Search PubMed⌕ Search

Biomedical subjects

H Hartmann

Publications and source records attributed to H Hartmann.

At least 181 records · Page 10Linked to original sources

The effect of a protein on the radiolysis of DNA studied by gel filtration.

Double stranded DNA from calf thymus was irradiated in the presence of bovine serum albumin with a ratio of 1:10 in weight under aerobic and anaerobic conditions. The irradiated biomolecules were separated by gel filtration on Sepharose Cl-2B with and without sodium dodecylsulphate. By scavenging OH-radicals the protein protects DNA, but in contrast to radiolysis of DNA in phosphate buffer, in the presence of serum albumin oxygen enhances the degradation of DNA. Radiolysis under N2 leads to crosslinking of serum albumin to DNA with higher yields at pH 5 than at pH 7. Oxygen largely prevents crosslinking.

Chemical Phenomena↗

The effect of a protein on the radiolysis of DNA studied by HPLC and pulse radiolysis.

Double-stranded DNA from calf thymus was irradiated in the presence of bovine serum albumin (BSA) with a ratio of 1:10 in weight, at pH7 and pH5, under aerobic and under anaerobic conditions. The irradiated biomolecules were separated by high-performance liquid-gel permeation chromatography. At pH 7, in the presence of the protein, degradation of DNA was enhanced by oxygen, while under anaerobic conditions formation of protein-DNA crosslinks was observed. At pH5, crosslinking of BSA to DNA occurred under anaerobic as well as under aerobic conditions, while fragmentation of DNA could not be detected with this method with doses up to 1600 Gy. Under nitrogen, the degradation of BSA was not altered by the addition of DNA, but in the presence of oxygen less BSA was lost for a given dose when DNA was present.

Chromatography, High Pressure Liquid↗

Inhibition of human immunodeficiency virus type I reverse transcriptase by suramin-related compounds.

Ninety analogues of suramin have been examined for their ability to inhibit the exogenous reverse transcriptase (RT) of human immunodeficiency virus type I (HIV-I). Of these compounds, 57 inhibited the poly(rC).oligo(dG)-dependent RT activity. Three classes of dose-response curves could be discriminated. Allocation of a compound to one class did not correspond with obvious structural features. Twenty-four substances were superior to suramin in our RT inhibition assay. The RT-inhibitory activity of these compounds did not correlate with their effect against filariae or trypanosomes. Preliminary antiviral evaluation in susceptible human T cells inoculated with HIV-I demonstrated in vitro therapeutic efficacy for some compounds with lower drug-related cellular toxicity than suramin. Certain structural features relevant for the RT-inhibitory effect of these compounds were recognized. Predictions are made for the design of more effective RT inhibitors. Such compounds will help to understand the molecular mechanism of reverse transcription and might be useful in the therapy of retroviral infections.

Cell Line↗

Inhibition of glycogenolysis and glycogen phosphorylase by insulin and proinsulin in rat hepatocyte cultures.

The inhibitory action of insulin and proinsulin on basal and glucagon-activated glycogenolysis was studied in cultured rat hepatocytes containing [14C]glycogen. Insulin or proinsulin given as sole hormones in the presence of 5 mM glucose decreased basal release of [14C]glucose from [14C]glycogen to 20%. Half-maximal effective concentration of insulin was approximately 0.15 nM and of proinsulin was approximately 5 nM. Inhibition of [14C]lactate release from [14C]glycogen required slightly higher hormone concentrations with a similar difference in potency for insulin and proinsulin. The glucagon-stimulated release of [14C]glucose was completely blocked by insulin or proinsulin with half-maximal effective concentrations of approximately 0.2 and approximately 8 nM, respectively. In contrast, release of [14C]lactate in the presence of glucagon was increased slightly by insulin and proinsulin. Basal and glucagon-activated phosphorylase activity was inhibited by approximately 50% in a dose-dependent manner by both hormones, with differences in potency similar to those for the inhibition of glycogenolysis. These data point to a direct regulatory role of insulin in the control of hepatic glycogen breakdown even when acting as sole hormone. The results do not support the notion of a preferential inhibitory potency of proinsulin on hepatic glycogenolysis.

Animals↗

[Spontaneous regression of a large liver tumor with markedly elevated serum enzyme levels].

The case of a liver tumor of 10 cm diameter in a 32-year-old asymptomatic woman is described with markedly elevated liver enzymes in the serum (transaminases and alkaline phosphatase). The tumor corresponded to a focal nodular hyperplasia or a hepatic adenoma. The regression of this hepatic tumor over a time period of 18 months after discontinuation of oral contraceptives was observed as well as a complete normalisation of laboratory findings. It is concluded that conservative management after withdrawal of hormonal contraception my be the preferable treatment for hepatic adenoma and focal nodular hyperplasia.

Adult↗

Cerebral distribution of beta-lipotropin and beta-endorphin in infantile progressive spinal muscular atrophy of Werdnig and Hoffman disease.

The regional distribution's profile of beta-endorphin (beta-EP) and beta-lipotropin (beta-LPH) was determined in the brain of an infant who died from Werdnig-Hoffmann's disease. Regional levels of beta-endorphin-like immunoreactivity (beta-ELIR), resulting from beta-EP and beta-LPH, were generally low in comparison to the homologous levels found in victims dying of other diseases.

Brain Chemistry↗

Serum levels of free non-protein bound clofibrinic acid after single dosing to patients with impaired renal function of various degrees--a multicenter study.

As a basis for establishing dosing guidelines in order to avoid side effects due to overdosage, the concentrations of total and free non-protein bound clofibrinic acid (CA) were determined before and after the administration of a single clofibrate dose (0, 2, 6, 12, 24, 48, 72, 96h) in patients with various degrees of impaired renal function and in a control group (n = 56). The clofibrate doses administered to the five groups were: group 0 = control group without renal impairment: 1,000 mg; group 1 = serum creatinine up to 354 mumol/l: 1,000 mg; group 2a = creatinine levels greater than 354 mumol/l up to levels requiring dialysis: 1,000 mg; group 2b = creatinine levels like 2a, but only 500 mg; group 3 = patients requiring dialysis: 500 mg. In addition, serum albumin, CK, GOT and GPT were controlled. Total CA was determined by gas chromatography, the unbound fraction by equilibrium dialysis. Increasing serum creatinine levels were correlated with a decrease of total CA but with a statistically significant increase in free CA concentrations. The levels of non-protein bound CA of groups 1 and 2a were significantly different from control group 0 (same dosing). In addition, a significantly negative correlation between free CA and serum albumin levels was demonstrated. Determination of free CA as a control parameter of clofibrate therapy in patients with impaired renal function allows clofibrate dosing to be closer related to the individual subject than the determination of total CA only.

Adult↗

Insulin-dependent inhibition of hepatic glycogenolysis by gastric inhibitory polypeptide (GIP) in perfused rat liver.

The effect of porcine gastric inhibitory polypeptide on hepatic glycogen metabolism was investigated in the isolated in situ perfused rat liver. Glycogenolysis was stimulated by infusion of glucagon into the portal vein (half maximal effective portal vein concentration approximately 30 pmol/l). When glucagon was infused at a final portal vein concentration of 0.5 nmol/l, simultaneous addition of insulin inhibited the glucagon-dependent glycogenolysis in a dose-dependent way (half maximal effective concentration for insulin about 2 nmol/l). Gastric inhibitory polypeptide alone at a concentration of 1 nmol/l reduced glucagon-dependent glycogenolysis only slightly. However, when infused simultaneously at low insulin concentrations (0.1 nmol/l), gastric inhibitory polypeptide suppressed hepatic glucose production dose-dependently up to 70%. The data suggest that gastric inhibitory polypeptide exerts direct metabolic effects on hepatic glycogen metabolism predominantly in a situation where insulin is simultaneously present, e.g. following ingestion of glucose.

Animals↗

Histochemical and immunohistochemical detection of putative preneoplastic liver foci in women after long-term use of oral contraceptives.

Localized areas with altered enzyme patterns were observed in liver tissue surrounding focal nodular hyperplasia in women after long-term use of oral contraceptives. These localized lesions were of three different types. Type I lesions were characterized by glycogen storage, a reduction in ATPase and an increase in gamma-glutamyltranspeptidase (gamma-GT) and UDP-glucuronyltransferase (UDP-GT) detected immunohistochemically. Type II lesions, which were morphologically very similar to small hyperplastic nodules, showed only a decreased ATPase reaction. Type III lesions showed an increase in gamma-GT (detected histochemically) and a slight reduction in ATPase. The results indicated that in human liver from patients given oral contraceptives long-term, localized lesions with altered enzyme patterns may occur which are very similar to those observed in animal models during experimental hepatic carcinogenesis.

Adenosine Triphosphatases↗

Hypersecretion of proinsulin does not explain the hyperinsulinaemia of patients with liver cirrhosis.

A radioimmunoassay using a proinsulin-specific antiserum that does not react preferentially with the split forms of proinsulin has been used to compare the response of circulating proinsulin to low (25 g) and high (75 g) oral glucose loads in healthy subjects and in patients with liver cirrhosis. The patients were divided into two groups: Group A (n = 7) with normal glucose tolerance and Group B with diabetic (n = 5) and impaired (n = 1) glucose tolerance. There was no apparent correlation between glucose tolerance and the results of quantitative liver function tests. In the fasted state, the concentrations of serum proinsulin did not differ significantly in patients of Group A (0.022 +/- 0.002 nmol/l) or Group B (0.026 +/- 0.004 nmol/l) from those in healthy subjects (0.021 +/- 0.002 nmol/l). After 75 g glucose, the rise in serum proinsulin to a maximum concentration of 0.082 +/- 0.012 nmol/l in patients of Group A and to 0.070 +/- 0.019 nmol/l in Group B was not significantly different at any time point up to 180 min from the rise in healthy subjects (to 0.063 +/- 0.005 nmol/l). After 25 g glucose, the response of serum proinsulin in Group B patients (maximum concentration 0.035 +/- 0.003 nmol/l) was not significantly different from that in healthy subjects (maximum concentration 0.032 +/- 0.003 nmol/l) but a slightly enhanced release was observed in the Group A patients (maximum concentration 0.049 +/- 0.003 nmol/l) that was significantly greater (P less than 0.05) at 60 min post-glucose. In contrast, the concentrations of serum immunoreactive insulin and immunoreactive C-peptide in all patients with cirrhosis were significantly elevated compared with healthy subjects both in the fasted state and at several time points following high and low oral glucose. In the fasted state, the serum proinsulin/C-peptide molar ratio, an index of the relative state of secretion of proinsulin and insulin, was significantly lower (P less than 0.05) in both groups of cirrhotic patients than in healthy subjects. After high and low glucose, this ratio fell in all patients and in the healthy subjects. We conclude that cirrhosis of the liver is associated with a hypersecretion of insulin but hyperproinsulinaemia does not contribute appreciably to the elevated concentration of immunoreactive insulin in the peripheral circulation.

Adult↗

Computer processed fluoroscopic images for digital intravenous renal angiography.

We investigated intravenous digital angiography using computer processed fluoroscopic images. Computer processed fluoroscopy (CPF) was compared to conventional digital subtraction angiography (DSA) in 39 patients referred for renal vessel evaluation. For assessment of CPF the anterior-posterior images were compared with the corresponding digital subtraction angiograms. 79% percent of DSA and 71% of CPF studies were diagnostic. Peripheral injection of contrast medium caused deterioration of CPF images. Skin dose measurements were obtained in 24 patients. The median dose for DSA was 8.2 rad, compared to 1.1 rad for CPF. It is concluded that sophisticated algorithms should be investigated for digital angiography, so that high image quality can be achieved with a reduced radiation exposure.

Adult↗

[Cyanide poisoning: forensic toxicology observations in the study of 54 cases of fatal poisoning].

The present study describes various observations made during the examination of 54 cases of lethal cyanide intoxication at the Institute of Forensic Medicine of the University of Zürich during a period of more than 40 years. Data pertain to the scene of death, the medicolegal inspection, the autopsy, the histological examinations, the chemical analyses, the various types of poisoning observed and the diagnostic criteria used. The intoxicated victims were mostly adults who had professional access to various cyanogenic compounds and had ingested them with the intention of committing suicide. Cases of accidental and criminal poisoning were rare. In spite of this fact, and although its frequency has not increased in the last few decades, cyanide poisoning has maintained undiminished importance.

Accidents, Occupational↗