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Biomedical subjects

H Hartmann

Publications and source records attributed to H Hartmann.

At least 127 records · Page 7Linked to original sources
PubMed1993

Effects of subchronic administration of pyritinol on receptor deficits and phosphatidylinositol metabolism in the brain of the aged mouse.

The effect of pyritinol, a commonly used nootropic drug, on receptor properties and function was investigated in different neuronal systems, possibly associated with age-related decline in brain function. Chronic treatment (15 days) of aged (22 months) female NMRI mice with pyritinol (200 mg/kg) restored the reduced density of N-methyl-D-aspartate receptors in the aged mouse brain. Furthermore, the total number of binding sites of the alpha 2-receptor ([3H]yohimbine binding) decreased after treatment with drug, while the number of high-affinity agonist binding sites ([3H]UK 14304 binding) was not changed. In both systems, receptor affinity was not influenced. The densities of other receptors investigated (muscarinic-cholinergic, benzodiazepine and beta-adrenergic) were not altered by treatment with pyritinol. Additionally, the effect of pyritinol on phosphatidylinositol (PI) metabolism was investigated in dissociated neurones from young and aged mice. Muscarinic-cholinergic induced accumulation of phosphatidylinositol and the inositol phosphate response due to activation of G-protein by fluoride was increased in aged animals, treated with drug. The inositolphosphate response after stimulation with pilocarpine was slightly but not significantly increased. The metabolism of phosphatidylinositol in young animals was not altered by treatment with drug. These results support the hypothesis of a nootropic-mediated restoration of age-related brain deficits. Changes caused by pyritinol may be due to beneficial effects on age-related alterations of the properties of the neuronal membrane.

Aging↗
PubMed1993

The potent free radical scavenger alpha-lipoic acid improves memory in aged mice: putative relationship to NMDA receptor deficits.

alpha-Lipoic acid (alpha-LA) improved longer-term memory of aged female NMRI mice in the habituation in the open field test at a dose of 100 mg/kg body weight for 15 days. In a separate experiment, no such effect could be found for young mice. alpha-LA alleviated age-related NMDA receptor deficits (Bmax) without changing muscarinic, benzodiazepine, and alpha 2-adrenergic receptor deficits in aged mice. The carbachol-stimulated accumulation of inositol monophosphates was not changed by the treatment with alpha-LA. These results give tentative support to the hypothesis that alpha-LA improves memory in aged mice, probably by a partial compensation of NMDA receptor deficits. Possible modes of action of alpha-LA based on its free radical scavenger properties are discussed in relation to the membrane hypothesis of aging.

Aging↗
PubMed1993

Home event recordings of oxygenation, breathing movements, and heart rate and rhythm in infants with recurrent life-threatening events.

For an evaluation of the usefulness of event recording in identifying mechanisms for apparent life-threatening events, 94 infants (median age, 3.1 months; range, 0.5 to 12 months) with a history of two or more apparent life-threatening events of hitherto unknown cause underwent event recording of transcutaneous oxygen pressure, arterial oxygen saturation, (not recorded in all patients), breathing movements, pulse waveforms, electrocardiogram, and instantaneous heart rate. Recordings were triggered by a fall in transcutaneous oxygen pressure to less than 20 mm Hg. During a median duration of event recording of 1.3 months (0.1 to 10 months), 52 events were recorded in 34 patients; 7 of the events had to be excluded because of uninterpretable signals. The following mechanisms were identified in the remaining 30 patients (45 events): a sudden change in skin perfusion but without hypoxemia (6 in 5 patients), hypoxemia induced by an epileptic seizure (6 in 5 patients), hypoxemia induced by suffocation by a parent (4 in 4 patients), and parental fabrication of events and medical history (7 in 6 patients). In the remaining 22 events in 12 patients, the precise mechanism of events could not be identified. Analysis of these as-yet-unexplained events showed prolonged abnormal hypoxemia (a fall in transcutaneous oxygen pressure to between 4 and 18 mm Hg and a fall in arterial oxygen saturation to 5% to 75%), lasting for 40 to 500 seconds in all. Only five of these events involved prolonged (> 20 seconds) apneic pauses, and only four an episode of bradycardia (heart rate < 80 or 60 beats/min). Thus event recording identified various mechanisms of apparent life-threatening events. In the events that remained unexplained, prolonged apneic pauses or episodes of bradycardia were found in only a minority. The identification of hypoxemia therefore may be more relevant to the early detection of these events than the identification of apnea or bradycardia or both. The relevance of these findings with regard to sudden infant death syndrome remains to be determined.

Apnea↗
PubMed1993

[Idiopathic ductopenia of adulthood: favorable effect of ursodeoxycholic acid therapy].

A 59-year-old woman presented with chronic, clinically asymptomatic cholestasis. Idiopathic adulthood ductopenia was diagnosed on the basis of clinical, laboratory and morphological findings. A retrograde cholangiographic study demonstrated intact large bile ducts with an apparent reduction of the small caliber intrahepatic ducts. The patient was treated with ursodeoxycholic acid (dosage 750 mg/day) which led to a decrease of alkaline phosphatase and Y-GT levels (before therapy: AP ca. 650 U/l; Y-GT ca. 150 U/l; after 6 month of treatment: AP ca. 350 and Y-GT ca. 30 U/l), suggesting, that the drug might be efficacious.

Bile Ducts, Intrahepatic↗
PubMed1992

The hydration shell of myoglobin.

The space in the unit cell of a metmyoglobin crystal not occupied by myoglobin atoms was filled with water using Monte Carlo calculations. Independent calculations with different amounts of water have been performed. Structure factors were calculated using the water coordinates thus obtained and the known coordinates of the myoglobin atoms. A comparison with experimental structure factors showed that both the low and the high resolution regime could be well reproduced with 814 Monte Carlo water molecules per unit cell with a B-value of 50 A2. The Monte Carlo water molecules yield a smaller standard R-value (0.166) than using a homogeneous electron density for the simulation of the crystal water (R = 0.212). A reciprocal space refinement of the water and the protein coordinates has been performed. Monte Carlo calculations can be used to obtain information for crystallographically invisible parts of the unit cell and yield better coordinates for the visible part in the refinement.

Monte Carlo Method↗
PubMed1992

Metabolic actions of insulin-like growth factor II in cultured adult rat hepatocytes are not mediated through the insulin-like growth factor II receptor.

Short- and long-term regulation of hepatic carbohydrate metabolism by insulin-like growth factor II was studied in primary cultures of adult rat hepatocytes and compared to the metabolic potency of insulin. Insulin-like growth factor II stimulated glycogen synthesis from [14C]glucose, uptake of [3H]aminoisobutyric acid and [14C]lactate formation from [14C]glucose up to three-fold. Basal glycogenolysis was inhibited to about 10%, and glucagon-activated glycogenolysis was blocked completely. The enzymatic activity of glucokinase and pyruvate kinase was induced two-fold, the glucagon-dependent induction of phosphoenolpyruvate carboxykinase was antagonized. Compared to insulin, half-maximal responses required up to 50 times higher insulin-like growth factor II concentrations ranging from 10-20 nmol/l. A similar difference was observed for binding affinity of insulin-like growth factor II to the insulin receptor. The interaction with the insulin-like growth factor II/mannose 6-phosphate (IGF-II/Man-6-P) receptor was examined by studying 125I-insulin-like growth factor II binding and uptake of lysosomal enzymes. The affinity of insulin-like growth factor II to the IGF-II/Man-6-P receptor was considerably higher than for the insulin receptor. Antibodies against the IGF-II/Man-6-P receptor did not affect metabolic responses to insulin-like growth factor II, while binding to its receptor and the receptor-mediated endocytosis of arylsulphatase A were strongly inhibited. Thus, in adult rat liver insulin-like growth factor II appeared to exert metabolic actions not via interaction with its own receptor but through low affinity binding to hepatic insulin receptors.

Aminoisobutyric Acids↗
PubMed1992

Acute actions of insulin-like growth factor II on glucose metabolism in adult rats.

The metabolic potency of recombinant human insulin-like growth factor II was studied in anaesthetized adult rats by obtaining dose-response curves for the hypoglycaemic action and for the stimulation of glucose metabolism during euglycaemic clamping. Compared to insulin, about 50 times higher doses of insulin-like growth factor II were required to result in identical in vivo responses, with half-maximally effective serum concentrations for the stimulation of glucose disposal during clamp studies of about 0.8 and 50 pmol/ml, respectively. A similar difference in potency was observed for the dose-dependent stimulatory actions on glucose metabolism in individual target tissues. Half-maximally effective serum concentrations in the range of 0.8 to 3.0 pmol/ml for insulin and of 40 to 70 pmol/ml for insulin-like growth factor II were seen to be required for 2-deoxyglucose uptake, glycogen formation in skeletal muscle and lipogenesis in epididymal fat. Maximal responses were identical with both peptides. These data suggest that in vivo acute metabolic actions of insulin-like growth factor II on carbohydrate metabolism occurred through insulin receptors.

Animals↗
PubMed1992

Mechanism of insulin resistance in CCl4-induced cirrhosis of rats.

Insulin action was studied in rats with CCl4/phenobarbital-induced cirrhosis of the liver using the euglycemic hyperinsulinemic clamp technique coupled with isotopic measurement of individual tissue glucose uptake, glycogen formation, and lipogenesis. In cirrhotic rats, dose response curves showed a reduction of insulin-stimulated total body glucose disposal of about 30%. Insulin action on tissue glucose uptake and initial phosphorylation (assessed with [3H]2-deoxyglucose) were unchanged; however, incorporation of [14C]glucose into lipids and particularly into glycogen was reduced substantially (being most pronounced in skeletal muscle and diaphragm) at maximally as well as half-maximally effective serum insulin concentrations during euglycemic clamping. At identical IV insulin infusion rates, steady-state serum insulin concentrations were elevated up to fourfold in cirrhotic animals. Antilipolytic action of insulin was unaltered. These data suggest that the principal metabolic pathway affected in insulin resistance of rats with experimental cirrhosis appeared to be insulin-stimulated glycogen formation in muscle tissues.

Adipose Tissue↗
PubMed1992

Comparison of subcutaneously administered soluble insulin and des-(B26-B30)-insulin-B25-amide in rabbit, pig and healthy man.

Subcutaneous injections of soluble human insulin and of the monomeric insulin analogue des-(B26-B30)-insulin-B25-amide were given to fasted rabbits, pigs and healthy man. The time course of blood glucose decline and the rate of appearance of the hormones in the peripheral circulation were studied for doses of 0.35 and 0.7 nmol/kg. In rabbits an identical time course with early glucose nadirs between 45 and 60 min and hormone peaks at about 20 min were observed for both hormones. Similar results were obtained for insulin and the analogue in pigs. When injected into humans, slightly earlier peaks of the analogue at 30 to 45 min were measured compared to insulin peaks at 60 min. In addition, a trend towards faster decline in blood glucose could be demonstrated after analogue injection. In contrast to monomeric insulin analogues produced by recombinant DNA technology, s.c. injections of des-(B26-B30)-insulin-B25-amide do not appear to meet mealtime insulin requirements better than soluble insulin.

Adult↗
PubMed1992

Increase of glomerular filtration rate and renal plasma flow by insulin-like growth factor-I during euglycaemic clamping in anaesthetized rats.

Renal function was studied in anaesthetized rats receiving i.v. infusions of recombinant human insulin-like growth factor-I (IGF-I) under euglycaemic clamp conditions. IGF-I increased glomerular filtration rate up to 35% and renal plasma flow up to 100%, this increase being dose dependent with half-maximal stimulation at serum IGF-I concentrations of about 24 pmol ml-1. Renal vascular resistance was reduced up to 50%, filtration fraction decreased up to 30% and urine flow increased up to three fold while arterial blood pressure was unchanged. Renal haemodynamics were affected at serum IGF-I concentrations that did not stimulate total body glucose disposal during euglycaemic clamping. IGF-I seemed to regulate renal function through IGF-I receptors apparently independent of acute changes of glucose metabolism.

Animals↗
PubMed1992

Self-organisation of cognitive processes and psychosis. Development and test of a theoretical model.

The development of a theory of self-control of brain processes leads to a model of disturbance of integration of brain processes in psychotic persons. The theory is that the "novelty-familiarity relation" of the current state of the processed information normally dominates the current mode of information processing. In the second part of the study adults with schizophrenia in remission and children with infantile autism were tested as to the manner in which they used newly introduced elements. The psychotic persons took the different character of the new elements less into consideration. The difference from the normal control persons is significant.

Adolescent↗
PubMed1991

F-actin capping by cap32/34 requires heterodimeric conformation and can be inhibited with PIP2.

The heterodimeric F-actin capping protein cap32/34 from Dictyostelium discoideum is a typical member of a widely distributed family of cytoskeletal proteins. To analyze its regulation and structure/function relationships we cloned and expressed the subunits separately in Escherichia coli using the ATG-expression vector pT7-7. Studies on the viscosity of F-actin solutions and the kinetics of actin polymerization in the presence of single subunits or the reconstituted protein showed that capping of F-actin absolutely requires the heterodimeric conformation. This activity can be inhibited by phosphatidyl bisphosphate (PIP2), an important component in signal transduction. The regulation of cap32/34 by PIP2 suggests an involvement of this protein in the re-organization of the actin cytoskeleton upon stimulation of D. discoideum cells with chemoattractant.

Actins↗
PubMed1991

Identification and characterization of Heliothis virescens midgut membrane proteins binding Bacillus thuringiensis delta-endotoxins.

To investigate the specificity of Bacillus thuringiensis var. kurstaki strain HD1 insecticidal crystal proteins (ICP), we used membrane preparations obtained from the midgut of Heliothis virescens larvae to perform separate ligand-blot experiments with the three activated CryIA toxins. The CryIA(a) and the CryIA(b) toxins bind the same 170-kDa protein, but most likely at two different binding sites. The CryIA(c) toxin binds two proteins of molecular masses 140 kDa and 120 kDa. We also demonstrate that the binding proteins for each of the B. thuringiensis toxins are not part of a covalent complex. Although the 170-kDa protein is a glycoprotein, endoglycosidase treatment does not prevent the binding of the CryIA(a) or CryIA(b) toxin. This indicates that the sugars are not important for the binding of these toxins. A model for a protein complex binding the B. thuringiensis HD1 ICPs is presented. Our results support the idea that binding proteins on membranes of the gut epithelial cells of H. virescens larvea are important for the specificity of the bacterial toxins.

Animals↗
PubMed1991

Growth-stimulating effect of adrenal androgens on the R3327 Dunning prostatic carcinoma.

Adrenal androgens are discussed as a reason for tumor progression after androgen ablation therapy. Because of the difference in the secretion of androgens by the adrenals of humans and rats, there is no reliable tumor model to study the role of adrenal androgens in tumor progression. Therefore, the main adrenal androgens were administered to rats in order to mimic human endocrine conditions. Application of dehydroepiandrosteron-sulfate (DHEA-S) alone or a mixture of androstendione (A), 11 beta-hydroxyandrostendione (OHA), dehydroepiandrosterone (DHEA), and its sulfate (DHEA-S) to castrated rats caused only a slight increase of prostate and seminal vesicle weight. Contrary to these findings, growth of the R3327 prostatic carcinoma in castrated rats was greatly stimulated by these adrenal androgens up to the level of the intact control. Thus, in spite of androgen ablation, tumor progression could be induced by exogenous adrenal androgens.

Adenocarcinoma↗
PubMed1991

In vivo metabolic action of insulin-like growth factor I in adult rats.

The acute metabolic actions of insulin-like growth factor I were studied in anaesthetized adult rats and its potency was compared to that of insulin. Following an i.v. bolus injection of insulin-like growth factor I a dose-dependent decrease of blood glucose and serum non-esterified fatty acid concentrations was noted with a potency of about 2% that of insulin. Stimulation of total body glucose disposal during euglycaemic clamping required approximately 50 times higher insulin-like growth factor I serum concentrations to achieve an identical half-maximal response. A similar difference in potency was observed for the stimulatory action on 2-deoxyglucose uptake and on glycogen formation in skeletal muscle. Lipogenesis in epididymal fat pads was increased dose-dependently by both hormones requiring approximately 30 times higher half-maximally effective serum concentrations of insulin-like growth factor I. These data demonstrate that insulin-like growth factor I exerted acute insulin-like metabolic actions in vivo with low potency. These effects were probably mediated via insulin receptors. A preferential stimulation of glucose metabolism in skeletal muscle was not observed.

Adipose Tissue↗
PubMed1990

Heterodimeric capping proteins constitute a highly conserved group of actin-binding proteins.

The two subunits of the heterodimeric protein cap32/34, an actin-binding protein, are encoded by separate single-copy genes. We have established the genomic structure of both genes. A sequence comparison of cap32/34 with capZ from chicken skeletal muscle and two partially known sequences from Saccharomyces cerevisiae and Xenopus laevis show that heterodimeric capping proteins belong to a highly conserved group of actin-binding proteins. This conclusion is supported by the cross-reaction of polyclonal antibodies against cap32 and cap34 with proteins from lower and higher eukaryotes. In addition, a system is presented that allows the expression of truncated cap34 polypeptides under the control of the cap34 promoter.

Actins↗
PubMed1990

Metabolic actions of insulin-like growth factor-I in cultured hepatocytes from adult rats.

Short-term and long-term regulation of hepatic carbohydrate metabolism by insulinlike growth factor-I was studied in primary cultures of adult rat hepatocytes and compared with the metabolic potency of insulin. Insulinlike growth factor-I stimulated the formation of [14C]lactate from [14C]glucose up to three-fold with a half-maximally effective concentration of approximately 50 nmol/L. Basal glycogenolysis was inhibited by about 20%, and glucagon-activated glycogenolysis was blocked completely by insulinlike growth factor-I with half-maximally effective concentrations of about 1.5 to 2 nmol/L. The activity of the key glycolytic enzymes glucokinase and pyruvate kinase were induced twofold. The glucagon-dependent induction of phosphoenolpyruvate carboxykinase--the key gluconeogenic enzyme--was antagonized with a half-maximally effective concentration of about 5 nmol/L. This inhibition of the glucagon-dependent induction of the enzyme was accompanied by a similar reduction of the increase in phosphoenolpyruvate carboxykinase-mRNA level as assessed by Northern blot analysis. The potency of insulinlike growth factor-I at half-maximally effective concentrations was approximately 2% to 4% that of insulin. Because binding studies demonstrated a comparably low affinity of insulinlike growth factor-I to the insulin receptor, it is suggested that in adult liver--in contrast to fetal and regenerating liver--insulinlike growth factor-I could exert short-term and long-term metabolic effects on parenchymal cells only through interaction with the insulin receptor.

Animals↗