Browse Health

Education ?

Medical School Score Rankings
University of Massachusetts (2004)
  • Currently 4 of 4 apples
Top 25%

Awards & Distinctions ?

Associations
American Board of Radiology

Publications & Research

Dr. Patel has contributed to 52 publications.
Title Development and Validation of a Simple Isocratic Hplc Method for Simultaneous Estimation of Phytosterols in Cissus Quadrangularis.
Date November 2011
Journal Indian Journal of Pharmaceutical Sciences
Excerpt

Cissus quadrangularis L. is a promising remedy prescribed in the ancient Ayurvedic literature for bone fracture healing properties. As this activity has been extensively investigated and well established, a range of formulations containing C. quadrangularis has been marketed. This work reports the development and validation of a reliable RP-HPLC method for the analysis of phytosterols in the various extracts of the plant. The proposed method utilizes a Cosmosil C(8) column (250 ΄ 4.6 mm) with a compatible Phenomenex C(8) guard column with isocratic elution of acetonitrile and water (95:5 v/v) at 25°. An effluent flow rate of 2 ml/min and UV detection at 202 nm was used for the analysis of phytosterols. The described method was linear in the range of 1-500 μg/ml, with excellent correlation coefficients. The precision, robustness and ruggedness values were also within the prescribed limits (less than 2%). The recovery values were within the range, which indicates that the accuracy of the analysis was good and that the interference of the matrix with the recovery of phytosterols was low. The phytosterols were found to be stable in a stock solution for 48 h (% RSD was below 2%) and no interfering extra peaks were observed under controlled stress conditions. The proposed method is simple, specific, precise, accurate, and reproducible and thus can be used for routine analysis of C. quadrangularis phytosterols in quality control laboratories.

Title A Review of Oral Antiretroviral Therapy for the Treatment of Chronic Hepatitis B.
Date October 2010
Journal The Annals of Pharmacotherapy
Excerpt

To describe the current evidence for the use of oral antiretroviral (ARV) agents in the treatment of chronic hepatitis B (CHB).

Title Influence of Season, Ethnicity, and Chronicity on Vitamin D Deficiency in Traumatic Spinal Cord Injury.
Date September 2010
Journal The Journal of Spinal Cord Medicine
Excerpt

Inadequate levels of vitamin D increase the risk of osteoporosis, a highly prevalent condition in patients with traumatic spinal cord injury (SCI). Reduced sunlight and dark skin further contribute to low vitamin D levels.

Title Staphylococcus Aureus Antimicrobial Susceptibility of Abscess Samples from Adults and Children from the Kaleida Health System in Western New York State, 2003 to 2006.
Date August 2010
Journal Journal of Clinical Microbiology
Excerpt

Staphylococcus aureus is the most common etiologic agent of skin abscesses. The regional rate of methicillin-resistant S. aureus (MRSA) abscesses may reflect the prevalence of local community-acquired MRSA (CAMRSA). A retrospective study was conducted to compare the antimicrobial susceptibility patterns of S. aureus isolates recovered from abscesses from 2003 to 2006 from patients at hospitals of the Kaleida Health System in western New York. S. aureus susceptibility information was obtained from a Vitek Legacy system, and the location and source of each isolate were identified. EpiInfo software was used to analyze the antimicrobial susceptibilities of all isolates and the trends in the rates of MRSA. A total of 2,848 S. aureus abscesses were identified by the Kaleida Health Clinical Microbiology Laboratory. Of those, 978 S. aureus abscess events occurred in four hospitals, including three adult facilities (547 episodes with 62 cases of bacteremia) and one children's facility (431 episodes with 2 cases of bacteremia). The MRSA rates in adults increased from 56% (2003) to 71% (2006), and that in children increased from 26% (2003) to 64% (2006). Of the MRSA isolates in the children's samples, more than 92% were susceptible to clindamycin. Of the MRSA isolates in the adult samples, 50% were susceptible to clindamycin in 2003 and 2004, whereas greater than 75% were susceptible in 2005 and 2006. The increased rates of MRSA abscesses with susceptibility to clindamycin may reflect the high prevalence level of CAMRSA in the western New York community. The variations in S. aureus susceptibilities could serve as an indicator of the changing resistance patterns within a broad urban community.

Title The Drosophila Deoxyhypusine Hydroxylase Homologue Nero and Its Target Eif5a Are Required for Cell Growth and the Regulation of Autophagy.
Date July 2009
Journal The Journal of Cell Biology
Excerpt

Hypusination is a unique posttranslational modification by which lysine is transformed into the atypical amino acid hypusine. eIF5A (eukaryotic initiation factor 5A) is the only known protein to contain hypusine. In this study, we describe the identification and characterization of nero, the Drosophila melanogaster deoxyhypusine hydroxylase (DOHH) homologue. nero mutations affect cell and organ size, bromodeoxyuridine incorporation, and autophagy. Knockdown of the hypusination target eIF5A via RNA interference causes phenotypes similar to nero mutations. However, loss of nero appears to cause milder phenotypes than loss of eIF5A. This is partially explained through a potential compensatory mechanism by which nero mutant cells up-regulate eIF5A levels. The failure of eIF5A up-regulation to rescue nero mutant phenotypes suggests that hypusination is required for eIF5A function. Furthermore, expression of enzymatically impaired forms of DOHH fails to rescue nero clones, indicating that hypusination activity is important for nero function. Our data also indicate that nero and eIF5A are required for cell growth and affect autophagy and protein synthesis.

Title Cytokine/jak/stat Signaling Mediates Regeneration and Homeostasis in the Drosophila Midgut.
Date July 2009
Journal Cell
Excerpt

Cells in intestinal epithelia turn over rapidly due to damage from digestion and toxins produced by the enteric microbiota. Gut homeostasis is maintained by intestinal stem cells (ISCs) that divide to replenish the intestinal epithelium, but little is known about how ISC division and differentiation are coordinated with epithelial cell loss. We show here that when enterocytes (ECs) in the Drosophila midgut are subjected to apoptosis, enteric infection, or JNK-mediated stress signaling, they produce cytokines (Upd, Upd2, and Upd3) that activate Jak/Stat signaling in ISCs, promoting their rapid division. Upd/Jak/Stat activity also promotes progenitor cell differentiation, in part by stimulating Delta/Notch signaling, and is required for differentiation in both normal and regenerating midguts. Hence, cytokine-mediated feedback enables stem cells to replace spent progeny as they are lost, thereby establishing gut homeostasis.

Title Phase I Study Combining Treatment with Temsirolimus and Sunitinib Malate in Patients with Advanced Renal Cell Carcinoma.
Date April 2009
Journal Clinical Genitourinary Cancer
Excerpt

Concurrent inhibition of multiple oncogenic signaling pathways might improve the efficacy of anticancer agents and abrogate resistance mechanisms. This phase I study evaluated temsirolimus in combination with sunitinib in patients with advanced RCC.

Title Phase Ii Trial of Lenalidomide in Patients with Metastatic Renal Cell Carcinoma.
Date July 2008
Journal Investigational New Drugs
Excerpt

Lenalidomide (CC-5013) is a structural derivative of thalidomide, with antiangiogenic and immunomodulatory effects. Fourteen patients with metastatic renal cell carcinoma (RCC) were enrolled on a phase 2 trial of lenalidomide administered orally at 25 mg daily for 21 days followed by a rest period of 7 days. The best response was stable disease in eight patients (57%) of the 14 evaluable patients. Toxicities included fatigue, hyperglycemia, dyspnea, and myelosuppression with decreased hemoglobin, lymphopenia, and neutropenia. Lenalidomide is tolerable, but no objective responses were observed in this clinical trial.

Title Clinical Integration Provides the Key to Quality Improvement: Structure for Change.
Date July 2008
Journal American Journal of Medical Quality : the Official Journal of the American College of Medical Quality
Title Using Drosophila and Yeast Genetics to Investigate a Role for the Rheb Gtpase in Cell Growth.
Date June 2008
Journal Methods in Enzymology
Excerpt

The small, Ras-like GTPase Rheb plays an important role in the regulation of cell growth by the insulin/PI3K and nutrient/TOR pathways in eukaryotic systems. Studies in genetically tractable organisms such as Drosophila melanogaster and fission yeast (S. pombe) were critical for establishing the significance of Rheb in cell growth. In Drosophila, we find that overexpression of Drosophila Rheb (dRheb) in S2 cells causes their accumulation in S phase and an increase in cell size. In contrast, treatment of S2 cells with double-stranded RNA (RNAi) toward dRheb results in G1 arrest and a reduction in cell size. These altered cell size phenotypes observed in culture are also recapitulated in vivo. Overexpression of dRheb results in increased cell and tissue size without an increase in cell number; reduction of dRheb function results in reduced cell and tissue size. In S. pombe, inhibition of Rheb (SpRheb) expression also results in small, rounded cells that arrest in G0/G1. We will discuss here how we use Drosophila and S. pombe to explain a mechanism by which Rheb promotes cell growth.

Title Early Progression of an Isolated Ventricular Septal Defect After Blunt Trauma.
Date January 2008
Journal The Journal of Trauma
Title Sipuleucel-t: a Vaccine for Metastatic, Asymptomatic, Androgen-independent Prostate Cancer.
Date January 2008
Journal The Annals of Pharmacotherapy
Excerpt

To review the design, efficacy, safety, dosing, therapeutic, and pharmacoeconomic considerations of sipuleucel-T, an investigational, autologous, dendritic, cell-based prostate cancer vaccine.

Title Proven Methods to Achieve High Payment for Performance.
Date October 2007
Journal The Journal of Medical Practice Management : Mpm
Excerpt

Clinical performance measures and cost per episode of care are key ingredients of healthcare "value" and are increasingly being viewed as belonging in the public domain. "Pay for performance" (P4P) programs reward high performance of clinical "processes" and "outcome" measures, in particular for those related to chronic disease, patient satisfaction, patient safety, use of information technology, and other measures. At the core of the Advocate Health Partners clinical integration approach are specific practice interventions linked with clinical performance targets and supported by an incentive P4P program. Techniques of improvement include the use of registries of patients with specific conditions; clinicalprotocols; patient outreach with education tools and reminders; office staff training programs; physician continuing medical education; ongoing performance feedback; and an incentive program that rewards individual performance as well as collaboration among hospitals, physician hospital organizations, and peers.

Title Striatal Leucine-rich Repeat Kinase 2 Mrna is Increased in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned Common Marmosets (callithrix Jacchus) with L-3, 4-dihydroxyphenylalanine Methyl Ester-induced Dyskinesia.
Date September 2007
Journal The European Journal of Neuroscience
Excerpt

The level of leucine-rich repeat kinase 2 (Lrrk2) mRNA expression was measured by reverse transcription-polymerase chain reaction in anterior striatum from normal and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated common marmosets (Callithrix jacchus) that had L-3,4-dihydroxyphenylalanine methyl ester (L-DOPA)-induced dyskinesia. The level of striatal Lrrk2 mRNA was increased in MPTP-treated common marmosets that had L-DOPA-induced dyskinesia compared with normal animals that did not receive l-DOPA. Marmosets that exhibited higher levels of dyskinesia had the greatest increase in striatal Lrrk2 mRNA. Lrrk2 mRNA expression was also measured in human striatum and substantia nigra from control subjects and patients dying with Parkinson's disease. In contrast to marmoset tissue, no alteration in Lrrk2 mRNA expression was found in parkinsonian human brain. However, the brain was from patients who had an overall low level of dyskinesia. The correlation between striatal Lrrk2 mRNA levels in MPTP-treated common marmoset striatum and L-DOPA-induced dyskinesia indicates that LRRK2 may have a role in the molecular alterations that cause L-DOPA-induced dyskinesia.

Title Targeting Von Hippel-lindau Pathway in Renal Cell Carcinoma.
Date March 2007
Journal Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Excerpt

Inheritance of a defective copy of the von Hippel-Lindau (VHL) gene leads to the most common cause of inherited renal cell carcinoma (RCC). In addition, most patients with sporadic RCC have aberrant VHL. In the absence of VHL, hypoxia-inducible factor alpha accumulates, leading to production of several growth factors, including vascular endothelial growth factor and platelet-derived growth factor. We review here the biology of RCC and how a combination of proximal and distal block of VHL/hypoxia-inducible factor alpha pathway by novel targeted agents, including sunitinib, sorafenib, bevacizumab, everolimus, and temsirolimus, has led to significant improvements in progression-free survival.

Title Increased Rheb-tor Signaling Enhances Sensitivity of the Whole Organism to Oxidative Stress.
Date January 2007
Journal Journal of Cell Science
Excerpt

The accumulation of free radical damage to an organism over its lifespan can cause premature aging and disease including cancer, atherosclerosis and neurodegenerative disorders. The well-conserved Rheb-Target-of-rapamycin (TOR)-S6-kinase (S6K) signaling pathway regulates several cellular processes and has been shown to influence lifespan and diseases such as cancer and neurodegenerative disorders. Using adult Drosophila, we describe for the first time in metazoans that TOR activity can influence the stress response. We find that mildly increasing systemic Rheb-TOR-S6K signaling sensitizes the whole organism to oxidative stress and promotes senescence of locomotor activity with age. Furthermore, we find that S6K is required for increased Rheb-TOR signaling to sensitize the whole organism to oxidative stress and promote the senescence of locomotor activity. Interestingly, we also find that increasing Rheb-TOR signaling in muscle can increase the sensitivity of adults to oxidative stress. These data imply that pathological situations that increase TOR activity might perturb the ability of the whole organism to cope with stress causing disease progression and aging.

Title Pitfalls in the Diagnosis of Enteroviral Infection in Young Children.
Date September 2006
Journal The Pediatric Infectious Disease Journal
Excerpt

Three infants with enteroviral infections were admitted to a neonatal intensive care unit (NICU). Investigation into the possible nosocomial spread of enterovirus identified 31 other infected infants. Only 1 of the 31 was truly positive; 30 were false-positive results.

Title Targeted Therapy for Metastatic Renal Cell Carcinoma.
Date April 2006
Journal British Journal of Cancer
Excerpt

Metastatic renal cell carcinoma (RCC) has historically been refractory to cytotoxic and hormonal agents; only interleukin 2 and interferon alpha provide response in a minority of patients. We reviewed RCC biology and explored the ways in which this understanding led to development of novel, effective targeted therapies. Small molecule tyrosine kinase inhibitors, monoclonal antibodies and novel agents are all being studied, and phase II studies show promising activity of sunitinib, sorafenib and bevacizumab. The results of phase III studies will determine the role of these agents in metastatic RCC.

Title Improved Asthma Outcomes Using a Coordinated Care Approach in a Large Medical Group.
Date September 2004
Journal Disease Management : Dm
Excerpt

The objective of this study was to review the development of a multidisciplinary asthma disease management program in a large medical group practice in an urban area, and evaluate the impact of the program on processes of care and health care utilization for adults and children with asthma. The disease management intervention included the development of a patient registry, a systematic approach to assessment of asthma control using the Asthma Therapy Assessment Questionnaire (ATAQ), case management, and physician education. An administrative database was used to examine hospital admissions and emergency department (ED) visits. A medical record audit was conducted to examine recorded compliance with asthma guidelines and documentation practices. The baseline study population included 3486 adults and children with asthma. The ATAQ suggested that, at baseline, control problems were frequent, with 34% of adult respondents missing work because of asthma. ATAQ also revealed several areas for care improvement. For example, only 20% of adult respondents reported having a written treatment plan. The chart review and administrative claims analyses showed that the program had beneficial results in several areas. Medical record documentation improved for asthma diagnosis (83.3% vs. 98.6%; p < 0.001) and patient education (15.7% vs. 26.1%; p < 0.001). No improvements were seen in documentation of peak flow ownership/use, smoking cessation advice, or influenza vaccination. ED visits related to asthma decreased from 148 per 1000 to 88 per 1000 (p < 0.001), and hospitalizations related to asthma decreased from 81 per 1000 to 37 per 1000 (p < 0.001). The outcomes suggest that this program was associated with a marked reduction in rates of hospitalization and ED usage for asthma, as well as significant improvement in several essential processes of care.

Title Drosophila Rheb Gtpase is Required for Cell Cycle Progression and Cell Growth.
Date May 2004
Journal Journal of Cell Science
Excerpt

Precise body and organ sizes in the adult animal are ensured by a range of signaling pathways. In a screen to identify genes affecting hindgut morphogenesis in Drosophila, we identified a P-element insertion in dRheb, a novel, highly conserved member of the Ras superfamily of G-proteins. Overexpression of dRheb in the developing fly (using the GAL4:UAS system) causes dramatic overgrowth of multiple tissues: in the wing, this is due to an increase in cell size; in cultured cells, dRheb overexpression results in accumulation of cells in S phase and an increase in cell size. Using a loss-of-function mutation we show that dRheb is required in the whole organism for viability (growth) and for the growth of individual cells. Inhibition of dRheb activity in cultured cells results in their arrest in G1 and a reduction in size. These data demonstrate that dRheb is required for both cell growth (increase in mass) and cell cycle progression; one explanation for this dual role would be that dRheb promotes cell cycle progression by affecting cell growth. Consistent with this interpretation, we find that flies with reduced dRheb activity are hypersensitive to rapamycin, an inhibitor of the growth regulator TOR. In cultured cells, the effect of overexpressing dRheb was blocked by the addition of rapamycin. These results imply that dRheb is involved in TOR signaling.

Title Traumatic Diaphragmatic Hernia: Delayed Presentation Seven Years After Penetrating Trauma.
Date December 2003
Journal Delaware Medical Journal
Title Quantitative Analysis of Bristle Number in Drosophila Mutants Identifies Genes Involved in Neural Development.
Date November 2003
Journal Current Biology : Cb
Excerpt

The identification of the function of all genes that contribute to specific biological processes and complex traits is one of the major challenges in the postgenomic era. One approach is to employ forward genetic screens in genetically tractable model organisms. In Drosophila melanogaster, P element-mediated insertional mutagenesis is a versatile tool for the dissection of molecular pathways, and there is an ongoing effort to tag every gene with a P element insertion. However, the vast majority of P element insertion lines are viable and fertile as homozygotes and do not exhibit obvious phenotypic defects, perhaps because of the tendency for P elements to insert 5' of transcription units. Quantitative genetic analysis of subtle effects of P element mutations that have been induced in an isogenic background may be a highly efficient method for functional genome annotation.

Title Case 54: Fournier Gangrene.
Date January 2003
Journal Radiology
Title Direct and Indirect Mechanisms for Regulation of Fatty Acid Synthase Gene Expression by Liver X Receptors.
Date May 2002
Journal The Journal of Biological Chemistry
Excerpt

The nuclear receptors LXRalpha and LXRbeta have been implicated in the control of lipogenesis and cholesterol homeostasis. Ligand activation of these receptors in vivo induces expression of the LXR target gene SREBP-1c and increases plasma triglyceride levels. Expression of fatty acid synthase (FAS), a central enzyme in de novo lipogenesis and an established target of the SREBP-1 pathway, is also induced by LXR ligands. The effects of LXR ligands on FAS expression have been proposed to be entirely secondary to the induction of SREBP-1c. We demonstrate here that LXRs regulate FAS expression through direct interaction with the FAS promoter as well as through activation of SREBP-1c expression. Induction of FAS expression in HepG2 cells by LXR ligands is reduced, but not abolished, under conditions where SREBP processing is suppressed. Moreover, LXR ligands induce FAS expression in CHO-7 cells without altering expression of SREBP-1. We demonstrate that in addition to tandem SREBP sites, the FAS promoter contains a high affinity binding site for the LXR/RXR heterodimer that is conserved in diverse animal species including birds, rodents, and humans. The LXR and SREBP binding sites independently confer LXR responsiveness on the FAS promoter, and maximal induction requires both transcription factors. Transient elevation of plasma triglyceride levels in mice treated with a synthetic LXR agonist correlates with transient induction of hepatic FAS expression. These results indicate that the LXR signaling pathway modulates FAS expression through distinct but complementary mechanisms and suggest that the FAS gene may be a critical target in the control of lipogenesis by LXRs.

Title Getting a Grip on How Dna Polymerases Function.
Date August 2001
Journal Nature Structural Biology
Title The Conserved Active Site Motif A of Escherichia Coli Dna Polymerase I is Highly Mutable.
Date July 2001
Journal The Journal of Biological Chemistry
Excerpt

Escherichia coli DNA polymerase I participates in DNA replication, DNA repair, and genetic recombination; it is the most extensively studied of all DNA polymerases. Motif A in the polymerase active site has a required role in catalysis and is highly conserved. To assess the tolerance of motif A for amino acid substitutions, we determined the mutability of the 13 constituent amino acids Val(700)-Arg(712) by using random mutagenesis and genetic selection. We observed that every residue except the catalytically essential Asp(705) can be mutated while allowing bacterial growth and preserving wild-type DNA polymerase activity. Hence, the primary structure of motif A is plastic. We present evidence that mutability of motif A has been conserved during evolution, supporting the premise that the tolerance for mutation is adaptive. In addition, our work allows identification of refinements in catalytic function that may contribute to preservation of the wild-type motif A sequence. As an example, we established that the naturally occurring Ile(709) has a previously undocumented role in supporting sugar discrimination.

Title A Single Highly Mutable Catalytic Site Amino Acid is Critical for Dna Polymerase Fidelity.
Date June 2001
Journal The Journal of Biological Chemistry
Excerpt

DNA polymerases contain active sites that are structurally superimposable and conserved in amino acid sequence. To probe the biochemical and structure-function relationship of DNA polymerases, a large library (200,000 members) of mutant Thermus aquaticus DNA polymerase I (Taq pol I) was created containing random substitutions within a portion of the dNTP binding site (Motif A; amino acids 605-617), and a fraction of all selected active Taq pol I (291 out of 8000) was tested for base pairing fidelity; seven unique mutants that efficiently misincorporate bases and/or extend mismatched bases were identified and sequenced. These mutants all contain substitutions of one specific amino acid, Ile-614, which forms part of the hydrophobic pocket that binds the base and ribose portions of the incoming nucleotide. Mutant Taq pol Is containing hydrophilic substitution I614K exhibit 10-fold lower base misincorporation fidelity, as well as a high propensity to extend mispairs. In addition, these low fidelity mutants containing hydrophilic substitution for Ile-614 can bypass damaged templates that include an abasic site and vinyl chloride adduct ethenoA. During polymerase chain reaction, Taq pol I mutant I614K exhibits an error rate that is >20-fold higher relative to the wild-type enzyme and efficiently catalyzes both transition and transversion errors. These studies have generated polymerase chain reaction-proficient mutant polymerases containing substitutions within the active site that confers low base pairing fidelity and a high error rate. Considering the structural and sequence conservation of Motif A, it is likely that a similar substitution will yield active low fidelity DNA polymerases that are mutagenic.

Title Prokaryotic Dna Polymerase I: Evolution, Structure, and "base Flipping" Mechanism for Nucleotide Selection.
Date June 2001
Journal Journal of Molecular Biology
Excerpt

Accurate transmission of DNA material from one generation to the next is crucial for prolonged cell survival. Following the discovery of DNA polymerse I in Escherichia coli, the DNA polymerase I class of enzymes has served as the prototype for studies on structural and biochemical mechanisms of DNA replication. Recently, a series of genomic, mutagenesis and structural investigations have provided key insights into how Pol I class of enzymes function and evolve. X-ray crystal structures of at least three Pol I class of enzymes have been solved in the presence of DNA and dNTP, thus allowing a detailed description of a productive replication complex. Rapid-quench stop-flow studies have helped define individual steps during nucleotide incorporation and conformational changes that are rate limiting during catalysis. Studies in our laboratory have generated large libraries of active mutant enzymes (8000) containing a variety of substitutions within the active site, some of which exhibit altered biochemical properties. Extensive genomic information of Pol I has recently become available, as over 50 polA genes from different prokaryotic species have been sequenced. In light of these advancements, we review here the structure-function relationships of Pol I, and we highlight those interactions that are responsible for the high fidelity of DNA synthesis. We present a mechanism for "flipping" of the complementary template base to enhance interactions with the incoming nucleotide substrate during DNA synthesis.

Title Multiple Amino Acid Substitutions Allow Dna Polymerases to Synthesize Rna.
Date January 2001
Journal The Journal of Biological Chemistry
Excerpt

DNA and RNA polymerase exhibit similarities in structures and catalytic mechanisms, suggesting that both classes of enzymes are evolutionarily related. To probe the biochemical and structure-function relationship between the two classes of polymerases, a large library (200,000 members) of mutant Thermus aquaticus DNA polymerase I (Taq pol I) was created containing random substitutions within a portion of the dNTP binding site (motif A; amino acids 605-617), and a fraction of all selected active Taq pol I (291 of 8000) was tested for the ability to incorporate successive ribonucleotides; 23 unique mutants that added rNTPs into a growing polynucleotide chain were identified and sequenced. These mutants, each containing one to four substitutions, incorporate ribonucleotides at a efficiency approaching 10(3)-fold greater than that of wild type Taq pol I. Several mutants added successive ribonucleotides and thus can catalyze the synthesis of RNA. Sequence analysis of these mutants demonstrates that at least two amino acid residues are involved in excluding ribonucleotides from the active site. Interestingly, wild type DNA polymerases from several distinct families selectively discriminate against rUTP. This study suggests that current DNA and RNA polymerases could have evolved by divergent evolution from an ancestor that shared a common mechanism for polynucleotide synthesis.

Title Dna Polymerase Active Site is Highly Mutable: Evolutionary Consequences.
Date June 2000
Journal Proceedings of the National Academy of Sciences of the United States of America
Excerpt

DNA polymerases contain active sites that are structurally superimposable and highly conserved in sequence. To assess the significance of this preservation and to determine the mutational burden that active sites can tolerate, we randomly mutated a stretch of 13 amino acids within the polymerase catalytic site (motif A) of Thermus aquaticus DNA polymerase I. After selection, by using genetic complementation, we obtained a library of approximately 8, 000 active mutant DNA polymerases, of which 350 were sequenced and analyzed. This is the largest collection of physiologically active polymerase mutants. We find that all residues of motif A, except one (Asp-610), are mutable while preserving wild-type activity. A wide variety of amino acid substitutions were obtained at sites that are evolutionarily maintained, and conservative substitutions predominate at regions that stabilize tertiary structures. Several mutants exhibit unique properties, including DNA polymerase activity higher than the wild-type enzyme or the ability to incorporate ribonucleotide analogs. Bacteria dependent on these mutated polymerases for survival are fit to replicate repetitively. The high mutability of the polymerase active site in vivo and the ability to evolve altered enzymes may be required for survival in environments that demand increased mutagenesis. The inherent substitutability of the polymerase active site must be addressed relative to the constancy of nucleotide sequence found in nature.

Title Evaluation of an Unused 1952 Ridley Intraocular Lens.
Date December 1999
Journal Journal of Cataract and Refractive Surgery
Excerpt

PURPOSE: To evaluate an unused 1952 historic Ridley intraocular lens (IOL) brought to Bombay, India, in 1952 from an Oxford Ophthalmologic Conference in England and given to 1 of the authors during his residency. SETTING: Alcon Laboratories, Fort Worth, Texas, USA. METHODS: The Ridley IOL was evaluated at Alcon Laboratories, Inc., using the established procedures of its Intraocular R&D Laboratories. Various optical and physical aspects of the Ridley lens were evaluated including (1) dimensions, (2) weight, (3) power, (4) resolution efficiency and modulation transfer function (MTF), (5) surface sphericity by interferometry, (6) ultraviolet (UV)-visible transmission characteristic, (7) attenuated total reflectance (ATR)-Fourier transform infrared reflectance spectrum, and (8) cosmetics by visual inspection using light microscopy. RESULTS: This 8.5 mm diameter, 2.4 mm thick, 23 diopter biconvex IOL weighed 108 mg. The ATR spectrum, UV-visible transmission, and refractive index confirmed its poly-(methyl methacrylate) material. The 0.56 MTF value at 100 line pairs/mm, per the International Standards Organization--IOL Optics Standard, and 93% resolution efficiency in water, per the American National Standard Institute IOL Optics Standard, revealed the IOL's excellent optics. This was confirmed by 0.278 wave root mean square surface figure as measured by Zygo interferometer using a 633 nm wavelength. Visual inspection revealed rough edges with sharp corners and some surface scratches. Early clinical experience with Ridley IOLs in Bombay, India, is briefly given. CONCLUSION: The Ridley IOL had excellent optical quality, meeting the requirements of current IOL optics standards. The selection of its dimensions was guided by the human crystalline lens, and the Ridley IOL was half as bulky. Although its clinical results were mixed, successful cases inspired subsequent improvements, leading to modern, highly satisfactory IOLs. This IOL represented a revolutionary innovation in ophthalmology.

Title Insights into Dna Polymerization Mechanisms from Structure and Function Analysis of Hiv-1 Reverse Transcriptase.
Date May 1995
Journal Biochemistry
Excerpt

When the single-stranded RNA genome of HIV-1 is copied into double-stranded DNA, the viral enzyme reverse transcriptase (RT) catalyzes the addition of approximately 20,000 nucleotides; however, the precise mechanism of nucleotide addition is unknown. In this study, we attempt to integrate the genetic data and biochemical mechanism of DNA polymerization with the structure of HIV-1 RT complexed with a dsDNA template-primer. The first step of polymerization involves the physical association of a polymerase with its nucleic acid substrate. A comparison of the structures of HIV-1 RT in the presence and absence of DNA indicates that the tip of the p66 thumb moves approximately 30 A upon DNA binding. This conformational change permits numerous interactions between residues of alpha-helices H and I in the thumb subdomain and the DNA. Measurements of DNA binding affinity for nucleic acids with double-stranded DNAs that have an increasing number of bases in the template overhang and molecular modeling suggest that portions of beta 3 and beta 4 within the fingers subdomain bind single-stranded regions of the template. Measurements of nucleotide incorporation efficiency (kcat/Km) show that the binding and incorporation of the next complementary nucleotide are not dependent on the length of the template overhang. Molecular modeling of an incoming nucleotide triphosphate (dTTP), based in part on the position of mercury atoms in a RT/DNA/Hg-UTP/Fab structure, suggests that portions of secondary structural elements alpha C-beta 6, alpha E, beta 11b, and beta 9-beta 10 determine the topology of the dNTP-binding site. These results also suggest that nucleotide incorporation is accompanied by a protein conformational change that positions the dNTP for nucleophilic attack. Nucleophilic attack by the oxygen atom of the 3'-OH group of the primer strand could be metal-mediated, and Asp185 may be directly involved in stabilizing the transition state. The translocation step may be characterized by rotational as well as translational motions of HIV-1 RT relative to the DNA double helix. Some of the energy required for translocation could be provided by dNTP hydrolysis and could be coupled with conformational changes within the nucleic acid. A structural comparison of HIV-1 RT, Klenow fragment, and T7 RNA polymerase identified regions within T7 RNA polymerase which are not present in the other two polymerases that might help this polymerase to remain bound with nucleic acids and contribute to the ability of the T7 RNA polymerase to polymerize processively.

Title Marked Infidelity of Human Immunodeficiency Virus Type 1 Reverse Transcriptase at Rna and Dna Template Ends.
Date February 1994
Journal Proceedings of the National Academy of Sciences of the United States of America
Excerpt

Human immunodeficiency virus type 1 (HIV-1) is genetically highly variable. This is attributed to the error-prone nature of HIV-1 replication and its proclivity for recombination. During replication and recombination, reverse transcriptase (RT) must polymerize DNA to the 5' ends of multiple RNA and DNA template termini while converting HIV-1 RNA to double-stranded DNA. We have determined the fidelity of HIV-1 RT in vitro during polymerization to the 5' ends of HIV-1 long terminal repeat DNA template sequences and to the end of a partial HIV-1 genomic RNA template that mimics a recombination intermediate. HIV-1 RT readily extended recessed DNA primers to form full-length blunt-end DNA-DNA and DNA-RNA duplexes. In addition, HIV-1 RT catalyzed high yields of products with one to four extra nucleotides at the 3' ends of the nascent DNAs. These products were formed processively via a nontemplated mechanism that is highly specific for the addition of purine nucleotides (A > G >> T > or = C). Thus, HIV-1 RT is extremely unfaithful at both DNA and RNA template ends, introducing errors (extra nucleotides) in one out of every two or three nascent strands processively polymerized. This error rate is 1000 times higher than for HIV-1 RT-catalyzed errors at internal template positions. Blunt-end additions were also catalyzed by other retroviral RTs at relative rates of HIV-1 approximately Moloney murine leukemia virus > avian myeloblastosis virus. These data suggest a potentially important mechanism for retroviral mutation mediated by nontemplated blunt-end addition of purines prior to forced copy-choice recombination.

Title Esophageal Contribution to Chest Pain in Patients with Coronary Artery Disease.
Date November 1990
Journal Chest
Excerpt

We conducted a prospective study to determine the role of the esophagus in causing chest pain in patients with established CAD on optimum therapy. Thirty-two men with documented CAD who complained of frequent and usually daily retrosternal chest pain were evaluated. Following a standard esophageal manometry and acid perfusion test, simultaneous two-channel ambulatory Holter monitor and esophageal pH record tests were performed for 24 hours. Fifty-three episodes of chest pain were documented in 20 patients; 11 patients were free of pain. Of the 20 patients who complained of chest pains, 17 (85 percent) demonstrated at least one episode of PPR, defined as a drop in distal esophageal pH to less than 4 within ten minutes before or after the onset chest pain. Episodes of asymptomatic GER were common. The correlation of PPR with chest pain was 70 percent (37/53 episodes) and of ischemic ECG changes with chest pain 13 percent (7/53); in the remaining, there was no correlation with either. Two patients demonstrated simultaneous PPR and ischemic ECG changes. Seventeen esophageal motility abnormalities were observed in 14 patients (45 percent). It is our conclusion that esophageal disorders contribute to chest pain in patients with documented CAD. In this group, GER plays a greater role than in those with normal coronary arteries. In addition, esophageal motility disorders are common in these patients. Esophageal testing can be undertaken safely in these patients.

Title Risk Factors for Pneumonia After Percutaneous Endoscopic Gastrostomy.
Date October 1990
Journal Journal of Clinical Gastroenterology
Excerpt

Percutaneous endoscopic gastrostomy (PEG) is currently a popular method of administering enteral feeding. Most of these patients are elderly, debilitated, and chronically ill. They are on a number of medications and have multiple diseases. With impaired consciousness and swallowing disability, these patients are prone to develop pneumonia. In order to identify possible risk factors, we followed 24 men who underwent PEG for the occurrence of pneumonia or until they died. We then analyzed the medical records of these patients for potential risk factors for pneumonia. The presence of esophagitis during PEG placement endoscopy and history of pneumonia prior to PEG were significant risk factors. Advanced age and cerebrovascular accident (CVA) tended to indicate a higher risk of pneumonia. Taking these risk factors into consideration may be beneficial in the management of such patients.

Title Dose Equivalent Response of a Tld Badge--influence of Body Backscatter.
Date October 1990
Journal Health Physics
Excerpt

In personnel monitoring, operational quantities recommended by ICRU Publication No. 39 for photon radiation can be realized by calibrating dosimeters on a phantom and considering body backscatter photons by using established conversion factors. Personnel dosimeters used in this study are based on CaSO4:Dy Teflon thermoluminescence dosimeter discs (TLD) that have a highly photon energy-dependent response. Since body backscattered photons have lower energies than the incidence photons, methods for correcting for energy dependence of both the incident and body backscattered photons have to be developed. By using readouts of two TLD discs (one under a composite metal filter and the other without a metal filter) in an empirical relation valid at all energies, it is possible to correct for the effect of change in response from change in the photon energies. It was found that the new operational quantities recommended by ICRU could be estimated to within +/- 15% by a TLD badge design based on this method. Angular dependence limits for photons in accordance with the new international standards and a high beta dose-equivalent discrimination in the mixed fields of beta and low-energy x rays could also be achieved.

Title The Value of Chiba Fine-needle Aspiration Biopsy in the Diagnosis of Hepatic Malignancy: a Comparison with Menghini Needle Biopsy.
Date April 1989
Journal Journal of Clinical Gastroenterology
Excerpt

The detection or exclusion of metastatic liver involvement is critical in the management and prognosis of patients with malignant disease. Noninvasive imaging modalities such as computed tomography, ultrasound, and technetium colloid liver scan are highly sensitive but nonspecific. Serum alkaline phosphatase is of similar value. A blind liver biopsy by the Menghini technique is often done to confirm the diagnosis, but its yield is low. We prospectively evaluated 74 patients using blind Menghini needle biopsy and concurrent Chiba fine-needle aspiration biopsy (FNAB) techniques. A positive diagnosis of malignancy was made in 30 patients (41%). In only 25 (34%) was the diagnosis made by Menghini biopsy, while Chiba FNAB confirmed the diagnosis in all 30 patients. Thus, concurrent use of both needles increased the diagnostic accuracy by 7%. Seven additional patients, considered to have one or more contraindications for the Menghini biopsy, underwent Chiba FNAB alone; the diagnosis was confirmed in all without complication. We conclude that FNAB alone or in combination with Menghini biopsy is valuable and safe in the diagnosis of metastatic liver disease.

Title Upper Gastrointestinal Hemorrhage Secondary to Gastric Ulcer Complicating Percutaneous Endoscopic Gastrostomy.
Date August 1988
Journal Gastrointestinal Endoscopy
Title Inadvertent Bronchial Ph Monitoring.
Date May 1988
Journal Gastrointestinal Endoscopy
Title Esophageal Motility Disturbances in Alcoholics.
Date November 1987
Journal Gastroenterology
Title Percutaneous Endoscopic Gastrostomy Tube Deterioration: How Common is the Problem?
Date August 1987
Journal The American Journal of Gastroenterology
Title Condyloma Acuminata Presenting As Rectal Polyps in a Heterosexual Man: Importance of Ct Scan of the Pelvis.
Date May 1987
Journal The American Journal of Gastroenterology
Excerpt

Condyloma acuminata generally occur in and outside the anal canal of young homosexual men who practice anal coitus. We report the occurrence of large condyloma acuminata in the rectum of an elderly heterosexual man. Its characteristic endoscopic, pathological and CT scan features are discussed. CT scan may be invaluable in assessing local infiltration.

Title A Patient with Carman-kirklin Sign on a Barium Study.
Date May 1987
Journal Journal of the Tennessee Medical Association
Title Carcinoma of the Pancreas.
Date April 1987
Journal Hospital Practice (office Ed.)
Title A Patient with Bone Pain.
Date January 1987
Journal Journal of the Tennessee Medical Association
Title Adaptation of a Bronchofiberscope for Percutaneous Endoscopic Gastrostomy.
Date August 1986
Journal Gastrointestinal Endoscopy
Title A Shaggy Esophagus.
Date August 1986
Journal Journal of the Tennessee Medical Association
Title Intrahepatic Filling Defects.
Date March 1986
Journal Journal of the Tennessee Medical Association
Title Familial X-linked Dominant Hypophosphatemic Vitamin D Refractory Rickets--a Family Study.
Date June 1983
Journal The Journal of the Association of Physicians of India
Title Occupational Exposures in Industrial Radiography Practice.
Date July 1981
Journal Health Physics
Title Film Vs Tld: a Choice for a Countrywide Personnel Monitoring Programme.
Date February 1976
Journal Health Physics
Title A Model for Integrating Independent Physicians into Accountable Care Organizations.
Date
Journal Health Affairs (project Hope)
Excerpt

The Affordable Care Act encourages the formation of accountable care organizations as a new part of Medicare. Pending forthcoming federal regulations, though, it is unclear precisely how these ACOs will be structured. Although large integrated care systems that directly employ physicians may be most likely to evolve into ACOs, few such integrated systems exist in the United States. This paper demonstrates how Advocate Physician Partners in Illinois could serve as a model for a new kind of accountable care organization, by demonstrating how to organize physicians into partnerships with hospitals to improve care, cut costs, and be held accountable for the results. The partnership has signed its first commercial ACO contract effective January 1, 2011, with the largest insurer in Illinois, Blue Cross Blue Shield. Other commercial contracts are expected to follow. In a health care system still dominated by small, independent physician practices, this may constitute a more viable way to push the broader health care system toward accountable care.

Similar doctors nearby

Dr. Ramzy Rimawi

Body Imaging
Brooklyn, NY

Dr. Constantin Constant

Diagnostic Radiology
44 years experience
Brooklyn, NY

Dr. Christina Giuliano

Diagnostic Radiology
21 years experience
Brooklyn, NY

Dr. Noel Nusbacher

Radiology
44 years experience
Brooklyn, NY

Dr. Jannine Benvenuto

Diagnostic Radiology
11 years experience
Brooklyn, NY

Dr. John Rusu

Diagnostic Radiology
46 years experience
Brooklyn, NY
Search All Similar Doctors