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Biomedical subjects

B Beyer

Publications and source records attributed to B Beyer.

At least 19 recordsLinked to original sources
PubMed2002

Two kinase activities are sufficient for sea urchin sperm chromatin decondensation in vitro.

Decondensation of compact and inactive sperm chromatin by egg cytoplasm at fertilization is necessary to convert the male germ cell chromatin to an active somatic form. We studied decondensation of sea urchin sperm nuclei in a cell-free extract of sea urchin eggs to define conditions promoting decondensation. We find that egg cytosol specifically phosphorylates two sperm-specific (Sp) histones in vitro in the same regions as in vivo. This activity is blocked by olomoucine, an inhibitor of cdc2-like kinases, but not by chelerythrine, an inhibitor of protein kinase C (PKC). PKC phosphorylates and solubilizes the sperm nuclear lamina, one requirement for decondensation. Olomoucine, which does not inhibit lamina removal, blocks sperm nuclear decondensation in the same concentration range over which it is effective in blocking Sp histone phosphorylation. In a system free of other soluble proteins, neither PKC nor cdc2 alone elicit sperm chromatin decondensation, but the two act synergistically to decondense sperm nuclei. We conclude that two kinases activities are sufficient for sea urchin male pronuclear decondensation in vitro, a lamin kinase (PKC) and a cdc2-like Sp histone kinase.

Alkaloids↗
PubMed2001

Electroconvulsive thresholds of inbred mouse strains.

The electroconvulsive threshold (ECT) test is used commonly in the screening of anti-epileptic drugs in rodent models, but little is known about its genetic or mechanistic basis. Thresholds for minimal clonic, maximal tonic, or psychomotor (partial) seizures were determined in 16 different inbred mouse strains in two different laboratories. A wide range of thresholds was observed, suggesting that a variety of neuroexcitability alleles exist in inbred strains. Although there was generally good cross-strain correlation between the three seizure types, several outlier strains were detected, showing that genetically encoded differences can affect the ability of a particular seizure type to spread through the brain. Furthermore, the relative seizure susceptibility of a strain was comparable between the two laboratories, suggesting that despite different test sites, instrumentation, and personnel, the ECT assay is portable and that common inbred strains can often be relied upon as calibration standards. Last, the ECT paradigm was also sensitive enough to detect single locus differences, laying the groundwork for mutation screens for new neuroexcitability models.

Animals↗
PubMed2001

Internal exposure to polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/PCDFs) of Bavarian chimney sweeps.

This study was carried out to evaluate the internal exposure to polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/PCDFs) of chimney sweeps in Bavaria compared to a control group without occupational exposure. The PCDD/PCDF concentrations in the blood fat of 227 chimney sweeps were compared with the concentrations in samples from 60 controls. Using an internal standard containing 17 (13)C(12)-labeled PCDD/F congeners, the samples were cleaned up after fat elution using standard methods. The statistical analysis was adjusted to account for demographic differences, dietary habits, smoking status, and both occupational and nonoccupational contact with chlorinated hydrocarbons. Detailed information on the type of heating in the households swept, the length of time the chimney sweeps had carried out the profession (min 34, med 195, max 466 months) and the protective measures employed, were used to examine the influence of the working conditions specific to chimney sweeps on the internal PCDD/PCDF exposure. The correlation between blood-fat PCB concentrations as well as urinary chlorophenol concentrations and the exposure to PCDDs/PCDFs was evaluated. The sum of PCDD/PCDF components in chimney sweeps, expressed by International Toxic Equivalents (I-TEQ), was significantly increased compared to the control group (median: 26.36 versus 20.75 pg I-TEQ/g blood fat). For 37 chimney sweeps (16.3%) the sum of PCDDs/PCDFs exceeded the 95th percentile of the control group, i.e., 38.23 pg I-TEQ/g blood fat. Multiple regression analysis revealed that in addition to occupation, the variables age, district, and proximity to a waste incineration plant seem to have an effect on the internal PCDD/PCDF exposure. An additional influence on the internal exposure could not be determined for any of the special aspects of the work. We identified no high correlations between the concentrations of PCBs and chlorophenols and PCDDs/PCDFs. This study revealed significantly higher internal exposure to PCDDs/PCDFs in chimney sweeps than in the control group. The differences are small and within the range of the internal exposure to PCDDs/PCDFs in blood found in the general population in Germany since 1989. Further investigations in to PCDD/PCDF-related diseases in these study groups were not carried out.

Adult↗
PubMed1999

A novel recombinant single-chain hepatitis C virus NS3-NS4A protein with improved helicase activity.

Hepatitis C virus (HCV) nonstructural protein 3 (NS3) has been shown to possess protease and helicase activities and has also been demonstrated to spontaneously associate with nonstructural protein NS4A (NS4A) to form a stable complex. Previous attempts to produce the NS3/NS4A complex in recombinant baculovirus resulted in a protein complex that aggregated and precipitated in the absence of nonionic detergent and high salt. A single-chain form of the NS3/NS4A complex (His-NS4A21-32-GSGS-NS3-631) was constructed in which the NS4A core peptide is fused to the N-terminus of the NS3 protease domain as previously described (Taremi et al., 1998). This protein contains a histidine tagged NS4A peptide (a.a. 21-32) fused to the full-length NS3 (a.a. 3-631) through a flexible tetra amino acid linker. The recombinant protein was expressed to high levels in Escherichia coli, purified to homogeneity, and examined for NTPase, nucleic acid unwinding, and proteolytic activities. The single-chain recombinant NS3-NS4A protein possesses physiological properties equivalent to those of the NS3/NS4A complex except that this novel construct is stable, soluble and sixfold to sevenfold more active in unwinding duplex RNA. Comparison of the helicase activity of the single-chain recombinant NS3-NS4A with that of the full-length NS3 (without NS4A) and that of the helicase domain alone suggested that the presence of the protease domain and at least the NS4A core peptide are required for optimal unwinding activity.

Amino Acid Sequence↗
PubMed1998

Construction, expression, and characterization of a novel fully activated recombinant single-chain hepatitis C virus protease.

Efficient proteolytic processing of essential junctions of the hepatitis C virus (HCV) polyprotein requires a heterodimeric complex of the NS3 bifunctional protease/helicase and the NS4A accessory protein. A single-chain recombinant form of the protease has been constructed in which NS4A residues 21-32 (GSVVIVGRIILS) were fused in frame to the amino terminus of the NS3 protease domain (residues 3-181) through a tetrapeptide linker. The single-chain recombinant protease has been overexpressed as a soluble protein in E. coli and purified to homogeneity by a combination of metal chelate and size-exclusion chromatography. The single-chain recombinant protease domain shows full proteolytic activity cleaving the NS5A-5B synthetic peptide substrate, DTEDVVCCSMSYTWTGK with a Km and k(cat) of 20.0 +/- 2.0 microM and 9.6 +/- 2.0 min(-1), respectively; parameters identical to those of the authentic NS3(1-631)/NS4A(1-54) protein complex generated in eukaryotic cells (Sali DL et al., 1998, Biochemistry 37:3392-3401).

Amino Acid Sequence↗
PubMed1996

Extra- and intracellular action of quaternary devapamil on muscle L-type Ca(2+)-channels.

1. The quaternary derivative of the potent verapamil-analogue, (-)-D888, (qD888, 4-cyano-4-(3,4-dimethoxyphenyl)-N-[2-(3-methoxy phenyl)ethyl]-N,N,5-trimethyl-1-hexanaminium) was synthesized as a novel membrane-impermeable probe to study the localization of phenylalkylamine (PAA) effector domains on L-type Ca2+ channels. Channel block by qD888 was investigated in smooth muscle-like (A7r5) cells after extra- and intracellular application by use of the whole-cell configuration of the patch clamp technique. 2. Extracellularly applied qD888 inhibited Sr2+ (Isr) (IC50 = 90 microM) and Na+ (IC50 = 27 microM) inward currents through L-type Ca(2+)-channels mainly in a resting-state-dependent manner. Structurally closely related quaternary PAAs (e.g. D890) were ineffective after extracellular application. 3. QD888 also blocked Isr from the cytoplasmic side, as did other quaternary PAAs (D890, D575). Intracellular block was clearly dependent on channel opening, which resulted in pronounced use-dependence. 4. We conclude that qD888 blocks L-type Ca2+ channels not only from the intracellular side, via interaction with the classical PAA binding domain, but also from the extracellular channel surface. The properties of Ca2+ channel block together with previous biochemical and structural data suggest that extracellular block may be mediated by a site that also confers tonic block by quaternary benzothiazepines.

Animals↗
PubMed1995

Calcium entry blockers and activators: conformational and structural determinants of dihydropyrimidine calcium channel modulators.

Dihydropyrimidines 4, 6, and 15, uniquely designed to unambiguously establish structural and conformational determinants for DHP receptor occupation and for modulation of calcium channel function, were prepared and examined for calcium channel modulation. Our results confirm and firmly establish a preference for syn-orientation of an unsymmetrically substituted aryl moiety at the DHP receptor (15d vs 15e). We propose a normal vs capsized DHP boat model to explain structural and conformational requirements for modulation of calcium channel function that requires an obligatory left-hand side alkoxy cis-carbonyl interaction for maximal DHP receptor affinity, the effect of channel function being determined by orientation of the 4-aryl group. Enantiomers having an up-oriented pseudoaxial aryl group (normal DHP boat) will elicit calcium antagonist activity, whereas enantiomers having a down-oriented pseudoaxial aryl group (capsized DHP boat) will elicit calcium agonist activity. Single enantiomers of macrocyclic lactone 15b demonstrate opposite channel activity. Antagonist activity resides in enantiomer 15b-A (S-configuration, left-hand side alkoxy cis-carbonyl with up-oriented pseudoaxial aryl group and normal DHP boat), whereas agonist activity resides in enantiomer 15b-B (R-configuration, left-hand side alkoxy cis-carbonyl with down-oriented pseudoaxial aryl group and capsized DHP boat). Moreover, this model is consistent with and provides a rational explanation of previous literature in this area, most notably the observation of chiral inversion and potency diminution upon replacement of ester by hydrogen in the Bay K 8644 series.

Animals↗
PubMed1995

Titanium distributions in zone melted materials measured by SIMS.

Using a zone melting apparatus the influence of the different solidification processes on the Ti distribution has been investigated in model alloys and a technical steel. The concentration profiles after the conventional zone melting process have been measured using secondary ion mass spectrometry and were used for the determination of the distribution coefficients of Ti in pure Fe-Ti- and Fe-C-Ti-alloys. The registration of lateral elemental maps helps to identify and to eliminate measuring artefacts and allows the investigation of dendritic solidification structures.

Journal Article↗
PubMed1993

[Use of the Glasgow Coma Scale in pediatric craniocerebral trauma].

Over five years the applicability of a modified Glasgow Coma Scale was analysed in 38 children (mean age 7.2 +/- 3.8 years) with head and associated injuries (47.4%). The score was estimated after the accident and in the course of intensive therapy. At the beginning of the treatment on the intensive care unit, the cases were staged according to the severity of the head injuries (Glasgow Coma Scale: 4-8, 9-12 and 13-19 points). At the stage evaluated as between 4 and 8 points, 50% of the patients died and the survivors were ventilated (11.7 +/- 10.7 days) and intensively treated (45.7 +/- 31.5 days). All patients had had neurological damage. Additional injuries worsened the prognosis in the acute phase. 42.9% of the patients received intracranial pressure monitoring. In the patients between 9 and 12 points, the time of ventilation (3.7 +/- 2.9 days) and of intensive therapy (19.5 +/- 13.3 days) decreased. Over 13 points, all patients had a shorter duration of treatment (10.8 +/- 8.8 days) and a quick and good recovery. The Glasgow Coma Scale has the advantage of an examination with a quantitative analysis and resulting effective diagnostic and therapeutic measures. Even the inexperienced physician can use the Glasgow Coma Scale with success at the site of the accident.

Adolescent↗
PubMed1990

[The effect of combined ALL therapy in childhood on body growth].

Female ALL long-term survivors who received cranial telecobalt radiation under the conditions of Therapy Study III of the Study Group on "Paediatric Haematology/Oncology" showed a significant reduction in adult height. On completion of therapy a drop in growth can already be observed in female ALL patients. This limitation on growth can probably be attributed to a disturbance in the hypothalamus-hypophysis system and to reduced GH secretion as a result of radiation.

Body Height↗
PubMed1989

Formaldehyde exposure at various workplaces.

The results of formaldehyde determinations in the air at various workplaces in the period 1980-1988 are presented. The airborne concentrations varied between less than 0.01 and 10.9 mg m-3 (mean 0.7 mg m-3). For ambient air monitoring, active sampling and capillary gas chromatography are reliable and sensitive methods. Formic acid excretion in urine is an unspecific and insensitive biological indicator for monitoring low-dose formaldehyde exposure.

Air Pollutants, Occupational↗
PubMed1989

[Formaldehyde determination in tobacco smoke--studies under experimental and actual conditions].

The estimation of an external exposure to formaldehyde in tobacco smoke requires a reliable analytical method. The gas chromatographic determination of formaldehyde shows in comparison to photometric methods a higher sensitivity and specificity. In the main stream smoke of various kinds of cigarettes the amount of formaldehyde vary between 3.4 micrograms to 8.8 micrograms/cigarette, this is equal to concentration between 2.3 to 6.1 ppm. In the air of lounges in hospitals formaldehyde concentrations up to 0.19 ppm can be detected after smoking of 15 cigarettes over a period of 1.5 h. In kindergartens without tobacco smoke the formaldehyde concentrations in air range from 0.005 to 0.01 ppm. The smoking of 30 cigarettes and one pipe in a non ventilated room over 1.5 h exceeded formaldehyde concentrations between 0.21 to 0.45 ppm. The concentration declines to 0.08 ppm within 2h after termination of smoking. The MAK-value of 0.5 ppm is not exceeded; in contrast to this the indoor limit of 0.1 ppm recommended by the German Bundesgesundheitsamt is exceeded in the vicinity of the smoker. The formaldehyde concentrations in tobacco smoke reported in the older literature can not be confirmed; this is due to the nonspecificity of the photometric methods. On the basis of our results can be concluded that the irritating effects of tobacco smoke to the mucous membranes are the result of the sum of irritating effects caused by several compounds and particles in the smoke and not only the impact of formaldehyde.

Air Pollutants↗
PubMed1989

Polyarthritis as the initial symptom of secondary syphilis: case report and review.

The differential diagnosis of the patient with acute polyarthritis is lengthy. We present the case of a young man with acute inflammation of the knees and ankles in whom a diagnosis of acute rheumatic fever was initially considered. The clinical course and laboratory findings suggested that secondary syphilis was also a likely etiology of his problem. We believe that in some patients with acute polyarthritis, secondary syphilis must be seriously considered as part of the differential diagnosis.

Adolescent↗
PubMed1985

Preparation and evaluation of a soluble derivative of the antiallergic compound trans-2, 3b, 4, 5, 7, 8b, 9, 10-octahydronaphtho [1, 2-c:5, 6-c'] dipyrazole (LC-6).

In the present report we describe the preparation of LC-6.2HCl, a soluble derivative of the synthetic bispyrazole LC-6. Because the latter was practically insoluble in aqueous and organic media, experiments which indicated that it had antiallergic activity were confined to in vivo studies following its oral administration. The availability of soluble LC-6.2HCl made it possible to administer the drug i.v. or i.p. Through these routes it exhibited greater antiallergic activity than by the oral route, as judged by lower ID50's and by the achievement of 100% PCA inhibition. The latter result had not previously been attained orally with the base. Furthermore, when injected i.v. or i.p. LC-6.2HCl showed prolonged inhibitory activity, a valuable attribute of the parent compound. The in vivo activity of the soluble salt, which we describe, further establishes the potential therapeutic value of the drug.

Administration, Oral↗