Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Of 631 renal allografts performed at our center between January 1, 1979 and June 30, 1989, 368 were from cadaver donors (CAD) and 263 were from living-related donors (LRD). The recipients were almost equally divided among 3 ethnic groups: Black, Hispanic, and non-Hispanic, non-Black (primarily of northern European background). Recipient ages ranged between 1 and 70 years. In the CAD group HLA matching was emphasized so that no patient received a kidney with less than a 1 DR match, and for the entire series there was a mean of 2.4 of 6 HLA antigens matched between donor and recipient. All patients (LRD and CAD) received at least 3 pretransplant blood transfusions. Overall actuarial 10-year patient and graft survival were 68% and 48% respectively, with 72% patient and 56% graft survival for LRD and 58% patient and 36% graft survival for CAD recipients. Factors adversely affecting long-term graft outcome were: a) Black race. Overall 10-year graft survival was 23% versus 55% for non-Blacks (p = 0.008); b) Type I Diabetes before transplant. Overall 10-year graft survival was 35% versus 51% for nondiabetics; and c) Compliance. This was the most significant factor influencing long-term survival, other than death due to cardiovascular disease. In a non-Black, nondiabetic category of less than 36 years of age at transplantation (n = 169), 10-year patient survival in LRD and CAD groups was 95% and 85%, respectively, and graft survival was 78% and 70%, respectively. This was markedly different from the entire series (p = 0.008). Even in this group, 4 of the 17 graft losses (including mortality) were due to documented prolonged noncompliance in teenagers. The 6 other deaths that occurred were due to hepatitis/cirrhosis (2), CMV (3), and AIDS (1). Among the factors not influencing graft survival in the CAD group was HLA matching after the minimum requirements were fulfilled, either by comparing 1 with 2 DR antigens, or total HLA (1-6) antigens matched.
 ...
PMID:Long-term results of kidney transplantation at the University of Miami. 248 68

A deceased 59-year-old woman with insulin dependent diabetes mellitus complicated by chronic thyroiditis and chronic hepatitis was autopsied. She had had diabetes mellitus since she was 30 years old, and insulin therapy was started at 34 years. Laboratory findings were as follows: s-GOT 85, s-GPT 31, gamma-globulin 2.45 g/dl. Immunological tests were positive for anti-smooth muscle antibody and anti-ENA antibody with high titers of antithyroglobulin and anti-microsome antibodies. HLA analysis revealed the presence of DR-4. The thyroid biopsy specimen showed microscopic features characteristic of chronic thyroiditis at 52 years of age. She had been repeatedly admitted for the control of diabetes mellitus. She was admitted for the 9th time in June, 1987 following complaints of abdominal pain. After admission, her general condition became gradually worse, and she died of peritonitis in September, 1987. Pathological examination of the liver revealed an expansion of fibrous tissue on Glisson's capsule accompanied by lymphocytic infiltration and was diagnosed to be chronic inactive hepatitis. As for the thyroid gland, fibrous tissue replaced an extensive area of the thyroid gland, and normal thyroid tissue was not observed. Lymphocytic infiltration was less in comparison with that in the previous biopsy. As for the pancreas, atrophy of exocrine pancreatic tissue and fibrous change in interstitial tissue was observed. Lymphocytic infiltration was also seen in the interstitial exocrine tissue but not in the islet. Immunohistochemical examination of the islets using anti-insulin, glucagon and somatostatin antibodies by ABC peroxidase method showed the selective disappearance of B cells in the islets. The pathological changes in the thyroid gland, liver and pancreas suggest that autoimmune mechanism may be involved in the pathogenesis of chronic thyroiditis, chronic hepatitis and IDDM with exocrine pancreatic impairment in this case.
 ...
PMID:[An autopsied case of insulin dependent diabetes mellitus complicated by chronic thyroiditis and chronic hepatitis]. 259 7

Epidemiologic studies suggest an association between insulin dependent diabetes mellitus and viral infections. Several candidates like cytomegalovirus, Coxsackie virus and hepatitis virus have a selective tropism for beta cells. Progress in the understanding of the pathogenic importance of such viruses has been facilitated by animal models with virus induced diabetes and infections of human pancreatic beta cells maintained in culture. Immunological studies of type I diabetes after viral infections suggest that virus may trigger pancreatic autoimmunity. Molecular mimicry between viral and tissue antigens may represent a possible mechanism. Loss of immune tolerance toward beta cells would only appear in genetically predisposed individuals. The better understanding of the pathogenesis of type I diabetes mellitus brings out new approaches to treatment.
 ...
PMID:[Virus and insulin-dependent diabetes mellitus. Etiopathogenic perspectives]. 327 88

We report on a 33-year-old male patient with generalized acquired lipodystrophy, insulin resistant diabetes mellitus and acanthosis nigricans (Lawrence Syndrome). First probable symptoms of lipodystrophy (weight loss, shrinkage of subcutaneous fatty tissue, and loss of muscular strength) became evident three years ago, with the onset of diabetes mellitus occurring about six months later. The patient suffered from the following clinical symptoms: IDDM with increasing insulin-requirement, extreme reduction of fatty tissue, fatty liver hepatitis with elevated liver enzymes, glomerulopathy, muscular and neuropathic pains, as well as hypertriglyceridaemia. A basal C-peptide concentration is rather high. Definitely, the endogenous insulin secretion is increased. In other words, insulin resistance is documented. In an effort to identify the pathogenetic mechanisms of lipoatrophic diabetes mellitus in this patient and to develop a therapeutic strategy, antibodies against different tissues and endocrinologic regulation were investigated. It was possible to demonstrate the presence of serum autoantibodies against lipocytes of the subcutis and other tissues, against hepatic stellate cells, together with autoantibodies against different endocrine organs. By studying the basis of diabetic abnormalities relating to the growth hormone (GH), the insulin-like growth factor (IGF) dynamics in this patient, i.e. reductions of GH, IGF-I, IGF-II, IGF-Binding protein (IGF-BP) 2 and IGF-BP 3, were detected. An immunosuppressive treatment strategy was not beneficial.
 ...
PMID:Dysregulation of insulin-like growth factors in a case of generalized acquired lipoatrophic diabetes mellitus (Lawrence Syndrome) connected with autoantibodies against adipocyte membranes. 951 65

We describe two patients with liver kidney microsomal antibody type 1 (LKM1)-positive autoimmune hepatitis (AIH) with associated endocrinopathies. The first patient had insulin-dependent diabetes (IDDM), and the second patient had Addison's disease and hypoparathyroidism, and is also positive for islet cell antibodies, without overt diabetes. To account for the existence of multiple endocrinopathy in these patients, we investigated whether there is sequence similarity between the target of LKM1 antibodies, cytochrome P4502D6 (CYP2D6), and other human proteins, and if so, whether this structural similarity produces a detectable cross-reactive immune response. Our database search identified two proteins, carboxypeptidase H, an autoantigen in insulin-dependent diabetes, and 21-hydroxylase, the major autoantigen in Addison's disease, that share sequence similarity to the second major LKM1 epitope on CYP2D6. We tested the reactivity of sera from these patients to the homologous regions of the three autoantigens using an enzyme-linked immunosorbent assay (ELISA). The cut-off for positivity was established by testing sera from 22 healthy children. To determine the significance of reactivity to the peptide homologues of the three autoantigens, we investigated 16 additional patients with LKM1 AIH and 20 children with chronic hepatitis B virus infection as pathological controls. We found that reactivity to the second major epitope of CYP2D6 is significantly associated with reactivity to the homologous regions of carboxypeptidase H (CPH) and 21-hydroxylase (21-OHase) in patients with LKM1 AIH, and that this simultaneous recognition is cross-reactive. We suggest that a cross-reactive immune response between homologous autoantigens may contribute to the development of multiple endocrinopathies in LKM1 AIH.
 ...
PMID:Immunological cross-reactivity to multiple autoantigens in patients with liver kidney microsomal type 1 autoimmune hepatitis. 979 98

Autoimmune polyglandular syndrome type 1 (APS1) is characterized by a variable combination of disease components: (1) mucocutaneous candidiasis; (2) autoimmune tissue destruction; (3) ectodermal dystrophy. The disease is caused by mutations in a single gene called APECED (autoimmune polyendocrinopathy-candidiasis-ectodermal-dystrophy) or AIRE (autoimmune regulator) coding for a putative transcription factor featuring two zinc-finger (PHD-finger) motifs. APS1 shows a penetrance of 100%, lack of female preponderance and lack of association with HLA-DR. Typically, onset of APS1 occurs in childhood and multiple autoimmune manifestations evolve throughout lifetime. Organ-specific autoantibodies associated with hypoparathyroidism, adrenal and gonadal failures, IDDM, hepatitis and vitiligo are discussed, and autoantibody patterns in APS1 patients are compared with autoantibodies in APS type 2 (APS2). APS2 is characterized by adult onset adrenal failure associated with IDDM and/or hyperthyroidism. APS2 is believed to be polygenic, characterized by dominant inheritance and association with HLA DR3.
 ...
PMID:Autoimmune polyglandular syndromes. 989 74

The aim of the present study was to evaluate the persistence of anti-hepatitis B protective levels in young patients with type 1 diabetes, successfully immunised with a recombinant hepatitis B vaccine. We re-evaluated, after a 4 year follow-up, 54 patients and 70 age and sex-matched healthy subjects. Protective antibodies levels were found in 50/54 (92%) patients and in 67/70 (96%) controls. Moreover, anti-HBs levels were similar in diabetic patients and controls (means of log-titre and (sd); 1.95 (0.88) and 2.18 (0.64) patients and controls, respectively; P=0.11). No cases of clinical hepatitis were reported and all patients and controls remained HBc negative. These data demonstrate the persistence of anti-HBs levels in children, adolescents and young patients with type 1 diabetes after recombinant hepatitis B vaccine showing evidence of longterm immunogenity and protective effect.
 ...
PMID:Long term persistence of anti-HBs protective levels in young patients with type 1 diabetes after recombinant hepatitis B vaccine. 1111 88

Coxsackieviral infections have been linked etiologically to multiple diseases. The serotype CB4 is associated with acute pancreatitis and autoimmune type 1 diabetes. To delineate the mechanisms of host survival after an acute infection with CB4 (strain E2), we have investigated the role of nitric oxide (NO), generated by the inducible form of nitric oxide synthase (NOS2), in viral clearance and pancreatic beta-cell maintenance. Mice deficient in NOS2 (NOS2-/- mice) and their wild-type (wt) counterparts were injected with CB4, after which both groups developed severe pancreatitis, hepatitis, and hypoglycemia within 3 days. Within 4 to 7 days postinfection (p.i.), most of the NOS2-/- mice died and at a strikingly higher mortality rate than wt mice. Histological examination of pancreata from both infected NOS2-/- and infected wt mice revealed early and complete destruction of the pancreatic acinar tissue, but intact, insulin-stained islets. When examined up to 8 weeks p.i., neither surviving NOS2-/-mice nor surviving wt mice developed hyperglycemia. However, the clearance of infectious CB4 was different between the mice. The spleens of NOS2-/- survivors were cleared of infectious virus with kinetics similar to that of wt mice, but the livers, pancreata, kidneys, and hearts of the NOS2-/- groups cleared virus more slowly than those of the wt group. This delayed clearance was particularly prominent in the livers of infected NOS2-/- mice, which also showed prolonged histopathological features of viral hepatitis. Taken together, this outcome suggests that NOS2 (and NO) is not required for the prevention of pancreatic beta-cell depletion after CB4 infection. Instead the critical actions of NOS2 apparently occur early in the host immune response, allowing mice to survive and clear virus. Moreover, the data support the existence of an organ-specific dependency on NO for a rapid clearance of CB4.
 ...
PMID:A critical role for inducible nitric oxide synthase in host survival following coxsackievirus B4 infection. 1127 93

Interferon (IFN)-alpha is used for the treatment of chronic viral hepatitis. It has been associated with various forms of autoimmune disease, e.g. autoimmune hepatitis, Hashimoto thyroiditis and insulin-dependent diabetes mellitus. Further, an increase of insulin resistance and development of non-insulin-dependent diabetes mellitus has been described after treatment with IFN-alpha. Several studies have investigated the induction of different autoimmune markers by IFN-alpha, but only few specified patients who developed insulin-dependent diabetes mellitus. We report the case of a 37-year-old man with chronic hepatitis C who was treated with IFN-alpha plus ribavirin. Thirty weeks after the start of treatment, the patient developed insulin-dependent diabetes mellitus and therapy was withdrawn. HLA typing showed an HLA-DR1,3 phenotype. At manifestation of diabetes mellitus, the C-peptide level was 0.37 ng/ml (normal range 0.5-3 ng/ml). The patient had a positive family history for type 2 diabetes. Several autoimmune markers were investigated before, during and 6 months after withdrawal of antiviral treatment. High titres of glutamic acid decarboxylase (GAD) antibodies were present before therapy. A significant increase in titres of islet cell antibodies, parietal cell antibodies and sperm antibodies was present after 14 weeks of IFN-alpha treatment. Six months after withdrawal of IFN-alpha therapy, these antibodies had significantly decreased whereas GAD antibodies remained unchanged. There was no clinical sign of any other autoimmune disease. Our data show that, in patients with a predisposition to insulin-dependent diabetes mellitus, the disease may become manifest as a side-effect during therapy with IFN-alpha. Several pathogenetic factors may be involved in this process, and, in addition to IFN-alpha, hepatitis C itself may induce autoimmune mechanisms. We conclude that screening for autoantibodies specific for type 1 diabetes should be performed before the start of IFN-alpha treatment. In patients found to be at increased risk of developing diabetes mellitus type 1, monitoring of titres of these antibodies during therapy could help to assess the individual risk-benefit ratio of IFN-alpha treatment.
 ...
PMID:Development of insulin-dependent diabetes mellitus in a patient with chronic hepatitis C during therapy with interferon-alpha. 1129 53

The mechanisms driving the immune-mediated destruction of hepatic tissues in autoimmune hepatitis (AIH) are unknown. Recently the autoimmune regulator (AIRE), a gene associated with the development of the autoimmune polyglandular syndrome type 1 (APS-1), was cloned. About 15% to 20% of APS-1 patients develop hepatitis. However, the role of AIRE mutations in AIH, primary sclerosing cholangitis (PSC), and primary biliary cirrhosis (PBC) is not known. To address this issue patients with AIH (n = 94), PSC (n = 60), and PBC (n = 30) were analyzed for the presence of mutations in exons 6, 8, and 10 of AIRE by single stranded conformation polymorphism and sequence analysis. Autoantibody patterns of patients with defects in AIRE were analyzed by indirect immunofluorescence, enzyme-linked immunosorbent assay and Western blot. Heterozygous mutations of AIRE were identified in 3 patients: a patient with PBC and a patient with AIH type 1 carried a R257X mutation, and a patient with AIH type 2, diabetes mellitus type 1 (IDDM), thyroid disease, and atrophic gastritis carried a G305S mutation in the first PHD ring finger domain of the AIRE protein. None of the 3 patients with a defective AIRE allele showed autoantibodies, which are known to associate with APS-1. These findings show a differential genetic association of autoimmune liver diseases and hepatitis in APS-1. The subgroup of patients with heterozygous mutations in AIRE does not represent patients with an incomplete APS-1 syndrome. However, the Aire gene defect showed that genes involved in the induction of immunologic tolerance provide candidates for etiologic factors in autoimmune liver diseases.
 ...
PMID:Autoimmune regulator AIRE: evidence for genetic differences between autoimmune hepatitis and hepatitis as part of the autoimmune polyglandular syndrome type 1. 1134 30


1 2 3 4 5 6 Next >>