pH of 5.7-6.0 for the environment of intracellular histidine. The half-height line widths of the delta- and omega,omega'-nitrogens of [15N]arginine were 15 and 26 Hz, respectively. In vitro studies showed that these line widths also are influenced by the presence of phosphate, and, after suitable allowance for this, the line widths indicate pH 6.1-6.5 for intracellular arginine. The half-height line widths for intracellular alanine and proline were 17 and 12 Hz, respectively, which are consistent with an intracellular pH of 7.1-7.2. Pools of histidine and arginine are found principally in the vacuole of Neurospora, most likely in association with polyphosphates. Proline and alanine are cytoplasmic. The results reported here are consistent with these localizations and indicate that the vacuolar pH is 6.1 +/- 0.4 while the cytoplasmic pH is 7.15 +/- 0.10. Comparisons of these estimates with those obtained by other techniques and their implications for vacuolar function are discussed.

    Title Effect of the Nitrogen Source on Glutamine and Alanine Biosynthesis in Neurospora Crassa. An in Vivo 15n Nuclear Magnetic Resonance Study.
    Date January 1983
    Journal The Journal of Biological Chemistry
    Excerpt

    The influences of different nitrogen sources on the relative rates of biosynthesis of glutamine and alanine have been studied by 15N nuclear magnetic resonance spectroscopy of intact Neurospora crassa mycelia suspensions. The rate of glutamine synthesis was fastest after growth in media deficient in free ammonium ion, whereas it was slowest following growth in media containing both glutamic acid and glutamine. The reverse trend was observed for the biosynthesis of alanine. A competition between the two biosynthetic pathways for the same substrate, glutamic acid, was found to limit the rate of alanine synthesis when glutamine synthesis was rapid. The observed in vivo rates of these reactions are compared to the reported specific activities of the enzymes catalyzing the reactions, and implications of these results for nitrogen regulation of these pathways under various physiological conditions are discussed.

    Title Nitrogen-15 Spin-lattice Relaxation Times of Amino Acids in Neurospora Crassa As a Probe of Intracellular Environment.
    Date January 1983
    Journal Biochemistry
    Excerpt

    The nitrogen-15 spin-lattice relaxation time, T1, and the nuclear Overhauser enhancement (NOE) have been measured for intracellular glutamine, alanine, and arginine in intact Neurospora crassa mycelia to probe their various intracellular environments. The relaxations of 15N gamma of glutamine, 15N alpha of alanine, and 15N omega, omega ' of arginine in N. crassa were found, on the basis of their NOE values, to be predominantly the result of 15N-H dipolar relaxation. These relaxations are therefore related to the microviscosities of the various environments and associations of the respective molecules with other cellular components that act to increase the effective molecular sizes. For 15N gamma of glutamine in the cytoplasm, the intracellular T1 (4.1 s) was only slightly shorter than that in the culture medium (4.9 s). This indicates that the microviscosity of the cytoplasm surrounding the glutamine molecules is not much greater than 1.3 cP. By contrast, for 15N omega, omega ' of arginine, which is sequestered in vacuoles containing polyphosphates, the intracellular T1 (1.1 s) was only one-fourth of that in the medium (4.6 s). In model systems, the T1 of 15N omega, omega ' in a 1 M aqueous solution of arginine containing 0.2 M pentaphosphate was 0.95 s, whereas in an isoviscous (2.8 cP) solution without pentaphosphate, the T1 was 1.8 s. These results suggest either that the vacuolar viscosity is substantially above 2.8 cP or that the omega, omega '-nitrogens of vacuolar arginine are associated with a polyanion, possibly polyphosphate. The implications of these results for the properties of the vacuolar interior are discussed in relation to the mechanism of amino acid compartmentation.

    Title Energetics of Vacuolar Compartmentation of Arginine in Neurospora Crassa.
    Date June 1982
    Journal Journal of Bacteriology
    Excerpt

    The energy requirements for the uptake and retention of arginine by vacuoles of Neurospora crassa have been studied. Exponentially growing mycelial cultures were treated with inhibitors of respiration or glycolysis or an uncoupler of respiration. Catabolism of arginine was monitored as urea production in urease-less strains. The rationale was that the rate and extent of such catabolism was indicative of the cytosolic arginine concentration. No catabolism was observed in cultures treated with an inhibitor or an uncoupler of respiration, but cultures treated with inhibitors of glycolysis rapidly degraded arginine. These differences could not be accounted for by alterations in the level or activity of arginase. Mycelia growing in arginine-supplemented medium and treated with an inhibitor or uncoupler of respiration degraded an amount of arginine equivalent to the cytosolic fraction of the arginine pool. The inhibitors and the uncoupler of respiration reduced the ATP pool and the energy charge. The inhibitors of glycolysis reduced the ATP pool but did not affect the energy charge. The results suggest that metabolic energy is required for the transport of arginine into the vacuoles but not for its retention. The latter is affected by inhibitors of glycolysis. The form of energy and the nature of the vacuolar transport mechanism(s) are discussed.

    Title Energy Requirement for the Mobilization of Vacuolar Arginine in Neurospora Crassa.
    Date June 1982
    Journal Journal of Bacteriology
    Excerpt

    The bulk of the intracellular arginine pool in exponentially growing mycelia of Neurospora crassa is sequestered in the vacuoles. Vacuolar arginine effluxes from the vacuoles into the cytosol and is catabolized to ornithine and urea upon nitrogen starvation. The energy requirement for mobilization has been studied by treating nitrogen-starved mycelia with inhibitors or respiration or glycolysis or an uncoupler of respiration. Mobilization was inhibited by the inhibitors or the uncoupler of respiration, but not by the inhibitors of glycolysis. The inhibitors and the uncoupler of respiration reduced the ATP pool and the energy charge of the treated mycelia. The inhibitors of glycolysis reduced the ATP pool but had no effect on the energy charge. The results indicate that mobilization of arginine from the vacuoles requires metabolic energy. The forms of this energy and the mode of its association with the mobilization process are discussed.

    Title Scanning Electron Microscope Autoradiography of Critical Point Dried Biological Samples.
    Date September 1981
    Journal Scanning Electron Microscopy
    Excerpt

    A technique has been developed for the localization of isotopes in the scanning electron microscope. Autoradiographic studies have been performed using a model system and a unicellular biflagellate alga. One requirement of this technique is that all manipulations be carried out on samples that are maintained in a liquid state. Observations of a source of radiation (125I-ferritin) show that the nuclear emulsion used to detect radiation is active under these conditions. Efficiency measurement performed using 125I-ferritin indicate that 125-I-SEM autoradiography is an efficient process that exhibits a 'dose dependent' response. Two types of labeling methods were used with cells, surface labeling with 125I and internal labeling with 3H. Silver grains appeared on labeled cells after autoradiography, removal of residual gelatin and critical point drying. The location of grains was examined on a flagellated green alga (Chlamydomonas reinhardi) capable of undergoing cell fusion. Fusion experiments using labeled and unlabeled cells indicate that 1. Labeling is specific for incorporated radioactivity; 2. Cell surface structure is preserved in SEM autoradiographs and 3. The technique appears to produce reliable autoradiographs. Thus scanning electron microscope autoradiography should provide a new and useful experimental approach.

    Title 15n Nmr Studies of Nitrogen Metabolism in Intact Mycelia of Neurospora Crassa.
    Date July 1981
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    Suspensions of intact mycelia of Neurospora crassa grown in medium containing 15NH4Cl have been found to give well-resolved 15N nuclear magnetic resonance spectra for metabolites that play crucial roles in intermediary nitrogen metabolism. These include the amide nitrogen of glutamine, the alpha-amino nitrogens of glutamate and other amino acids, the guanidino nitrogens of arginine, the ureido nitrogen of citrulline, the side-chain nitrogens of ornithine or lysine, or both, and uridine diphosphates. The turnover time of glutamine in vivo was estimated to be less than 1 hr by using nuclear magnetic resonance spectroscopy in conjunction with tracer methodologies. Applications of these techniques to the study of nitrogen metabolism are discussed.

    Title Acetylglutamate Kinase. A Mitochondrial Feedback-sensitive Enzyme of Arginine Biosynthesis in Neurospora Crassa.
    Date November 1980
    Journal The Journal of Biological Chemistry
    Excerpt

    The radioisotopic method used to assay acetylglutamate kinase (EC 2.7.2.8) of Neurospora crassa has been shown to detect two distinct enzymatically catalyzed reactions. The enzymes were separated by differential centrifugation into a cytosolic activity and an organellar activity. Both activities required ATP and were thermal-labile. The cytosolic activity was insensitive to inhibition by arginine and formed a stable reaction product in the absence of hydroxylamine. The organellar activity had an absolute requirement for hydroxylamine in order to form a stable reaction product. The product of the cytosolic activity was separated from acetylglutamate hydroxamate (the product of the organellar activity) and was identified as the cyclic amide pyroglutamate by cation exchange chromatography. The organellar activity has been implicated in arginine biosynthesis by the following criteria: it was completely and specifically inhibited by arginine concentrations as low as 200 microM; its level was elevated 2-fold in a mutant strain with derepressed levels of arginine biosynthetic enzymes; and it was absent in an arginine auxotrophic strain (the cytosolic activity was present). The organellar activity co-sedimented with mitochondria during isopycnic gradient centrifugation. The metabolic problems posed by a mitochondrial location of a feedback-sensitive enzyme and the cytosolic location of its effector are discussed.

    Title Generalizability Theory and the Coding of Marital Interactions.
    Date October 1980
    Journal Journal of Consulting and Clinical Psychology
    Title Isolation and Characterization of Neurospora Crassa Mutants Impaired in Feedback Control of Ornithine Synthesis.
    Date June 1980
    Journal Journal of Bacteriology
    Excerpt

    Thirty-two independent mutants were isolated which overcame the proline requirement of pro-3 mutations in Neurospora crassa. The mutations were not revertants, appeared to be allelic, were closely linked or allelic to arg-6, and in strains unable to degrade ornithine no longer suppressed the proline requirement. The suppressor mutations did not alter the levels of biosynthetic or catabolic enzymes, yet allowed accumulation of ornithine. Suppressed strains unable to degrade arginine still produced ornithine (as detected by growth) in arginine-supplemented medium. The results suggest that the suppressor mutants were impaired in the feedback inhibition of ornithine synthesis by arginine. The activity of the appropriate biosynthetic enzyme was less sensitive to inhibition by arginine. The potential usefulness of such mutations is discussed.

    Title Effect of Carbon Source on Enzymes and Metabolites of Arginine Metabolism in Neurospora.
    Date April 1980
    Journal Journal of Bacteriology
    Excerpt

    The levels of enzymes and metabolites of arginine metabolism were determined in exponential cultures of Neurospora crassa grown on various carbon sources. The carbon sources decreased in effectiveness (as determined by generation times) in the following order: sucrose, acetate, glycerol, and ethanol. The basal and induced levels of the catabolic enzymes, arginase (EC 3.5.3.1) and ornithine transaminase (EC 2.6.1.13), were lower in mycelia grown on poor carbon sources. Arginase was more sensitive to variations in carbon source than was ornithine transaminase. Induction of both enzymes was sensitive to nitrogen metabolite control, but this sensitivity was reduced in mycelia grown on glycerol or ethanol. The pools of arginine and ornithine were reduced in mycelia grown in unsupplemented medium containing poor carbon sources, but the biosynthetic enzyme ornithine transcarbamylase (EC 2.1.3.3) was not derepressed. The arginine pools were similar, regardless of carbon source, in mycelia grown in arginine-supplemented medium. The ornithine pool was reduced by growth on poor carbon sources. The rate of arginine degradation was proportional to the level of arginase in both sucrose- and glycerol-grown mycelia. The distribution of arginine between cytosol and vesicles was only slightly altered by growth on glycerol instead of sucrose. The slightly smaller cytosolic arginine concentration did not appear to be sufficient to account for the alterations in basal and induced enzyme levels. The results suggest a possible carbon metabolite effect on the expression or turnover of a variety of genes for enzymes of arginine metabolism in Neurospora.

    Title Control of Arginine Metabolism in Neurospora: Flux Through the Biosynthetic Pathway.
    Date April 1980
    Journal Journal of Bacteriology
    Excerpt

    The flux into the arginine biosynthetic pathway of Neurospora crassa was investigated using a mutant strain lacking the ornithine-degrading enzyme ornithine aminotransferase (EC 2.6.1.13). Flux was measured by the increase in the sum of the radioactivity (derived from [14C]glutamic acid) in the ornithine pool, the arginine pool, and arginine incorporated into proteins. Complete cessation of flux occurred immediately upon the addition of arginine to the growth medium. This response occurred prior to expansion of the arginine pool. After short-term exposure to arginine (80 min), flux resumed quickly upon exhaustion of arginine from the medium. This took place despite the presence of an expanded arginine pool. Initiation of flux required approximately 80 min when the mycelia were grown in arginine-supplemented medium for several generations before exhaustion of the exogenous arginine. The arginine pool of such mycelia was similar to that found in mycelia exposed to exogenous arginine for only 80 min. The results are consistent with rapid onset and release of feedback inhibiton of arginine biosynthesis in response to brief exposure to exogenous arginine. The insensitivity of flux to the size of the arginine pool is consistent with a role for compartmentation in this regulatory process. The lag in initiation of flux after long-term growth in the presence of exogenous arginine suggests the existence of an additional regulatory mechanism(s). Several possibilities are discussed.

    Title Mobilization of Sequestered Metabolities into Degradative Reactions by Nutritional Stress in Neurospora.
    Date September 1979
    Journal Journal of Bacteriology
    Excerpt

    The pools of arginine and ornithine rapidly disappear during nitrogen starvation of Neurospora crassa. Much of this disappearance can be accounted for by degradation catalyzed by preexisting catabolic enzymes. Purine degradation is also initiated by nitrogen metabolic stress. Mobilization of these compounds into degradative reactions does not appear to be a general response to nutritional stress since neither carbon starvation nor inhibition of protein synthesis elicits this response. It is suggested that nitrogen starvation may specifically alter the distribution of arginine and ornithine between vesicles and cytosol. This would be sufficient to initiate and maintain their degradation. These result suggest that compartmentation of amino acids provides a metabolic reserve to be utilized during periods of specific nutritional stress.

    Title Enzyme Assays Using Permeabilized Cells of Neurospora.
    Date July 1979
    Journal Analytical Biochemistry
    Title Intracellular Compartmentation and Transport of Metabolites.
    Date July 1979
    Journal Journal of Supramolecular Structure
    Excerpt

    The intracellular locations of enzymes and metabolites were determined for ornithine metabolism in Neurospora. Pulse label experiments were used to measure the rates of intracellular translocations and the sizes of compartmented pools of metabolites in the mitochondrial, cytosolic and vesicular compartments. The results indicate that rapid equilibration occurs between these pools during growth in minimal medium, although the vast majority of the ornithine is confined to the vesicular compartment. Arginine, the biosynthetic end-product of ornithine metabolism, regulates ornithine utilization through a combination of feedback inhibition, repression, and control of intracellular translocations. The last phenomenon plays a decisive role indicating that the regulation of intercompartmental translocations may be a common mechanism in rapid adaptation responses in eukaryotic cells.

    Title Marital Satisfaction and Depression As Predictors of Physical Health Status.
    Date March 1979
    Journal Journal of Consulting and Clinical Psychology
    Title Comparative Evaluation of Therapeutic Components Associated with Behavioral Marital Treatments.
    Date March 1979
    Journal Journal of Consulting and Clinical Psychology
    Title Mycoplasma Capping on Lymphocytes.
    Date February 1979
    Journal Nature
    Excerpt

    When mycoplasmas infect lymphocytes they behave as multivalent ligands and cap on the lymphoid cell surface in the absence of added specific antibody. There is an apparent high correlation between mycoplasma capping and blast transormation of the infected lymphocytes. Mycoplasma caps are shed from the surface of cells as an aggregate containing host membrane vesicles. This novel interaction may suggest a physiological role for the phenomenon of capping and may play a part in mycoplasma pathogenesis.

    Title Methods for Protoplast Formation in Escherichia Coli.
    Date November 1978
    Journal Methods in Cell Biology
    Title Behavioral Marriage Therapy. Iii. The Contents of Gurman Et Al. May Be Hazardous to Our Health.
    Date October 1978
    Journal Family Process
    Excerpt

    This paper was written as a reply to a critique of behavioral marital therapy (BMT) by Gurman, Kniskern, and Knudson (6, 7). The reply is divided into four sections. First, the paper addresses the critics' comments on the conceptual model put forth by BMT, correcting and clarifying various misconceptions, and restating some of the basic ideological principles in the behavioral model. Second, the paper discusses behavioral change techniques and technology, along with extratechnological treatment considerations. Again, misrepresentations of BMT are corrected. Third, an analysis of the literature investigating the therapeutic efficacy of BMT is reviewed, and the conclusion is reached that BMT is demonstrably effective, at least for a substantial number of mildly to moderately distressed couples. Criticisms are made of the analysis of the same literature conducted by Gurman et al. We conclude that, contrary to the spirit of the paper by Gurman et al., BMT is a viable framework for conceptualizing and treating relationship problems and that the commitment of its adherents to experimental investigation promises continued evolution, refinement, and improvement.

    Title Control of Arginine Metabolism in Neurospora. Induction of Ornithine Aminotransferase.
    Date November 1977
    Journal The Journal of Biological Chemistry
    Title Site-specific Membrane Particle Arrays in Magnesium-depleted Escherichia Coli.
    Date June 1977
    Journal The Journal of Cell Biology
    Excerpt

    The ultrastructure and polypeptide composition of a novel membrane junction in magnesium-starved Escherichia coli are described in this report. Freeze-fracture replicas reveal the junction as a site-specific membrane particle array with four fracture faces. Each junction consists of a cell membrane, a midline zone and a coupled membrane. Membrane particles associated with the junction extend from the hydrophobic region of the cell membrane across the hydrophilic midline zone and into the hydrophobic region of the coupled membrane. After negative staining or after rotary shadowing of freeze-fractured specimens, these particles were seen to consist of two similar but slightly offset bracket-shaped subunits separated by a small space. Optical analysis confirms this structure. Since the apposing membranes are bracketed or linked by their component particles, the name "bracket junction" is proposed for the complex. Methods are described for isolating a membrane fraction enriched in these junctional complexes; the fraction contains a prominent glycoprotein (mol wt 90,000) as well as a number of other components. The bracket junction is compared with the vertebrate gap junction in terms of both structure and possible roles in facilitating the permeation of the cell by small molecules.

    Title Control of Arginine Utilization in Neurospora.
    Date April 1977
    Journal Journal of Bacteriology
    Excerpt

    The response of Neurospora to changes in the availibility of exogenous arginine was investigated. Upon addition of arginine to the growth medium, catabolism is initiated within minutes. This occurs prior to expansion of the arginine pool or augmentation of catabolic enzyme levels. (Basal levels are approximately 25% of those found during growth in arginine-supplemented medium.) Catabolism of arginine is independent of protein synthesis, indicating that the catabolic enzymes are active but that arginine is not available for catabolism unless present in the medium. Upon exhaustion of the supply of exogenous arginine, catabolism ceases abruptly, despite an expanded arginine pool and induced levels of the catabolic enzymes. The arginine pool supports protein synthesis until the cells regain their normal capacity for endogenous arginine synthesis. These observations, combined with the known small level of induction of arginine catabolic enzymes, non-repressibility of most biosynthetic enzymes, and vesicular localization of the bulk of the arginine pool, suggest that compartmentation plays a significant role in controlling arginine metabolism in Neurospora.

    Title Membrane Particle Arrays Associated with the Basal Body and with Contractile Vacuole Secretion in Chlamydomonas.
    Date February 1977
    Journal The Journal of Cell Biology
    Excerpt

    Freeze-fracture replicas reveal that five distinct types of intramembranous particle arrays coexist within a small sector of the C. reinhardtii cell flagellar membrane. Of these, three are newly described in this report. (a) Flagellar bracelets, which encircle the flagellar bases, appear to be intrinsically ordered strands of particles of unknown function. (b) Strut arrays, representing nine sites where the basal body attaches to the membrane, appear to serve a mechanical function. (c) Contractile vacuole arrays, which develop into circular plaques of particles, appear to serve as "membrane gates" through which water is discharged from the cell.

    Title Membrane Differentiations at Sites Specialized for Cell Fusion.
    Date February 1977
    Journal The Journal of Cell Biology
    Excerpt

    Fusion of plasma membranes between Chlamydomonas reinhardtii gametes has been studied by freeze-fracture electron microscopy of unfixed cells. The putative site of cell fusion developes during gametic differentiation and is recognized in thin sections of unmated gametes as a plaque of dense material subjacent to a sector of the anterior plasma membrane (Goodenough, U.W., and R.L. Weiss. 1975.J. Cell Biol. 67:623-637). The overlying membrane proves to be readily recognized in replicas of unmated gametes as a circular region roughly 500 nm in diameter which is relatively free of "regular" plasma membrane particles on both the P and E fracture faces. The morphology of this region is different for mating-type plus (mt+) and mt- gametes: the few particles present in the center of the mt+ region are distributed asymmetrically and restricted to the P face, while the few particles present in the center of the mt- region are distributed symmetrically in the E face. Each gamete type can be activated for cell fusion by presenting to it isolated flagella of opposite mt. The activated mt+ gamete generates large expanses of particle-cleared membrane as it forms a long fertilization tubule from the mating structure region. In the activated mt- gamete, the E face of the mating structure region is transformed into a central dome of densely clustered particles surrounded by a particle-cleared zone. When mt+ and mt- gametes are mixed together, flagellar agglutination triggeeeds to fuse with an activated mt- region. The fusion lip is seen to develop within the particle-dense central dome. We conclude that these mt- particles play an active role in membrane fusion.

    Title Protoplast Formation in Escherichia Coli.
    Date December 1976
    Journal Journal of Bacteriology
    Excerpt

    A procedure for protoplast formation in Escherichia coli is described. Removal of the cell wall was confirmed by examination of cells in thin-section preparations.

    Title Compartmentation and Control of Arginine Metabolism in Neurospora.
    Date September 1976
    Journal Journal of Bacteriology
    Excerpt

    The fate of [14-C]arginine derived from the medium or from biosynthesis has been examined in Neurospora growing in arginine-supplemented medium. In both cases the label enters the cytosol, where it is used efficiently for both protein synthesis and catabolism before mixing with the majority of the endogenous [12C]arginine pool. Both metabolic processes appear to use the same cytosolic arginine pool. It is calculated that the nonorganellar cytoplasm contains approximately 20% of the intracellular arginine pool when the cells are growing in arginine-supplemented medium. The results suggest that compartmentation of arginine is a significant factor in controlling arginine metabolism in Neurospora. The significance of these results for studies of amino acid metabolism in other eukaryotic systems is discussed.

    Title Gametic Differentiation in Chlamydomonas Reinhardtii. Iii. Cell Wall Lysis and Microfilament-associated Mating Structure Activation in Wild-type and Mutant Strains.
    Date February 1976
    Journal The Journal of Cell Biology
    Excerpt

    Cell fusion between mating type plus (mt+) and minus (mt-) gametes of Chlamydomonas reinhardtii is analyzed structurally and subjected to experimental manipulation. Cell wall lysis, a necessary prelude to fusion, is shown to require flagellar agglutination between competent gametes; glutaraldehyde-fixed gametes ("corpses") of one mating type will elicit both agglutination and cell wall lysis in the opposite mating type, whereas nonagglutinating impotent (imp) mutant strains are without effect. The fusion process is mediated by a narrow fertilization tubule which extends from the mt+ gamete and establishes contact with the mt- gamete. Formation of the tubule requires the "activation" of a specialized mating structure associated with the ml+ cell membrane; activation causes microfilaments to polymerize from the mating structure into the growing fertilization tubule. Mating structure activation is shown to depend on gametic flagellar agglutination; isoagglutination mediated by the lectin concanavalin A has no effect. Gametes carrying the imp-l mt+ mutation are able to agglutinate but not fuse with mt- cells; the imp-l gametes are shown to have structurally defective mating structures that do not generate microfilaments in response to gametic agglutination.

    Title The Relationship Between Enzyme Activity, Cell Geometry, and Fitness in Saccharomyces Cerevisiae.
    Date July 1975
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    The relationship between enzyme activity, cell geometry, and the ploidy levels has been investigated in Saccharomyces cerevisiae. Diploid cells have 1.57 times the volume of haploid cells under nonlimiting growth conditions (minimal medium). However, when diploid cells are grown under conditions of carbon limitation, they have the same volume as haploid cells. Thus, by altering the environmental conditions, cell size can be varied independently of the degree of ploidy. The results indicate that the basic biochemical parameters of the cell are primarily determined by cell geometry rather than ploidy level. RNA content, protein content, and ornithine transcarbamylase (carbamoylphosphate: L-ornithine carbamoyltransferase, EC 2.1.3.3), tryptophan synthetase [L-serine hydro-lyase (adding indole), EC 4.2.1.20], and invertase (alpha-D-glucoside glucohydrolase, Ec 3.2.1.20) activity are related to cell volume, whereas acid phosphatase (orthophosphoric-monoester phosphohydrolase, EC 3.1.3.2) activity, a cell surface enzyme, is related to the surface area of the cells. Fitness is determined by the activity of certain cell surface enzymes, such as acid phosphatase, diploids would be expected to have a lower fitness than haploids because of the lower surface area/volume ratio. However, when fitness is determined by the activity of an internal enzyme, diploids would be expected to have the same fitness as haploids. Results from competition experiments between haploids and diploids are consistent with these predictions. The significance of these results to the evolution of diploidy as the predominant phase of the life cycle of higher plants and animals is discussed.

    Title A System for Dental Patient Education - Study Reports on Its Effectiveness and Feasibility.
    Date May 1975
    Journal Dental Hygiene
    Title A Behavioral Analysis of the Determinants of Marital Satisfaction.
    Date March 1975
    Journal Journal of Consulting and Clinical Psychology
    Title Factor Structure of Fears in the Mentally Retarded.
    Date January 1975
    Journal Journal of Clinical Psychology
    Title Theta: Teenage Health Education Teaching Assistants.
    Date August 1974
    Journal Journal of the American Dental Association (1939)
    Title Subunit Cell Wall of Sulfolobus Acidocaldarius.
    Date June 1974
    Journal Journal of Bacteriology
    Excerpt

    The cell wall of Sulfolobus acidocaldarius has been isolated. Cells were mechanically disrupted with a French press, and the cytoplasmic membrane was removed by extracting cell-envelope fragments with Triton X-100. The Triton-insoluble cell wall material retained the characteristic subunit structure when examined in the electron microscope. Isolated cell wall fragments formed in open sheets that were easily separated from cytoplasmic contamination. Chemical studies showed that the Triton-insoluble cell wall fragments consisted of lipoprotein with small amounts of carbohydrate and hexosamine. The amino acid composition indicated a highly charged hydrophobic cell surface. The presence of diaminopimelic acid with only traces of muramic acid indicates that the cell envelope does not have a rigid peptidoglycan layer. The results of chemical analyses and electron microscopy suggest a wall-membrane interaction stabilizing the cell envelope. The chemical and physical properties of this type of cell envelope would appear to form the basis for a new major division of bacteria with the definitive characteristics of a morphologically distinct subunit cell wall devoid of peptidoglycan.

    Title Intracellular Localization of Ornithine and Arginine Pools in Neurospora.
    Date March 1974
    Journal The Journal of Biological Chemistry
    Title Intracellular Localization of Enzymes of Arginine Metabolism in Neurospora.
    Date March 1974
    Journal The Journal of Biological Chemistry
    Title Use of External, Biosynthetic, and Organellar Arginine by Neurospora.
    Date September 1973
    Journal Journal of Bacteriology
    Excerpt

    The fate of very low amounts of (14)C-arginine derived from the medium or from biosynthesis was studied in Neurospora cells grown in minimal medium. In both cases, the label enters the cytoplasm, where it is very briefly used with high efficiency for protein synthesis without mixing with the bulk of the large, endogenous pool of (12)C-arginine. The soluble (14)C-arginine which is not used for protein synthesis is sequestered in a vesicle with the bulk of the endogenous arginine pool. After this time, it is selectively excluded from use in protein synthesis except by exchange with cytoplasmic arginine. The data suggest that in vivo, the non-organellar cytoplasm contains less than 5% of the soluble, cellular arginine. The cellular organization of Neurospora described here also prevents the catabolism of arginine. Our results are discussed in relation to previous work on amino acid pools of other eukaryotic systems.

    Title Surface Structure of Intact Cells and Spheroplasts of Pseudomonas Aeruginosa.
    Date May 1973
    Journal Journal of Bacteriology
    Excerpt

    This report describes the ultrastructural features of Pseudomonas aeruginosa after freeze-etching of intact cells and enzymatically prepared spheroplasts. Freeze-etching of intact cells revealed two convex layers of the cell wall and particles within the hydrophobic interior of the cell membrane. Areas of the membrane free of particles were sometimes elevated in the form of rather large dome-shaped structures. Spheroplasts were formed from intact cells by the addition of trypsin to a reaction mixture of lysozyme and ethylenediaminetetraacetic acid. Spheroplasts contained the outer lipoid layer of the cell wall. It was possible to observe this cell wall layer in freeze-etch preparations of spheroplasts. The spheroplast membrane like that of intact cells was cleaved along a central plane to expose particles and particle-free areas.

    Title The Structure and Isolation of Pili (fimbriae) of Pseudomonas Aeruginosa.
    Date April 1973
    Journal The Australian Journal of Experimental Biology and Medical Science
    Title Cations and Ribosome Structure. I. Effects on the 30s Subunit of Substituting Polyamines for Magnesium Ion.
    Date March 1973
    Journal Biochemistry
    Title Cations and Ribosome Structure. 3. Effects on the 30s and 50s Subunits of Replacing Bound Mg 2+ by Inorganic Cations.
    Date March 1973
    Journal Biochemistry
    Title A Comparison of the Plaque-removing Ability of a Standard and an Unconventional Toothbrush.
    Date January 1973
    Journal Asdc Journal of Dentistry for Children
    Title Sulfolobus: a New Genus of Sulfur-oxidizing Bacteria Living at Low Ph and High Temperature.
    Date October 1972
    Journal Archiv Für Mikrobiologie
    Title Role of Value of Reward and Model Affective Response in Vicarious Reinforcement.
    Date April 1972
    Journal Journal of Personality and Social Psychology
    Title Mass Communications Media Plus Local Participation Equals Community Dental Health Education.
    Date March 1972
    Journal Journal of the American Dental Association (1939)
    Title The Structure and Occurrence of Pili (fimbriae) on Pseudomonas Aeruginosa.
    Date March 1972
    Journal Journal of General Microbiology
    Title The Inality of Polyamines to Maintain Ribosome Structure and Function.
    Date June 1970
    Journal Biochimica Et Biophysica Acta
    Title New Patterns in Continuing Dental Education.
    Date April 1969
    Journal Proceedings / State Secretaries Management Conference, American Dental Association
    Title Some Influences of Rumen Volatile Fatty Acids Upon Carcass Composition and Performance in Growing and Fattening Steers.
    Date October 1967
    Journal Journal of Animal Science
    Title Perspective on Continuing Education.
    Date December 1966
    Journal The Journal of the American College of Dentists
    Title Some Determinants of Emitted Reinforcing Behavior: Listener Reinforcement and Birth Order.
    Date June 1966
    Journal Journal of Personality and Social Psychology
    Title Anxiety and Response Stereotypy: an Experimental Critique.
    Date May 1966
    Journal Perceptual and Motor Skills
    Title Motivational Interviewing As a Mechanism for Change in Men Who Batter: a Randomized Controlled Trial.
    Date
    Journal Violence and Victims
    Excerpt

    The present study reports on the potential effectiveness of motivational interviewing (MI) in changing the way batterers think about their violent behavior. Thirty-three domestic violence offenders who were court-mandated to treatment were randomly assigned to MI or a control condition before attending their first mandated treatment group. Consistent with predictions, the MI group demonstrated generally more improvement on stages of change subscales than the control group. Further, the MI group demonstrated a significantly greater decrease in the extent to which they blamed their violence on external factors. Current data indicate that MI has the potential to increase batterers' motivation to change, although validation trials with larger sample sizes and more refined measures are required.

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