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

Alcohol feeding to rats produced hepatomegaly, associated with enlargement of the hepatocytes. The increase in liver dry weight was accounted for not only by fat but also by protein accumulation, primarily in microsomes and cytosol, with a selective increase in export proteins: concentrations of both immunoreactive albumin and transferrin were augmented in liver microsomes and cytosol of ethanol-fed rats. To investigate the mechanism of this protein accumulation, [14C]leucine was injected intravenously and its incorporation into both liver and serum proteins was measured after various time intervals. Rates of synthesis and export were assessed from protein labeling and specific activities of leucyl-tRNA. Synthesis of liver protein and proalbumin were enhanced by chronic ethanol feeding, but this was not associated with a corresponding rise in serum albumin output. Actually, there was a significant retention of the label in liver albumin and transferrin with delayed appearance in the serum of ethanol-fed rats. This indicated that, regardless of the changes in synthesis, the export of protein from the liver into the plasma was impaired. This alteration in export was associated with a decreased amount of polymerized tubulin in the liver of ethanol-treated animals. Thus, both enhanced protein synthesis and defective export contribute to the ethanol-induced accumulation of liver protein, and the decrease in liver microtubules represents a possible site for impairment of protein export.
 ...
PMID:Pathogenesis of alcohol-induced accumulation of protein in the liver. 56 Nov 18

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.
 ...
PMID:Generalized lipodystrophy: in vivo evidence for hypermetabolism and insulin-resistant lipid, glucose, and amino acid kinetics. 164 Aug 69

Severe cachexia of extremely rapid onset typifies the young Black African patient with hepatocellular carcinoma (HCC). In order to assess whether this is a consequence of tumor-associated increases in protein metabolism or simply due to inadequate dietary intake, the following study was undertaken. The technique of constant i.v. infusion of 14C-labeled leucine was used to measure whole body protein flux, breakdown, synthesis, and oxidation rates in 8 adults with HCC, 4 patients with massive hepatomegaly due to metastatic adenocarcinoma from bowel, 6 patients with chronic liver disease, and 10 controls. Endogenous protein breakdown and oxidation were similar between patients with chronic liver disease (breakdown, 4.4 +/- 1.2 g/kg/day; oxidation, 0.8 +/- 0.4 g/kg/day) and controls but were significantly (P less than 0.002) higher in patients with liver tumors, the highest rates being observed in those with HCC (breakdown, 8.5 +/- 4.3 g/kg/day; oxidation, 1.4 +/- 0.5 g/kg/day). Protein turnover was generally higher in the HCC group, with increased rates of reincorporation of amino acids into protein synthesis (P less than 0.05). In one HCC patient a synchronized diagnostic liver biopsy demonstrated high fractional synthesis of rates of HCC proteins of 86%/day. In addition, the incorporation rates of labeled amino acid into fibrinogen, immunoglobulin G, and transferrin were also highest (P less than 0.03) in HCC patients. In order to assess the relative importance of diet in weight loss, dietary intake levels were assessed from hospital records of HCC patients and by dietary recall during the week prior to study. Intakes ranged from 30 to 70% of calculated requirement levels. In conclusion, our results suggest that the rapid wasting seen in patients with HCC is due to an imbalance between the metabolic demands, which can be elevated in some patients, and inadequate dietary replenishment.
 ...
PMID:Contribution of elevated protein turnover and anorexia to cachexia in patients with hepatocellular carcinoma. 215 53

Virus associated adult T-cell leukemia/lymphoma (ATLL), which includes both adult T-cell leukemia (ATL) and its non-leukemic counterpart (NLATL) was studied clinically, histologically, and immunologically. The disease usually occurred in the sixth decade in both sexes equally. The patients had a rapid clinical course with frequent leukemic changes, lymphadenopathy, hepatomegaly, and occasional skin rash. Bone marrow involvement with mild infiltration and hypercalcemia were more frequent in ATL than in NLATL. Histologically the disease was categorized as malignant lymphoma, diffuse pleomorphic type with cerebriform nuclear giant cells. The lymphoma was characterized by diffuse proliferation of tumor cells with irregular nuclear configurations, varying in size and shape, and the presence of giant cells with highly convoluted cerebriform nuclei. The giant cells seemed to be a diagnostic marker. Immunologically, the tumor cells usually possessed the surface antigens recognized by OKT 3, 4, Leu 8 and anti-Tac antibodies, indicating that they were lymphomas of helper/inducer peripheral T-cells with the receptor for interleukin 2, but they demonstrated no helper/inducer functions. The patients often died of opportunistic infections due to T-cell dysfunction caused by the disease itself and strong chemotherapy.
 ...
PMID:Virus associated adult T-cell leukemia (ATL) in Japan: clinical, histological and immunological studies. 300 99

3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMG-CoA lyase) is an inborn error of leucine catabolism which often leads to life-threatening illness in the neonatal period. The cardinal clinical features include severe infantile hypoglycemia, metabolic acidosis, hepatomegaly, lethargy or coma and apnea. Hyperammonemia is variable. There is a characteristic absence of ketosis. Considerable heterogeneity has been observed in clinical and biochemical presentation. Acute episodes of illness have been mistaken for Reye syndrome. The pattern of organic acids in the urine includes large amounts of 3-hydroxy-3-methylglutaric, 3-methyl-glutaconic, 3-methylglutaric and 3-hydroxyisovaleric acids. Smaller, but appreciable levels of glutaric, adipic and other dicarboxylic acids may also be excreted in the urine. Lactic acid may be present in sizable amounts at times of acute illness. The primary defect is a deficiency of 3-hydroxy-3-methylglutaryl-coenzyme A lyase, a key enzyme in the cycle of ketogenesis.
 ...
PMID:3-Hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: review of 18 reported patients. 306 29

The clinical, morphological, immunological and molecular features of seven patients with a stable picture of chronic granular lymphocytosis, observed over a period of up to 4 years, were studied. Mild splenomegaly was detected in one patient, while lymphoadenopathy and hepatomegaly were absent. Surface marker analysis showed in five patients the common membrane phenotype of granular T-cell lymphocytosis (T3+, T4-, T8+, Leu-7+); of the remaining two, one presented an unusual phenotype (T3+, T4+, T8+) and the other showed a marked positivity with the Leu-11 and M1 monoclonal antibodies, but lacked the T3, T4, T8 antigens. Three cases had a low (less than 30%) expression of the T1 antigen. Functional studies showed that the proliferative response to PHA and the NK function were reduced in four of the seven cases. Molecular analysis, performed in six cases, revealed a monoclonal rearrangement of the T-cell receptor beta-chain gene in three, a polyclonal T-cell configuration in two and a germ-line arrangement in the last. All three monoclonal cases showed a depressed NK activity and two a reduced PHA response. The results of this study document the heterogeneity of granular lymphocyte expansions and suggest that the clonal or reactive nature of these often indolent proliferations, suspected on the basis of immunologic functional studies, may be recognized at the DNA level.
 ...
PMID:Heterogeneity of large granular lymphocyte proliferations: morphological, immunological and molecular analysis in seven patients. 349 16

Young rats were force-fed a lysine + arginine-devoid diet or a complete diet for 3 days, and selected biochemical and morphologic studies were conducted. Rats force-fed the experimental diet in comparison with those force-fed the control diet for 3 days showed decreased body weight gain, hepatomegaly with periportal fatty liver, pancreatic and splenic atrophy, and enhanced 14C-leucine incorporation into hepatic proteins. Differences in the experimental animals were observed in the free amino acid levels of serum (decreased lysine, arginine, and ornithine) and liver (decreased ornithine), in blood chemistries (decreased levels of ammonia N2, uric acid, cholesterol, protein, albumin, alkaline phosphatase, LDH and SGOT) and in hematologic findings (leukocytopenia and thrombocytopenia after a morning feeding). The experimental findings in young rats force-fed the lysine + arginine-devoid diet were compared with those reported to develop in children with lysinuric protein intolerance (LPI), an autosomal recessive defect in diamino acid transport. Children with LPI as described by others reveal a number of similarities as well as a number of differences in comparison to the findings in the experimental animals. The comparison suggests that some of the pathological manifestations of LPI may be related to a deficiency of diamino acids but others must be due to different alterations in this complex human disease.
 ...
PMID:Chemical pathology of diamino acid deficiency: considerations in relation to lysinuric protein intolerance. 393 96

Male rats treated with a single dose of 1,2-dibromo-3-chloropropane (DBCP) were tested for their ability to carry out the synthesis of liver proteins. In animals treated for 12 h, we found no changes in the uptake of [14C]orotic acid into liver RNA or the uptake of [3H]leucine into liver or serum protein. Uptake of [3H]leucine into the soluble fraction of the enlarged liver increased in proportion to liver size, while the uptake of [14C]orotic acid was unchanged. Examination of the ultrastructure of liver cells from rats treated for 12, 24, or 48 h revealed that the structure of the rough and smooth endoplasmic reticulum (RER; SER) were modified. An absence of ordered stacks of the RER and the presence of tangled nets of SER were noted.
 ...
PMID:The integrity of liver protein synthesis in male rats treated with 1,2-dibromo-3-chloropropane. 618 May 25

The rat was used as an animal model to explore the mechanism responsible for the development of hepatomegaly and hypoproteinemia which commonly occur after jejunoileal bypass. Sprague-Dawley rats. 300 to 350 g, were divided into three groups of 12 animals. Six of the 12 rats per group served as study animals and six as controls. The first six were subjected to 90% jejunoileal bypass and the six controls were sham-operated and pair-fed. In the second group, six animals were subjected to 90% jejunoileal resection and six controls were sham-operated and pair-fed. Six animals in the third group were underfed so that their weights mimicked that of the bypassed animals and six controls were fed ad libitum. After 8 wk the animals were killed. Liver weights, hepatic protein content, and serum protein and triglycerides were determined. Synthesis and secretion of proteins and glycoproteins were measured using incorporation of 14C-leucine and 14C-glucosamine, respectively, into hepatic and medium proteins by liver slices. Bypassed animals demonstrated hepatomegaly, decreased serum proteins and triglycerides, and increased hepatic protein content. While both protein and glycoprotein synthesis remained normal, the secretion of these proteins into the medium appeared to be impared. Comparable changes did not occur after jejunoileal resection or after underfeeding. This study suggests that the impairment of glycoprotein and protein secretion may be a contributing factor in the increased liver weight and protein content in conjunction with decreased serum protein observed in the bypassed rat.
 ...
PMID:Hepatic protein synthesis and secretion after jejunoileal bypass in the rat. 684 85

A boy, aged 7 months, of consanguineous parents presented with an acute onset of vomiting, fever, nonketotic hypoglycemia and acidosis and died from cardiac arrest after ventricular fibrillation. He had hepatomegaly and echocardiographically a non-obstructive cardiomyopathy. Autopsy was not allowed. After birth the child had suffered from a severe respiratory distress syndrome, transient metabolic acidosis and had a sweaty feet odour. Later on, development was retarded with a severe muscular hypotonia. Post mortem, numerous unusual organic acids were found in high concentrations in urine, e.g. dicarbonic acids, 2-hydroxyisobutyric, isovaleric, 3-hydroxyisovaleric acid, N-acyl glycines, isovalerylglutamic acid and sarcosine. This pattern indicated deficiencies of several acyl-Co A dehydrogenases in the metabolism of leucine, isoleucine, valine, lysine, short-chain fatty acids and sarcosine. This could be confirmed using cultured skin fibroblasts which were shown to degrade the corresponding labeled substrates insufficiently to 14CO2. It is assumed that the functional multiple acyl-Co A dehydrogenation deficiency is caused by a deficiency of a common link in the electron transfer system of these dehydrogenases which is inherited autosomal recessively in this family. Among the 12 patients reported, 7 died within the first 5 days of age.
 ...
PMID:Multiple acyl-Co A dehydrogenation deficiency (MADD) in a boy with nonketotic hypoglycemia, hepatomegaly, muscle hypotonia and cardiomyopathy. Detection of N-isovalerylglutamic acid and its monoamide. 686 97


1 2 Next >>