Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

AO-128 is a potent and structurally novel inhibitor of the intestinal disaccharidases, such as maltase and sucrase. Genetically obese-diabetic mice, KKA(y), were used to examine the acute or long-term effectiveness of this compound. AO-128 decreased a postprandial rise in blood glucose after sucrose solution loading dose-dependently; the ED50 to reduce a delta increment of blood glucose by 50% was 0.22 mg/kg. The intestinal sucrase and maltase activities were suppressed to 7 and 48% of the control levels, respectively, at a dose of 0.21 mg/kg. Four-week-old female KKA(y) mice were kept on a laboratory diet containing 10 or 50 ppm of AO-128 for 12 weeks. The high dose of AO-128 reduced food intake and body weight gain throughout the experimental period. On the other hand, the low dose reduced body weight gain for the first 4 weeks without any effect on food intake. Development of the hyperglycemia and hyperinsulinemia characteristic of KKA(y) mice was moderately prevented by the low dose, and completely by the high dose. Hypertriglyceridemia tended to be suppressed by the AO-128 treatment. The high dose decreased the hemoglobin A1 level and parametrial adipose tissue weight. Hepatomegaly and fatty liver were ameliorated by AO-128 dose-dependently. Nephropathy was ameliorated by the high dose. These findings indicate that AO-128 may be useful for treating human obesity and diabetes.
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PMID:Antiobesity and antidiabetic actions of a new potent disaccharidase inhibitor in genetically obese-diabetic mice, KKA(y). 162 84

Stable isotope tracers and indirect calorimetry were used to evaluate whole-body energy, glucose, lipid, and amino acid metabolism in a patient with generalized lipodystrophy during basal conditions and in response to insulin therapy. The results were compared with those obtained in previous studies in normal volunteers. The basal rate of glucose production (33.7 mumol/kg.min) was three times higher than normal. The basal rate of glycerol appearance in blood, an index of lipolysis, was 60% greater than normal when expressed per kilogram body weight (3.82 mumol/kg.min), but was more than 10 times normal when expressed per kilogram body fat mass (123.2 mumol/kg.min) because of the marked decrease in body fat in our patient (3% of total body weight). Leucine rate of appearance, an index of protein breakdown, and nonoxidative leucine disposal, an index of protein synthesis, were also greater than normal. Resting energy expenditure (REE) was 30% greater than normal. The effect of insulin infusion on these metabolic parameters was markedly blunted. These metabolic abnormalities help explain many of the clinical findings such as hyperglycemia, hypertriglyceridemia, fat depletion, hepatomegaly, and steatosis observed in patients with lipodystrophy. Ineffective insulin function in many tissues appears to be an important factor in the pathophysiology of lipodystrophy.
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PMID:Generalized lipodystrophy: in vivo evidence for hypermetabolism and insulin-resistant lipid, glucose, and amino acid kinetics. 164 Aug 69

Mauriac syndrome (MS) consists of a triad of poorly controlled diabetes, profound growth retardation, and hepatomegaly. The mechanisms involved in the growth retardation of those patients are not well understood. In an attempt to determine whether the growth retardation was secondary to somatroph secretory failure, abnormal pulsatile secretion, deletion of the growth hormone (GH) receptor, inadequate insulin-like growth factor I (IGF-I) generation, or abnormal IGF-I binding proteins (IGFBPs) two patients with MS were studied and their results compared with those of age-matched diabetic boys of similar glycemic control who were growing well. Overnight GH profiles in the MS and normally growing diabetics were analyzed by the CLUSTER program. The mean 12-hour GH concentrations, pulse amplitude, and pulse frequency were not different in either group of patients and did not change during acute normalization of the serum glucose overnight in the MS patients. The GH-binding proteins (GHBPs) relative binding were found to be the same in both groups of patients and did not differ from normal nondiabetic sera (62% +/- 8.0% relative specific binding in MS patients, v 53% +/- 4.3% in diabetic controls). The IGF-I concentrations were normal and comparable in both groups of patients (1.1 +/- 0.1 U/mL MS, v 1.1 +/- 0.3 diabetic controls). The IGFBPs were comparable in both groups of patients as well. One of the patients with MS had no meaningful increase in his growth velocity after 1 year on GH therapy despite good compliance. In conclusion, our data show normal hypothalamic-pituitary function, normal GHBP, IGF-I generation, and IGFBPs in two patients with MS when compared with normally growing diabetic children. These data, and the lack of linear growth in response to exogenous GH therapy in one patient, suggest a GH-resistant state, either secondary to impaired bioactivity of IGF-I, or a defect at or distal to the IGF-I receptor.
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PMID:Function of the growth hormone-insulin-like growth factor I axis in the profoundly growth-retarded diabetic child: evidence for defective target organ responsiveness in the Mauriac syndrome. 171 38

The purpose of the study was differential diagnosis of lactic acidosis in 44 children aged from 2 weeks to 4 years. In all of them the lactate level in repeated determinations exceeded 27 mg/100 ml. From the point of view of clinical manifestations the children were divided into three groups: 26 with hepatomegaly and hypoglycaemia (I), 6 with ataxia and retardation of somatic development (II), 12 with mental retardation and muscular hypotonia (III). Together with basic biochemical studies other tests were done, if necessary, including glucose and alanine loading, lactate determination in cerebrospinal fluid, analysis of urinary organic acids by the GC-MS method, morphological examinations of muscle biopsy material, enzymatic determinations in liver biopsy material. In group I glycogenosis was suspected and its type was finally established after biochemical and enzymatic tests (types I, Ib, III, VI, VIa, XI). In one case fructose-1,6-diphosphatase deficiency was suspected. In group II the clinical manifestations resembled Leigh's syndrome. The tests demonstrated an inhibition of glucose formation from alanine, and lactate level in the cerebrospinal fluid was evidently raised above that in the serum. Gasometric index showed the presence of respiratory alkalosis with metabolic compensation rather than primary lactate acidosis. In group III, with considerable clinical variety of signs, in only nine out of 12 children the cause of lactate acidosis could have been established (pathological changes of mitochondria in 4 cases, secondary increase of lactate without pathogenetic importance in 4, and 3-hydroxy-3-methylglutaric acidosis in 1 case. In conclusion it is thought that this combination of diagnostic methods is useful in differential diagnosis of congenital lactate acidosis in children.
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PMID:Congenital lactic acidosis in children--differential diagnosis in 44 cases. 184 18

An eleven year old boy was referred because of sudden loss of consciousness, muscular weakness, poor general health, severe hypoglycemia with seizures and hepatomegaly. Response to oral glucose and galactose increased blood lactic acid and glucose at different times. Fasting values of blood lactic was normal, but glucose was found at 33 mg/dl. Similar test made up two hours after feeding revealed hyperlactatemia (35-50 mg/dL) and hyperglycemia (129 mg/dL). Glucagon did not result in a rise of glucose at fasting or feeding. Hepatic glycogen content was found 15 gm/100 mg of tissue. The enzyme activities revealed a deficiency of the liver debranching enzyme while leukocytes had normal enzyme activity. Hepatic biopsy showed liver fibrosis. The present case had the clinical characteristics of severe form of glycogen storage disease. A low carbohydrate and high protein diet was indicated in order to increase the gluconeogenic precursors. Although debranching enzyme deficiency is almost always benign a high carbohydrate diet induced a more severe expression of the disease.
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PMID:Diet therapy in severe clinical expression of debrancher deficiency. 184 14

The present study was conducted to determine the dermal toxicity of coal coprocessing products and to assess their potential health hazards. Groups of 10 male and 10 female Sprague-Dawley rats were administered dermally coal coprocessing products (light gas oil, LGO; heavy gas oil I, HGOI; heavy gas oil II, HGOII) at 1 g/kg body weight/d for 14 d. The control and positive control groups received normal saline and a coal liquefaction product (CLP) at the same dose level, respectively. Treatment with either the three fractions of coprocessing products or CLP caused decreased growth rate and food consumption in animals of both sexes. Liver enlargement occurred in groups treated with HGOI, HGOII, and CLP. Decreased serum glucose was observed in animals of both sexes treated with the three fractions and CLP. Treatment with HGOI and CLP caused an elevation of hepatic microsomal ethoxyresorufin deethylase activity in the rat of both sexes. The three fractions and CLP caused mild anemia. Mild treatment-related histological changes were observed in the liver, spleen, thyroid, bone marrow, and kidney. All three fractions of coprocessing products were tested for their mutagenicity in five strains of Salmonella typhimurium: TA98, TA100, TA1535, TA1537, and TA1538. HGOI, after metabolic activation, was found to be mutagenic in the strains of TA98, TA100, and TA1538. In contrast, HGOII was mutagenic in the five strains with or without metabolic activation. These data indicate that HGOI and HGOII are more toxic than LGO, and should be subjected to further studies to determine their long-term effects.
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PMID:Short-term dermal toxicity and mutagenicity of coal coprocessing products in the rat. 185 79

The renal disease in an adult woman with Type 1 glycogen storage disease (GSD) is reported. Since she was 15 years old, several episodes of gouty arthritis had developed. At the age of 18, proteinuria was pointed out. Hepatomegaly, renomegaly out of proportion to the impairment of renal function, hyperuricemia, hyperlipidemia, fasting hypoglycemia and lactic acidemia were observed. The diagnosis of GSD was established on the basis of a glucose tolerance test, glucagon test and liver biopsy. The findings of renal biopsies performed at the ages of 24 and 27 years old suggested that glomerular damage might have preceded the tubulo-interstitial lesion.
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PMID:Renal disease in an adult with type 1 glycogen storage disease. 203 36

A 31-year-old male patient with type Ia glycogen storage disease was admitted to our department complaining of general fatigue and right hypochondriac pain. He exhibited massive hepatomegaly with systemic hypoglycemia, lactic acidosis, hyperuricemia, hyperpyruvatemia and hyperlipemia. The failure of blood glucose levels to increase after a glucagon loading test, and a reduced lactate level on glucose tolerance test were also observed. Various imaging techniques suggested hepatic adenoma with hemorrhage in the tumor, which was confirmed histologically. There was a complete absence of glucose 6-phosphatase activity, as determined by an enzyme assay on resected liver specimens, which proved the case to be type Ia glycogen storage disease. We also reviewed all previously reported cases of hepatic tumor and glycogen storage diseases. We conclude that, since hepatic adenoma is not rare in this disease, and is complicated by hemorrhage, rupture and malignancy, careful follow-ups are necessary.
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PMID:A case of type Ia glycogen storage disease complicated by hepatic adenoma. 217 Feb 59

Most inborn errors of intermediary metabolism presenting in the neonatal period fall schematically into three clinical categories: (1) those which lead to a neurological distress 'intoxication type' with a symptom-free interval, vomiting, comas, hypertonia, abnormal movements and frequent humoral disturbances (organic acidaemias, congenital urea cycle defects); (2) those which lead to a neurological distress 'energy deficiency' type. Frequent symptoms in this group include hyperlactacidaemia, severe hypotonia, cardiomyopathy, failure to thrive and malformations (congenital lactic acidaemias, fatty acid oxidation defects, peroxysomal disorders); (3) those which present evidence of liver dysfunction and hepatomegaly (glycogenesis, neoglucogenesis defects, galactosaemia, fructosaemia, tyrosinaemia type I). According to these three major clinical presentations and according to the proper use of few screening tests (blood gases, glucose, ammonia, lactic acid, electrolytes, acetest), we propose a method of diagnosis which groups these children into five schematical syndromes: type I MSUD; type II organic acidaemias; type III; congenital lactic acidosis; type IVa, urea cycle defects; type IVb, non-ketotic hyperglycinaemia, sulfite oxidase deficiency, peroxisomal disorders; type V liver dysfunctions. Once the above classification has been made, sophisticated and specific investigations can be planned (amino acid chromatography, organic acid chromatography, enzymatic studies, etc).
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PMID:Clinical approach to inherited metabolic disorders in neonates. 226 19

We previously reported that streptococcal preparation (OK-432), which is a TNF inducer, inhibits insulitis and development of autoimmune diabetes in nonobese diabetic (NOD) mice and Bio-Breeding (BB) rats, as animal models of insulin-dependent diabetes mellitus. We have recently shown that recombinant human (h)TNF-alpha also suppresses development of diabetes in NOD mice. In this study we have extended our observation on TNF to BB rats in order to see whether TNF generally inhibits autoimmune diabetes. A total of 5 x 10(4) U of rhTNF-alpha was administered i.p., twice a week to male and female BB rats from 4 to 27 wk of age. The cumulative incidence of diabetes by 27 wk of age in nontreated rats was 36.4% (8/22), whereas that in hTNF-alpha-treated rats was 0% (0/21) (p less than 0.001). The hTNF-alpha-treated rats did not lose body weight and maintained normal blood glucose concentrations. Immunologic and histologic examinations were performed at the end of the experiment. Spleen cell cytotoxicities for NK-sensitive YAC-1 and rat insulinoma (RINm5F) cells in hTNF-alpha-treated rats significantly decreased in comparison with nontreated and nondiabetic BB rats. Intensity of insulitis was also inhibited in hTNF-alpha-treated rats. Interestingly, a huge hepatomegaly and splenomegaly was found in two of the 21 hTNF-alpha-treated rats. The latter consisted of W3/13dull+ and W3/25dull+ cells, which did not exhibit cytotoxicity for either YAC-1 or RINm5F cells. These results indicate that the chronic and systemic administration of TNF has a regulatory role in autoimmune diabetes in BB rats as well as in NOD mice, and that these animals may have a defect in TNF-mediated immunoregulation.
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PMID:Inhibition of type 1 diabetes in BB rats with recombinant human tumor necrosis factor-alpha. 238 63


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