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Biomedical subjects

M Huber

Publications and source records attributed to M Huber.

At least 271 records · Page 15Linked to original sources

Ketoconazole inhibits corticotropic cell function in vitro.

The effects of ketoconazole (KC) on secretion and biosynthesis of ACTH and generation of cAMP in rat anterior pituitary cells were investigated in vitro. KC inhibits CRF-stimulated ACTH release from rat anterior pituitary fragments in a dose-dependent fashion between 1.5 and 100 microM. The effect of CRF as a releaser of ACTH was fully restored after KC was removed from the medium. Similar effects were observed in primary cultures of rat anterior pituitary cells. KC dose-dependently decreased basal and CRF-stimulated ACTH release. In addition, basal and CRF-stimulated mRNA coding for the ACTH precursor were reduced after preincubation with KC. The effects of KC on ACTH release and biosynthesis seem to be mediated by cAMP, since KC inhibits basal and CRF-stimulated cAMP release and content within the same dose range. Since the stimulatory effects of cholera toxin, sodium fluoride, and forskolin were dose-dependently inhibited by KC and since the addition of (Bu)2cAMP abolished the inhibiting effect of KC, it is concluded that KC acts by inhibition of the catalytic component of the adenylate cyclase holoenzyme.

1-Methyl-3-isobutylxanthine↗

Diuretic use as a marker for eating problems and affective disorders among women.

Fourteen female symptomatic volunteers between the ages of 18 and 40 who used diuretics on a regular basis for reasons that were not medically necessary were evaluated. Seven (50%) were diagnosed as having a current or past syndromal or subsyndromal eating disorder, and 9 (64%) were diagnosed as having a current or past affective disorder. The results of this pilot study suggest that chronic diuretic use in young women should signal to the clinician the possibility of an unrecognized eating problem and/or an affective disorder.

Adolescent↗

Inhibition of leukotriene D4 catabolism by D-penicillamine.

Inhibition of the catabolism of the most biologically potent cysteinyl leukotriene, LTD4, was studied in rat hepatoma cells in vitro and in the rat in vivo. LTD4 dipeptidase, an ectoenzyme on the surface of AS-30D hepatoma cells, exhibited an apparent Km value of 6.6 microM for LTD4. D-Penicillamine and L-penicillamine inhibited this enzyme activity with apparent Ki values of 0.46 mM and 0.21 mM respectively. Bestatin, an inhibitor of the aminopeptidase activity of hepatoma cells, did not affect LTD4 hydrolysis at concentrations as high as 5 mM, indicating that the aminopeptidase did not contribute to LTD4 catabolism. In the rat in vivo, D-penicillamine also inhibited LTD4 catabolism. After intravenous injection of [3H]LTC4 an accumulation of [3H]LTD4 and a retarded formation of [3H]LTE4 were observed in the circulating blood after D-penicillamine pretreatment. Within 1 h after intravenous [3H]LTC4 injection, about 80% of the administered radioactivity was recovered in bile. After D-penicillamine pretreatment [3H]LTD4 was the major biliary leukotriene metabolite, whereas in untreated controls leukotriene metabolites more polar than LTC4 predominated in bile. After stimulation of endogenous leukotriene production in vivo by platelet-activating factor, N-acetyl-LTE4 was the major cysteinyl leukotriene detected in bile. D-Penicillamine treatment prior to platelet-activating factor resulted in the accumulation of LTD4, which under these circumstances was the major endogenous leukotriene metabolite detected in bile.

Animals↗

The influence of copper on the induction of tyrosinase and laccase in Neurospora crassa.

The influence of copper on the cycloheximide-induced synthesis of the copper-containing enzymes tyrosinase and laccase in Neurospora crassa was studied by enzyme activity measurements and immunological means. The amount of active enzyme molecules is far higher when the culture medium is copper-supplemented before cycloheximide induction. The synthesis of the apoproteins is not dependent on the presence of copper. This suggests the existence of a copper-storage protein for which metallothionein is a likely candidate.

Catechol Oxidase↗

[SGPT determination as a routine screening procedure in blood donors?].

Liver biopsy was carried out in 103 patients with elevated transaminases. In 46 patients (44.5%) histological examination produced the diagnosis of a chronic persistent non-A, non-B hepatitis, whereas in 57 patients (55.5%) steatosis was found. Laboratory findings showed that SGOT is of little use in distinguishing these two diseases. SGPT and the SGOT/SGPT quotient indicate the existence of a CPH-NANB in 93.5 and 89% respectively. We therefore conclude that SGPT should be determined in all blood donors as indirect screening to identify carriers of NANB.

Adult↗

Leukotriene C4 metabolism by hepatoma cells and liver.

The metabolism of the glutathionyl leukotriene LTC4 in the mercapturic acid pathway was studied in suspensions of AS-30D hepatoma cells and hepatocytes, as well as in vivo in the bile duct-cannulated rat and in primates. 1. Isolated hepatocytes actively took up cysteinyl leukotrienes and metabolized LTC4 not only to LTD4 and LTE4 but also to N-acetyl-LTE4 and to metabolites more polar than LTC4. 2. AS-30D hepatoma cells are deficient in the transport system for the uptake of cysteinyl leukotrienes. Peptide cleavage of LTC4 to LTD4 and LTE4 was catalyzed by ectoenzymes of these cells. Inactivation of gamma-glutamyltransferase by acivicin and inhibition of LTD4 dipeptidase by penicillamine largely prevented further catabolism of LTC4 and LTD4, respectively. 3. [3H]LTC4 injected i.v. into rats was rapidly eliminated from the circulating blood, taken up by the liver, and excreted into bile where 77% of the administered radioactivity was recovered within 1 hr. The biliary LTC4 metabolites included LTD4, N-acetyl-LTE4, and metabolites more polar than LTC4. 4. Inhibition of [3H]LTC4 metabolism in vivo by i.v. penicillamine shifted the pattern of biliary cysteinyl leukotrienes; an extended half-life of [3H]LTD4 was associated with a retarded formation of N-acetyl-LTE4 and of polar metabolites. 5. Endogenous cysteinyl leukotrienes elicited by trauma were measured after HPLC separation by radioimmunologic analysis in plasma and bile of rats. The biliary concentration of these leukotrienes was up to 100 times as great as in plasma. N-Acetyl-LTE4 was the predominant endogenous metabolite in rat bile. 6. In the monkey Macaca fascicularis, cysteinyl leukotrienes were predominantly eliminated from blood via the liver into bile; renal excretion amounted to about 50% of the hepatobiliary elimination. Absorption of cysteinyl leukotrienes from the intestine resulted in enterohepatic circulation of these mediators. 7. Metabolites of [3H]LTC4 injected i.v. in the monkey were analyzed in bile and urine. In addition to polar metabolites and a small percentage of [3H]LTD4, [3H]LTE4 was a predominant metabolite particularly in bile. LTE4 was also the major endogenous cysteinyl leukotriene detected by radioimmunologic analysis in monkey bile. 8. LTE4 was the predominant endogenous cysteinyl leukotriene measured in human bile in patients suffering from acute pancreatitis. The detected amounts of LTE4 may be sufficient to induce known phenomena associated with acute pancreatitis including the shock-like reaction.

Animals↗

Entamoeba histolytica: cloning and characterization of actin cDNA.

In order to study gene expression in the human parasite Entamoeba histolytica, a cDNA library of E. histolytica strain 200:NIH was constructed using the phage vector lambda gt10. Three cDNA clones (A, B and C) were selected for further analysis. Each of the three clones hybridized to a distinct mRNA. Two of these mRNAs were translated in vitro after hybrid selection, and yielded distinct translation products. One of these mRNAs, selected by hybridization to clone A, encodes the most abundantly expressed protein in E. histolytica. DNA sequence analysis of this cDNA clone identified the DNA as that encoding actin. The deduced amino acid sequence of E. histolytica actin resembles both cytoplasmic and muscle actins and has an unusual N-terminal glycine residue. We have shown that a family of actin genes is present in E. histolytica. Six different E. histolytica actin clones were obtained from a lambda gt10 genomic library using subcloned cDNA probes. Southern analysis of three different E. histolytica strains (200:NIH, Rhaman, and HM-1:IMSS) revealed at least four different actin genes. Strain HM-1:IMSS, however, differs by the presence of an additional actin gene.

Actins↗

Galactomannan antigenemia and antigenuria in aspergillosis: studies in patients and experimentally infected rabbits.

Purified galactomannan (GM) from Aspergillus fumigatus was used in both a radioimmunoassay and an enzyme-linked immunoassay for antigen detection. Results of the two tests seemed interchangeable. By one or both assays, GM was detected in serum from four of 12 rabbits lethally infected with A. fumigatus in concentrations ranging from 108 to 356 ng/ml. Serum antigen was detected in only two of 12 patients with invasive aspergillosis. Results of assay for GM in urine were far more encouraging. Urinary GM was detectable throughout the course of lethal aspergillosis in all 16 rabbits, in concentrations of 24-1,900 ng/ml. Urine from seven of 13 patients with invasive aspergillosis had GM concentrations of 1-83 ng/ml. Antigen excretion roughly paralleled extent of disease.

Animals↗

[Fibrolamellar hepatoma].

Unlike hepatocellular hepatoma (HCC), the so-called fibrolamellar hepatoma (FLH) is found almost exclusively in the non-cirrhotic, non-infected liver. Patient characteristics and the course of the disease in FLH differ markedly from HCC. FLH represents only a small portion of hepatomas in general (approx. 2%), but accounts for over 40% of hepatomas in young adults. We present the case of a 38-year-old woman showing the typical histological findings of polygonal eosinophilic tumor cells and characteristic lamellar bundles of fibrous stroma, which led to the diagnosis of FLH. The approx. 140 cases of FLH published in the world literature are also presented and discussed. The usefulness of additional examinations (neurotensin, vitamin B12 binding capacity and copper stains) is mentioned. The difficulty in diagnosing FLH lies in its histological differentiation from focal nodular hyperplasia. When diagnosed early, however, FLH is characterized by good resectability with a chance of cure or at least a markedly better survival rate than HCC.

Adult↗

Preoperative cervical dilatation for first trimester induced abortion: comparison of two prostaglandin analogues.

The present study compares two methods of local application of prostaglandins prior to surgical abortion in the first trimester. Fifty patients were treated with a vaginal tablet of Gemeprost (E1 analogue); 50 others by the intra-cervical application of PGF2 alpha gel. Gemeprost was found to be superior to the PGF2 alpha gel. Several hypotheses are formulated to explain this observation. The side effects of the two methods are compared and discussed.

Abortion, Induced↗