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Biomedical subjects

H Greten

Publications and source records attributed to H Greten.

At least 73 records · Page 4Linked to original sources
PubMed1995

A case of disseminated Mycobacterium bovis infection in an AIDS patient.

The first case of disseminated Mycobacterium bovis infection with meningitis in an AIDS patient is reported. A 54-year-old male HIV-positive patient was admitted for evaluation of fever, weight loss, inappetence, fatigue and malaise. Mycobacterium bovis (non-BCG) was isolated from blood, bone marrow, stool, urine, sputum, abdominal lymph nodes and cerebrospinal fluid. Antituberculous therapy using a five-drug regimen plus steroids resulted in complete recovery.

AIDS-Related Opportunistic Infections↗
PubMed1995

Trials of the effects of drugs and hormones on lipids and lipoproteins.

Recent trials on the efficacy of drugs and hormones in lowering cholesterol and correcting lipoprotein profiles are reviewed. Emphasis is placed on the risk-benefit ratio, which determines the clinical value of therapeutic regimens. Whereas 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibitors have set a standard for treatment of hyperlipidaemia, the role of hormone replacement therapy in postmenopausal women in the prevention of coronary artery disease has more recently become better defined.

Clinical Trials as Topic↗
PubMed1995

Apolipoprotein E and lipoprotein lipase co-ordinately enhance binding and uptake of chylomicrons by human hepatocytes.

ApoE and LpL are important in the metabolism of triglyceride rich lipoproteins, and defects in either or both may result in hyperlipidaemia. It has previously been shown that ApoE and LPL specifically enhance cellular catabolism of lipoproteins by various cell lines. The authors determine in this paper the effect of ApoE and LpL on chylomicron and LDL binding and uptake by human hepatocytes in primary culture. Separate addition of ApoE and LpL greatly enhanced binding and uptake of chylomicrons. Simultaneous addition of ApoE and LPL further increased chylomicron uptake in an additive way. For LDL a different situation was observed: neither ApoE nor LPL mediated a significant increase of lipoprotein uptake. The authors conclude that ApoE and LpL co-ordinately enhance binding and uptake of chylomicrons by primary human hepatocytes. The effect appears to be independent of LDL receptors and the co-ordinate effect of ApoE and LPL may be important for normal chylomicron catabolism.

Apolipoproteins E↗
PubMed1995

Effect of in vivo thyroid hormone status on insulin signalling and GLUT1 and GLUT4 glucose transport systems in rat adipocytes.

To examine the effect of thyroid hormone status on insulin action in isolated rat adipocytes, age- and weight-matched Sprague-Dawley rats were rendered hypothyroid (h) by i.p. injection of 2 mCi [131I]/kg. Another group of rats was made hyperthyroid (H) by i.p. injection of 500 micrograms L-thyroxine/kg/day for 7 days. The T4 levels in experimental groups were: controls, 33.5 +/- 0.95; h, 12.3 +/- 1.59; H, 133.2 +/- 8.8 micrograms/l. Adipocytes were isolated and 3-O-methylglucose transport (GT), insulin binding (IB) and insulin receptor kinase activity (IRKA) were determined. Subcellular membrane fractions (low-density microsomes, plasma membranes) were prepared and GLUT1 and GLUT4 glucose transporter immunodetected. Hyperthyroidism caused no significant effect on either IB or IRKA but increased insulin-stimulated GT by 43.6%. This increase of GT was associated with an increase of primarily GLUT4 glucose transporters. Hypothyroidism was associated with both increased insulin receptor affinity and enhanced IRKA. Despite a marked reduction of primarily GLUT4 glucose transporters, basal and insulin-stimulated GT was not reduced when compared with control. These results suggest that (1) in hyperthyroidism, increased insulin-stimulated glucose transport is associated with an increase of primarily GLUT4 glucose transporters, which may be responsible for the increment of peripheral glucose utilization in hyperthyroidism, and (2) the effect of hypothyroidism on insulin action in adipocytes is characterized by a state of increased insulin sensitivity, as indicated by the increase in insulin receptor affinity and tyrosine kinase activity. Despite the marked reduction of primarily GLUT4 glucose transporters, insulin-stimulated glucose transport is not diminished, which may suggest that functional activity of plasma membrane glucose transporters is enhanced in hypothyroidism.

Adipose Tissue↗
PubMed1995

Blastocystis hominis in human immunodeficiency virus-related diarrhea.

BACKGROUND: A wide variety of bacterial, viral, and parasitic pathogens can cause severe diarrhea in patients with advanced human immunodeficiency virus (HIV) infection. Conflicting evidence exists as to whether Blastocystis hominis should also be included among the infectious agents capable of causing HIV-related diarrhea. METHODS: We determined the prevalence and clinical significance of B. hominis in a cohort of 262 patients with HIV infection, presenting at the infectious diseases department of a tertiary referral university hospital in northern Germany. RESULTS: B. hominis was detected in stool samples of 99 patients (38%). The isolation rate varied highly between the different groups. Homosexual men (43%; odds ratio (OR), 2.1; p = 0.01) had a higher detection rate than patients from other risk groups (26%), and patients with acquired immunodeficiency syndrome (46%; OR, 1.8; p = 0.03) were more likely to carry B. hominis than patients in earlier stages of their HIV infection (32%). An association with clinical symptoms was not evident. Presence of B. hominis, however, was frequently associated with the concurrent isolation of other enteric pathogens or apathogenic parasites. CONCLUSIONS: The data suggest that the isolation of B. hominis does not justify treatment even in symptomatic, severely immunocompromised patients. Most patients will either have spontaneous resolution of symptoms or successful identification of other infectious or noninfectious etiologies. Therapy should be limited to patients with persistent unexplained symptoms after a thorough evaluation and a complete screening for alternative etiologies, including the use of endoscopic procedures and the careful examination of multiple specimens.

AIDS-Related Opportunistic Infections↗
PubMed1995

A 5' splice-region mutation and a dinucleotide deletion in the lysosomal acid lipase gene in two patients with cholesteryl ester storage disease.

Cholesteryl ester storage disease (CESD) results from inherited deficiencies of the lysosomal hydrolase, acid lipase (LAL; E.C. 3.1.1.13). To establish the molecular defects in LAL deficiency, two unrelated probands with severely reduced LAL activity were examined. DNA amplification by reverse-transcription polymerase chain reaction and subsequent sequence analysis of LAL cDNA identified two mutant alleles. Patient 1, presenting with hepatosplenomegaly, mildly elevated liver function tests, and hyperlipidemia, was homozygous for a deletion of nucleotides 823 to 894 of the LAL cDNA. This 72-bp deletion maintained the reading frame and resulted in a loss of 24 amino acids from the LAL protein. Analysis of genomic DNA revealed that the 72 bp corresponded to an exon of the LAL gene. A single G to A point mutation at the last exon position was observed in the genomic DNA of patient 1, indicating a splicing defect with consecutive exon skipping underlying the 72-bp deletion. Patient 2 was a compound heterozygote for the 72-bp deletion and a dinucleotide deletion at positions 967 and 968. This deletion resulted in a shifted reading frame carboxyterminal of codon 296, and 43 random amino acids followed the frame shift. A premature stop at codon 339 truncated the mutant LAL protein by 34 amino acids. Allele-specific hybridization confirmed that patient 1 was homozygous for the 72-bp deletion mutation, and that patient 2 was a compound heterozygote for the 72-bp deletion and the 2-bp deletion.

Adult↗
PubMed1995

Apolipoprotein E isoforms and rare mutations: parallel reduction in binding to cells and to heparin reflects severity of associated type III hyperlipoproteinemia.

The LDL receptor-independent binding of human apolipoprotein E isoforms and rare apoE mutations were studied on LDL receptor-deficient human fibroblasts using chemical cross-linking and cell binding studies. The cross-linking experiments demonstrated that all apoE variants bind to the low density lipoprotein receptor-related protein, a potential receptor for remnant lipoproteins. In cell binding studies, the effect of the apoE variants on binding of beta-VLDL was investigated. Addition of normal apoE-3 to the binding assay resulted in a 12-fold increase of beta-VLDL particle binding, whereas this effect was reduced in the clinically defective variants: apoE-2, (Arg158-->Cys), 24.4% of apoE-3; apoE-1, (Gly127-->Asp, Arg158-->Cys), 49.2% of apoE-3; apoE-1(Lys146-->Glu), 18.2% of apoE-3. Heparin binding studies with the same variants showed a parallel reduction in proteoglycan binding (apoE-2(158), 58.2% of apoE-3; apoE-1(127,158), 37.9%; apoE-1(146), 20.6%). We conclude that LDL receptor-independent mechanisms contribute to remnant clearance. The functionally dominant mutation apoE-1(146) was most defective in heparin binding studies in vitro. In cell binding studies, apoE-1(146) did mediate lipoprotein binding only 18% compared to apoE-3. This indicates the important role of the apoE interaction with proteoglycans in vivo and could explain the development of type III hyperlipoproteinemia in patients with such apoE variants.

Animals↗
PubMed1994

Treatment of primary hypercholesterolemia: fluvastatin versus bezafibrate.

The effects of fluvastatin and bezafibrate on lipids, lipoproteins, and apoproteins (apo) were investigated in a multicenter randomized, double-blind, parallel-group study. After 8 weeks of strictly controlled (computer-based assessment) dietary stabilization, patients with primary hypercholesterolemia (low-density lipoprotein cholesterol [LDL-C] > or = 160 mg/dL; triglycerides < or = 300 mg/dL) were enrolled into a 6-week placebo phase. Altogether, 131 patients were randomized to receive either fluvastatin at 40 mg once daily (n = 64; mean age 53 years) or bezafibrate at 400 mg once daily (n = 67; mean age 52 years) for 12 weeks. Compliance with the diet was monitored (3-day food records) after 6 and 12 weeks. Fluvastatin led to significant reductions in LDL-C (-23%), total cholesterol (-17%), LDL-C/high-density lipoprotein cholesterol (HDL-C) (-24%) and apo B (-19%). Fluvastatin significantly increased LpA-I (+8%) and apo E (+20%). Bezafibrate produced significant reductions in LDL-C (-17%), total cholesterol (-13%), LDL-C/HDL-C (-24%), triglycerides (-28%), apo B (-15%), and LpA-I (-10%) and significantly increased HDL-C (+12%), apo A-I (+9%), apo A-II (+30%), apo E (+14%), and Lp(a) (+3%). No clinically notable increases in levels of liver enzymes or creatine phosphokinase were observed with either treatment. Both treatments were well tolerated. There was a low incidence of adverse events that tended to be mild and included headache, muscular pain, angina, and dyspepsia. The frequency of adverse events was similar in both treatment groups, and no significant differences in dietary behavior were observed. In conclusion, fluvastatin is a well tolerated 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor for the treatment of primary hypercholesterolemia. Effects of fluvastatin on LpA-I occur irrespective of changes in HDL-C.

Adult↗
PubMed1994

[Disseminated histoplasmosis in AIDS].

A 41-year-old man infected with HIV-1 developed fever up to 39.8 degrees C together with nonproductive cough and dyspnoea. Lactate dehydrogenase concentration rose from a level of 998 U/l to 6307 U/l. As pneumocystis carinii pneumonia was at first suspected he was treated with co-trimoxazole (1600 mg sulfamethoxazole and 320 mg trimethoprim, four times daily). But the symptoms did not abate. Bone-marrow puncture revealed numerous macrophages containing ovoid inclusions typical of Histoplasma capsulatum varietas capsulatum. The diagnosis of disseminated histoplasmosis was confirmed by culture and serologically by an increase in Histoplasma polysaccharide antigen. On treatment with amphotericin B (at first 10 mg, then 50 mg daily for 4 weeks) the symptoms regressed within a few days. After the concentrations of lactate dehydrogenase and Histoplasma antigen had become normal again, maintenance treatment was changed to itraconazole (200 mg twice daily), after a total amphotericin B dose of 1150 mg. The patient has remained free of recurrence.

AIDS-Related Opportunistic Infections↗
PubMed1994

[Localized fibrous pleural mesothelioma. Value of image-producing methods for the differentiation from supradiaphragmatic tumors of the liver].

A 38-year-old woman in good health suddenly developed pain in the right chest and mild dyspnoea. She reported two bronchial infections in the preceding year. Physical examination revealed cyanosis of the lips and finger clubbing, slightly dulled percussion sounds and decreased breath sounds at the basis of the right chest, but no other abnormalities. Activity of the tumour marker CA 125 was raised (60 kU/l). The chest radiography showed a shadow in the right lower segment, resembling a high diaphragm. Computed tomography failed to separate the abnormal structure from the liver substance. Needle puncture discovered a small haemorrhagic effusion with mesothelial cells. Magnetic resonance imaging and a scintigraphy of the liver provided evidence that the mass was separate from the liver. At thoracotomy a tumour, 20 x 15 x 10 cm in size and connected by a pedicle to the pleura, was identified and excised. Immunocytochemical tests showed it to be a fibrous pleural mesothelioma without signs of malignancy. The patient was discharged 10 days postoperatively in good general condition.

Adult↗
PubMed1994

Purification, characterization and molecular cloning of human hepatic lysosomal acid lipase.

Lysosomal acid lipase (LAL) is a hydrolase essential for the intracellular degradation of cholesteryl esters and triacylglycerols. This report describes a multi-step procedure for the purification of LAL from human liver. After solubilization with non-ionic detergent, acid hydrolase activity was purified 17000-fold to apparent homogeneity by sequential chromatography on Concanavalin A Sepharose, carboxymethyl-cellulose, phenyl Superose, Mono S cation exchange and Superose 12 gel-filtration columns. This procedure yielded two silver-staining protein bands of 56 kDa and 41 kDa on SDS/PAGE. Size-exclusion chromatography of the 41-kDa protein indicated that the enzyme was catalytically competent as a monomer of approximately 38 kDa. When assayed in the presence of cholesteryl oleate or trioleoylglycerol, purified acid lipase had Vmax values of 4390 nmol fatty acid.min-1.mg protein and 4756 nmol fatty acid.min-1.mg protein-1, and apparent Km values of 0.142 mM and 0.138 mM, respectively. The purified enzyme was most active at low pH (4.5-5.0) and required non-ionic detergent and ethylene glycol for optimal stability. Incubation of the 41-kDa acid lipase with endoglucosaminidase H reduced the molecular mass by 4-6 kDa, demonstrating Asn-linked glycosylation with high-mannose oligosaccharides. Deglycosylation did not affect enzymic activity, indicating that carbohydrates are not required for LAL activity. Based on partial peptide sequence, an oligonucleotide was synthesized and utilized to isolate LAL cDNA clones from a human liver cDNA library. A full-length LAL cDNA contained 2626 nucleotides and coded for a predicted protein of 372 amino acids, preceded by a 27 residue hydrophobic signal peptide. Hepatic LAL differed from fibroblast acid lipase at the N-terminus and revealed extensive similarities with human gastric lipase and rat lingual lipase, confirming a gene family of acid lipases. Northern hybridization using the complete LAL cDNA as a radiolabeled probe indicated striking differences in mRNA expression among human tissues. LAL mRNA was most abundant in brain, lung, kidney and mammary gland. Placenta and HeLa cells expressed intermediate amounts of LAL mRNA, while RNA extracted from liver and heart showed low levels of expression.

Amino Acid Sequence↗
PubMed1994

Annexin VI, a marker protein of hepatocytic endosomes.

Three highly purified endosomal fractions from rat liver were used to purify and characterize a major protein of endosomal membranes. Intravenously injected ligands, which are taken up via receptor-mediated endocytosis, accumulate first in the fraction of intermediate density, the compartment of uncoupling of receptors and ligands. The high density membranous fraction is highly enriched in a receptor recycling compartment. The endosomal fraction of lowest density is composed of multivesicular bodies, which appear to be the immediate prelysosomal compartment. The most prominent membrane protein of these endosomes is one of 68 kDa, as revealed by silver and Coomassie Brilliant Blue staining of SDS-gel electrophoretograms. This protein dominates profiles obtained from purified membranes of the compartment of uncoupling of receptors and ligands, multivesicular bodies, and receptor recycling compartment, but is greatly reduced in those obtained from plasma membranes and lysosomes. The 68-kDa protein was purified from endosomes and digested with trypsin, and cleavage products were analyzed by protein sequencing. The tryptic fragments of the endosomal 68-kDa protein share 96% identity with corresponding sequences of mouse annexin VI and 91% identity with sequences of human annexin VI. Using immunoblots, high concentrations of annexin VI with an apparent molecular mass of 68 kDa were detected in endosomal membranes by specific antiserum to annexin VI. Significant amounts of annexin VI were also detected in Golgi membranes. Yet, the concentration was substantially lower than that of the three endosomal fractions. The association of annexin VI with endosomal membranes is calcium-dependent, as revealed by the complete solubilization from endosomal membranes by EGTA. Incubation of intact endosomes with Pronase leads to a complete degradation of annexin VI without any detectable disintegration of proteins localized on the luminal surface of endosomal membranes. Evidently, annexin VI is localized on the cytoplasmatic leaflet of the membrane of endosomes and may be of significance for their intracellular trafficking.

Amino Acid Sequence↗
PubMed1994

Signal transduction pathway of the muscarinic receptors mediating gallbladder contraction.

In gallbladder smooth muscle, carbachol interacts with M3 receptors to mediate contraction. To examine components of the intracellular second messenger system that is coupled to these receptors we have tested whether carbachol stimulates the formation of inositol phosphates (IP) to cause contraction. Guinea pig gallbladder muscle strips were prelabeled with [3H]inositol and were incubated with 0.1 mmol/l carbachol, a concentration causing maximal contraction. [3H]inositol monophosphates, [3H]inositol bisphosphates and [3H]inositol trisphosphates and contraction were measured at various times (0-90 s). To examine whether a pertussis toxin-sensitive guanine nucleotide binding protein is coupled to the muscarinic receptors, guinea pigs were pretreated with pertussis toxin (180 micrograms/kg i.v./24 h). The effectiveness of pertussis toxin treatment was determined by measuring [32P]ADP-ribosylation of a approximately 40/41 kDa protein from gallbladder homogenates. Carbachol caused a significant time-dependent increase in the formation of [3H]inositol monophosphates, [3H]inositol bisphosphates and [3H]inositol trisphosphates. The time course of [3H]inositol trisphosphate turnover caused by carbachol was biphasic, and was detectable at 15 s and maximal at 60 s; at 75 s and 90 s formation of [3H]inositol trisphosphates decreased, whereas the time course of carbachol-induced contraction of the gallbladder smooth muscle strips reached a plateau after 90 s. The effects of carbachol on [3H]inositol trisphosphates and on contraction were abolished by atropine.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate Ribose↗
PubMed1994

The prognostic value of hypocholesterolemia in hospitalized patients.

Clinical observations show that severe illness often leads to hypocholesterolemia. To verify this finding and to define the relationship between serum cholesterol and a patient's prognosis, a study was conducted in two large hospital populations. Of 24,000 and 61,463 adult patients (populations I and II) an average of 3.8% and 3.6% died in hospital, respectively. The mean serum cholesterol levels of patients who died was significantly lower than that of those who survived (163.6 mg/dl versus 217.8 mg/dl; P < 0.0001). The average cholesterol of surviving patients was similar to that of 6,543 healthy controls. During hospitalization serum cholesterol levels of < or = 100 mg/dl were encountered in 1.2% and 3.6% of patients of populations I and II, respectively. The mortality of these hypocholesterolemic patients was about tenfold higher than average and showed a strong, inverse, linear relationship with serum cholesterol concentrations. Patients whose serum cholesterol level dropped to less than 45 mg/dl did not survive. These data show that in severely ill patients serum cholesterol may decline to very low concentrations, and the prognosis is reflected by the degree of hypocholesterolemia, which thus may serve as a clinically useful prognostic parameter.

Adult↗
PubMed1994

Pneumococcal parotitis and cervical lymph node abscesses in an HIV-infected patient.

The case of a 33-year-old patient with rapid onset of bilateral parotid gland and lymph node abscesses is described. The patient was positive for human immunodeficiency virus 1 and presented with a history of interstitial lymphocytic pneumonia and pneumococcal meningitis prior to admission. The patient received cotrimoxazole as primary prophylaxis against Pneumocystis carinii pneumonia. Fine needle aspiration from the abscesses yielded Streptococcus pneumoniae. Penicillin G treatment in combination with surgical drainage of the lesions led to healing with minimal residual lymph node enlargement. No relapse was noted until 12 months after presentation.

AIDS-Related Opportunistic Infections↗