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)

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

This case of hepatocellular carcinoma (HCC) with alcoholic liver fibrosis, which was not associated with hepatitis viruses, was accompanied by hypoglycaemia. The immunoreactive insulin level was low and other hormonal examinations were almost normal. Immunohistochemical studies showed a high level of insulin-like growth factor II (IGF2) peptide in the HCC section and the size heterogeneity of serum IGF2 investigated by western blot revealed a large form at approximately 15 kDa. These results suggest that the HCC with alcoholic liver fibrosis produced IGF2 and that the hypoglycaemia was caused by tumour-associated IGF2.
 ...
PMID:Case report: Insulin-like growth factor II expression in hepatocellular carcinoma with alcoholic liver fibrosis accompanied by hypoglycaemia. 973 71

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

Chronic disease conditions that are associated with elevated proliferation are well established as risk factors for cancer development. These may be due to viruses (for example, in the case of hepatitis and liver cancer), bacterial infections, parasite infestation or physical trauma. In addition to these exogenous agents there are also metabolic abnormalities that can contribute, caused by genetic or epigenetic influence. In the latter case, an increase in serum levels of the hormones oestrogen, testosterone and insulin may be of special importance. The present review concentrates attention on factors that induce elevated cell turnover and for which there is epidemiological and/or experimental evidence of a link with neoplasia, with particular stress on the individual organ or tissue level.
 ...
PMID:Chronically elevated proliferation as a risk factor for neoplasia. 988 83

Serum insulin (SI) levels were determined in 36 severe hepatitis patients by RIA. The average level of SI in chronic severe hepatitis (CSH) patients was 43.18 +/- 27.12 mu.L-1, and subacute severe hepatitis (SSH) patients 28.91 +/- 12.77 mu.L-1. Both were increased significantly as compared with normal controls (P < 0.01), and the level of SI in patients died from SSH and CSH was increased significantly than those alive (P < 0.05). The level of SI at the fastiguium stage of the disease was significantly higher as compared with that of the convalescence stage (P < 0.05). The results suggest that SI may aid to evaluate the severity of the illness and to estimate the outcome of the patients.
 ...
PMID:[The serum insulin level in severe hepatitis patients]. 1007 91

Glucocorticoid excess causes insulin resistance i.e. a reduced effectiveness of insulin to suppress hepatic glucose production and to increase glucose uptake in muscle and fat tissue. Persons who cannot compensate for the resulting additional insulin need develop overt diabetes during glucocorticoid therapy. In the field of gastroenterology, glucocorticoids are mainly employed for the therapy of chronic inflammatory bowel diseases, alcoholic and autoimmune hepatitis, and after liver transplantation. The risk of developing steroid diabetes depends among other things on the genetic predisposition, the body composition, the underlying gastrointestinal disease, the age, and the steroid dose. The treatment of glucocorticoid-induced diabetes resembles essentially the treatment of type 2-diabetes. In addition to dietary measures, oral antihypoglycemic drugs and/or insulin are applied. If oral antihypoglycemic drugs are used, specific problems that might result from the gastrointestinal diseases need to be observed. In the short and medium term, the prognosis of glucocorticoid-induced diabetes is good since it is well treatable. If glucocorticoid treatment is continued for a long time, the alterations of glucose metabolism and the resulting hyperinsulinemia may lead to increased cardiovascular risk.
 ...
PMID:[Glucocorticoid-induced diabetes mellitus in gastrointestinal diseases]. 1044 14

Corticosteroid withdrawal after orthotopic liver transplantation (OLT) represents an attractive therapeutic option for ameliorating post-OLT metabolic complications, although several reports suggest patients who undergo transplantation for autoimmune hepatitis (AIH) may have a greater incidence of acute and chronic rejection when withdrawn from corticosteroid therapy. The aim of this study is to evaluate the success of corticosteroid withdrawal in patients with AIH after OLT. Twenty-six patients underwent successful OLT for AIH. In 21 of these patients, stable maintenance immunosuppression consisted of cyclosporine (CSA) and prednisone (n = 20) or tacrolimus (TAC) and prednisone (n = 1). In this group, a trial of prednisone withdrawal was initiated when patients were 6 months or more post-OLT, with normal liver function, and receiving an average prednisone dosage of 10 mg/d. Five additional patients treated with either TAC (n = 4) or CSA (n = 1) plus mycophenolate mofetil underwent a 14-day taper of prednisone. Overall, 17 of 25 patients (68%) were successfully withdrawn from corticosteroids, with a mean follow-up of 22 months (range, 1 to 34 months). Of the remaining 8 patients, 5 patients received a lower dosage of prednisone or required prednisone to control inflammatory bowel disease. Only 3 patients remained dependent on prednisone to maintain stable liver allograft function. Withdrawal from 10 to 5 mg of prednisone (n = 21) resulted in four episodes of steroid-responsive and two episodes of steroid-resistant rejection in 3 patients, and 18 of 21 patients (86%) were rejection free. Withdrawal from 5 to 0 mg prednisone (n = 17) resulted in eight episodes of steroid-responsive and no episodes of steroid-resistant rejection in 4 patients; 13 of 17 patients (76%) were rejection free. Of the 5 patients in the 14-day prednisone-taper group, 3 patients had steroid-responsive rejection and 1 patient required OKT3. Seventeen of 21 patients (81%) with AIH were successfully withdrawn from corticosteroids. It is notable that corticosteroid withdrawal was associated with a reduction in serum cholesterol levels, decreased use of antihypertensive agents, and reduced need for insulin or oral hypoglycemic agents. We propose corticosteroid withdrawal should be attempted in patients with underlying AIH who undergo OLT because most will benefit without significantly jeopardizing the liver allograft.
 ...
PMID:Successful withdrawal of prednisone after adult liver transplantation for autoimmune hepatitis. 1047 51

Autoantibodies against aromatic L-amino acid decarboxylase (AADC) are present in about 50 percent of sera from patients with autoimmune polyendocrine syndrome type I (APS I) but absent in sera from patients with different organ-specific autoimmune diseases, such as insulin-dependent diabetes mellitus, Hashimoto's thyroiditis, and Graves' disease. AADC is expressed in the pancreatic beta-cells, the liver, and the nervous system; and the presence of AADC antibodies has been shown to correlate to hepatitis and vitiligo in APS I patients. Among 101 investigated patients with autoimmune Addison's disease, 15 had high titers of AADC antibodies. According to the clinical characteristics of these patients, only 3 had APS I. The remaining 12 had either isolated Addison's disease or associated diabetes mellitus, hypothyroidism, vitiligo, alopecia, gonadal failure, and pernicious anemia. Autoantibodies against 21-hydroxylase were present in 9 of 12, whereas autoantibodies against side-chain cleavage enzyme and 17alpha-hydroxylase were present in 3 of 12. Two patients had only autoantibodies against AADC. DNA was available from 3 of these 12 patients. One of the patients, a woman with Addison's disease, autoimmune thyroiditis, and premature menopause was heterozygous for a point mutation (G1021A, Val301Met) in the first plant homeodomain zinc finger domain of the autoimmune regulator (AIRE) gene. The presence of AADC autoantibodies identifies patients with APS I and a subgroup of Addison patients who may have a milder atypical form of APS I or represent a distinct entity. Measurement of autoantibodies against AADC should be included in the evaluation of Addison's disease.
 ...
PMID:Autoantibodies against aromatic L-amino acid decarboxylase identifies a subgroup of patients with Addison's disease. 1063 24

Open (OC) or laparoscopic (LC) cholecystectomy is considered a relative contraindication in patients with liver cirrhosis. The effect of LC and OC on the hepatic catabolic stress response was studied in patients with postnecrotic liver cirrhosis and chronic hepatitis to define the most suitable procedure from a metabolic point of view. Altogether 14 patients with cirrhosis and 14 with chronic hepatitis were randomized to LC or OC (n = 7 in each group). The increase in the functional hepatic nitrogen clearance (FHNC) was quantified. Changes in glucose, insulin, glucagon, cortisol, epinephrine, norepinephrine, and prostaglandin E(2) (PGE(2)) were observed. There was no difference in FHNC between LC and OC in any of the patients. Among cirrhotic patients OC caused a 132% increase in FHNC (p < 0.05) and among the hepatitis patients a 69% increase (p < 0.05). In contrast, there was no significant increase following LC in any of the patients. OC increased fasting glucose and insulin in the hepatitis patients (p < 0.01 and p < 0.001, respectively) and in the cirrhosis group (p < 0.01 and p < 0.05, respectively). Alanine stimulation increased glucose in hepatitis patients after OC (p < 0.05) and after LC (p < 0.01). Stimulated glucagon increased after OC in the hepatitis group (p < 0.05). During stimulation cortisol was higher following LC in hepatitis patients (p < 0.01) and cirrhotic patients (p < 0.05). Fasting PGE(2) was down-regulated after LC in hepatitis patients (p < 0.05) and cirrhotic patients (p < 0.01) and after OC in the hepatitis group (p < 0.001). FHNC is similar after LC and OC. Thus from a metabolic point of view, LC has no advantage over OC.
 ...
PMID:Postoperative hepatic catabolic stress response in patients with cirrhosis and chronic hepatitis. 1065 74

Troglitazone, a PPAR-gamma agonist, is a new drug for type 2 diabetes. The drug decreases blood glucose via enhancing insulin action. Recently Sankyo pharmaceutical company is warning severe hepatotoxicity by troglitazone. It recommends to examine liver function every month in diabetic patients treated with the drug in order early to find drug-induced hepatitis. In Japan 153 diabetic patients treated with the drug developed severe hepatitis and 8 of them died of drug-side effects. Quinone metabolite of troglitazone predominantly in the liver to a sulfate conjugate and activation of PPAR gamma and PXR(pregnane X receptor) by troglitazone are supposed to be factors of hepatotoxic mechanism.
 ...
PMID:[Clinical effect and side effect of troglitazone]. 1070 61


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>