Biomedical subjects

S Hartmann

Publications and source records attributed to S Hartmann.

At least 37 records · Page 2Linked to original sources

PubMed1999

NIH shift in flavin-dependent monooxygenation: mechanistic studies with 2-aminobenzoyl-CoA monooxygenase/reductase.

The flavoprotein 2-aminobenzoyl-CoA monooxygenase/reductase from the eubacterium Azoarcus evansii catalyzes the dearomatization of 2-aminobenzoyl-CoA. The reaction consists in an O2-dependent monooxygenation at the benzene position 5, which is followed immediately by an NADH-dependent hydrogenation of the intermediate at the same catalytic locus. The reaction was studied by 1H, 2H, and 13C NMR spectroscopy of the products. The main product was characterized as 5-oxo-2-aminocyclohex-1-ene-1-carboxyl-CoA by two-dimensional NMR spectroscopy. Thus, [5-2H]2-aminobenzoyl-CoA was converted into [6-2H]5-oxo-2-aminocyclohex-1-ene-1-carboxyl-CoA, indicating a 5 --> 6 shift of the [5-2H] label. Label from NAD2H was transferred to the 3 position of the cyclic eneamine, whereas label from solvent D2O was incorporated into the 4 and the 6 positions of 5-oxo-2-aminocyclohex-1-ene-1-carboxyl-CoA. The labeling pattern is compatible with the monooxygenation proceeding via what is formally an NIH shift, yielding 5-oxo-2-aminocyclohex-1, 3-diene-1-carboxyl-CoA as a protein-bound intermediate. It is suggested that this shift in flavin-dependent monooxygenation may have general validity.

Acyl Coenzyme A↗

PubMed1999

Physical exercise during pregnancy--physiological considerations and recommendations.

Controversial findings in numerous studies involving physiological and endocrinological parameters indicate that physical exercise during pregnancy is complex and somewhat poorly understood. But despite this reservation, it is safe to say that on the basis of the current state of scientific research in this area, physical exercise is to be recommended during pregnancy so long as women are aware of potential dangers and contraindications. Due to thermoregulatory advantages, the beneficials effects of immersion and its joint protective character "aquatic exercise" can be highly recommended during pregnancy. Psychologically speaking, physical exercise offers a variety of benefits such as the encouragement of cooperation and competition which can be experienced as fun and gratifying. The physiological and psychological benefits of physical exercise are not only available to healthy women, but have also proven to be valuable for the prevention and treatment of illnesses such as gestational diabetes. The activation of large groups of muscles allow for an improved glucose utilization by simultaneously increasing insulin sensitivity.

Body Temperature Regulation↗

PubMed1999

Neonatal screening for hearing disorders in infants at risk: incidence, risk factors, and follow-up.

OBJECTIVE: To determine the incidence and risk factors for hearing disorders in a selected group of neonates and the feasibility of selective hearing screening. SETTINGS: Multicenter prospective trial at five centers in Germany. METHODS: Enrollment criteria: in addition to previously defined risk factors by the Joint Committee on Infant Hearing (family history of hearing loss, in utero infections, craniofacial anomalies, birth weight <1500 g, critical hyperbilirubinemia, ototoxic medications, bacterial meningitis, postnatal asphyxia, mechanical ventilation >5 days, stigmata, or syndromes associated with hearing loss), the impact of maternal drug abuse, birth weight <10th percentile, persistent pulmonary hypertension, and intracranial hemorrhage more than or equal to grade III or periventricular leukomalacia on infant hearing were evaluated. The screening procedure was performed by automated auditory brainstem response (A-ABR; ALGO 1-plus; Natus Med Inc, San Carlos, CA). STATISTICS: univariate analyses of risk factors versus A-ABR results and a multivariate regression analysis were used; additionally, the total test time was recorded. RESULTS: Seven hundred seventy recordings from 777 infants enrolled consecutively constitute the basis of this analysis. Mean gestational age was 33.8 +/- 4.3 weeks, birth weight 2141 +/- 968 g; 431 infants being male and 339 female; 41 (5.3%) infants exhibited pathologic A-ABR results (16 bilateral and 25 unilateral). Meningitis or sepsis, craniofacial malformations, and familial hearing loss were independent significant risk factors. Median total test time was 25 minutes. Follow-up examinations in 31 infants revealed persistent hearing loss in 18 infants (13 infants sensorineural, 5 from mixed disorders), 7 requiring amplification. CONCLUSION: Hearing screening in high-risk neonates revealed a total of 5% of infants with pathologic A-ABR (bilateral 2%). Significant risk factors were familial hearing loss, bacterial infections, and craniofacial abnormalities. Other perinatal complications did not significantly influence screening results indicating improved perinatal handling in a neonatal population at risk for hearing disorders.

Analysis of Variance↗

PubMed1999

[Melancholia and neurotic depression].

The author considers the psychopathological distinction between endogenous and neurotic depression as one of differing psychodynamics. In so doing he embeds both illnesses within psychoanalytic theory while at the same time allowing a sharp differentiation. Even the premorbid personalities of patients with endogenous and neurotic depression are different. The personalities of those with endogenous depression bear a similarity to those with obsessional character and betray a pathological super-ego monopolized by defence mechanisms. The personalities of patients with neurotic depression show an oral-dependent structure characterised by a structural deficit of the ego functions and of an autonomous super-ego. These factors are responsible for the greatly differing pathodynamics found in these illnesses and point to different etiological factors in socialization.

Depressive Disorder↗

PubMed1998

Modulation of NMDA receptors by glycine--introduction to some basic aspects and recent developments.

Glycine is a co-agonist at NMDA receptors and it's presence is a prerequisite for channel activation by glutamate or NMDA. Physiological concentrations reduce one form of NMDA receptor-desensitization. Interactions between the glycineB site and other domains of the NMDA receptor are complex and include the glutamate, Mg2+ and polyamines sites. Glycine shows different affinities at various NMDA receptor subtypes probably via to allosteric interactions between NMDA2 subunits and the glycine recognition site on the NMDAR1 subunit. There is still some debate whether the glycineB site is saturated in vivo but it seems likely that this depends on regional differences in receptor subtype expression, local glycine or D-serine concentrations and the expression of specific glycine transporters. GlycineB antagonists and partial agonists have been reported to have good therapeutic indices as neuroprotective agents against focal ischaemia and trauma, anti-epileptics, anxiolytics, anti-psychotomimetics and in models of chronic pain. They clearly lack two potentially serious side effects classically associated with NMDA receptor blockade, namely neurodegenerative changes in the cingulate/retrosplenial cortex and psychotomimetic-like effects. This improved therapeutic profile may be partially due to the ability of full glycineB antagonists to reveal glycine-sensitive desensitization and possibly also via functional and/or regional NMDA receptor subtype selectivity.

Animals↗

PubMed1998

Budipine is a low affinity, N-methyl-D-aspartate receptor antagonist: patch clamp studies in cultured striatal, hippocampal, cortical and superior colliculus neurones.

The NMDA receptor antagonistic effects of budipine were assessed using concentration- and patch-clamp techniques on cultured striatal, hippocampal, cortical and superior colliculus neurones. Inward current responses of striatal neurones to NMDA (200 microM) at -70 mV were antagonized by budipine in a concentration-dependent manner (50% inhibitory concentration (IC50) 59.4 +/- 10.7 microM, n = 17) with 24 times lower potency than memantine but similar potency to amantadine. In striatal neurones, budipine blocked outward currents at +70 mV with an IC50 of 827 microM, suggesting that the binding site is less deep in the channel (delta = 0.45) than for memantine. However, more detailed analysis of the fractional block by budipine 300 microM in hippocampal neurones gave a delta-value of 0.90, but revealed that 28% block is mediated at a voltage-independent site. This voltage-insensitive site was accessible in the absence of agonist. Budipine exhibited concentration-dependent open channel blocking kinetics (kappa(on) = 0.71 x 10(4) M(-1) s(-1)) whereas the fast offset rate was concentration-independent (kappa(off) = 0.63 s(-1)). Calculation of the ratio kappa(off)/kappa(on) revealed an apparent Kd value of 88.7 microM. Budipine, memantine and amantadine had similar effects against NMDA-induced currents in cultured hippocampal, cortical and superior colliculus neurones, although amantadine was somewhat more potent in cultured striatal neurones. The relevance of NMDA receptor antagonism to the anti-Parkinsonian effects of budipine remains to be established.

Amantadine↗

PubMed1998

Recognition signal for C-mannosylation of Trp-7 in RNase 2 consists of sequence Trp-x-x-Trp.

C2-alpha-Mannosyltryptophan was discovered in human RNase 2, an enzyme that occurs in eosinophils and is involved in host defense. It represents a novel way of attaching carbohydrate to a protein in addition to the well-known N- and O-glycosylations. The reaction is specific, as in RNase 2 Trp-7, but never Trp-10, which is modified. In this article, we address which structural features provide the specificity of the reaction. Expression of chimeras of RNase 2 and nonglycosylated RNase 4 and deletion mutants in HEK293 cells identified residues 1-13 to be sufficient for C-mannosylation. Site-directed mutagenesis revealed the sequence Trp-x-x-Trp, in which the first Trp becomes mannosylated, as the specificity determinant. The Trp residue at position +3 can be replaced by Phe, which reduces the efficiency of the reaction threefold. Interpretation of the data in the context of the three-dimensional structure of RNase 2 strongly suggests that the primary, rather than the tertiary, structure forms the determinant. The sequence motif occurs in 336 mammalian proteins currently present in protein databases. Two of these proteins were analyzed protein chemically, which showed partial C-glycosylation of recombinant human interleukin 12. The frequent occurrence of the protein recognition motif suggests that C-glycosides could be part of the structure of more proteins than assumed so far.

Amino Acid Sequence↗

PubMed1998

[Affect and mimetic behavior].

The relationship between facial expression and experienced affect presents many problems. The two diametrically opposed positions proposing solutions to this problem are exemplified using the conceptions of Mandler u. Izard. The underlying premises of both conceptions still prevail in various forms. The authors reject the concepts according to which facial expression is merely correlated to the affects (see Mandler 1975) as well as the view that facial expression controls the affects (see Izard 1977). The relationship between affect and facial expression is reexamined, subjecting it to a semiotic, essentially semantic analysis similar to the Ogden and Richards' language and meaning approach. This analysis involves a critical discussion of Scherer's attempt of a purely communicational interpretation using Bühler's organon model. In the author's approach, facial expression is seen not simply as a system of signals, but as a system of representative signs which signify the affects and refer to the emotive meaning of things for the subject. The authors develop the thesis that human beings are not born simply with the ability to speak, but also with the abstract possibility of performing facial expressions. This ability develops by way of coordinating patterns of expressions, which are presumably phylogenetically determined, with affects that take on a socially determined individual form, similar to language acquisition during socialisation. The authors discuss the methodological implications arising for studies investigating the affective meaning of facial expressions.

Affect↗

PubMed1998

Safety of vitamin A: recent results.

A still unresolved public health concern is that excessive vitamin A intake, like vitamin A deficiency, possibly causes birth defects not only in animals but also in man. Due to the low incidence of possibly vitamin A-related malformations in man, available data cannot convincingly define the upper safe limit of periconceptional vitamin A intake. Direct human intervention studies are not feasible for ethical reasons. Therefore, a novel approach in addressing this issue was chosen by combining teratogenicity data from a validated animal model with data on systemic exposure to vitamin A and its major metabolites in female volunteers. In a study in pregnant women endogenous plasma concentrations of vitamin A metabolites during early pregnancy ranged from 0.26 to 7.72 ng/ml. Since they did not cause any foetal malformations, retinoid plasma levels in this range can be considered non-teratogenic. Results of a trial in non-pregnant women document that daily oral vitamin A supplements of 4000, 10,000 and 30,000 IU given for 3 weeks were in the range or slightly above the range of endogenous plasma levels seen in early pregnancy. Even after a 3-week treatment with 30,000 IU/day, peak plasma levels of retinoic acid and isotretinoin were within or just slightly above the range of their physiological levels. In cynomolgus monkeys (average weight: 3-4 kg), a NOAEL (no observed adverse effect level) of 7500 IU per kg body weight and a LOAEL (lowest observed adverse effect level) for developmental toxicity of 20,000 IU/kg was found. Considering these results in the cynomolgus monkey, a dose of 30,000 IU/day should also be considered as non-teratogenic in man.

Abnormalities, Drug-Induced↗

PubMed1997

Simultaneous determination of anabolic and catabolic steroid hormones in meat by gas chromatography-mass spectrometry.

A rapid and economical method for the determination in meat of androgens, estrogens, progestogens and corticoids, including some precursors and metabolites, has been developed. The extracted steroids are separated in a polar, a neutral, and a phenolic fraction by C8-SPE followed by a liquid-liquid extraction of the phenolates. Each fraction is separately purified by normal-phase SPE. The different steroid fractions can be analysed either together to obtain a comprehensive hormone pattern in one step or separately to enhance detection selectivity and sensitivity. Using a universally applicable silylation of the hydroxyl and keto groups, detection limits of 0.02-0.1 microg/kg are reached by GC-MS (EI) in the selected ion monitoring mode.

Adrenal Cortex Hormones↗

PubMed1997

A filarial cysteine protease inhibitor down-regulates T cell proliferation and enhances interleukin-10 production.

Filarial nematodes are a cause of chronic debilitating diseases in the tropics. A hallmark of filariasis is the marked down-regulation and polarization of host immune responses, yet molecular constituents of parasites causing this state have remained undefined. We describe a 17-kDa antigen (Av17) of the rodent filarial parasite Acanthocheilonema viteae, which shows amino acid homologies to cystatin C, a major cysteine protease inhibitor belonging to family 2 of the cystatin superfamily. Av17 is released by filariae in vitro. Exported molecules of A. viteae worms are shown to markedly suppress mitogen-induced T cell proliferation of mice and jirds. Av17 accounts for 45.5% of this suppressive activity in the murine system. Recombinant Av17 (rAv17), expressed in Escherichia coli, exhibits biological activity as a cysteine protease inhibitor and was used to examine the immunomodulatory effects, rAv17 induces down-regulation of murine T cell responses to mitogens, to T cell receptor cross-linking by anti-CD3 antibodies and to specific antigens, and at the same time up-regulation of interleukin-10. Hence, this filarial cystatin is a likely effector molecule of immunomodulation and a potential target for antifilarial intervention.

Animals↗

PubMed1997

A 41-kDa antigen of the rodent filaria Acanthocheilonema viteae with homologies to tropomyosin induces host-protective immune responses.

A purified 41-kDa protein of the rodent filaria Acanthocheilonema viteae was shown to protect jirds against a challenge infection. Subcutaneous immunization with the protein reduced the number of adult worms by up to 65% and the number of circulating microfilariae declined by up to 93% in these animals. The protein is located in the muscle tissues of adult worms and was identified as tropomyosin by N-terminal sequencing of the purified protein.

Amino Acid Sequence↗

PubMed1997

Anxiolytic activity of glycine-B antagonists and partial agonists--no relation to intrinsic activity in the patch clamp.

On the basis of animal models, anxiety was one of the first suggested clinical applications of partial agonists of the glycineB site coupled to the NMDA receptor. It is not certain, however, whether these findings can be extended to full glycineB antagonists and what is the relation between intrinsic activity (degree of NMDA receptor antagonism) and anxiolytic effect. In the present study several NMDA receptor antagonists, including several glycineB antagonists/partial agonists, were tested for anxiolytic activity in the Vogel conflict test and the elevated plus-maze. Additionally, the intrinsic activities of the glycineB partial agonists used [ACPC, (R,+)-HA-966 and D-cycloserine] were compared in patch-clamp experiments in cultured neurones. In the plus-maze the most striking increase in the time spent in open arms (index of anxiolytic effect) was seen after diazepam and D-cycloserine (at doses that did not change locomotion). Also reliable (dose-dependent), although weaker, anxiolytic activity was produced by the uncompetitive NMDA receptor antagonist (+)MK-801 and the competitive antagonist CGP 39551. Modest anxiolytic-like effect in the plus-maze was also observed after the glycineB antagonist L-701,324 and the partial agonist (+,R)-HA-966. Uncompetitive antagonists memantine and amantadine, the glycineB partial agonist ACPC (up to 600 mg/kg) or the full antagonists MRZ 2/570, MRZ 2/571 and MRZ 2/576 had no effect. In the Vogel conflict test neither memantine, nor any of the full glycineB antagonists tested (L-701,324 and MRZ 2/576), showed anxiolytic activity. Patch-clamp studies revealed that the intrinsic activity of (+,R)-HA-966, D-cycloserine and ACPC was 13, 57 and 92%, respectively, as compared to that of glycine itself (100%). In conclusion, for the agents tested there is no clear relation between the levels of intrinsic activity, i.e. degree of NMDA receptor inhibition, and anxiolytic activity. Moreover, L-701,324 and MRZ-type glycineB full antagonists do not exchibit anxiolytic activity in the elevated plus-maze and Vogel conflict test.

Animals↗

PubMed1997

Otoacoustic emissions as indicators of neurologically based hearing loss in childhood.

One of the most frequent causes of sensorineural hearing loss in childhood is damage to outer hair cells of the cochlea. The presence of otoacoustic emissions, generated by outer hair cells, provides evidence for normal hearing. This finding, however, may give rise to false reassurance, because even severe hearing loss, localized behind the cochlea, can be associated with normal otoacoustic emissions. The coexistence of otoacoustic emissions and hearing loss calls for the prompt exclusion of neurological disease.

Child↗

PubMed1997

Treatment of patent ductus arteriosus with ibuprofen.

AIM: To evaluate the efficiency and side effects of ibuprofen for the early treatment of patent ductus arteriosus (PDA) and compare it with indomethacin. METHODS: Forty preterm infants with gestational ages of less than 33 weeks, with respiratory distress syndrome (RDS) and echocardiographically confirmed PDA, were randomly assigned at days 2 to 3 of life to receive either intravenous indomethacin 3 x 0.2 mg/kg at 12 hour intervals or intravenous ibuprofen 1 x 10 mg/kg, followed by 5 mg/kg 24 and 48 hours later. RESULTS: PDA closed in 15 of 20 patients from the indomethacin group (75%) and in 16 of 20 (80%) from the ibuprofen group. Seven patients (three indomethacin, four ibuprofen) required a second treatment with indomethacin and in five (three in the indomethacin group and two in the ibuprofen group) the duct was ultimately ligated. Ibuprofen patients had a better urinary output and showed no increase in serum creatinine concentrations compared with the indomethacin group. Ibuprofen was not associated with any other side effect. CONCLUSIONS: Ibuprofen treatment seems to be as efficient as indomethacin in closing PDA on the third day of life in preterm infants with respiratory distress syndrome and seems to have fewer renal side effects.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1997

Influences of breed, sex, and susceptibility to malignant hyperthermia on lipid composition of skeletal muscle and adipose tissue in swine.

OBJECTIVE: To determine influences of breed, sex, and susceptibility to malignant hyperthermia on composition of skeletal muscle and adipose tissue in swine. ANIMALS: 35 male and female swine of German Landrace and Pietrain breeds and of 2 genotypes, normal (MHN) and susceptible to malignant hyperthermia (MHS). PROCEDURE: Pigs were fed a standard diet ad libitum. After attaining body weight of approximately 100 kg, pigs were slaughtered and skeletal (longissimus thoracis and supraspinatus) muscle and adipose tissue (3 sites) specimens were removed. For each specimen, lipids were extracted by chloroform/methanol and fatty acid (FA) pattern, and cholesterol concentration was determined by gas chromatography. RESULTS: The overall lipid contents differed significantly between breeds and genotypes; the MHS Pietrain pigs had the lowest lipid quantities. The relative amounts of saturated FA in all tissues were highest in Landrace pigs (P < 0.05), whereas the relative contents of monoenic FA were lower. In addition, for both breeds, the MHN pigs had significantly higher saturated and lower polyunsaturated FA values in all tissues, compared with MHS pigs. More specifically, MHS females of both breeds had the highest relative amounts of polyunsaturated FA. In general, relative cholesterol contents were found to vary little between identified groups. CONCLUSIONS: These data may indicate that, not only does mutation of the calcium release channel of the sarcoplasmatic reticulum, which occurs in MHS swine, influence secondary changes in lipid composition, but so do hormone concentrations and other genotypic factors. Observed differences in lipid content and FA composition could consequently influence specific membrane properties, such as fluidity and cell signaling.

Adipose Tissue↗

PubMed1997

Novel systemically active antagonists of the glycine site of the N-methyl-D-aspartate receptor: electrophysiological, biochemical and behavioral characterization.

A series of novel tricyclic pyrido-phthalazine-dione derivatives was tested for antagonistic effects at the strychnine-insensitive modulatory site of the N-methyl-D-aspartate (NMDA) receptor (glycineB). All compounds displaced [3H]MDL-105,519 binding to rat cortical membranes with IC50 values of between 90 nM and 3.6 microM. In patch-clamp experiments, steady-state inward current responses of cultured hippocampal neurons to NMDA (200 microM, glycine 1 microM) were antagonized by these same compounds with IC50 values of 0.14 to 13.8 microM. The antagonism observed was typical for glycineB antagonists, i.e., they induced desensitization and their effects were not use or voltage dependent. Moreover, increasing concentrations of glycine were able to decrease their apparent potency. Much higher concentrations (>100 microM) were required to antagonize alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-induced currents. They were potent, systemically active NMDA receptor antagonists in vivo against responses of single neurons in the rat spinal cord to microelectrophoretic application of NMDA with ID50 values in the low milligram per kilogram i.v. range. They also inhibited pentylenetetrazol-, NMDA- and maximal electroshock-induced convulsions in mice with ED50 values ranging from 8 to 100 mg/kg i.p. The duration of anticonvulsive action was rather short but was prolonged by the organic acid transport inhibitor probenecid (200 mg/kg). The agents tested represent a novel class of systemically active glycineB antagonists with greatly improved bioavailability.

Animals↗

PubMed1997

[Occupational health promotion in Germany--2: Prevention of musculoskeletal disorders].

As a major part of a detailed study about worksite health promotion and disease prevention the standard of prevention programmes for musculoskeletal disorders was investigated. Only every 10th company doesn't offer such programmes. Within these programmes the prevention concept is based on a reduced narrow understanding of musculoskeletal disorders, mainly focussed on behavioural biomechanical risk factors. The organisational aspects of the programmes are well designed. The number of programme participants in relation to epidemiological measures is low. Scientific evaluation of the health benefits of the worksite health programmes is rare.

Adult↗