Biomedical subjects

G Hauser

Publications and source records attributed to G Hauser.

At least 55 records · Page 3Linked to original sources

PubMed1987

Molecular geometries and steric energies of phorbol 10,11-diacetate and 1,2-diacetylglycerol molecules.

Protein kinase C, an enzyme that is stimulated physiologically by diacylglycerol (DAG) and phospholipids in the presence of Ca2+, is involved in a novel cellular signaling system that is activated by the binding of appropriate agonists to certain classes of receptors. Phorbol esters are tumor promoters that can replace DAG in the activation of protein kinase C. Molecular similarities between the two compounds have been proposed to be responsible for the capacity to activate the enzyme. We have studied the molecular geometries and conformational energies of DAGAc and PDAc using the Molecular Mechanics II program and parameter set developed by Allinger and Yuh (1980). This was done to establish whether conformers of the two compounds are geometrically similar and which hydroxyl group of the phorbol molecule corresponds to the C3 hydroxyl of DAG which must be unsubstituted for activation of protein kinase C.

Calorimetry↗

PubMed1987

Modulation of rat brain cytosolic phosphatidate phosphohydrolase: effect of cationic amphiphilic drugs and divalent cations.

The effects of three cationic amphiphilic drugs on rat brain cytosolic phosphatidate phosphohydrolase and their mechanisms of action were studied utilizing membrane-bound, emulsified, and emulsified sonicated phosphatidate as substrates. With the membrane-bound substrate, chlorpromazine, desmethylimipramine, and propranolol inhibited the activity in a dose-dependent fashion with an IC50 of 30-50 microM. In the presence of the emulsified substrate, chlorpromazine was a more potent inhibitor than desmethylimipramine or propranolol but 200 microM was needed for 50% inhibition of activity. Addition of heat-inactivated microsomes to the emulsified substrate, to simulate the conditions with the membrane-bound substrate, did not alter this value. Both Mg2+ and Ca2+ stimulated the enzyme activity but only Ca2+ counteracted the effect of chlorpromazine. Kinetic studies indicate that chlorpromazine acts as a noncompetitive inhibitor of the enzyme. Emulsified sonicated phosphatidate was a good substrate at low (less than 10 microM) concentrations. It was a poor substrate at 1 mM, but at this concentration chlorpromazine stimulated the activity instead of inhibiting. This drug altered the integrity of phosphatidate vesicle membranes as visualized by electron microscopy. The different results obtained with the three types of substrate indicate the importance of the configuration of phosphatidate for the expression of enzyme activity and for its susceptibility to the action of cationic amphiphilic drugs.

Animals↗

PubMed1987

Stimulation of luteinizing hormone release by melittin and phospholipase A2 in rat pituitary cells.

Gonadotropin release in rat pituitary monolayer cultures was stimulated by phospholipase A2, as well as by its activator melittin. A dose-dependent stimulation of luteinizing hormone secretion by melittin was observed in a dose range of 10(-8) to 10(-4) M. A higher dose (1 mM) melittin had a sub-optimal effect. The stimulatory action of melittin was calcium-dependent and blocked by phospholipase A2 inhibitors, chloroquine and quinacrine. Similar to melittin, phospholipase A2 enhanced the effect of LH release in a dose range of 0.1-100 units/ml. The effect of this enzyme was also calcium-dependent with optimal calcium concentrations at 1.5 mM, as obtained also for melittin. In superfusion experiments, the stimulatory action of melittin and phospholipase A2 was reproducible in their effects on LH release in gonadotrophs. In addition, melittin (10(-7) M) stimulated LH and 3H-arachidonic acid efflux in superfused pituicytes following prelabelling with radiolabelled arachidonate. These data suggest that phospholipase A2, which releases arachidonic acid from phospholipids, may participate in controlling gonadotropin secretion in gonadotrophs, since arachidonic acid and its metabolites have previously been found to enhance gonadotropin release.

Animals↗

PubMed1987

Stimulation of phosphoinositide hydrolysis by serotonin in C6 glioma cells.

5-Hydroxytryptamine (serotonin or 5-HT) stimulated the incorporation of 32Pi into phosphatidylinositol (PI) but not into polyphosphoinositides in C6 glioma cells with an EC50 of 1.2 X 10(-7) M. The phosphoinositide response was blocked by the 5-HT2 antagonists ketanserin and spiperone but inhibited only partly by methysergide and mianserin. Atropine, prazosin, and yohimbine did not block the response, whereas fluphenazine and haloperidol did so partially but also inhibited basal incorporation by approximately 30%. The 5-HT1A agonist 8-hydroxy-2(di-n-propylamino)tetralin did not cause stimulation. Incubation with 5-HT (1 microM) for 1 h increased the incorporation of [2-3H]myoinositol into all phosphoinositides but not into inositol phosphates (IPs). Li+ alone at 10 mM increased labeling in inositol bisphosphate (IP2) and trisphosphate (IP3), whereas labeling in IP and phosphoinositides remained unaltered. Addition of 5-HT had no effect on this increase. Mn2+ at 1 mM enhanced labeling in PI, PI-4-phosphate, lyso-PI, glycerophosphoinositol, and IP, but the presence of 5-HT again did not cause further stimulation. 5-HT also stimulated the release of IPs in cells prelabeled with [2-3H]myo-inositol, incubated with LiCl (10 mM) and inositol (10 mM), and then exposed to 5-HT (1 microM). Radioactivity in IP2 and IP3 was very low, was stimulated approximately 50% as early as 30 s, and remained elevated for at least 20 min. Radioactivity in IP was at least 10 times as high as in IP3 but was increased only from 3 min on with a peak at 20 min, when the elevation was approximately 40 times that in IP3.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1986

Chlorpromazine induces accumulation of inositol phosphates in C6 glioma cells.

The capacity to modify the incorporation of [2-3H]myo-inositol into inositides and inositol phosphates was different for three psychotropic cationic amphiphilic drugs. Chlorpromazine, desmethylimipramine and propranolol were able to increase the labeling of inositol-containing lipids, but only chlorpromazine dramatically increased the incorporation into inositol phosphate, -bisphosphate and -trisphosphate. The increase was 10- to 50-fold in 60 min as compared with controls. This effect is not due to stimulation of lipid labeling, because in chase experiments radioactivity in inositol phosphates increased to a greater extent than in their parent lipids. It is possible that the alteration of phosphoinositide catabolism is related to the neuroleptic activity of the drug.

Animals↗

PubMed1986

Effects of pre-weaning undernutrition and post-weaning rehabilitation on polyphosphoinositide pools in rat brain regions.

In order to assess the effects of undernutrition during the pre-weaning period on polyphosphoinositide (PolyPI) pools in rat cerebral cortex, brain stem, and cerebellum, dams were fed 5% (L-) or 22% (L+) protein diets from birth to weaning and the pups were used at this age for analyses. To examine rehabilitation post-weaning, L- and L+ pups were fed 22% protein diets (P+) for an additional six week period. Rats were decapitated and the dissection begun either immediately ("0 min" samples) or 10 min later (10 min samples). Body and tissue weights, and cerebroside levels were determined in addition ot PolyPI concentrations. In brain the extent of disappearance of PolyPI during the 10 min post-mortem period paralleled the content of gray matter: cerebral cortex greater than cerebellum greater than brain stem in all groups regardless of diet. Levels of PtdIns4P and PtdIns4,5P2 were decreased by 40% and 70% respectively in cerebral cortex of L- "0 min" samples. Deficits of both lipids in brain stem and cerebellum were 40-50%. In the L- 10 min samples, deficits were 20-30% in all three regions as compared with L+ 10 min levels, indicating the presence of a portion of both lipids affected only moderately by nutritional insufficiency. The effects on this relatively inert pool, much of it localized in myelin, were reversed on nutritional rehabilitation. The PolyPI pool lost post-mortem in L+ brain regions was practically absent in L- brain regions and was not restored in L-P+ animals. Thus, this study indicates that a metabolically labile pool, primarily located in gray matter structures, is more sensitive to nutritional deprivation during the pre-weaning period than the more stable pool. The precise role and function of these pools remain to be determined.

Animals↗

PubMed1986

Effects of pre- and postweaning undernutrition on polyphosphoinositide pools in rat kidney.

The effects of undernutrition on polyphosphoinositide levels in rat kidneys removed and frozen immediately after animal death or 10 min later were determined. Weanling (21-day-old) rats of dams fed a 5 or 22% protein diet and litters fed either normal or protein-deficient diets for an additional six wk were used. Nutritional deprivation lowered phosphatidylinositol-4-phosphate (PtdIns4P) preferentially (35-40%) but preserved phosphatidylinositol-4,5-bisphosphate (PtdIns4,5P2) at weaning. This effect was not completely reversed in animals nutritionally rehabilitated after weaning. Postweaning protein deficiency did not reduce the levels of these lipids. Postmortem loss was the same for all five groups, minimal for PtdIns4P and about one-third for PtdIns4,5P2.

Aging↗

PubMed1986

Variations of supraorbital bony structures in Sienese skulls.

Various non-metrical traits were examined in the supraorbital region in a series of skulls of recorded sex (147 males, 130 females), age (18-80 years) and provenance (Siena and surroundings), using a standard method of categorization and notation introduced by two of the authors in 1983. The results are discussed from a topographic-anatomical point of view in relation to trait variation and with respect to the usefulness of the method applied for population studies.

Adult↗

PubMed1986

Palatal rugae in Swazi, southern Africa.

In a sample of Swazi (47 males and 70 females) the palatal rugae were studied and the results compared with those in the literature. The rugae are generally strong and show considerable complexity. Strength of ridges is associated with arch height, which suggests common factors in development.

Adolescent↗

PubMed1985

Life skill training: psychoeducational training as mental health treatment.

Fifty-four patients of a Veterans Administration Medical Center were assigned to either a life-skill training program that emphasized psychoeducational instruction and skill building or to a group counseling control condition. Subjects assigned to life-skill training were provided with 28 hours of instruction in interpersonal communication, purpose in life problem solving, and physical fitness/health maintenance. Control subjects received equal time engaged in psychiatric treatment that emphasized the analysis and exploration of personal problems, but with no direct coping skill training. Significant differences between the two groups were found on measures of interpersonal communication and meaningful purpose in life. Both groups received lower staff ratings on psychopathological behavior and demonstrated improvement on ratings of health and physical fitness upon completion of treatment. Twelve- and 24-month follow-up data that include rehospitalization rates are presented for each group.

Adaptation, Psychological↗

PubMed1985

Variations in form of the hypoglossal canal.

Variation in the nature and extent of division of the hypoglossal canal can be classified by a simple scoring scheme. Applied to three series of crania of differing provenance, the results indicate a continuity in expression of the trait rather than the dichotomous character utilized in previous studies. The similarity in results in these three populations, of widely differing environment, suggests fairly strict canalization of development.

Adolescent↗

PubMed1985

Variations in the method of the division of the hypoglossal canal in Sienese skulls of known age and sex.

In 300 Sienese skulls of known age and sex (146 male and 154 female) 6 modes of expression of bipartition of the hypoglossal canal were studied on the basis of a new scheme of notation that takes into account gradually increasing intensity. The analysis of data, including also the traditional method of notation confirms the criticisms expressed by various authors on the loss of information when the variability of this trait is neglected, especially with reference to age-dependent changes (hyperostotic effects).

Adolescent↗

PubMed1985

Multi-dimensional complexes of skull traits.

The simultaneous incidence of sutural bones was studied by a multidimensional analysis (Wanke method). On a medieval sample of 249 male and female skulls from Lower Austria the presence of two main complexes of sutural and fontanelle bones was observed. The interaction of possible genetic factors and developmental growth incongruences in causing these phenomena are discussed. The necessity of further studies considering such basic biological aspects with minor skeletal traits is stressed.

Analysis of Variance↗

PubMed1984

[Dermatoglyphics in families with Potter type III polycystic kidney degeneration].

Several dermatoglyphic studies of patients suffering from genetically determined disorders which are not manifest at birth, indicate an early direct or indirect influence of the causative factors on the formation of dermatoglyphics. On the basis of these observations the present study gives an analysis of the quantitative and qualitative dermatoglyphic characteristics of fingers, palms and soles, as well as body and head measurements and morphological traits of the head and face of nine patients with adult polycystic kidney disease (APCD) type III and of their first and second degree relatives. No malformations nor any significant variation of these variables were observed, i.e. no differences were recorded between patients and controls or patients and their healthy relatives. Yet some interesting trends appeared in dermatoglyphic ridge counts when special methods for intrafamilial comparison were applied. Thus, APCD type III ridge counts on fingers and palms were somewhat lower when plotted against their mid-parent values than those of their healthy sibs. Nevertheless, only studies of additional family material may permit the conclusion that such a constellation is due to type III APCD, and not merely a spurious finding.

Adult↗

PubMed1984

Effect of ethanol on rat brain polyphosphoinositides.

Female rats were allowed to consume ethanol during gestation and lactation, and brain polyphosphoinositides of the 21-day-old pups were quantified. Ethanol intake prevented the disappearance of the metabolically labile pools of phosphatidylinositol-4-phosphate and phosphatidylinositol-4,5-bis-phosphate, which are rapidly degraded in the control group. In contrast, preweaning undernutrition left the size of these pools virtually unchanged, indicating a differential effect of the two nutritional regimens.

Animals↗

PubMed1983

On the variability of "flexion creases" in the distal plantar areas of newborns.

The plantae of 83 male and 95 female healthy, full-term Caucasian newborns from Austria (gestational age 235-301 days) were photographed and the flexion creases in the distal part were examined. Analysis of the creases was done under four different aspects, the main evaluation based on a scheme of nine creases introduced by Schenk and Patzer (1959). Two transversal (No. 1 and No. 9) and three longitudinal (Nos. 3, 6, and 7) creases are always or predominantly present, a finding corresponding with the data of Schenk on 52 male and 48 female newborns from Germany. In addition, the nine plantar creases were evaluated according to six degrees of expression, and some typical cease combinations are shown. Bilateral and bisexual similarity prevails. The results of this study might serve investigations of different populations and of medical disorders.

Dermatoglyphics↗

PubMed1983

Evidence from phospholipid metabolism changes for muscarinic cholinergic receptors on rat anterior pituitary cells.

In incubations of dissociated adult rat anterior pituitary cells with [32P]orthophosphate, carbamylcholine causes an increase in phosphatidic acid labeling accompanied by a small reduction in phosphatidylinositol labeling. Carbamylcholine and oxotremorine produce about the same maximum change while that caused by pilocarpine is smaller. Low concentrations of atropine, quinuclidinyl benzilate, and scopolamine completely inhibit the effect caused by carbamylcholine, whereas d-tubocurarine does not decrease the stimulation, even at higher concentrations. The muscarinic antagonists alone produce a rise in phosphatidylinositol labeling and a drop in phosphatidic acid labeling, an effect opposite from that produced by the agonists, but d-tubocurarine alone has no effect. Thus changes in phospholipid metabolism are mediated through muscarinic cholinergic receptors in dissociated rat anterior pituitary cells, confirming the presence of functional binding sites. The present studies also demonstrate the utility of experiments on precursor incorporation into phospholipids in identifying the existence on cells or tissues of certain receptor classes.

Animals↗

PubMed1983

Propranolol-induced inhibition of rat brain cytoplasmic phosphatidate phosphohydrolase.

Propranolol, a cationic amphiphilic drug, caused enhanced incorporation of labeled precursor into phosphatidic acid and its metabolites in rat cerebral cortex mince, suggesting increased biosynthesis or reduced degradation. Inhibition of phosphatidate phosphohydrolase could explain the observed drug-induced accumulation of phosphatidic acid and other acidic lipids. Propranolol exhibited differential effects on the free and membrane-bound forms of phosphatidate phosphohydrolase. The drug inhibited cytoplasmic enzyme in a dose-dependent manner only when membrane-bound substrate was used but had practically no effect on the membrane-bound enzyme irrespective of the nature of the substrate used or on the cytoplasmic enzyme when free substrate was used. Brain cytoplasmic enzyme obtained from rats sacrificed 30 min after intraperitoneal injections of propranolol did not show any inhibition. propranolol bound to membranes may prevent cytoplasmic enzyme action, probably by decreasing the availability of substrate through the formation of stable lipid-drug-protein complexes.

Animals↗