J P Mordes

University of Massachusetts Medical School, Worcester, Massachusetts, United States

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Publications (186)1003.72 Total impact

  • John P Mordes, Laura C Alonso
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    ABSTRACT: Objective: To describe the evaluation and treatment of hyperinsulinemic hypoglycemia in adults who had undergone gastric bypass surgery.Background: A small number of patients who undergo Roux-en-Y bypass surgery develop post-prandial hypoglycemia in the absence of dumping. In some cases, such patients have been treated with pancreatectomy.Methods: We report the demographics, diagnostic results, response to medical therapy, and subsequent course of six referral patients with post-Roux-en-Y hypoglycemia.Results: Characteristic clinical and metabolic parameters consistent with hyperinsulinemic hypoglycemia were identified. Parameters were similar for both spontaneous and glucosechallenge-induced hypoglycemia. In the context of exclusively post-prandial symptoms, simultaneous glucose ≤55 mg/dL, insulin ≥17 μU/ml, c-peptide ≥3.0 ng/ml, and an insulin: glucose ratio >0.3 were associated with Roux-en-Y gastric bypass hyperinsulinemic hypoglycemia. Five of six patients improved on therapy consisting of dietary modification plus either calcium channel blockade, acarbose, or both. Two have remained on therapy for 12 to 15 months. The non-responder was atypical and had had hypoglycemic events for several decades. Three treated patients were subsequently observed to have undergone partial or complete remission from hypoglycemic episodes after 2 to 37 months of therapy. None of the six have undergone pancreatectomy and none have evidence of insulinoma. Invasive diagnostic procedures were of limited utility.Conclusion: In a subset of patients with post-Roux-en-Y hyperinsulinemic hypoglycemia, medical management can be efficacious and an alternative to partial pancreatectomy. In some cases the disorder remits spontaneously.
    08/2014;
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    ABSTRACT: Genetic studies of type 1 diabetes (T1D) have been advanced by comparative analysis of multiple susceptible and resistant rat strains with a permissive class II MHC haplotype, RT1(u). LEW.1WR1 (but not resistant LEW.1W or WF) rats are susceptible to T1D induced by a TLR3 agonist polyinosinic:polycytidylic acid followed by infection with parvovirus. We have mapped genetic loci for virus-induced T1D susceptibility, identifying a major susceptibility locus (Iddm37) near the MHC. The Iddm37 homologs on mouse and human chromosomes are also diabetes linked. We report that a major effect gene within Iddm37 is diubiquitin (Ubd). Gene expression profiling of pancreatic lymph nodes in susceptible and resistant rats during disease induction showed differences in Ubd transcript abundance. The LEW.1WR1 Ubd promoter allele leads to higher inducible levels of UBD than that of LEW.1W or WF. Using zinc-finger nucleases , we deleted a segment of the LEW.1WR1 Ubd gene and eliminated its expression. UBD-deficient rats show substantially reduced diabetes after viral infection. Complementary studies show that there may be another diabetes gene in addition to Ubd in the Iddm37 interval. These data prove that Ubd is a diabetes susceptibility gene, providing insight into the interplay of multiple genes and environmental factors in T1D susceptibility.Genes and Immunity advance online publication, 23 January 2014; doi:10.1038/gene.2013.72.
    Genes and immunity 01/2014; · 4.22 Impact Factor
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    ABSTRACT: The earliest events leading to autoimmune type 1 diabetes (T1D) are not known in any species. A T-cell receptor variable region, TCR-Vβ13, is required for susceptibility to autoimmune diabetes in rats, and selective depletion of Vβ13(+) T-cells with an allele-specific monoclonal antibody prevents disease in multiple rat strains. To investigate the role of Vβ13 early in diabetes, we examined islet T-cell transcripts in susceptible (LEW.1WR1) and resistant (LEW.1W and WF) strains induced with polyinosinic:polycytidylic acid (poly I:C). Vβ13(+) T-cells displayed antigenic focusing in LEW.1WR1 islets five days post-induction and were characterized by a substantial decrease in CDR3 diversity. This occurred prior to significant islet T-cell accumulation (day 7) or frank diabetes (day 10-14). Vβ13(+) transcripts increased in LEW.1WR1 islets during diabetes progression but not in resistant rats. We also analyzed transcript clonality of rat TCR-Vα5, ortholog of the dominant TCR-Vα chain found on insulin B:9-23-reactive T-cells in NOD islets. We observe clonal expansion of Vα5(+) transcripts in pre-diabetic LEW.1WR1 islets, suggesting that rat Vα5 is also an important component of islet autoantigen recognition. These data provide additional evidence that genome-encoded TCR sequences are important determinants of genetic susceptibility to T1D.
    Diabetes 10/2013; · 7.90 Impact Factor
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    ABSTRACT: The dilute plasma cytokine milieu associated with type 1 diabetes (T1D), while difficult to measure directly, is sufficient to drive transcription in a bioassay that uses healthy leukocytes as reporters. Previously, we reported disease-associated, partially IL-1 dependent, transcriptional signatures in both T1D patients and the BioBreeding (BB) rat model. Here, we examine temporal signatures in congenic BBDR.lyp/lyp rats that develop spontaneous T1D, and BBDR rats where T1D progresses only after immunological perturbation in young animals. After weaning, the BBDR temporal signature showed early coincident induction of transcription related to innate inflammation as well as IL-10- and TGF-β-mediated regulation. BBDR plasma cytokine levels mirrored the signatures showing early inflammation, followed by induction of a regulated state that correlated with failure of virus to induce T1D in older rats. In contrast, the BBDR.lyp/lyp temporal signature exhibited asynchronous dynamics, with delayed induction of inflammatory transcription and later, weaker induction of regulatory transcription, consistent with their deficiency in regulatory T cells. Through longitudinal analyses of plasma-induced signatures in BB rats and a human T1D progressor, we have identified changes in immunoregulatory processes that attenuate a preexisting innate inflammatory state in BBDR rats, suggesting a mechanism underlying the decline in T1D susceptibility with age.Genes and Immunity advance online publication, 6 June 2013; doi:10.1038/gene.2013.31.
    Genes and immunity 06/2013; · 4.22 Impact Factor
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    ABSTRACT: Type 1 diabetes (T1D) is a T cell-mediated disease. It is strongly associated with susceptibility haplotypes within the major histocompatibility complex, but this association accounts for an estimated 50% of susceptibility. Other studies have identified as many as 50 additional susceptibility loci, but the effect of most is very modest (odds ratio (OR) <1.5). What accounts for the "missing heritability" is unknown and is often attributed to environmental factors. Here we review new data on the cognate ligand of MHC molecules, the T cell receptor (TCR). In rats, we found that one allele of a TCR variable gene, V β 13A, is strongly associated with T1D (OR >5) and that deletion of V β 13+ T cells prevents diabetes. A role for the TCR is also suspected in NOD mice, but TCR regions have not been associated with human T1D. To investigate this disparity, we tested the hypothesis in silico that previous studies of human T1D genetics were underpowered to detect MHC-contingent TCR susceptibility. We show that stratifying by MHC markedly increases statistical power to detect potential TCR susceptibility alleles. We suggest that the TCR regions are viable candidates for T1D susceptibility genes, could account for "missing heritability," and could be targets for prevention.
    Journal of Diabetes Research 01/2013; 2013:737485. · 3.54 Impact Factor
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    ABSTRACT: In earlier studies of the Iddm14 diabetes susceptibility locus in the rat, we identified an allele of the T-cell receptor (TCR) β-chain, Tcrb-V13S1A1, as a candidate gene. To establish its importance, we treated susceptible rats with a depleting anti-rat Vβ13 monoclonal antibody and then exposed them to either polyinosinic:polycytidylic acid or a diabetogenic virus to induce diabetes. The overall frequency of diabetes in the controls was 74% (n = 50), compared with 17% (n = 30) in the anti-Vβ13-treated animals, with minimal islet pathology in nondiabetic treated animals. T cells isolated from islets on day 5 after starting induction showed a greater proportion of Vβ13(+) T cells than did peripheral lymph node T cells. Vβ13 transcripts recovered from day 5 islets revealed focused Jβ usage and less CDR3 diversity than did transcripts from peripheral Vβ13(+) T cells. CDR3 usage was not skewed in control Vβ16 CDR3 transcripts. Anti-rat Vβ13 antibody also prevented spontaneous diabetes in BBDP rats. The Iddm14 gene is likely to be Tcrb-V13, indicating that TCR β-chain usage is a determinant of susceptibility to autoimmune diabetes in rats. It may be possible to prevent autoimmune diabetes by targeting a limited element of the T-cell repertoire.
    Diabetes 02/2012; 61(5):1160-8. · 7.90 Impact Factor
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    ABSTRACT: We tested the effectiveness of a community-based, literacy-sensitive, and culturally tailored lifestyle intervention on weight loss and diabetes risk reduction among low-income, Spanish-speaking Latinos at increased diabetes risk. Three hundred twelve participants from Lawrence, Massachusetts, were randomly assigned to lifestyle intervention care (IC) or usual care (UC) between 2004 and 2007. The intervention was implemented by trained Spanish-speaking individuals from the community. Each participant was followed for 1 year. The participants' mean age was 52 years; 59% had less than a high school education. The 1-year retention rate was 94%. Compared with the UC group, the IC group had a modest but significant weight reduction (-2.5 vs 0.63 lb; P = .04) and a clinically meaningful reduction in hemoglobin A1c (-0.10% vs -0.04%; P = .009). Likewise, insulin resistance improved significantly in the IC compared with the UC group. The IC group also had greater reductions in percentage of calories from total and saturated fat. We developed an inexpensive, culturally sensitive diabetes prevention program that resulted in weight loss, improved HbA1c, and improved insulin resistance in a high-risk Latino population.
    American Journal of Public Health 02/2012; 102(2):336-42. · 3.93 Impact Factor
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    Samir Malkani, John P Mordes
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    ABSTRACT: Until 2010, the diagnosis of diabetes mellitus was based solely on glucose concentration, but the American Diabetes Association (ADA) recommendations now include a new criterion: hemoglobin A1C ≥6.5%. Because this change may have significant implications for diabetes diagnosis, we conducted a comprehensive literature review including peer-reviewed articles not referenced in the ADA report. We conclude that A1C and plasma glucose tests are frequently discordant for diagnosing diabetes. A1C ≥6.5% identifies fewer individuals as having diabetes than glucose-based criteria. Convenience of A1C test might increase the number of patients diagnosed, but this is unproven. Diagnostic cut-points for both glucose and A1C are based on consensus judgments regarding optimal sensitivity and specificity for the complications of hyperglycemia. A1C may not accurately reflect levels of glycemia in some situations, but in comparison with glucose measurements, it has greater analytic stability and less temporal variability. When choosing a diagnostic test for diabetes, the limitations of each choice must be understood. Clinical judgment and consideration of patient preference are required to appropriately select among the diagnostic alternatives.
    The American journal of medicine 05/2011; 124(5):395-401. · 5.30 Impact Factor
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    ABSTRACT: Proteomic profiling of serum is a powerful technique to identify differentially expressed proteins that can serve as biomarkers predictive of disease onset. In this study, we utilized two-dimensional (2D) gel analysis followed by matrix-assisted-laser desorption/ionization time-of-flight mass spectrometry analysis to identify putative serum biomarkers for autoimmune type 1 diabetes (T1D) in biobreeding diabetes resistant (BBDR) rats induced to express the disease. Treatment with toll-like receptor 3 ligand, polyinosinic:polycytidilic acid (pIC), plus infection with Kilham rat virus (KRV), a rat parvovirus, results in nearly 100% of young BBDR rats becoming diabetic within 11-21 d. Sera collected from prediabetic rats at early time points following treatment with pIC + KRV were analyzed by 2D gel electrophoresis and compared with sera from control rats treated with phosphate-buffered saline, pIC alone or pIC + H1, a non-diabetogenic parvovirus. None of the latter three control treatments precipitates T1D. 2D gel analysis revealed that haptoglobin, an acute phase and hemoglobin scavenger protein, was differentially expressed in the sera of rats treated with pIC + KRV relative to control groups. These results were confirmed by Western blot and enzyme-linked immunosorbent assay studies, which further validated haptoglobin levels as being differentially increased in the sera of pIC + KRV-treated rats relative to controls during the first week following infection. Early elevations in serum haptoglobin were also observed in LEW1.WR1 rats that became diabetic following infection with rat cytomegalovirus. The identification and validation of haptoglobin as a putative serum biomarker for autoimmune T1D in rats now affords us the opportunity to test the validity of this protein as a biomarker for human T1D, particularly in those situations where viral infection is believed to precede the onset of disease.
    Experimental Biology and Medicine 11/2010; 235(11):1328-37. · 2.80 Impact Factor
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    ABSTRACT: Inflammatory mediators associated with type 1 diabetes are dilute and difficult to measure in the periphery, necessitating development of more sensitive and informative biomarkers for studying diabetogenic mechanisms, assessing preonset risk, and monitoring therapeutic interventions. We previously utilized a novel bioassay in which human type 1 diabetes sera were used to induce a disease-specific transcriptional signature in unrelated, healthy peripheral blood mononuclear cells (PBMCs). Here, we apply this strategy to investigate the inflammatory state associated with type 1 diabetes in biobreeding (BB) rats. Consistent with their common susceptibility, sera of both spontaneously diabetic BB DRlyp/lyp and diabetes inducible BB DR+/+ rats induced transcription of cytokines, immune receptors, and signaling molecules in PBMCs of healthy donor rats compared with control sera. Like the human type 1 diabetes signature, the DRlyp/lyp signature, which is associated with progression to diabetes, was differentiated from that of the DR+/+ by induction of many interleukin (IL)-1-regulated genes. Supplementing cultures with an IL-1 receptor antagonist (IL-1Ra) modulated the DRlyp/lyp signature (P < 10(-6)), while administration of IL-1Ra to DRlyp/lyp rats delayed onset (P = 0.007), and sera of treated animals did not induce the characteristic signature. Consistent with the presence of immunoregulatory cells in DR+/+ rats was induction of a signature possessing negative regulators of transcription and inflammation. Paralleling our human studies, serum signatures in BB rats reflect processes associated with progression to type 1 diabetes. Furthermore, these studies support the potential utility of this approach to detect changes in the inflammatory state during therapeutic intervention.
    Diabetes 10/2010; 59(10):2375-85. · 7.90 Impact Factor
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    ABSTRACT: The centrosome is important for microtubule organization and cell cycle progression in animal cells. Recently, mutations in the centrosomal protein, pericentrin, have been linked to human microcephalic osteodysplastic primordial dwarfism (MOPD II), a rare genetic disease characterized by severe growth retardation and early onset of type 2 diabetes among other clinical manifestations. While the link between centrosomal and cell cycle defects may account for growth deficiencies, the mechanism linking pericentrin mutations with dysregulated glucose homeostasis and pre-pubertal onset of diabetes is unknown. In this report we observed abundant expression of pericentrin in quiescent pancreatic beta-cells of normal animals which led us to hypothesize that pericentrin may have a critical function in beta-cells distinct from its known role in regulating cell cycle progression. In addition to the typical centrosome localization, pericentrin was also enriched with secretory vesicles in the cytoplasm. Pericentrin overexpression in beta-cells resulted in aggregation of insulin-containing secretory vesicles with cytoplasmic, but not centrosomal, pericentriolar material and an increase in total levels of intracellular insulin. RNAi- mediated silencing of pericentrin in secretory beta-cells caused dysregulated secretory vesicle hypersecretion of insulin into the media. Together, these data suggest that pericentrin may regulate the intracellular distribution and secretion of insulin. Mice transplanted with pericentrin-depleted islets exhibited abnormal fasting hypoglycemia and inability to regulate blood glucose normally during a glucose challenge, which is consistent with our in vitro data. This previously unrecognized function for a centrosomal protein to mediate vesicle docking in secretory endocrine cells emphasizes the adaptability of these scaffolding proteins to regulate diverse cellular processes and identifies a novel target for modulating regulated protein secretion in disorders such as diabetes.
    PLoS ONE 01/2010; 5(7):e11812. · 3.53 Impact Factor
  • Clinical Immunology - CLIN IMMUNOL. 01/2010; 135.
  • PLoS ONE 01/2010; 5(7). · 3.53 Impact Factor
  • Clinical Immunology - CLIN IMMUNOL. 01/2010; 135.
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    ABSTRACT: The contribution of antecedent viral infection to the development of type 1 diabetes in humans is controversial. Using a newer rat model of the disease, we sought to 1) identify viruses capable of modulating diabetes penetrance, 2) identify conditions that increase or decrease the diabetogenicity of infection, and 3) determine whether maternal immunization would prevent diabetes. About 2% of LEW*1WR1 rats develop spontaneous autoimmune diabetes, but disease penetrance is much higher if weanling rats are exposed to environmental perturbants including Kilham rat virus (KRV). We compared KRV with other viruses for diabetogenic activity. Both KRV and rat cytomegalovirus (RCMV) induced diabetes in up to 60% of LEW*1WR1 rats, whereas H-1, vaccinia, and Coxsackie B4 viruses did not. Simultaneous inoculation of KRV and RCMV induced diabetes in 100% of animals. Pretreatment of rats with an activator of innate immunity increased the diabetogenicity of KRV but not RCMV and was associated with a moderate rate of diabetes after Coxsackie B4 and vaccinia virus infection. Inoculation of LEW*1WR1 dams with both KRV and RCMV prior to pregnancy protected weanling progeny from virus-induced diabetes in a virus-specific manner. Exposure to viruses can affect the penetrance of autoimmune diabetes in genetically susceptible animals. The diabetogenicity of infection is virus specific and is modified by immunomodulation prior to inoculation. Maternal immunization protects weanlings from virus-induced diabetes, suggesting that modification of immune responses to infection could provide a means of preventing islet autoimmunity.
    Diabetes 09/2009; 59(1):110-8. · 7.90 Impact Factor
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    ABSTRACT: To identify genes that confer susceptibility to autoimmune diabetes following viral infection in the LEW.1WR1 rat. About 2% of LEW.1WR1 rats develop spontaneous autoimmune diabetes. Immunological perturbants including viral infection increase both the frequency and tempo of diabetes onset. To identify diabetes susceptibility genes (LEW.1WR1 x WF), F2 rats were infected with Kilham rat virus following brief pretreatment with polyinosinic:polycytidylic acid. This treatment induces diabetes in 100% of parental LEW.1WR1 rats and 0% of parental WF rats. Linkage to diabetes was analyzed by genome-wide scanning. Among 182 F2 rats, 57 (31%) developed autoimmune diabetes after a mean latency of 16 days. All diabetic animals and approximately 20% of nondiabetic animals exhibited pancreatic insulitis. Genome-wide scanning revealed a requirement for the Iddm14 locus, long known to be required for diabetes in the BB rat. In addition, a new locus near the RT1 major histocompatibility complex (MHC) was found to be a major determinant of disease susceptibility. Interestingly, one gene linked to autoimmune diabetes in mouse and human, UBD, lies within this region. The Iddm14 diabetes locus in the rat is a powerful determinant of disease penetrance in the LEW.1WR1 rat following viral infection. In addition, a locus near the MHC (Iddm37) conditions diabetes susceptibility in these animals. Other, as-yet-unidentified genes are required to convert latent susceptibility to overt diabetes. These data provide insight into the polygenic nature of autoimmune diabetes in the rat and the interplay of genetic and environmental factors underlying disease expression.
    Diabetes 09/2009; 58(12):2930-8. · 7.90 Impact Factor
  • Nina Guseva, David Phillips, John P Mordes
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    ABSTRACT: To describe the successful treatment of severe noninsulinoma hyperinsulinemic hypoglycemia with use of a calcium channel blocking agent in an adult patient who had previously undergone a gastric bypass surgical procedure. A 65-year-old woman who had undergone a gastric bypass surgical procedure 26 years earlier was hospitalized because of severe postprandial hypoglycemia. During and after hospitalization, the patient underwent assessment with conventional measurements of glucose, insulin, proinsulin, and C-peptide; toxicologic studies; magnetic resonance imaging studies of the pancreas; and determination of hepatic vein insulin concentrations after selective splanchnic artery calcium infusion. Metabolic variables were consistent with the diagnosis of hyperinsulinemic hypoglycemia. Magnetic resonance imaging revealed the presence of a side branch intraductal papillary mucinous tumor that had been stable for more than 1 year. The results of the calcium-stimulated insulin release study were consistent with nonlocalized hypersecretion of insulin. A trial of frequent small feedings failed to prevent hypoglycemia. On the basis of reports of successful treatment of childhood nesidioblastosis, the patient was then prescribed nifedipine, 30 mg daily. She has subsequently remained free of symptomatic hypoglycemia for 20 months. A calcium channel blocking agent may be efficacious and a potential alternative to partial pancreatectomy in cases of noninsulinoma hyperinsulinemic hypoglycemia in adults.
    Endocrine Practice 08/2009; 16(1):107-11. · 2.49 Impact Factor
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    ABSTRACT: T cells expressing the RT6 surface alloantigcn perform important immunoregulatory functions in the rat. Diabetes prone (DP) BB rats arc deficient in circulating RT6+ T cells and develop spontaneous autoimmune diabetes mellitus. Transfusions leading to cngraftment of RT6 ′ T cells prevent the disease. Coisogcnic diabetes resistant (DR) BB rats do circulate RT6^ T cells and are free of disease. We investigated the basis for the deficiency of RT6 * T cells in the DP-BB rat and made the following observations. 1. Thymectomy causes the rapid loss of most peripheral T cells in the DP-BB rat. 2. Concomitant with the loss of T cells is the total loss of mRNA encoding RT6. 3. In contrast to the effects observed in peripheral lymphoid tissues, thymectomy does not lead to a detectable loss in RT6+ protein found in the small intestine. We conclude that the deficiency of RT6 + peripheral T cells in the DP-BB rat is due either to their short life span or to their reduced proliferative capacity following release from the thymus.
    Autoimmunity 07/2009; 18(1):15-22. · 2.77 Impact Factor
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    ABSTRACT: Congenic DRF.(f/f) rats are protected from type 1 diabetes (T1D) by 34 Mb of F344 DNA introgressed proximal to the gimap5 lymphopenia gene. To dissect the genetic factor(s) that confer protection from T1D in the DRF.(f/f) rat line, DRF.(f/f) rats were crossed to inbred BBDR or DR.(lyp/lyp) rats to generate congenic sublines that were genotyped and monitored for T1D, and positional candidate genes were sequenced. All (100%) DR.(lyp/lyp) rats developed T1D by 83 days of age. Reduction of the DRF.(f/f) F344 DNA fragment by 26 Mb (42.52-68.51 Mb) retained complete T1D protection. Further dissection revealed that a 2 Mb interval of F344 DNA (67.41-70.17 Mb) (region 1) resulted in 47% protection and significantly delayed onset (P < 0.001 compared with DR.(lyp/lyp)). Retaining <1 Mb of F344 DNA at the distal end (76.49-76.83 Mb) (region 2) resulted in 28% protection and also delayed onset (P < 0.001 compared with DR.(lyp/lyp)). Comparative analysis of diabetes frequency in the DRF.(f/f) congenic sublines further refined the RNO4 region 1 interval to approximately 670 kb and region 2 to the 340 kb proximal to gimap5. All congenic DRF.(f/f) sublines were prone to low-grade pancreatic mononuclear cell infiltration around ducts and vessels, but <20% of islets in nondiabetic rats showed islet infiltration. Coding sequence analysis revealed TCR Vbeta 8E, 12, and 13 as candidate genes in region 1 and znf467 and atp6v0e2 as candidate genes in region 2. Our results show that spontaneous T1D is controlled by at least two genetic loci 7 Mb apart on rat chromosome 4.
    Physiological Genomics 04/2009; 38(1):89-97. · 2.81 Impact Factor
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    ABSTRACT: Recent studies have implicated the cell surface receptor Programmed Death-1 (PD-1) in numerous models of T cell anergy, though the specific mechanisms by which the PD-1 signal maintains tolerance is not clear. We demonstrate that the depletion of PD-1 with siRNA results in a complete reversal of clonal anergy in the A.E7 T cell model, suggesting that the mechanism by which PD-1 maintains the anergic phenotype is a T-cell-intrinsic phenomenon, and not one dependent on other cell populations in vivo. We have also shown that the neutralization of IL-2 during restimulation abrogates the effect of PD-1 depletion, suggesting that tolerance mediated by PD-1 is wholly IL-2 dependent, and likewise intrinsic to the tolerized cells.
    Cellular Immunology 03/2009; 256(1-2):86-91. · 1.74 Impact Factor

Publication Stats

5k Citations
1,003.72 Total Impact Points

Institutions

  • 1982–2014
    • University of Massachusetts Medical School
      • • Department of Medicine
      • • Department of Surgery
      • • Graduate School of Biomedical Sciences
      Worcester, Massachusetts, United States
  • 2005–2013
    • Drexel University College of Medicine
      • Department of Microbiology & Immunology
      Philadelphia, Pennsylvania, United States
  • 2008–2010
    • University of Massachusetts Amherst
      Amherst Center, Massachusetts, United States
  • 2006
    • Harvard Medical School
      Boston, Massachusetts, United States
  • 1999
    • University of the Sciences in Philadelphia
      Philadelphia, Pennsylvania, United States
  • 1998
    • National Heart, Lung, and Blood Institute
      Maryland, United States
  • 1997
    • National Institutes of Health
      Maryland, United States
  • 1990
    • University of Washington Seattle
      • Department of Medicine
      Seattle, WA, United States