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Biomedical subjects

E L Krawitt

Publications and source records attributed to E L Krawitt.

At least 37 records · Page 2Linked to original sources
PubMed1991

Suppressor T-cell deficiency in primary sclerosing cholangitis. Case and family study.

Primary sclerosing cholangitis is considered to be an autoimmune disease of the liver in which there is an association with the HLA phenotypes B8 and DR3 and in which circulating autoantibodies occur. Abnormalities of immune regulation may be present but whether or not they are primary or acquired is not known. This report is of a patient with primary sclerosing cholangitis who was homozygous for HLA B8 DR3, had a circulating antinuclear antibody, and a defect in nonspecific suppressor T-cell activity despite glucocorticosteroid treatment. Nevertheless, family studies revealed no evidence of an immunoregulatory defect in first-degree relatives despite the presence of Raynaud's phenomenon and malignancy in two sisters.

Adult↗
PubMed1991

Expression of HLA antigens and T cell infiltrates in chronic viral hepatitis. A comparison of biopsy and fine-needle aspiration findings.

To evaluate the expression of hepatocyte HLA Class I and II antigens and the infiltration of CD8-positive lymphocytes in patients with chronic hepatitis, cells obtained by the technique of fine-needle aspiration were compared with those obtained by percutaneous liver biopsy. In general, correlation between cytological and histological specimens of HLA Class I and Class II antigen expression and CD8 lymphocyte infiltration was excellent when comparing results of the core biopsy expressed semiquantitatively, and results from fine-needle aspiration quantitatively as percentage of cells stained. Although the major potential of multiple fine-needle aspiration sampling probably will be in the surveillance of patients who have received orthotopic liver transplants, the results of this study indicate that fine-needle aspiration can provide a useful technique for following antigen expression and inflammatory changes in studies in which frequent periodic samples may be necessary to monitor efficacy or toxicity of treatment regimens.

Biopsy↗
PubMed1991

Effects of treadmill exercise on fuel metabolism in hepatic cirrhosis.

We studied whole body and regional fuel metabolism before, during, and after 90 min of treadmill exercise at 50% of maximal aerobic capacity (VO2max) in four subjects with hepatic cirrhosis and in four normal volunteers. Rates of endogenous glucose production (EGP) were measured using D-[6-3H]glucose infusions and fuel oxidation using indirect calorimetry. In the basal state, cirrhotic subjects had similar rates of EGP compared with controls. Forearm release of alanine and lactate was significantly greater in cirrhotic subjects (P less than 0.05), suggesting increased basal rates of gluconeogenesis. During exercise, EGP increased 2- to 2.5-fold in control subjects (P less than 0.01) but did not increase in cirrhotic subjects. Despite lower glucose concentrations in cirrhotic subjects, progressive hypoglycemia did not occur during exercise, probably because cirrhotic subjects demonstrated increased plasma concentrations of fat-derived substrates and derived a greater percentage of total energy requirement from fat oxidation than did controls (P less than 0.05) and because forearm muscle glucose extraction was significantly lower in cirrhotic subjects compared with controls (0.5 vs. 3.6%, respectively; P less than 0.05). During recovery, control subjects demonstrated significant increases in EGP rates compared with both the basal and exercise periods, but cirrhotic subjects showed no increase. In conclusion, cirrhotic subjects failed to demonstrate the normal increase in EGP during and after exercise. Significant hypoglycemia during exercise did not occur, possibly because of the increased availability of fat-derived fuels, which may spare the requirement for circulating glucose as an oxidative fuel for exercising muscle tissues.

Adult↗
PubMed1989

Benign recurrent intrahepatic cholestasis: treatment with S-adenosylmethionine.

S-Adenosylmethionine (800 mg i.v. per day) was used to treat two brothers and a brother and sister from each of two kindreds with benign recurrent intrahepatic cholestasis. Symptoms, routine tests of liver function, concentrations of total bile acids, and the oral clearances of [11,12-2H]chenodeoxycholic acid and [24-13C]cholic acid were determined before and after treatment with S-adenosylmethionine. S-Adenosylmethionine did not ameliorate symptoms or biochemical parameters of cholestasis but reduced bile acid clearances in 3 of 4 subjects. Transaminase levels in both subjects of one kindred rose during treatment. These limited, preliminary observations suggest that S-adenosylmethionine may be ineffective in the therapy of benign recurrent intrahepatic cholestasis and may be hepatotoxic in some patients.

Bile Acids and Salts↗
PubMed1988

An immunogenetic study of suppressor cell activity in autoimmune chronic active hepatitis.

Some patients with autoimmune chronic active hepatitis as well as their disease-free first degree relatives show decreased suppressor cell activity of peripheral blood T lymphocytes. Studies were therefore undertaken in families ascertained by the presence of a single chronic active hepatitis patient to determine if this abnormality of immune regulation represents a genetic phenotype simply controlled by a gene or genes at a putative disease susceptibility locus and, further, if this locus showed linkage to either the HLA or the immunoglobulin constant region loci. In addition to determining circulating autoantibody status and genotyping for HLA and immunoglobulin allotypes, suppressor T cells were evaluated by surface markers and by determining their ability to suppress IgG secretion in vitro. The results suggest that immunoregulatory dysfunction in autoimmune chronic active hepatitis is a familial abnormality, but that this abnormality occurs independent of circulating autoantibody status and of the segregation of genes for HLA or immunoglobulin allotypes.

Antigens, Differentiation↗
PubMed1988

Association and linkage studies of immunoglobulin heavy chain allotypes in inflammatory bowel disease.

Inflammatory bowel disease is a familial disorder of unknown etiology, characterized by a variety of immunological abnormalities for which there are no proven genetic markers. Studies of immunoglobulin heavy chain and light chain allotypes were undertaken in 89 patients with Crohn's disease and in 18 families with ulcerative colitis or Crohn's disease in at least two first-degree relatives, to search for association and/or linkage between a postulated disease susceptibility locus and an immunoglobulin allotype locus. No evidence of association or linkage with a specific immunoglobulin allotype was found.

Adolescent↗
PubMed1986

Thymosin effects on immunoglobulin synthesis and suppressor T cell activity in normal subjects and patients with primary biliary cirrhosis.

Peripheral blood lymphocytes from patients with primary biliary cirrhosis previously have been reported to demonstrate reduced pokeweed mitogen-stimulated immunoglobulin synthesis and diminished function of suppressor T cells. To determine whether thymic hormone preparations reverse these immunologic defects in vitro, the effects of thymosin fraction 5 and thymosin alpha 1 on immunoglobulin synthesis and concanavalin A-induced suppression of immunoglobulin synthesis were investigated in normal subjects and patients with primary biliary cirrhosis. In normal subjects, no effects of thymosin were observed on unstimulated and pokeweed mitogen-stimulated immunoglobulin synthesis, nor on Con A-induced suppressor cell activity. Lymphocytes from patients with PBC synthesized less IgG and IgM than normals when stimulated by pokeweed mitogen, and this difference was enhanced by both thymosin fraction 5 and thymosin alpha 1. Con A suppression of immunoglobulin synthesis was abnormal in only one PBC subject so that thymosin effects on impaired suppressor T cell activity could not be tested.

Adult↗
PubMed1986

HLA typing and autoantibodies in hepatitis B surface antigen-negative chronic active hepatitis.

HLA types, serum autoantibodies and serum globulin levels were surveyed in 46 patients with HBsAg-negative chronic active hepatitis. Patients with chronic active hepatitis with viral risk factors were less likely than those without viral risk factors to be HLA type B8 (10% vs 44%) or to have autoantibodies (antinuclear and/or anti-smooth muscle antibodies) (38% vs 84%). Thirty patients (10 with and 20 without viral risk factors) were treated with glucocorticosteroids. Of the 11 patients who were HLA-B8, 100% responded to treatment. Of the 20 patients who were ANA positive, 80% responded. The data suggest that the presence of HLA-B8 may be a useful predictor of response to anti-inflammatory treatment and may define a genetic subset of HBsAg-negative chronic active hepatitis that will benefit from glucocorticosteroid therapy.

Adult↗
PubMed1983

Pleural and mediastinal changes following endoscopic injection sclerotherapy of esophageal varices.

Postero-anterior and lateral chest radiographs of patients undergoing endoscopic injection sclerotherapy of esophageal varices were reviewed. Radiographs were obtained prior to and within 48 hours of treatment. Following sclerotherapy, pleural effusions and densities were commonly seen at the azygoesophageal reflection and the posterior wall of the bronchus intermedius; however, on follow-up they had resolved. Most patients were asymptomatic, and morbidity was low. These findings suggest that inflammation developing after endoscopic injection sclerotherapy extends beyond the esophageal wall into the mediastinum and pleural space.

Adult↗
PubMed1983

Pure RBC aplasia and myasthenia gravis. Coexistence of two diseases associated with thymoma.

Pure RBC aplasia (PRCA) and myasthenia gravis (MG) are occasionally associated with thymoma, although the occurrence of all three in a single patient is rare. We describe a patient in whom PRCA and MG occurred in conjunction with the presence of serum autoantibodies, evidence for a serum inhibitor of erythropoiesis, and elevation of circulating thymosin alpha 1. Although a thymoma could not be detected before death, postmortem examination of the mediastinum found scattered cells within a nodule, suggestive of a lymphoepithelial thymic neoplasm.

Aged↗
PubMed1982

Demonstration of non-specific B-cell stimulation in patients with cirrhosis.

Using a sensitive enzyme-linked immunosorbent assay technique to measure immunoglobulins produced by peripheral lymphocytes, patients with cirrhosis with, and without, hypergammaglobulinaemia were found to produce significantly more spontaneous IgG than controls (p less than 0.005). There was no difference in IgG production when pokeweed mitogen, a T-cell dependent B-cell mitogen, was added to the system. Contrary to our findings in a T-cell proliferative assay, there was no evidence of increased prostaglandin-producing suppressor cell activity in this system. To study the importance of B-cell stimulation in cirrhotic hyperglobulinaemia, normal mononuclear cells were exposed either to cirrhotic or to control sera before measuring spontaneous IgG production. Cells exposed to cirrhotic sera produced significantly more IgG than those exposed to the control sera (p less than 0.02). These findings suggest that non-specific B-cell activity occurs with patients in cirrhosis and it is argued that the severity of the hypergammaglobulinaemia in patients with cirrhosis is more likely to depend on the degree of non-specific B-cell stimulation than on the competence of the immunoregulatory system.

Adolescent↗
PubMed1982

Functional suppressor T cell activity in Crohn's disease and the effects of sulphasalazine.

Suppressor T cell activity was measured in 18 patients with Crohn's disease and 20 controls, using two different functional assays. The effects of sulphasalazine and its metabolites on in vitro suppressor cell activity were also studied. The activity of a Con A-induced suppressor cell system in patients with Crohn's disease did not differ from that of controls, suggesting that the previously reported abnormalities are a secondary phenomenon. Furthermore, the activity of a non-induced suppressor T cell system was also normal in these patients. There was no evidence either in vivo or in vitro to suggest that sulphasalazine exerts its beneficial action by an effect on this aspect of immunoregulation.

Aminosalicylic Acids↗