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Biomedical subjects

S Hartmann

Publications and source records attributed to S Hartmann.

At least 55 records · Page 3Linked to original sources
PubMed1996

Cystatins up-regulate nitric oxide release from interferon-gamma-activated mouse peritoneal macrophages.

Up-regulation of nitric oxide (NO) production by activated murine macrophages was observed during infection by Trypanosoma cruzi, the etiological agent of Chagas' disease. Cell infection by T. cruzi depends at least in part on cruzipain, a membrane-associated papain-related proteinase which is sensitive to inhibition by synthetic inhibitors of cysteine proteinases. Using the natural cysteine proteinase inhibitor chicken cystatin, a representative member of cystatin family 2, to investigate the effect of cruzipain on macrophage infection and NO release, we found that the inhibitor alone up-regulated NO release from interferon-gamma-activated macrophages. A 12-fold increase in NO production was observed in the presence of 1 microM chicken cystatin. This overproduction was concentration-dependent and could be detected at concentrations as low as 10 nM and remained in the presence of polymyxin B. Representative members of the other cystatin families, i.e. stefin B (family 1), T-kininogen, and its inhibitory domains (family 3), were also able to enhance NO production from interferon-gamma-activated macrophages. Neither E64, an irreversible inhibitor of cysteine proteinases, nor inhibitors of aspartyl and serine proteinases (aprotinin, pepstatin, and soybean trypsin inhibitor) enhanced NO production. Upon complexation with saturating amounts of reduced-alkylated papain, cystatins still remained active in increasing NO production, suggesting that the cystatin inhibitory site was not involved in the mechanism. The results demonstrate that members of all 3 cystatin families share another common property unrelated to their function of cysteine proteinase inhibitors, i.e. up-regulation of NO production, which biological significance remains to be elucidated.

Animals↗
PubMed1996

Interactions of 2,3-benzodiazepines and cyclothiazide at AMPA receptors: patch clamp recordings in cultured neurones and area CA1 in hippocampal slices.

1. The 2,3-benzodiazepines GYKI 52466, GYKI 53405 and GYKI 53655 antagonized AMPA-induced currents in cultured superior colliculus neurones in a non use-dependent manner (steady state IC50s: GYKI 52466 9.8 +/- 0.6 microM; GYKI 53405 3.1 +/- 0.6 microM; GYKI 53655 0.8 +/- 0.1 microM). 2. Higher concentrations of all three antagonists slowed the onset kinetics and quickened the offset kinetics of AMPA-induced currents indicative of an allosteric interaction with the AMPA recognition site. 3. Cyclothiazide (3-300 microM) dramatically slowed desensitization of AMPA-induced currents and potentiated steady state currents (EC50 10.0 +/- 2.5 microM) to a much greater degree than peak currents. Both tau on and tau off were also increased by cyclothiazide in a concentration-dependent manner (EC50: tau on 42.1 +/- 4.5 microM; tau off 31.6 +/- 6.6 microM). 4. Cyclothiazide (10-100 microM) shifted the concentration-response curves of the 2,3-benzodiazepines to the right. For example, with 10 microM cyclothiazide the IC50s of GYKI 52466 and GYKI 53405 on steady-state AMPA-induced currents were 57.9 +/- 9.5 and 41.6 +/- 1.5 microM, respectively. 5. GYKI 53405 and GYKI 52466 concentration-dependently reversed the effects of cyclothiazide (100 microM) on offset kinetics (GYKI 53405 IC50 16.6 +/- 4.2 microM). However, the 2,3-benzodiazepines were unable to reintroduce desensitization in the presence of cyclothiazide and even concentration-dependently slowed the onset kinetics of AMPA responses further (GYKI 53405 EC50 8.0 +/- 2.8 microM). 6. GYKI 52466 decreased the peak amplitude of hippocampal area CA1 AMPA receptor-mediated excitatory postsynaptic currents (e.p.s.cs) (IC50 10.8 +/- 0.8 microM) with no apparent effect on response kinetics. Cyclothiazide prolonged the decay time constant of AMPA receptor-mediated e.p.s.cs (EC50 35.7 +/- 6.5 microM) with less pronounced effects in slowing e.p.s.c. onset kinetics and increasing e.p.s.c. amplitude. 7. Cyclothiazide (330 microM) shifted the concentration-response curve for the effects of GYKI 52466 on AMPA receptor-mediated e.p.s.c. peak amplitude to the right (GYKI 52466 IC50 26.9 +/- 9.4 microM). Likewise, GYKI 52466 (30-100 microM)) shifted the concentration-response curve for the effects of cyclothiazide on AMPA receptor-mediated e.p.s.c. decay time constants to the right. 8. In conclusion, cyclothiazide and the 2,3-benzodiazepines seem to bind to different sites on AMPA receptors but exert strong allosteric interactions with one another and with other domains such as the agonist recognition site. The interactions of GYKI 52466 and cyclothiazide on AMPA receptor-mediated e.p.s.cs in area CA1 of hippocampal slices provide evidence that the decay time constant of these synaptic events are not governed by desensitization.

Animals↗
PubMed1996

[Diagnosis and therapy of dysphagia after partial horizontal laryngectomy].

Due to an increase in the numbers of function-preserving laryngectomies and the utilization of laser techniques in cancer surgery, more patients after supraglottic partial laryngectomies are experiencing dysphagia of different intensities. We therefore developed a functional therapy program that we use for patients after supraglottic partial laryngectomies following a special diagnostic evaluation including video-laryngoscopy and, if necessary, high-speed cine-radiography. This therapeutic treatment was developed from conventional treatment for patients with dysphagia caused by neurological disorders and includes body posture, altered mouth movements, food consistency and swallowing technique. In so doing, exercises are used to achieve closure of the vocal folds, aids for swallowing liquids and general directions. This method for evaluation and treatment is presented in 12 patients as examples. We now report our positive long-term results and demonstrate the possibilities and limits of therapy. Additional procedures for isolated cases are discussed critically with regard to their indications and treatment.

Aged↗
PubMed1996

[Gamma nail osteosynthesis--progress in geriatric surgery].

The treatment of coxal femoral fractures in elderly patients is gaining vital significance. Short immobilization times, immediate full load capacity and fast reintegration into the home can be achieved only by early stable osteosynthesis. In an analysis of 222 patients hospitalized between 1988 and 1995 with peri- and subtrochanteric fractures of the femur we are able to show the advantages of the gamma nail in comparison to former osteosynthesis techniques.

Aged↗
PubMed1995

Mechanism of action of chemoprotective ursodeoxycholate in the azoxymethane model of rat colonic carcinogenesis: potential roles of protein kinase C-alpha, -beta II, and -zeta.

Several lines of evidence from our laboratory and others indicate that epigenetic alterations in protein kinase C (PKC) are involved in colonic carcinogenesis in both man and experimental animals. Furthermore, bile salts, known activators of PKC, have also been implicated in colonic tumor development. Recently, however, our laboratory has demonstrated that, whereas dietary cholic acid increased the occurrence of azoxymethane (AOM)-induced rat colonic tumors, ursodeoxycholic acid was associated with a significant protective effect. In the present studies, we therefore examined changes in PKC isoforms that accompanied AOM-induced tumor formation and investigated whether the chemopromotional and/or chemopreventional actions of these supplemental dietary bile salts involved changes in specific isoforms of PKC. Rats treated with vehicle (saline) or AOM and maintained on bile salt unsupplemented or supplemented diets were used to isolate control colonocytes and carcinogen-induced tumors, which were then subjected to subcellular fractionation. The homogenates and subcellular fractions were then probed for individual PKC isoforms by quantitative Western blotting using isoform-specific antibodies. Normal rat colonocytes expressed PKC-alpha, -beta II, -delta, -epilson, and -zeta. AOM, in unsupplemented or cholate-supplemented groups, caused significant down-regulation of PKC-alpha, -delta and -zeta and up-regulation of PKC-beta II, while increasing particulate PKC-alpha, -beta II, and -zeta in carcinogen-induced tumors compared to normal colonocytes. Dietary supplementation with ursodeoxycholic acid, in marked contrast to these groups, prevented the changes in the subcellular distributions of PKC-alpha, -beta II, and -zeta, and preserved the expression of PKC-zeta in AOM-induced tumors. These studies suggest that changes in specific isoforms of PKC (particularly, PKC-alpha, -beta II, -delta, and/or -zeta) are involved in colonic malignant transformation in the AOM model but do not account for the chemopromotional actions of cholic acid in this model. Furthermore, the ability of ursodeoxycholic acid to block AOM-induced increases in particulate PKC-alpha, -beta II, and -zeta, and/or inhibit down-regulation of PKC-zeta, may contribute to the chemopreventive effects of this bile acid.

Animals↗
PubMed1995

Suppression of tumorigenicity of breast cancer cells by transfer of human chromosome 17 does not require transferred BRCA1 and p53 genes.

A number of candidate tumor suppressor genes located on the human chromosome 17 are thought to have a role to play in the development of breast cancer. In addition to the p53 gene on 17p13.1 and the BRCA1 gene mapped to 17q12-21, other chromosomal regions for tumor suppressor genes have been suggested to exist on 17p13.3 and both the central and the distal parts of 17q, although definitive functional proof of their involvement in breast cancer tumorigenesis is still lacking. In this report we show that microcell transfer of a human chromosome 17 into wild-type p53 breast cancer cells CAL51 results in loss of tumorigenicity and anchorage-independent growth, changes in cell morphology and a reduction of cell growth rates of the neo-selected microcell hybrids. In the hybrid cells, which express the p53 wild-type protein, only the p- and the distal parts of the q arm of donor chromosome 17 are transferred. Thus, our results provide functional evidence for the presence of one or more tumor suppressor gene(s) on chromosome 17, which are distinct from the p53 and the BRCA1 genes.

Animals↗
PubMed1995

[Determination of naturally occurring sex steroid hormones (androgens and progestagens) in beef].

The content of 10 naturally occurring steroidal sex hormones (androgens and progestogens), their biosynthetic precursors and metabolites was determined in 62 samples of beef (bulls, steers, heifers). After enzymatic hydrolysis of their conjugates, the steroids were extracted from the tissue by liquid-liquid extraction and purified by solid phase extraction. The identification and quantification was carried out by GC-MS of the trimethylsilyl ethers. The progestogens progesterone and pregnenolone were quantitatively dominant (43.7 and 6.5 micrograms/kg respectively). The highest steroid concentrations were determined in female cattle.

Androgens↗
PubMed1995

Orphenadrine is an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist: binding and patch clamp studies.

Orphenadrine has been used as an antiparkinsonian, antispastic and analgesic drug for many years. Here we show that orphenadrine inhibits [3H]MK-801 binding to the phencyclidine (PCP) binding site of the N-methyl-D-aspartate (NMDA)-receptor in homogenates of postmortem human frontal cortex with a Ki-value of 6.0 +/- 0.7 microM. The NMDA receptor antagonistic effects of orphenadrine were assessed using concentration- and patch-clamp techniques on cultured superior colliculus neurones. Orphenadrine blocked open NMDA receptor channels with fast kinetics and in a strongly voltage-dependent manner. The IC50-value against steady state currents at -70 mV was 16.2 +/- 1.6 microM (n = 6). Orphenadrine exhibited relatively fast, concentration-dependent open channel blocking kinetics (Kon 0.013 +/- 0.002 10(6) M-1S-1) whereas the offset rate was concentration-independent (Koff 0.230 +/- 0.004 S-1). Calculation of the ratio Koff/Kon revealed an apparent Kd-value of 17.2 microM which is nearly identical to the IC50 calculated at equilibrium.

Aged↗
PubMed1995

An epidemiologic study of food consumption habits in Germany.

Food consumption habits were studied in subgroups of subjects in the German Nutrition Survey (Nationale Verzehrstudie [NVS]) on the basis of body weight. Our study was performed in an 18- to 88-year-old representative subgroup of 2,006 noninstitutionalized volunteers with no significant pathology (known as the Verbundstudie, Ernährungserhebung, and Risikofaktorenanalytik [VERA] subgroup). Using the German Food Code, food and nutrient intakes were calculated from 7-day dietary records. A stratification analysis was used to determine significant differences in food consumption habits of overweight subjects in comparison to normal-weight subjects. The results showed an increase in the prevalence of overweight (body mass index [BMI], 25 to 30) with age, from 15% in the group aged 18 to 24 years to 50% in the group aged more than 55 years. The prevalence of severe overweight (BMI, 30 to 40) increased from 3% to 17% in the same age groups, whereas morbid obesity (BMI, > 40) was found in only 0.4% of the study population. The calculated daily energy intake showed only a very weak correlation with BMI, probably because individual energy requirements and expenditures were not taken into account. However, differences were found between BMI subgroups in terms of the types of food consumed: a high BMI was associated with a higher consumption of meat and meat products but a lower consumption of milk and dairy products and bread and other cereal-based foods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Comparison of the potency, kinetics and voltage-dependency of a series of uncompetitive NMDA receptor antagonists in vitro with anticonvulsive and motor impairment activity in vivo.

The amino-adamantane derivatives memantine (1-amino-3,5-dimethyladamantane) and amantadine (1-amino-adamantane) are relatively low affinity, uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists which have been used clinically in the treatment of dementia and Parkinson's disease respectively for several years without serious side effects. The aim of this study was to test whether memantine, amantadine and other low affinity uncompetitive NMDA receptor antagonists also have better therapeutic indices than high affinity antagonists in preclinical models of epilepsy by assessing the potency, kinetics and voltage-dependency of open channel blockade for a series antagonists in vitro and comparing these effects to anticonvulsive and motor impairment activity in vivo. The compounds tested were memantine, amantadine, 14 other amino-adamantanes, (+)-MK-801, ketamine, dextrorphan, dextromethorphan and phencyclidine. The offset kinetics of open-channel blockade assessed with whole cell patch clamp recordings from cultured superior colliculus neurones were highly correlated to potency i.e. the less potent antagonists showed faster unblocking kinetics (Koff, r = 0.904). Although, onset kinetics as assessed by Kon were not correlated to potency (r = 0.023), tau on estimated at IC50 is perhaps a more meaningful measure of onset kinetics at equieffective concentrations and was also well correlated to potency (r = -0.863). All amino-adamantanes tested were strongly voltage-dependent. There was also a good correlation between the in vitro potencies of uncompetitive NMDA receptor antagonists assessed with patch clamp recordings and displacement of equilibrium [3H](+)-MK-801 binding and their in vivo activity against maximal electroshock (MES) and pentylenetetrazol (PTZ) induced tonic convulsions and NMDA-induced lethality in mice. Memantine and four other amino-adamantanes with somewhat lower potency and faster blocking kinetics had better therapeutic indices (ED50 rotarod and traction reflex over ED50 in MES-induced convulsions; TI = 2-4) than substances with higher affinity such as ketamine, dextrorphan and (+)-MK-801 (TI < 2). However, amantadine and several other amino-adamantanes with lower potency than memantine actually had poorer therapeutic indices (TI < or = 0.5) which may have been due to additional actions at other ion channels or receptors at the doses necessary to protect against seizures. In fact, ED50 in the MES test was negatively-correlated to therapeutic indices (traction r = -0.790, rotarod r = -0.797) i.e. the less potent uncompetitive antagonists had worse therapeutic indices. The data from the present study do not lend support to the idea that low affinity, open channel NMDA receptor blockers are also effective in models of epilepsy at doses having little effect on physiological processes. It should be stressed that these data do not contradict the known therapeutic safety of memantine and amantadine in dementia and Parkinson's disease respectively. Thus the good clinical profile of memantine in dementia has been attributed not only to its fast blocking/unblocking kinetics but also to its strong voltage-dependency. These biophysical properties may allow therapeutically-relevant concentrations to block chronic, low level pathological activation of NMDA receptors whilst leaving their synaptic activation intact. Precisely these properties may also underlie the poor therapeutic indices seen in the present study on antiepileptic activity due to the synaptic nature of both seizures and normal glutamatergic transmission.

Amantadine↗
PubMed1995

Contralateral cerebellar diaschisis 7 hours after MCA-occlusion in primates.

2,3,5-triphenyltetrazoliumchloride (TTC) as an indicator of mitochondrial function in combination with regional cerebral blood flow measurements was used in six baboons 6.9 +/- 1.2 h after permanent occlusion of the left middle cerebral artery. Staining with TTC was compared with blood flow data obtained during normocapnia using the microsphere method. Five animals showed a focal area of unstained tissue in the left middle cerebral artery territory. Mean blood flow in the unstained area was 28.3 +/- 15.4 ml min-1 100 g-1. Five of 6 animals showed a significant decrease of contralateral cerebellar blood flow in the presence of normal TTC staining. We conclude that at this early stage of infarction contralateral cerebellar diaschisis is caused by functional deactivation.

Animals↗
PubMed1995

[Marginal copper and iron supply in pigs. 2. Effect on fatty acid composition in various tissues].

The objective of the present study was to investigate the effect of a deficient copper and iron supply on the fatty acid composition of various tissues in pigs. An experiment was conducted with 4 x 12 growing pigs of the crossbreed Pietrain x Deutsche Landrasse. The animals were fed for a period of 119 days with a diet poor of copper (1.5 mg Cu/kg diet) and/or poor of iron (35 mg Fe/kg diet). Control animals were supplied adequately with copper (4.8 mg Cu/kg diet) and iron (85 mg Fe/kg diet). The diet was given according to weight. The copper and iron supply can be characterized as marginal due to a former report of this study. The total lipid and cholesterol content in serum, erythrocytes, liver and backfat was not influenced due to marginal copper and iron supply. Only in muscle there was a slightly reduction in these parameters. Marginal copper supply had no striking effect on the fatty acid composition in all examined tissues. After marginal iron supply there were some changes in the fatty acid composition in serum, erythrocytes and muscle. Saturated fatty acids raised due to declined monoenoic fatty acids, which is concluded as a reduced delta-9 desaturation.

Adipose Tissue↗
PubMed1995

Effects of bromocriptine on cardiovascular regulation in healthy humans.

Bromocriptine, a dopamine agonist with central nervous system actions, may reduce sympathetic nervous system activity. We tested this hypothesis by measuring arterial blood pressure, central venous pressure, heart rate, muscle sympathetic nerve activity, and forearm blood flow before and after unloading the arterial baroreceptors with sodium nitroprusside (0.5 to 1.5 mcg/kg per minute IV), before and after unloading the cardiopulmonary baroreceptors with incremental lower body negative pressure (0 to -15 mm Hg), and before and after immersion of the hand in ice-cold water for 2 minutes (cold pressor test). After obtaining basal responses to provocative maneuvers, we gave 20 healthy subjects either 5 mg oral bromocriptine (n = 10) or placebo (n = 10) in a randomized, double-blind fashion. Bromocriptine did not affect resting mean arterial pressure, heart rate, or forearm blood flow. Bromocriptine decreased resting central venous pressure by 1.2 mm Hg (P < .05) and tended to increase total integrated muscle sympathetic nerve activity (from 151 +/- 44 to 212 +/- 82 U/min, P = NS). The reflex increases in muscle sympathetic nerve activity to nitroprusside infusion and lower body negative pressure were unchanged by bromocriptine; however, vascular responsiveness to both maneuvers was impaired after bromocriptine administration compared with control. Without bromocriptine, the reflex increase in muscle sympathetic nerve activity after nitroprusside-induced hypotension maintained forearm blood flow at a constant level, whereas with bromocriptine the forearm blood flow increased from 1.9 +/- 0.3 to 2.8 +/- 0.6 mL/min per 100 mL (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

[Alexithymic verbal behavior in patients with Crohn disease].

This study investigates the language of Morbus Crohn patients using a quantitative, objective linguistic method which was developed by M. v. Rad (1983). Significant results were: The language of Morbus Crohn patients is more generalized and includes not only fewer emotional terms but also fewer differential emotional terms than the language of neurotic patients. This result supports the hypotheses that the language of Morbus Crohn patients is alexithyme and that the Morbus Crohn disease belongs to psychosomatic disorders.

Adult↗
PubMed1994

Stereochemistry of 2,4-dimethyleicos-2-enoate from the pyruvylated glycolipid of Mycobacterium smegmatis.

The absolute stereochemistry of 2,4-dimethyleicos-2-enoic acid, isolated from the pyruvylated glycolipid of Mycobacterium smegmatis, has been determined. The two enantiomers of methyl 2,4-dimethyleicos-2-enoate were synthesised for the first time but could not be separated by gas chromatography on cyclodextrin phases. (E)-2-Methyloctadec-2-enoate, an intermediate in the synthesis, is a characteristic component of acyl trehalose glycolipids from Mycobacterium fortuitum. Ozonolysis of the fatty acid ester mixture, obtained from the pyruvylated glycolipid produced 2-methyloctadecanoate. It was identified as the (S)-enantiomer by comparison with (2R) and (2S)-2-methyloctadecanoic acid, intermediates in the synthesis of (4R)- and (4S)-2,4,-dimethyleicos-2-enoic acid, using enantioselective gas chromatography of the methyl esters with heptakis(2,6-di-O-methyl-3-O-pentyl)-beta-cyclodextrin as a chiral stationary phase. The natural acid was therefore determined to be 2E-(4S)-2,4-dimethyleicos-2-enoic acid.

Fatty Acids, Monounsaturated↗