Family Physicians
15 years of experience

Accepting new patients
Whiteoak
12311 Copper Way
Ste 100
Charlotte, NC 28277
704-540-1640
Locations and availability (2)

Education ?

Medical School Score Rankings
New York Institute of Technology (1995)
  • Currently 3 of 4 apples
Top 50%

Awards & Distinctions ?

Awards  
Patients' Choice 5th Anniversary Award (2012 - 2013)
Patients' Choice Award (2008 - 2013)
Compassionate Doctor Recognition (2011 - 2013)
Appointments
Ny College Of Osteopathic Medicine Of Ny Inst. Of Technology, Old Westbury, Ny (1998 - Present)

Affiliations ?

Dr. Bauer is affiliated with 11 hospitals.

Hospital Affilations

Score

Rankings

  • Carolinas Medical Center
    8800 N Tryon St, Charlotte, NC 28262
    • Currently 4 of 4 crosses
    Top 25%
  • Presb Orthopaedic Hospital
    1901 Randolph Rd, Charlotte, NC 28207
    • Currently 4 of 4 crosses
    Top 25%
  • Presbyterian Hospital Matthew
    1500 Matthews Township Pkwy, Matthews, NC 28105
    • Currently 2 of 4 crosses
  • Presbyterian Hospital
    200 Hawthorne Ln, Charlotte, NC 28204
    • Currently 2 of 4 crosses
  • Presbyterian Hospital Huntersville
  • Good Samaritan Hospital
  • PH Charlotte/Ortho
  • Brunswick General Hospital
  • Good Samaritan Hospital Medical Center
  • Presbyterian HospitalPresbyterian Orthopaedic Hospital
  • Presbyterian Hospital Charlotte
  • Publications & Research

    Dr. Bauer has contributed to 36 publications.
    Title Effect of Body Mass Index on Bleeding Frequency and Activated Partial Thromboplastin Time in Weight-based Dosing of Unfractionated Heparin: a Retrospective Cohort Study.
    Date January 2010
    Journal Mayo Clinic Proceedings. Mayo Clinic
    Excerpt

    To assess bleeding and activated partial thromboplastin time (APTT) in relation to body mass index (BMI) in patients prescribed weight-based dosing of intravenous unfractionated heparin (UFH) for cardiac indications without a maximum (dose-capped) initial bolus or capped initial infusion rate.

    Title Corticosteroids in Acute Lung Injury and Acute Respiratory Distress Syndrome.
    Date September 2009
    Journal Critical Care Medicine
    Title Lack of an Effect of Body Mass on the Hemodynamic Response to Arginine Vasopressin During Septic Shock.
    Date September 2008
    Journal Pharmacotherapy
    Excerpt

    STUDY OBJECTIVE: To determine whether body mass alters the effectiveness of a fixed-dose infusion of arginine vasopressin. DESIGN: Retrospective medical record review. SETTING: All intensive care units of a tertiary medical center. PATIENTS: Sixty-six mechanically ventilated patients who received a fixed-dose intravenous infusion of arginine vasopressin at 0.04 U/minute as the sole agent for hemodynamic support during septic shock. MEASUREMENTS AND MAIN RESULTS: Patients were divided into four groups on the basis of body mass index. Effectiveness was measured as hemodynamic stability, which was defined as the proportion of patients achieving a mean arterial pressure (MAP) of 65 mm Hg or higher, the magnitude of the change in MAP at 1 hour, and the need for additional rescue vasopressors. Secondary outcomes included mortality and length of stay. Baseline characteristics of all four groups were comparable for age, sex, and severity of illness determined by using Acute Physiology and Chronic Health Evaluation II (APACHE II), Simplified Acute Physiology II (SAPS II), and Sequential Organ Failure Assessment (SOFA) scores. The only significant differences in baseline characteristics among the groups were in their central venous pressures. The four groups similarly achieved hemodynamic stability at 1 hour after the administration of arginine vasopressin (p=0.41). We observed no significant differences among groups in the magnitude of MAP change (p=0.62), need for rescue catecholamine vasopressors (p=0.17), 28-day mortality rates (p=0.31), or length of stay in the intensive care unit (p=0.43). CONCLUSION: Body mass index did not alter the effects of arginine vasopressin on hemodynamic stability or changes in MAP when the drug was administered as a fixed-dose infusion of 0.04 U/minute. Our results do not support weight-based dosing of vasopressin, unlike the dosing for catecholamine vasopressors.

    Title Dlk1 Influences Differentiation and Function of B Lymphocytes.
    Date August 2008
    Journal Stem Cells and Development
    Excerpt

    The Dlk1 (delta-like-1) gene is a member of the epidermal growth factor (EGF)-like homeotic gene family. It influences cell-cell interactions between stromal cells and pro-B cells in vitro. To define the in vivo role of the dlk protein in B cell development, we established a Dlk1-/- mouse model. In spleens of Dlk1-/- mice, transitional B cell numbers were increased and the ratio between transitional B cell subsets was altered. Numbers of follicular B cells decreased, while the number of marginal zone B cells and the size of the marginal zone were increased. Loss of dlk resulted in increased immunoglobulin G1 (IgG1) and IgG3 in preimmune sera. Furthermore, there was an exaggerated primary T-dependent antigen-specific humoral immune response. In bone marrow, the lack of dlk led to increased numbers of the earliest B lineage cells in young mice without affecting numbers of later B lineage cells. In vitro experiments showed that lack of dlk on either stromal cells or pro-B cells caused changes in differentiation and proliferation of pro-B cells, suggesting that lack of dlk leads to changes in cell-cell interactions in the bone marrow microenvironment. These results show that dlk expression is essential for normal B cell development.

    Title Predictors of Acquired Lipodystrophy in Juvenile-onset Dermatomyositis and a Gradient of Severity.
    Date May 2008
    Journal Medicine
    Excerpt

    We describe the clinical features of 28 patients with juvenile dermatomyositis (JDM) and 1 patient with adult-onset dermatomyositis (DM), all of whom developed lipodystrophy (LD) that could be categorized into 1 of 3 phenotypes, generalized, partial, or focal, based on the pattern of fat loss distribution. LD onset was often delayed, beginning a median of 4.6 years after diagnosis of DM. Calcinosis, muscle atrophy, joint contractures, and facial rash were DM disease features found to be associated with LD. Panniculitis was associated with focal lipoatrophy while the anti-p155 autoantibody, a newly described myositis-associated autoantibody, was more associated with generalized LD. Specific LD features such as acanthosis nigricans, hirsutism, fat redistribution, and steatosis/nonalcoholic steatohepatitis were frequent in patients with LD, in a gradient of frequency and severity among the 3 sub-phenotypes. Metabolic studies frequently revealed insulin resistance and hypertriglyceridemia in patients with generalized and partial LD. Regional fat loss from the thighs, with relative sparing of fat loss from the medial thighs, was more frequent in generalized than in partial LD and absent from DM patients without LD. Cytokine polymorphisms, the C3 nephritic factor, insulin receptor antibodies, and lamin mutations did not appear to play a pathogenic role in the development of LD in our patients. LD is an under-recognized sequela of JDM, and certain DM patients with a severe, prolonged clinical course and a high frequency of calcinosis appear to be at greater risk for the development of this complication. High-risk JDM patients should be screened for metabolic abnormalities, which are common in generalized and partial LD and result in much of the LD-associated morbidity. Further study is warranted to investigate the pathogenesis of acquired LD in patients with DM.

    Title Transforming Growth Factor-beta1 Sensitivity is Altered in Abl-myc- and Raf-myc-induced Mouse Pre-b-cell Tumors.
    Date February 2007
    Journal Stem Cells (dayton, Ohio)
    Excerpt

    Understanding the mechanisms leading to transformation of early B-lineage precursors is an important step leading to rational design of new treatments for precursor (pre)-B-cell leukemia. We used normal mouse pre-B cells to determine if and how transforming growth factor (TGF)-beta1 affects these precursors to the B-cell lineage and whether transformed pre-B cells respond to TGF-beta1. We found that normal pre-B cells proliferating in the presence of interleukin (IL)-7 enter cell-cycle arrest after exposure to TGF-beta1. However, clonally related IL-7-independent tumors induced by oncogenes abl + myc or raf + myc have reduced sensitivity to TGF-beta1. In contrast, tumor cells induced by myc alone remain sensitive to TGF-beta1 growth suppression. These results suggest that lesions in different molecular signaling pathways can lead to loss of TGF-beta1 sensitivity in a single cell type. The approach of using normal pre-B-cell lines and transformation by overexpression of different oncogenes provides a system to compare and contrast molecular pathways that lead to full malignancy.

    Title The External Rna Controls Consortium: a Progress Report.
    Date November 2005
    Journal Nature Methods
    Excerpt

    Standard controls and best practice guidelines advance acceptance of data from research, preclinical and clinical laboratories by providing a means for evaluating data quality. The External RNA Controls Consortium (ERCC) is developing commonly agreed-upon and tested controls for use in expression assays, a true industry-wide standard control.

    Title Localization of Recombination Activating Gene 1/green Fluorescent Protein (rag1/gfp) Expression in Secondary Lymphoid Organs After Immunization with T-dependent Antigens in Rag1/gfp Knockin Mice.
    Date June 2001
    Journal Blood
    Excerpt

    Secondary rearrangements of immunoglobulin gene segments that generate a new antibody repertoire in peripheral B cells have been described as receptor revision and occur by as yet unknown mechanisms. To determine the importance of recombination activating gene (RAG) expression in receptor revision, heterozygous rag1/green fluorescent protein (gfp) knockin mice were used to examine the location of RAG1 expression in the germinal centers (GCs) of lymphoid follicles after immunization with a variety of T-cell-dependent antigens. Immunization of rag1/gfp heterozygous mice or rag1 homozygous knockout mice reconstituted with rag1/gfp heterozygous spleen cells caused the down-regulation of RAG1/GFP signal in GCs. Although some RAG1/GFP(+) cells appeared in regions surrounding the peanut agglutinin (PNA)(+)GL-7(+) GC area, RAG1/GFP(+) cells did not accumulate in the central region. In addition, the stimulation of spleen B cells with anti-mu antibody plus interleukin-4 (IL-4) or with anti-CD40 monoclonal antibody plus IL-7 did not induce GFP signals at detectable levels in vitro. These results clearly demonstrate that RAG1 re-expression either does not occur or is at extremely low levels in antigen-driven B cells in GCs of secondary lymphoid follicles, suggesting that other mechanisms may mediate the gene rearrangements observed in receptor revision.

    Title Working Toward an Adenoviral Vector Testing Standard.
    Date January 2001
    Journal Molecular Therapy : the Journal of the American Society of Gene Therapy
    Title Interaction of Abl and Raf with Il-7 Signaling Pathway and Transformation of Pre-b Cells from Resistant Mice.
    Date November 1998
    Journal Oncogene
    Excerpt

    After in vivo inoculation with abl/myc- and raf/myc-containing retroviruses, BALB/c mice predominantly develop late stage B cell tumors (plasmacytomas) and less frequently develop earlier B-lineage tumors while DBA/2 mice do not develop B-lineage tumors. We have investigated the in vitro tumorigenic potential of these viruses using cultured normal pre-B cell lymphocytes from both BALB/c and DBA/2 mice. Interestingly, both viruses infect cultured pre-B lymphocytes from both mouse strains. Following infection, IL-7 dependent pre-B cells become independent of normal in vitro growth requirements within 24 h and can rapidly form in vivo pre-B lymphomas in both mouse strains. Mechanisms mediating loss of IL-7 dependence are different depending on whether the raf or abl gene is present in myc-containing viruses. IL-7 JAK-STAT signaling is constitutively active in abl/myc induced pre-B cell tumors. In contrast, IL-7 JAK-STAT signaling is not constitutive in raf/myc induced pre-B cell tumors, demonstrating that subversion of this component of IL-7 signal transduction is not obligatory for pre-B cell transformation or loss of IL-7 dependence.

    Title Modulated Expression of the Epidermal Growth Factor-like Homeotic Protein Dlk Influences Stromal-cell-pre-b-cell Interactions, Stromal Cell Adipogenesis, and Pre-b-cell Interleukin-7 Requirements.
    Date September 1998
    Journal Molecular and Cellular Biology
    Excerpt

    A close relationship exists between adipocyte differentiation of stromal cells and their capacity to support hematopoiesis. The molecular basis for this is unknown. We have studied whether dlk, an epidermal growth factor-like molecule that intervenes in adipogenesis and fetal liver hematopoiesis, affects both stromal cell adipogenesis and B-cell lymphopoiesis in an established pre-B-cell culture system. Pre-B-cell cultures require both soluble interleukin-7 (IL-7) and interactions with stromal cells to promote cell growth and prevent B-cell maturation or apoptosis. We found that BALB/c 3T3 fibroblasts express dlk and function as stromal cells. Transfection of these cells with antisense dlk decreased dlk expression and increased insulin-induced adipocytic differentiation. When antisense transfectants were used as stroma, IL-7 was no longer required to support the growth of pre-B cells and prevent maturation or apoptosis. Antisense dlk transfectants of S10 stromal cells also promoted pre-B-cell growth in the absence of IL-7. These results show that modulation of dlk on stromal cells can influence their adipogenesis and the IL-7 requirements of the pre-B cells growing in contact with them. These results indicate that dlk influences differentiation signals directed both to the stromal cells and to the lymphocyte precursors, suggesting that dlk may play an important role in the bone marrow hematopoietic environment.

    Title A Role for C-myc in the Regulation of Thymocyte Differentiation and Possibly Positive Selection.
    Date June 1996
    Journal Journal of Immunology (baltimore, Md. : 1950)
    Excerpt

    The purpose of thymocyte differentiation is to establish the T cell repertoire and eliminate nonfunctional and autoreactive T cells. In an analysis of potential regulators of this process, we have found that c-myc expression is down-regulated dramatically during early thymocyte differentiation and subsequently up-regulated along with TCR/CD3 in CD4+8+ cells. Transgenic E beta-myc mice that constitutively express c-myc in thymocytes have a larger proportion of thymocytes with high TCR/CD3 and low heat-stable antigen-1 expression than controls, and an increase in the number of transitional cells with a CD4+CD8low phenotype. Mature E beta-myc T cells respond less vigorously than controls to activation through their TCR/CD3 complex, as measured by proliferation and induction of the activation marker CD69. These results are consistent with a hypothesis in which activation of immature T cells through TCR/CD3 induces c-myc up-regulation and drives thymocytes through the initial stage of positive selection.

    Title Transforming Growth Factor-beta 1 Null Mice. An Animal Model for Inflammatory Disorders.
    Date March 1995
    Journal The American Journal of Pathology
    Excerpt

    Approximately 40% of transforming growth factor-beta 1 null (knockout) mice generated in our laboratory develop normally to term, but 60% die in utero. The animals appear normal during the first 2 weeks of life but develop a rapid wasting syndrome and die by 3 to 4 weeks of age. All of the knockout mice have a multifocal inflammatory disease in many tissues. The heart and lungs are most severely affected. Increased adhesion of leukocytes to the endothelium of pulmonary veins is the initial lesion seen at day 8 postnatally and is soon followed by perivascular cuffing as well as inflammatory infiltrates in lung parenchyma. The lesions in the heart begin as endocarditis and then progress to myocarditis and pericarditis. Within the lung, chronic inflammatory infiltrates consist of T and B lymphocytes, including plasma cells, whereas macrophages are the primary inflammatory cell type in the heart. Increased expression of major histocompatibility complex class I and II proteins is seen in pulmonary vascular endothelium as early as day 8. An immunoblastic response in mediastinal and mandibular lymph nodes and spleen is also seen. In the absence of any pathogens, this massive inflammatory disease, together with overexpression of major histocompatibility complex class I and II proteins and overproduction of immunoglobulins by lymphocytes, offers circumstantial evidence for an autoimmune etiology.

    Title Polymerase Chain Reaction-based Mrna Quantification Using an Internal Standard: Analysis of Oncogene Expression.
    Date July 1993
    Journal Methods in Enzymology
    Title Loss of P53 Expression in Myc-induced B Lineage Tumors.
    Date March 1993
    Journal Current Topics in Microbiology and Immunology
    Excerpt

    Tumors are formed following the accumulation of several genetic changes in genes which normally function to regulate cell growth. As yet it is unclear why multiple mutations are required, which type of alterations can collaborate with each other, and if collaboration is cell-type specific. In our myc transgenic mouse model system both point mutations and loss of mRNA expression for the p53 tumor suppressor gene have been found in the myc-induced B-lineage tumors arising spontaneously in these mice. This demonstrates the collaboration between these two growth control genes in cellular transformation. The observation that alterations in the expression of p53 is a common phenomenon in tumors formed in myc transgenic mice as well as a variety of different types of human tumors suggests that inactivation of the p53 growth control pathway may be required for transformation, and that alterations in p53 itself might be the most efficient way to achieve this inactivation. An analysis of the molecular mechanism for p53 alterations has implications for what kind of factors, both environmental and physiological, can influence tumor formation. The identification of collaboration groups has implications for the process of tumor formation, growth regulation, and will some day be important for the diagnosis of cancer, the prognosis of the individual and the design of specific therapeutic agents for treatment.

    Title Pre-b Lymphocyte-specific Transcriptional Control of the Mouse Vpreb Gene.
    Date February 1992
    Journal European Journal of Immunology
    Excerpt

    The VpreB genes, which encode surrogate immunoglobulin light chain molecules, are expressed as RNA almost exclusively in pre-B cells. We have investigated the transcriptional control mechanisms which are responsible for the pre-B cell-specific RNA expression of the mouse VpreB1 and VpreB2 genes. Nuclear run-on analyses demonstrate that the pre-B cell-specific expression of both VpreB genes is controlled primarily at the level of initiation of transcription. S1 nuclease protection-mapping defined two or three major start sites of transcription for the VpreB genes. To find a promoter and other potential cis-acting regulatory elements, a 700-bp fragment 5' of the transcription start sites of the VpreB1 gene was used in gene transfer experiments and found to act as a promoter in pre-B lymphocytes. Deletion experiments showed that 191 bp upstream of the most 5' transcription start site is required for the pre-B cell promoter activity. DNA sequence analysis of the 5' region of the mouse VpreB1, VpreB2 and human VpreB genes reveal that this region of approximately 200 bp is strongly conserved. This 200-bp promoter region contains several conserved nucleotide sequence motifs which may act to mediate the pre-B cell-specific transcription of the VpreB genes.

    Title B Cell Development in Fetal Liver.
    Date December 1991
    Journal Advances in Experimental Medicine and Biology
    Title Vpreb Gene Expression in Hematopoietic Malignancies: a Lineage- and Stage-restricted Marker for B-cell Precursor Leukemias.
    Date October 1991
    Journal Blood
    Excerpt

    We show here that analysis of VpreB gene transcription can be a specific way to identify acute leukemias of cells at very early stages of B-cell development. Northern blot analysis of RNAs from 63 leukemia samples showed that VpreB RNA was present in malignancies of precursor B cells, the expression being a feature of both common acute lymphoblastic leukemia (ALL) (CD10+) and null ALL (CD10-). It was absent from malignancies of mature B cells (surface Ig positive), from acute leukemias of the T-cell lineage and granulocyte-macrophage lineages, and from normal tonsil B and T lymphocytes. Chronic myeloid leukemia blast crises of the B-precursor-cell type expressed the VpreB gene while myeloid blast crises did not. VpreB RNA was also expressed in the neoplastic cells of one of three patients with acute undifferentiated leukemias. These data show that VpreB RNA expression is a marker of the malignant forms of precursor B cells, and that it appears at least as early as cytoplasmic CD22 and CD19 in tumors of the B-cell lineage.

    Title Tumorigenesis in Transgenic Mice Expressing the C-myc Oncogene with Various Lymphoid Enhancer Elements.
    Date April 1991
    Journal Current Topics in Microbiology and Immunology
    Title Cellular Stages and Molecular Steps of Murine B-cell Development.
    Date August 1990
    Journal Cold Spring Harbor Symposia on Quantitative Biology
    Excerpt

    Development of B cells in fetal liver occurs in one synchronous wave and involves probably no more than four critical divisions. This leads us to suggest that the main pool of proliferating progenitors that replenish the peripheral B-cell pool are progenitors before Ig gene rearrangement, that the four Ig gene rearrangements (DH to JH, VH to DHJH, VK to JK, and V lambda to J lambda) might occur in four critical divisions, and that a stromal-cell-dependent phase of pre-B development in which all rearrangements are made is succeeded by a stromal-cell-independent phase of sIG+ pre-B-cell maturation to mature mitogen-reactive B cells. We speculate on the molecular nature of the tightly controlled steps of Ig rearrangements during pre-B-cell development that might involve the pre-B-cell specific genes Vpre-B and lambda 5 and the B-lineage-specific gene mb-1 in interactions with stromal cells.

    Title Precursor B Lymphocytes--specific Monoclonal Antibodies and Genes.
    Date December 1989
    Journal Advances in Experimental Medicine and Biology
    Title Altered Myc Gene Transcription and Intron-induced Stabilization of Myc Rnas in Two Mouse Plasmacytomas.
    Date July 1989
    Journal Oncogene
    Excerpt

    Accumulation of unusually high amounts of larger-than-normal c-myc mRNAs occurs in two mouse plasmacytomas, TEPC 1165 and TEPC 2027. Southern blot and DNA sequence analyses showed that both tumors have undergone translocations of immunoglobulin heavy chain loci to positions 5' of the c-myc gene promotors resulting in removal of DNA sequences encoding a negative transcriptional regulatory element. In contrast to other mouse plasmacytomas, TEPC 1165 and TEPC 2027 rearranged myc genes show increased transcription, partially explaining their abundance of myc RNA. Similar to other mouse plasmacytomas, the abundance of myc RNA in TEPC 1165 and TEPC 2027 is also influenced by increased stability of structurally atypical myc RNAs. Two myc mRNAs are found in TEPC 2027, a 2.4 kb species including all 3 myc exons and a 4.0 kb species with the 3 exons plus the first intron. The two major myc mRNAs in TEPC 1165, 3.0 and 3.9 kb species, also include all three myc exons plus portions of the first intron. S1 nuclease protection analyses show that the 5' initiation and 3' untranslated (UT) regions of the unusual TEPC 1165 RNAs are normal showing that the size differences arise solely from inclusion of first intron sequences in the large myc RNAs. DNA sequence analysis showed that the presence of first intron sequences in the large myc RNAs is due to mutations affecting the splice donor region at the 3' end of exon 1 in both tumors. SDS-PAGE analysis of immunoprecipitated TEPC 1165 and TEPC 2027 myc proteins showed them to be of normal electrophoretic mobility but no more abundant than in a pre-B cell line 18-81 that contains at least 10 fold less myc RNA. The 4.0 kb myc mRNA of TEPC 2027 is atypically stable while the 2.4 kb myc mRNA undergoes normal rapid turnover within the same cell, demonstrating that the presence of first intron sequences in the large myc RNA stabilizes it despite the presence of 3' UT and putative exon 1 destabilizing sequences. These results show that myc intron 1 sequences can counteract the effect of 3' UT region destabilizing sequences in myc RNA and suggest that the increased myc RNA stability noted in TEPC 1165 and TEPC 2027 is largely due to the presence of the intron 1 sequences.(ABSTRACT TRUNCATED AT 400 WORDS)

    Title Restriction Fragment Analysis of V Preb and Lambda 5 Within the Genus Mus.
    Date April 1989
    Journal European Journal of Immunology
    Excerpt

    DNA from a panel of inbred strains of mice and colony bred mice, isolated from different geographical locations, was hybridized to mouse V preB and lambda 5 probes under stringent conditions, indicating sequence similarities greater than 80%. The probe for lambda 5 detects one gene and the probe for V preB detects two genes (V preB1 and V preB2) in the inbred strains of mice examined under the stringency used. No restriction endonuclease fragment length polymorphisms (RFLP) were detected with the V preB and lambda 5 DNA probes among the inbred strains of mice using Bam HI and Hind III. Very few RFLP were detected among Mus musculus subspecies, and the intensity of the hybridization did not differ significantly with either DNA probe. The number of RFLP increased slightly when different species and subgenera were examined, and the intensity of the hybridization signal began to decrease in samples from the different subgenera, suggesting a slight decrease in sequence similarity for both V preB genes with increased time of divergence. Fewer RFLP were detected with the lambda 5 DNA probe. DNA from 11 different Mus species representing 4 subgenera, genetically isolated from laboratory mice for approximately 1-12 million years, continued to hybridize under high stringency conditions using both DNA probes. A comigrating lambda 5 and V preB restriction endonuclease fragment was detected in most of the samples examined, suggesting the close physical linkage of V preB1 and lambda 5 is maintained within the genus Mus. These results suggest that V preB1, V preB2 and lambda 5 have been present for over 12 million years.

    Title The Human Vpre B Gene is Located on Chromosome 22 Near a Cluster of V Lambda Gene Segments.
    Date November 1988
    Journal Immunogenetics
    Excerpt

    The chromosomal location of the human VpreB gene was determined by Southern blotting analysis of restriction enzyme-digested DNAs from a panel of 17 mouse-human somatic cell hybrids. The pattern of hybridization of a Vpre B-specific probe in conjunction with earlier analysis of several marker genes allowed the following conclusions: 1) Vpre B is on human chromosome 22 within band 22q11.2 distal to the bcr-like gene, bcr-2 and proximal to the bcr-like gene, bcr-4. 2) Vpre B has been localized relative to several constitutional and tumor-specific breakpoints within 22q11.2, segregates in hybrids retaining 22q- chromosomes with some but not with all members of the V lambda 1 subgroup of the V lambda genes, and is amplified with these genes in K562 cells. 3) The order of the loci on chromosome 22 is centromere----bcr-2, Vpre B, V lambda 1----bcr-4----C lambda----bcr-1----bcr-3----sis.

    Title Conservation of the Organization of the Pre-b Cell Specific Vpreb1/vpreb2/lambda 5 Loci in the Genus Mus.
    Date October 1988
    Journal Current Topics in Microbiology and Immunology
    Title Restriction Fragment Length Polymorphism Near the Igh Locus on Mouse Chromosome 12.
    Date October 1988
    Journal Nucleic Acids Research
    Title Structure and Pre-b Lymphocyte Restricted Expression of the Vpreb in Humans and Conservation of Its Structure in Other Mammalian Species.
    Date May 1988
    Journal The Embo Journal
    Excerpt

    DNA from several mammals, including humans, was found to contain one or more restriction enzyme digested DNA fragments which hybridized to the mouse VpreB gene under stringencies demonstrating at least 70% nucleotide sequence homologies, indicating that the VpreB locus may be widespread and highly conserved among mammals. A human VpreB genomic clone was isolated and sequenced. Two exons and the intervening intron are spaced almost identically as in the mouse VpreB1 gene, and show 76% sequence homology to the mouse gene. As in the mouse VpreB1 gene, the 5' end of the human VpreB gene contains characteristic features of Ig domains, while the 3' end is Ig non-related. This 3' Ig non-related structure of the VpreB gene(s) may, therefore, have existed before the speciation of humans and mice over 65 million years ago. Sequences encoding the entire putative second framework region and a stretch in the third framework region are identical in human and mouse VpreB. the human VpreB gene appears to be selectively expressed in human pre-B cell lines as an 0.85 kb poly(A)+ RNA. Its expression promises to be a useful marker for the detection of normal and malignant human pre-B lymphocytes.

    Title Mutations Which Stabilize Myc Transcripts and Enhance Myc Transcription in Two Mouse Plasmacytomas.
    Date February 1987
    Journal Current Topics in Microbiology and Immunology
    Title Clonal Relationship of the Lymphoblastic Cell Line P388 to the Macrophage Cell Line P388d1 As Evidenced by Immunoglobulin Gene Rearrangements and Expression of Cell Surface Antigens.
    Date July 1986
    Journal Journal of Immunology (baltimore, Md. : 1950)
    Excerpt

    A lymphocytic tumor of early B cell lineage, P388, and a mature macrophage tumor, P388D1, appear to have been derived from a common precursor based on identical immunoglobulin gene rearrangements and shared cell surface antigens. These cell lines may have resulted from differential maturation of a transformed cell that is an immediate cellular precursor to both the B cell and myeloid lineages. This supports earlier findings that suggest a close relationship between early B cell and myeloid differentiation pathways.

    Title Chromosome Translocations Clustered 5' of the Murine C-myc Gene Qualitatively Affect Promoter Usage: Implications for the Site of Normal C-myc Regulation.
    Date October 1985
    Journal The Embo Journal
    Excerpt

    Five novel murine plasma cell (PC) tumors with chromosome translocations 350-500 bp 5' of the first c-myc exon are described. The t(12;15)s of TEPC 1194, ABPC 33 and TEPC 1165 position the intact c-myc locus 5' of the Cu, C gamma 2a and C alpha IgCH genes respectively. In ABPC 17, the IgH enhancer element and adjacent switch (Su) sequences were found 5' of the first c-myc exon while this enhancer is associated with the reciprocal products of the TEPC 1194, ABPC 33 and TEPC 1033 translocations. Quantitative S1 nuclease analyses demonstrate that the ratios of transcription from the two c-myc promoters (P1 and P2) are increased 4-to 7-fold in these five tumors. With the exception of TEPC 1165, (which contains a small deletion in exon 1), such increases in P1:P2 ratios appear to be manifested by a reduction in P2 usage in comparison to other tumors without such promoter shifts. A survey of 27 additional PC and non-PC B lymphoid tumors and cell lines revealed that myc promoter shifts of this magnitude are unique to PC tumors with 5'-proximal translocations. We propose that (i) these clustered breakpoints identify a normal c-myc regulatory element located at least 350 bp 5' of c-myc exon 1; (ii) the loss or disruption of this cis-acting upstream element and the linkage of c-myc to the IgCH locus would result in abnormal expression of this oncogene in these as well as most other PC tumors.

    Title Increased Expression of Myc-related Oncogene Mrna Characterizes Most Balb/c Plasmacytomas Induced by Pristane or Abelson Murine Leukemia Virus.
    Date June 1983
    Journal Proceedings of the National Academy of Sciences of the United States of America
    Excerpt

    RNA blots of poly(A)-containing RNA from normal livers and spleens and from a number of transplantable hematopoietic and lymphoid BALB/c tumors, including early and late generation plasmacytomas, were hybridized with probes for four onc genes. abl RNA was abundant only in those tumors producing Abelson virus, bas RNA was found in approximately equal amounts in normal tissues and plasmacytomas, and myb RNA was absent in normal liver and plasmacytomas. Normal liver and spleen RNA showed faint traces of myc hybridization, but myc RNA was increased in most plasmacytomas. In one plasmacytoma, TEPC 1165, a particularly abundant amount of myc RNA was found, principally as a 3.5-kilobase band. In the other plasmacytomas, bands of 2.4- or 1.8-kilobase myc RNA were found. Southern blots of DNA from tumors that contained 2.4-kilobase or larger myc RNA showed myc hybridization to an EcoRI fragment of about 21 kilobase pairs, similar to the myc band in normal DNA. EcoRI digests of DNA from two tumors that expressed myc RNA of 1.8 kilobases showed an additional smaller myc band, suggesting that the myc gene is rearranged in these plasmacytomas. The basis for increased myc gene transcription in plasmacytomas is not understood, but the evidence suggests that different mechanisms may be operating in different plasmacytomas. Apparently, neither myc gene amplification nor myc gene rearrangement is required for increased myc transcription.

    Title Dna Rearrangement and Altered Rna Expression of the C-myb Oncogene in Mouse Plasmacytoid Lymphosarcomas.
    Date June 1983
    Journal Science (new York, N.y.)
    Excerpt

    Three types of tumors termed plasmacytomas (ABPC's), lymphosarcomas (ABLS's), and plasmacytoid lymphosarcomas (ABPL's) arise in BALB/c mice treated with pristane and Abelson murine leukemia virus (A-MuLV). While most ABPC's and BLS's contain integrated A-MuLV proviral genome and synthesize the v-abl RNA, most ABPL's do not. The ABPL tumors were examined for the expression of other oncogenes that may be associated with their transformed state, in the absence of transforming virus. These tumors expressed abundant c-myb RNA of unusually large size and showed DNA rearrangements of the c-myb locus.

    Title A Comparative Study of Iodine Uptake by Thyroid and Thymus Glands of Male and Female Sprague-dawley Rats of Different Ages.
    Date June 1977
    Journal Acta Endocrinologica
    Excerpt

    The iodine concentrating ability of thyroid glands, thymus gland and skin in Sprague-Dawley rats was assessed by determining the tissue/blood radioiodide concentration ratios. Tissue/blood ratios are significantly affected by the age of the rats, however, thymus/blood radioiodide ratios never exceeded unity. The comparative uptake of 131I by thymus and thyroid tissue expressed as thymus/thyroid (%) for neonate animals was 10-16 times greater than those obtained for older rats. Moreover, the fraction of injected dose of radioiodide in thymus tissue never exceeded that of the thyroid or skin and paralleled the concentration of radio-activity in the blood. These results indicate that although neonate thymus tissue contains a significantly greater amount of radioactivity than the thymus of older rats, an active iodide concentration mechanism is not involved.

    Title Self-image Disparity, Repression-sensitization, and Extraversion-introversion: a Unitary Dimension?
    Date June 1976
    Journal Journal of Personality Assessment
    Excerpt

    To determination (1) whether self-image disparity, repression-sensitization, and extraversion-introversion intercorrelated to a degree indicative of a unitary personality dimension and, (2) whether the interrelationships among these variables was accounted for by cognitive developmental variance, Byrne's Revised Repression-Sensitization Scale, Giedt and Downing's Extraversion-Introversion Scale, and two measures of self-image disparity were administered to 20 male college freshmen and 20 male seniors. All the correlations among the four measures were significant, but none correlated significantly with cognitive development, as measured by SATs. Factor analysis yielded a clearcut personality factor and a clearcut cognitive factor, indicating that the personality measures reflect a unitary dimension, even after cognitive developmental variance is extracted.

    Title Effect of Corticosteroids on Arginine Vasopressin-containing Vasopressor Therapy for Septic Shock: a Case Control Study.
    Date
    Journal Journal of Critical Care
    Excerpt

    PURPOSE: Studies showing corticosteroids decrease time to shock reversal in septic shock did not include arginine vasopressin, which also may reduce the duration of catecholamine therapy. Thus, the effect of corticosteroids on vasopressin-containing vasopressor regimens is unknown. We designed this study to evaluate the effect of corticosteroids on time to vasopressin-containing vasopressor withdrawal and the proportion of patients alive without vasopressors at day 7. METHODS: This retrospective, case-control study included patients admitted to the intensive care units of an academic medical center who received vasopressin-containing vasopressor regimens for septic shock with or without concomitant corticosteroids. Twenty-one corticosteroid-treated patients were matched to those without corticosteroids. RESULTS: Both groups had similar Acute Physiology And Chronic Health Evaluation (APACHE) II, Simplified Acute Physiology Score (SAPS) II, and Sequential Organ Failure Assessment (SOFA) scores. There was no significant difference in median time to vasopressor withdrawal (65 hours vs 20 hours, P = .09) whether corticosteroids were given or withheld. Patients who received corticosteroids, however, were significantly more likely alive without vasopressors at day 7 than patients who received a vasopressin-containing vasopressor regimen alone (80.9% vs 47.6%, P = .02). CONCLUSIONS: Although corticosteroids did not improve the time to withdrawal of vasopressin-containing vasopressor therapy they significantly increased the proportion of patients alive without vasopressors at day 7.

    Title Therapeutic Drug Monitoring of Piperacillin-tazobactam Using Spent Dialysate Effluent in Patients Receiving Continuous Venovenous Hemodialysis.
    Date
    Journal Antimicrobial Agents and Chemotherapy
    Excerpt

    Sepsis and multisystem organ failure are common diagnoses affecting nearly three-quarters of a million Americans annually. Infection is the leading cause of death in acute kidney injury, and the majority of critically ill patients who receive continuous dialysis also receive antibiotics. Dialysis equipment and prescriptions have gradually changed over time, raising concern that current drug dosing recommendations in the literature may result in underdosing of antibiotics. Our research group directed its attention toward antibiotic dosing strategies in patients with acute renal failure (ARF), and we sought data confirming that patients receiving continuous dialysis and antibiotics actually were achieving therapeutic plasma drug levels during treatment. In the course of those investigations, we explored "fast-track" strategies to estimate plasma drug concentrations. As most antimicrobial antibiotics are small molecules and should pass freely through modern high-flux hemodialyzer filters, we hypothesized that continuous renal replacement therapy (CRRT) effluent could be used as the medium for drug concentration measurement by reverse-phase high-pressure liquid chromatography (HPLC). Here we present the first data demonstrating this approach for piperacillin-tazobactam. Paired blood and dialysate trough-peak-trough samples were drawn from 19 patients receiving piperacillin-tazobactam and continuous venovenous hemodialysis (CVVHD). Total, free, and dialysate drug concentrations were measured by HPLC. Dialysate drug levels predicted plasma free drug levels well (r(2) = 0.91 and 0.92 for piperacillin and tazobactam, respectively) in all patients. These data suggest a strategy for therapeutic drug monitoring that minimizes blood loss from phlebotomy and simplifies analytic procedures.


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