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)

2-Deoxy-D-galactose, in a dose of 3 mmol/kg, was administered intraperitoneally twice daily to young rats for periods up to 12 weeks. This dosage schedule resulted in recurrent phosphate trapping predominantly in liver. UTP deficiency was excluded by simultaneous uridine injections. Phosphate trapping was caused by the rapid accumulation of 2-deoxy-D-galactose 1-phosphate and was most pronounced in liver but also demonstrated in small intestine, brain, spleen, and thymus. The marked, although transient, drop in the hepatic content of inorganic phosphate triggered the catabolism of adenine nucleotides and a loss of ATP. Other metabolic pathways affected by phosphate deficiency include glycogenolysis and glycolysis. Increasing with time, repeated doses of the galactose analog led to retardation and arrest of growth, hepatomegaly, and splenomegaly. The average relative liver and spleen weights were elevated 2.5- and 4.5-fold, respectively, after 12 weeks of treatment. Liver damage was indicated by hyperbilirubinaemia and a progressive rise in the activity in plasma of sorbitol dehydrogenase, alkaline phosphatase, and gamma-glutamyltransferase. Examination by light and electron microscopy showed increasing numbers of vacuoles, surrounded by a single membrane, in hepatocytes, sinusoidal endothelial cells, and Kupffer cells. Focal cytoplasmic degeneration in hepatocytes was occasionally indicated by formation of autophagic vacuoles and finger print lysosomes. Hepatocytes of 2-deoxy-D-galactose-treated rats showed a dissociation and fragmentation of the rough endoplasmic reticulum. Sinusoidal endothelial cells and Kupffer cells were markedly enlarged, the latter contained a PAS-positive but amylase resistant substance. Extrahepatic changes included an increased occurrence of vacuolated cells in thymus. Phosphate trapping and its metabolic consequences are common phenomena in the experimental injury induced b 2-deoxy-D-galactose and in some hereditary diseases such as uridylyltransferase deficiency galactosaemia, fructose intolerance and glucose-6-phosphatase deficiency.
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PMID:Consequences of recurrent phosphate trapping induced by repeated injections of 2-deoxy-D-galactose. Biochemical and morphological studies in rats. 4 10

A case of hepatoma in a 79-year old woman is reported. The patient had an enlarged liver and a pathological liver scintigram. Percutaneous liver biopsies were performed both with Menghini-and fine needles. The most prominent feature was the presence of hyaline cytoplasmic PAS-negative inclusions in liver parenchymal cells. There was no nuclear atypia. Electron microscopy disclosed two types of cytoplasmic changes. One consisted of a lamellar ultrastructure and was interpreted as a hyperplasia of smooth-surfaced endoplasmic reticulum. The other change consisted of smooth globular non-membrane limited regions containing amorphous or finely fibrillar material. This was interpreted as corresponding to the hyaline inclusions visible in the light microscope. The presence of PAS-negative hyaline cytoplasmic inclusions may thus be a sign of hepatoma. This may be of relevance for the diagnostic considerations of material obtained by fine needle biopsy.
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PMID:Hyaline cytoplasmic inclusions in human hepatoma. A case report. 19 65

The relationship between liver enlargement and drug metabolism was investigated in female rats. Hepatomegaly (e.g., 31% increase in liver weight in a 17-day experiment) was induced by injection of lyophylized anterior pituitary (LAP) extract. The liver enlargement seemed to be due to an increase in the number and the size (enhanced water content and PAS-positive material) of hepatocytes. Electron microscopic examination of the liver revealed slight proliferation of the smooth endoplasmic reticulum and pronounced fragmentation and dilation of the rough endoplasmic reticulum. Zoxazolamine paralysis time was significantly prolonged (+55% and +102%) after 4 and 17 days, respectively, of treatment with LAP. Metabolism of zoxazolamine by the 9000 g supernatant fraction of the liver of rats given LAP for 17 days was reduced by 73%. Thus, the marked hepatomegaly induced by LAP was associated with a prolonged action of the drug which may result from a decrease in hepatic drug metabolism.
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PMID:Massive liver enlargement accompanied by decreased drug metabolism. Effect of anterior pituitary extract on hepatic ultrastructure, zoxazolamine paralysis, and metabolism in the rat. 92 87

Among 424 children with liver disease, 20 had alpha1-antitrypsin deficiency associated with protease inhibitor ZZ phenotype. This disorder manifested itself as cholestasis in early infancy in 19 children. Jaundice and pruritus cleared in 16 of these by 7 months of age, but hepatomegaly and laboratory evidence of mild hepatic dysfunction persisted in all. Biliary cirrhosis and portal hypertension eventually developed or was suspected in eight, and hypoplasia of intraheptic bile ducts was demonstrated in another four. Routine screening revealed intermediate alpha1-antitrypsin deficiency in 16 other children with various types of liver disease. The phenotype in these patients was MZ, MS, or SZ. PAS-positive granules were present in liver of all patients with the ZZ phenotype and in none with other phenotypes. The findings indicate that manifestations and prognosis of this inherited liver disease are extremely variable.
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PMID:Alpha1-antitrypsin deficiency and liver disease in children: phenotypes, manifestations, and prognosis. 108 71

A 67-year-old man with a 3-month history of jaundice presented with hepatomegaly. Laboratory studies revealed abnormal liver tests with raised bilirubin. Renal function was normal. Endoscopic retrograde cholangiopancreatography revealed normal extrahepatic bile ducts. Liver biopsy showed severe bilirubinostasis and a typical bile infarct. Laminar and globular deposits of PAS-positive diastase-resistant non-congophilic material were observed in the sinusoidal walls. In addition, congophilic material was detected in the portal tracts. Immunohistochemistry revealed the presence of lambda-light chain deposits both in the sinusoids and in the portal tracts. Collagens type I and IV and fibronectin appeared markedly increased in the perisinusoidal space. On electron microscopy, the deposited material in the Disse spaces was mainly composed of fibrils indistinguishable from amyloid, admixed with small amounts of granular electron-dense material. The similarities of light chain deposition disease and AL amyloidosis are discussed.
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PMID:Light chain deposition disease of the liver associated with AL-type amyloidosis and severe cholestasis. 190 Oct 75

A 20-year-old man was admitted to our hospital because of fever and knee joint pain on March 20, 1986. Physical examination revealed generalized lymphadenopathy and hepatomegaly. White blood cell count was 32,800 microliters with 74.4% blast cells. Bone marrow was hypercellular with 93.6% blast cells. Blast cells were weakly positive for acid phosphatase and PAS stainings but were negative for peroxidase, sudan black B and esterase stainings. Cell surface marker analysis of blast cells disclosed that they were positive for anti-HLA-DR, CD19, CD24, CD33 and CD38, but were negative for CD10 and CD20. Cytoplasmic immunoglobulin of blast cells was negative and TdT activity by immunofluorescent method was positive. Chromosomal analysis of bone marrow samples revealed normal karyotype. Therefore, this case was diagnosed as having acute lymphoblastic leukemia (L2) and achieved complete remission with LVP therapy consisting of 1-asparaginase, vincristine and prednisolone. Gene analysis of blast cells disclosed germ-line configuration of both the immunoglobulin heavy chain gene and T cell receptor beta chain gene. We speculated that the phenotype of leukemic cells might precede the genotype in some cases of acute leukemia.
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PMID:[Germ-line configuration of the immunoglobulin heavy chain gene in a case of B cell precursor acute lymphoblastic leukemia]. 255 12

Analysis of remission induction rates for 1,117 children 18 months to 10 years of age (group 1) and 90 infants less than 18 months of age (group 2) with acute lymphoid leukemia (ALL) and of duration of continuous complete remission (CCR) for 454 in group 1 and 33 in group 2 revealed that infants fared significantly worse in both measures of outcome (P = .03 and P less than .0001). To examine potential reasons for the poor prognosis of affected infants, clinical and biologic features of their ALL were compared. Infants had higher WBC counts (P less than .001), a higher incidence of massive splenomegaly (P less than .001), massive hepatomegaly (P less than .001), more central nervous system (CNS) disease at diagnosis (P less than .01), and lower platelet counts (P less than .001). Also, their blasts were less often PAS+ (P = .02). The incidence of non(T, B, pre-B), T and pre-B immunophenotypes of ALL did not differ significantly between the two groups. However, in patients with non(T, B, pre-B) ALL, the majority (51%) of infants had common ALL antigen (CALLA)-negative blasts, as compared with only 7% in group 1 (P less than .001). Furthermore, infants with non(T, B, pre-B) cell ALL who were less than 12 months of age were almost always CALLA- (18 of 21). The blasts of children from both groups usually expressed Ia-like antigens. These data illustrate that infants with ALL have extensive and bulky disease more often than do older children and are more often affected with a prognostically unfavorable phenotype of acute leukemia (AL) which expresses Ia-like antigens but is more often PAS- and CALLA-. We believe that these clinical and biological differences predict and explain in part the observed poor response to treatment of infants with ALL.
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PMID:Clinical and biologic features predict a poor prognosis in acute lymphoid leukemias in infants: a Pediatric Oncology Group Study. 293 4

Liver biopsies of a 58-year-old clinically healthy patient with a hepatomegaly and intracisternal PAS-negative globular hyaline bodies were immunofluorescent-optically examined for the content of the complement components C 1 q, C 4, C 9, C 1-inactivator, C 3-activator. Further examinations were performed for fibrinogen, IgG, IgA, IgM, IgD, IgE, L-chain (type chi and lambda), alpha 1-antitrypsin, alpha 1-fetoprotein, alpha 1- and alpha 2-glycoprotein, cholinesterase, ceruloplasmin, myoglobin, hemopexin, HBsAg and HBsAg. Th inclusion bodies reacted with antisera against the complement components C 4, C 3 and C 3-activator, as also identified by double immunofluorescence. Probably this is a disturbance of the protein metabolism of the liver cell with abnormal complement storage in the presence of normal total complement and normal complement components in the serum.
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PMID:Storage of the complement components C4, C3, and C 3-activator in the human liver as PAS-negative globular hyaline bodies. 628 41

This report describes the pathology of kappa light-chain deposition in a 55-year-old patient who presented with respiratory insufficiency and hepatomegaly. Biopsies of lung and liver showed PAS-positive deposits which did not stain with congo red, crystal violet, or thioflavin-T. By indirect immunoperoxidase techniques, the deposits were composed of kappa light-chain immunoglobin. Electron microscopy revealed granular and fibrillar electron-dense material which lacked the characteristics of amyloid. Subsequent clinical studies showed this patient had a plasma cell dyscrasia. These data show that kappa light-chain deposition is not limited to the kidney, and that the first manifestation of a plasma cell dyscrasia may be systemic deposits of light chain. These deposits can be distinguished from amyloid by their immunochemical, tinctorial, and ultrastructural appearance.
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PMID:Systemic kappa light-chain deposition. An ultrastructural and immunohistochemical study. 640 47

A report on 9 cases of infantile hepatopathy and cirrhosis of the liver respectively in cases of hereditary autosome-recessive alpha 1-antitrypsin deficiency (alpha 1-ATM). The genetic variants of the serum-protease-inhibitor (Pi) alpha 1-antitrypsin (alpha 1-AT) were examined by means of iso-electric focusing (Polyacrylamidgelen). The gene incidence was of the allel PiZ 0,0138 in the 868 blood donors from the Tyrol and was therefore within the range of the PiZ-frequencies seen in other Central-European populations. The other alleles PiM1, PiM2, PiM3, and PiS, point to the incidence of 0.7062, 0.1480, 0.1037, and 0.0225. The patients under observation (9) are homozygote PiZZ, the clinically healthy parents heterozygote PiZM. Risk of repetition in siblings of the patients is 25%. Early indicative symptoms are prolonged jaundice, acholic stools and hepatomegaly. Further developments are the fading of the hyperbilirubinaemia, temporary improvement in the pathological liver values, a freedom of symptoms for different lengths of time in each case, in the case of two patients, finally, decompensated cirrhosis of the liver and death in hepatic coma. The histological picture of the liver tissue shows PAS-positive storage granula in hepatozytes, intrahepatic hypoplasia of the bile duct, cholestasis as well as early cell necrobiosis, fibrosis and cirrhotic transformation. Course and severity of the liver complaint differ greatly, and are independent of the quantitative alpha 1-antitrypsin deficiency revealed, treatment is purely symptomatic.
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PMID:[Hereditary alpha 1-antitrypsin deficiency and infantile cirrhosis of the liver]. 676 50


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