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Biomedical subjects

David A Sass

Publications and source records attributed to David A Sass.

15 recordsLinked to original sources
PubMed2006

The MCP-1 -2518 A/G polymorphism is not a susceptibility factor for chronic pancreatitis.

BACKGROUND AND AIMS: Chronic pancreatitis (CP) is an inflammatory process initiated by recurrent acute pancreatitis and characterized by progressive parenchyma destruction and fibrosis. Genetic factors influence susceptibility and modify progression. The monocyte chemotactic protein-1 (MCP-1) -2518 G allele, which modifies the severity of acute pancreatitis, was investigated as a susceptibility factor for CP. METHODS: A genetic association study was performed on 177 CP patients and 116 healthy controls from the NAPS2 Study. The MCP-1 A/G genotype was determined by RFLP and confirmed by DNA sequencing. RESULTS: Compared to the control group the MCP-1 -2518 genotypes were similar: A/A (57% vs. 50%), A/G (34.5% vs. 40%) and G/G (8.5% vs. 10%). These allele frequencies were not statistically different (p = 0.267). CONCLUSIONS: Although the pro-inflammatory chemokine MCP-1 -2518 G allele is a severity factor for AP, it does not significantly alter susceptibility to CP.

Adolescent↗
PubMed2006

Genetic control of anti-Sm autoantibody production in NOD congenic mice narrowed to the Idd9.3 region.

Anti-Smith (anti-Sm) autoantibodies are directed to proteins in the small-nuclear ribonucleoprotein (snRNP) family and are considered specific for systemic lupus erythematosus (SLE) in both humans and mice. We previously established that NOD.c3c4 mice, carrying B6 and B10 congenic segments from chromosomes 3 to 4 on an nonobese diabetic (NOD) background, and NOD.Idd9R28 mice, carrying a B10 segment on c4 alone, developed significant penetrance of anti-Sm antibody production. Here we determine autoantibody incidence in additional NOD.Idd9 congenic strains and use a congenic mapping approach to narrow the interval necessary for enhanced autoantibody production to a approximately 5.6-Mb region containing insulin-dependent diabetes (Idd)9.3. The Idd9.3 interval contains the candidate molecule cluster of differentiation (CD)137, which is a member of the tumor necrosis factor (TNF) receptor superfamily, functions as an inducible costimulator of T cells, and controls T-B interactions. The NOD and B10 CD137 alleles have sequence polymorphisms and different functional effects on T cells; the NOD CD137 allele mediates weaker T cell proliferative responses and decreased interleukin (IL)-2 production after CD137-mediated costimulation. Our work establishes CD137 as a candidate gene for control of autoantibody production in NOD.Idd9.3 congenic mice.

Animals↗
PubMed2006

Alcoholic hepatitis.

Alcoholic hepatitis is a form of hepatic injury that carries a significant morbidity and mortality. The clinical presentation is that of fatigue, malaise, and jaundice in individuals who have abused excessive quantities of alcohol. Severity at presentation, traditionally calculated using the Maddrey Discriminant Function, determines outcome; the short-term mortality can be exceptionally high, with many persons dying within 1 month of hospitalization. This article summarizes the epidemiology, pathogenesis, pathology, and clinical features of alcoholic hepatitis. Prognostic scoring systems and therapeutic options receive special emphasis.

Hepatitis, Alcoholic↗
PubMed2005

Nonalcoholic fatty liver disease: a clinical review.

Nonalcoholic fatty liver disease may be the most common liver disease in the United States, with a high prevalence in the obese, type 2 diabetic population, and it is probably underestimated as a cause for cirrhosis. Clinicopathologically, it represents a wide spectrum of histologic abnormalities and clinical outcomes, ranging from benign hepatic steatosis to cirrhosis. Pathophysiologically, insulin resistance is thought to be pivotal in the development of steatosis, after which a second oxidative stressor produces lipid peroxidation and nonalcoholic steatohepatitis (NASH). Liver biopsy is the gold standard for diagnosis and prognosis. The need for an effective treatment is both clear and urgent, yet in the absence of proven therapies, treatment is directed toward weight loss and comorbidity management. For patients with NAFLD at risk of disease progression, there is a lack of large, randomized, placebo-controlled trials of adequate treatment duration, with baseline stratification according to histologic severity.

Fatty Liver↗
PubMed2005

Is the monocyte chemotactic protein-1 -2518 G allele a risk factor for severe acute pancreatitis?

BACKGROUND & AIMS: Acute pancreatitis (AP) reflects the intensity of the inflammatory response and is divided into mild AP (MAP) or severe AP (SAP). Monocyte chemotactic protein-1 (MCP-1) gene expression is altered by an A/G polymorphism (-2518), with the G allele increasing MCP-1 production. Our aim was to determine whether the MCP-1 -2518 A/G polymorphism affects the severity of AP. METHODS: Seventy-seven consecutive patients and 116 controls were evaluated. The A/G genotype was evaluated by polymerase chain reaction amplification, restriction fragment length polymorphism, and DNA sequencing. MCP-1 serum levels were quantified using a fluorescence bead-based immunoassay. RESULTS: Sixty-three of 77 patients had MAP (82%) and 14 of 77 had SAP (18%). Patients with SAP had a significantly greater proportion of the G allele (12 of 14; 86%) than did control subjects (50 of 116; 43%) (odds ratio [OR], 7.9; 95% confidence interval [CI], 1.7-37, P < .003) or MAP patients (29 of 63; 46%) (OR, 7.0; 95% CI, 1.5-34; P < .007). Patients with pancreatitis and AA genotype had a low risk for SAP (OR, .13; 95% CI, .01-.61; P < .003). As predicted by the genotype, the serum MCP-1 levels were significantly higher in the SAP patients when compared with the MAP patients ( P = .002) and they also predicted death. CONCLUSIONS: MCP-1 -2518 G allele is a risk factor for severe AP. MCP-1 serum levels, measured early in the course of AP, appear to be an accurate predictor of severity of acute pancreatitis and death.

Acute Disease↗
PubMed2004

Genetic control of autoimmunity: protection from diabetes, but spontaneous autoimmune biliary disease in a nonobese diabetic congenic strain.

At least 20 insulin-dependent diabetes (Idd) loci modify the progression of autoimmune diabetes in the NOD mouse, an animal model of human type 1 diabetes. The NOD.c3c4 congenic mouse, which has multiple B6- and B10-derived Idd-resistant alleles on chromosomes 3 and 4, respectively, is completely protected from autoimmune diabetes. We demonstrate in this study, however, that NOD.c3c4 mice develop a novel spontaneous and fatal autoimmune polycystic biliary tract disease, with lymphocytic peribiliary infiltrates and autoantibodies. Strains having a subset of the Idd-resistant alleles present in the NOD.c3c4 strain show component phenotypes of the liver disease: NOD mice with B6 resistance alleles only on chromosome 3 have lymphocytic liver infiltration without autoantibody formation, while NOD mice with B10 resistance alleles only on chromosome 4 show autoantibody formation without liver infiltration. The liver disease is transferable to naive NOD.c3c4 recipients using splenocytes from affected NOD.c3c4 mice, demonstrating an autoimmune etiology. Thus, substitution of non-NOD genetic intervals into the NOD strain can prevent diabetes, but in turn cause an entirely different autoimmune syndrome, a finding consistent with a generalized failure of self-tolerance in the NOD genetic background. The complex clinical phenotypes in human autoimmune conditions may be similarly resolved into largely overlapping biochemical pathways that are then modified, potentially by alleles at a few key chromosomal regions, to produce specific autoimmune syndromes.

Adoptive Transfer↗
PubMed2004

Relationship of visceral adipose tissue to recurrence of adenomatous polyps.

OBJECTIVES: Insulin is a growth factor for colorectal cancer. Visceral adipose tissue (VAT) is strongly associated with insulin levels, and insulin and visceral obesity have been associated in cohort studies with colorectal cancer. The aim of this investigation was to determine whether VAT is associated with recurrence of adenomatous polyps, the precursor to colorectal cancer. METHODS: As an ancillary study to the Polyp Prevention Trial, a randomized clinical trial that evaluated the effect of a low-fat, high-fiber, high vegetable and fruit diet on adenomatous polyp recurrence, subjects at one clinical center underwent measurement of VAT with a single-slice CT scan through the L4-L5 interspace. The scan was performed around the time of the subject's year 4 colonoscopy that determined adenoma recurrence. RESULTS: Of 119 subjects, 44 of 84 men (52%) and 16 of 35 women (46%) had a recurrent adenoma (p= 0.51). Body mass index (BMI) and weight at baseline and at year 4 colonoscopy were unrelated to adenoma recurrence. In a multivariate model including visceral fat quartile, remote history of polyps, gender, age, and randomization group, only remote history of polyps was statistically significantly associated with recurrent adenoma with a relative risk of 4.6 (95% CI 1.7, 12.4, p= 0.001). There was no consistent monotonic trend of increased or decreased risk of recurrence as one ascended quartiles of adipose tissue for visceral, subcutaneous, or total abdominal fat. CONCLUSION: In this study, no association between visceral adipose tissue and adenomatous polyp recurrence was observed. Further study and exploration of the role of VAT in adenoma progression is required.

Adenomatous Polyps↗
PubMed2004

Jejunal gastrointestinal stromal tumor: a cause of obscure gastrointestinal bleeding.

In cases of obscure gastrointestinal bleeding, when a source for blood loss is not apparent from examination of the colon and upper gastrointestinal tract, the small bowel usually becomes the focus of investigation. A tumor with interesting pathologic features was found in a patient who presented with recurrent episodes of massive obscure gastrointestinal hemorrhage. This case highlights the importance of considering small intestinal tumors as the likely cause of obscure gastrointestinal hemorrhage in young patients and how a noninvasive test, eg, abdominal computed tomography scan, might obviate the need for more invasive testing.

Adult↗
PubMed2003

Fulminant hepatic failure.

FHF is a devastating illness of varied causes, carrying considerable mortality and affecting patients with previously healthy livers. The clinical presentation varies widely but encephalopathy is the defining criterion. Management requires a multidisciplinary approach, including rapid triage, monitoring, and referral to a transplantation center for further evaluation. Early prognostication and timely availability of donor livers are essential for a successful outcome. A donor shortage, however, continues to pose problems for both hepatologists and surgeons. Effective liver support devices may greatly prolong the window of opportunity to provide a donor liver, or alternatively to allow the native liver to regenerate. Despite decades of great progress in the field of liver support systems, the ideal system is still a long-cherished goal in hepatology. Hybrid systems have garnered most of the recent attention, but the quest for improved synthetic function has not yet been realized. It is hoped that rapid conceptual and technologic developments with respect to hybrid systems, hepatocyte transplantation, and xenografting will yield a safe and accessible tool for managing these critically ill patients. Controlled, multicenter trials in well-defined patient groups and with standard outcome measures are essential to evaluate the clinical value of these devices. A better understanding of mechanisms responsible for liver cell death and multiorgan failure, and the development of strategies to enhance liver regeneration, may allow a more targeted approach to therapy.

Algorithms↗