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Biomedical subjects

H Hartmann

Publications and source records attributed to H Hartmann.

At least 163 records · Page 9Linked to original sources

[Loss of renal functional reserve following kidney transplantation and in patients with advanced disorders of liver function].

Renal functional reserve capacity was evaluated in healthy controls, kidney transplant recipients and patients with impaired liver function by simultaneous measurements of periodic clearances of inulin, PAH and creatinine every 30 minutes before, during and after infusion of an amino acid (AA) solution. During AA infusion glomerular filtration rate rose in 10 healthy controls to about 35% above basal values (inulin clearance from 107 +/- 6 to 144 +/- 7 ml/min, p less than or equal to 0.0005), renal plasma flow increased by 27% (PAH clearance from 530 +/- 25 to 675 +/- 40 ml/min, p less than or equal to 0.002). 8 renal transplant recipients with good and stable renal function (creatinine clearance above 65 ml/min) showed no rise in GFR and RPF, as did 10 patients with severe impairment of liver function and normal basal kidney function (creatinine clearance above 100 ml/min). The lack of renal functional reserve in kidney transplant recipients might indicate a hyperfiltration of the transplanted kidney. This could affect the longtime prognosis of these patients. The liver seems to play a role in the mediation of the amino acid-induced rise of GFR, supporting the hypothesis of a putative liver hormone regulating GFR after protein ingestion or AA infusion.

Adult↗

Actin-binding proteins are conserved from slime molds to man.

DNA clones encoding the actin-binding proteins alpha-actinin and severin from Dictyostelium discoideum were isolated and sequenced. Comparisons of the deduced amino acid sequences with proteins from other species showed striking similarities at distinct regions. The F-actin cross-linking molecule alpha-actinin carries two characteristic EF-hand structures highly homologous to the Ca2+-binding loops of proteins from the calmodulin superfamily. An N-terminal region that is conserved in alpha-actinin from D. discoideum and vertebrates is also related to parts of the dystrophin sequence and might represent the F-actin binding site. Severin, gelsolin, villin, and fragmin share homologous sequences that are believed to participate in the severing activity of these proteins.

Amino Acid Sequence↗

Enhanced in vitro inhibition of HIV-1 replication by 3'-fluoro-3'-deoxythymidine compared to several other nucleoside analogs.

Nucleoside analogs were synthesized and tested for anti-HIV-1 activity in two in vitro test systems using MT-4 cells and peripheral blood lymphocytes. Cytotoxicity was assessed in both assays and additionally in several human lymphoblastoid cell lines. One analog, 3'-fluoro-3'-deoxythymidine, exhibited higher antiviral potency and slightly higher cytotoxicity than 3'-azido-3'-deoxythymidine. Analogs showing lower cytotoxicity than 3'-azido-3'-deoxythymidine demonstrated reduced antiviral activity. 3'-fluoro-3'-deoxythymidine may become an alternative chemotherapeutic agent because of its high antiretroviral potency. Its toxicity, however, deserves further investigation.

Cell Line↗

Famotidine versus cimetidine in the treatment of acute duodenal ulcer. Double-blind, randomized clinical trial comparing nocturnal administration of 40 mg famotidine to 800 mg cimetidine.

The efficacy of famotidine, a potent new long-acting H2 receptor antagonist, was compared with cimetidine in 78 patients with endoscopically proven acute duodenal ulcers. Additional antacid self-medication was allowed if needed for relief of pain. Thirty-nine patients were allocated to each group, receiving a nocturnal oral dose of either 40 mg famotidine or 800 mg cimetidine. Patients were reassessed by endoscopy at 2, 4 and 6 weeks if ulcer healing had not occurred at the respective earlier control date. A diary was kept to record the duration and intensity of day and night pain and the amount of antacids ingested. After 2 and 4 weeks of treatment healing rates were not significantly different for either group (famotidine 31 and 95%, cimetidine 23 and 85%, respectively). Pain relief was rapid in both treatment groups with a tendency for better response of nighttime pain in famotidine-treated patients. Antacid consumption was not different in either group. Famotidine appears to be an effective treatment for acute duodenal ulcer. Compared to cimetidine, healing rates and relief of pain are not significantly different.

Acute Disease↗

[Comparison of quantitative liver function tests to clinical, laboratory chemical and biopsy findings in patients with liver diseases].

Quantitative liver function tests (QLFT), e.g. 1) galactose elimination capacity (GEK) and 2) fractional indocyanine-green elimination constant k (ICG) were performed in patients with various liver diseases. Retrospectively the results of QLFT were compared to clinical, histological and laboratory findings which are known to reflect severity of liver disease. Patients showing clinical symptoms like ascites and/or encephalopathy demonstrated lower values for GEK and ICG. In addition similar data were obtained for those patients who showed histological evidence of cirrhosis. When dividing up the group of cirrhotics according to PUGH's classification, correspondingly lower results of QLFT were observed between different PUGH classes, however, due to a substantial overlap an individual classification could not be achieved by QLFT. Compared to routine laboratory tests which might estimate hepatic functional impairment the following correlations were found: GEK to albumin: r = 0.47, p < 0.01, to Quick: r = 0.44, p < 0.001, to bilirubin: r = -0.23, p < 0.05, ICG to albumin: r = 0.45, p < 0.01, to Quick: r = 0.53, p < 0.001, to bilirubin: r = -0.42, p < 0.001. No correlation could be demonstrated to transaminase activity. The results obtained support the view that QLFT are capable of estimating hepatic function, however, compared to conventional characteristics of advanced liver disease only moderate correlations were detected. A superiority of quantitative liver function tests could not be detected.

Adult↗

Hypoglycaemic effect of proinsulin and insulin in intact and eviscerated rats.

The hypoglycaemic potency of biosynthetic human proinsulin and human insulin was studied in intact anaesthetized rats and in eviscerated hepatectomized rats, the latter serving as model for an in vivo muscle/fat tissue preparation. Intravenous dose response curves demonstrated a similar about 5-times smaller potency of proinsulin in both experimental conditions (half-maximal effective dose in intact rats for insulin 3.5, for proinsulin 17.5 nM/kg body weight; in eviscerated rats for insulin 3.6, for proinsulin 18.5 nM/kg). In intact rats hepatic glycogen content 2 h after hormone injection was higher in proinsulin than in insulin treated animals despite similar preceding hypoglycaemia which might suggest a preferential inhibitory action of proinsulin on hepatic glycogen breakdown (135 mumol glycosyl units/g liver for proinsulin-injected and 82 mumol glycosyl units/g liver for insulin-injected rats at half-maximal hypoglycaemia).

Animals↗

[Autoaggression and pulse rate--a longitudinal study].

This article presents a model of autoaggressive behavior in which a distinction is made between determining and maintaining factors. Specific environmental, in particular social, and organismic variables are linked to them. The two types of variables interact, thus causing or maintaining autoaggressive behavior. A theory of autoaggression must therefore rely on multicausal/multimodal explanations. A connection between autoaggression and a high level of arousal suggests itself. In this single-case longitudinal study a comparison was made between heart rate and frequency of autoaggressive behavior. High heart rates were found to be correlated with low frequencies of autoaggressive behavior and vice versa. Decreasing autoaggressive behavior was coupled with increasing muscle relaxation and increasing motor activity. However, abnormally high heart rates were associated with both low and high levels of motor activity.

Adult↗

Thermal expansion of a protein.

The thermal expansion of a protein, metmyoglobin, was investigated by analysis of the refined X-ray crystal structures at 80 and 255-300 K. On heating from 80 to 300 K, the volume occupied by myoglobin increases by approximately 3%. The linear thermal expansion coefficient is estimated to be 115 X 10(-6) K-1. This value is more than twice as large as that of liquid water but less than that of benzene. As the temperature is raised, the internal volume change does not come from the large, atom-sized internal cavities in the structure but from an increase in the small, subatomic free volumes between atoms. The largest expansion occurs in the region of the CD and GH corners; both these regions move away from the center of the protein. The remainder of the expansion results from the lengthening of contacts between segments of secondary structure.

Animals↗

Structural disorder in proteins. A comparison of myoglobin and erythrocruorin.

The refinement of X-ray structural data gives the mean square displacements, (chi 2), at each position in the protein molecule. In order to get information on the significance of such values different refinement methods have been compared. The metmyoglobin structure was determined at 300 K and (chi 2)-values were obtained with the restrained refinement procedure in reciprocal space of Konnert and Hendrickson. A comparison with the results of Frauenfelder et al. was used for an error estimation. The inclusion of surface bound water increases the accuracy of the results but does not change the general picture. For erythrocruorin (CTT3) a refinement was performed in reciprocal space and compared with a refinement in real space performed earlier. The (chi 2)-values obtained from both procedures are similar although the reciprocal space refinement gives results which are physically more reasonable. A comparison of the disorder in myoglobin and erythrocruorin showed that the structural similarity results in a similarity in the disorder. Contacts of molecules in the crystal do not dominate the disorder although they locally influence (chi 2)-values. CTT3 shows large disorder in the heme region in contrast to myoglobin. The differences in the rigidity of the F-helix can be correlated with the oxygen affinities supporting models for O2 binding developed by Frauenfelder et al.

Crystallography↗

Low temperature X-ray investigation of structural distributions in myoglobin.

The results of X-ray structure analysis of metmyoglobin at 300 K, 185 K, 165 K, 115 K and 80 K are reported. The lattice vectors a and b decrease linearly with temperature while c shows non-linearity above 180 K, indicating some type of phase transition. Cooling does change the myoglobin structure but only within the structural distribution as determined by individual (chi 2)-values at room temperature. Two residues showed significant alternative positions for side-chains at higher temperatures while only one position is occupied at low temperatures. In the case of LEU 61 a jump between different positions of the side-chain reduces the potential barrier for the entrance of the O2 molecule to the heme pocket. The mean square displacements, (chi 2), of the individual residues decrease linearly with temperature in most cases, indicating a parabolic envelope for the potential responsible for motions. A separation of rotational and translational disorder of the entire molecule is discussed. Comparison with Mössbauer spectroscopy indicates that protein dynamics on a time scale faster than 10(-7) s is not simply a harmonic process. Extrapolation of the structural distributions to T = 0 K shows that a large zero point distribution of the myoglobin structure exists, thus proving that there is no absolute energy minimum for one well defined conformation.

Binding Sites↗

Regulation of liver metabolism by the hepatic nerves.

In the isolated rat liver perfused as usual via the portal vein, joint electrical stimulation of the nerve fibers around the artery and the portal vein in the liver hilus increased glucose output, shifted lactate uptake to output, decreased urea and glutamine formation as well as ammonia uptake, reduced ketone body production, lowered oxygen uptake and reduced perfusion flow simultaneously changing the intrahepatic flow distribution; it was accompanied by an overflow of noradrenaline into the hepatic vein. All effects were mediated predominantly via alpha-receptors; they were dependent on extracellular calcium. In livers perfused both via the artery and the portal vein, separate stimulation of the plexus at the common hepatic artery or at the portal vein caused similar effects on glucose and lactate balance and on perfusion flow. Arterial stimulation caused the higher metabolic responses and alterations not only in arterial but also 'transhepaticly' in portal flow, and conversely, portal flow elicited the smaller metabolic responses and alterations in both portal and 'transhepaticly' arterial flow. If sympathetic nerve actions were blocked using alpha- and beta-antagonists, the resulting parasympathetic stimulation increased glucose uptake in the presence of insulin and antagonized the glucagon stimulated glucose release, both alone and more strongly in the presence of insulin. The sympathetic nerves may act directly at the parenchymal cells or indirectly via an overflow of neurotransmitter from the vasculature into the sinusoids or via hemodynamic changes. Experiments with the smooth muscle relaxant sodium nitroprusside and with retrograde flow indicate that neither hemodynamic changes nor noradrenaline overflow from the vasculature can play a major role in the mechanism of action of sympathetic liver nerves on glucose and lactate metabolism. Comparative studies with perfused livers of rats, guinea pigs and tupaias are in line with the view that in the rat the sympathetic nerves act via contacts with only a few periportal hepatocytes, from where the signal is propagated through gap junctions, while in guinea pig and tupaia the nerves act via contacts with almost all parenchymal cells. Sympathetic nerve stimulation of the perfused rat liver caused an increase in the activity of glycogen phosphorylase and a decrease of glycogen synthase, but left the activity of pyruvate kinase unaltered; fructose 2,6-bisphosphate and cAMP were only slightly enhanced.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗