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Biomedical subjects

M Weiss

Publications and source records attributed to M Weiss.

At least 487 records · Page 27Linked to original sources

Sympathoadrenergic regulation and the adrenoceptor system.

We investigated the effects of endurance and high-intensity training periods on the plasma catecholamine (CA) concentration at rest; on the basal alpha- and beta-adrenoceptor density, regulation, and function on circulating cells; and on the cardiovascular adaptation in long-distance runners and swimmers. The findings of each period were compared with those of untrained men. Endurance training of the long-distance runners and the swimmers led both to a reduced sympathetic activity at rest, indicated by lower CA values, and to a lower beta-receptor density and responsiveness on circulating lymphocytes and an increased alpha 2-receptor sensitivity on circulating platelets. During the high-intensity training period beta-receptor density and responsiveness increased, alpha 2-receptor sensitivity normalized, and heart rate as well as blood pressure values increased in both trained groups. The basal sympathetic activity remained reduced, but the norepinephrine-to-epinephrine (NE/EPI) ratio increased. The NE/EPI ratio might play an important part in the regulation of adrenoceptor density during these different training periods. Swimming-specific characteristics caused different physiological impacts compared with running training, but an attenuated baroreceptor sensitivity might be indicated in both intensively trained groups.

Adenylyl Cyclases↗

Tuberous sclerosis with pulmonary involvement.

Pulmonary involvement in tuberous sclerosis (pTS) is very rare and seems to be associated with a more benign course, compared to tuberous sclerosis without pulmonary manifestation (TS). Furthermore, pTS seems to be related to lymphangiomyomatosis (LAM). We present the case of a 33-year-old woman in whom the overlap of TS, pTS and LAM is demonstrated. Treatment with medroxyprogesterone was initiated, but without success.

Adult↗

Neurotoxic effect of domoic acid: mediation by kainate receptor electrophysiological studies in the rat.

Domoic acid, an excitatory amino acid structurally related to kainic acid, has recently been identified as being responsible for the severe intoxication presented, in 1987, by more than 150 people having eaten mussels grown in Prince Edward Island. The present in vivo electrophysiological studies, using unitary extracellular recordings obtained from pyramidal neurons of the CA1 and of the CA3 regions of the rat dorsal hippocampus, were undertaken to study the effect of kainic acid and domoic acid applied by microiontophoresis and compare their potencies to that of agonists of the 2 other subtypes of glutamatergic receptors or neuropeptides. The activation induced by domoic acid and kainate was more than 20-fold more potent in the CA3 than in the CA1 region, whereas no such regional difference could be detected with all the other substances tested. In the CA1 as well as in the CA3 region, domoic acid was about 3 times more potent than kainate. A selective lesion of the mossy fibre system originating from the dentate gyrus and projecting to the CA3 region of the dorsal hippocampus, drastically reduced the excitatory effect of kainic acid and domoic acid in this later area, without affecting the response to the other substances tested. Several class of pharmacological agents were studied in an attempt to find an antagonist of kainate and domoic acid. Only benzodiazepines could selectively suppress the neuronal activation induced by kainate, however, with a lower efficacy in the CA3 than in the CA1 region. These results demonstrate that domoic acid is a potent agonist of kainate receptors and that, in the CA3 region, it might produce its neurotoxic effects through activation of kainate receptors located on mossy fibre terminals. Finally, in the event of a new wave of intoxication, our results suggest that a rapid treatment with high doses of benzodiazepines could possibly prevent the important and irreversible hippocampal damage.

Acetylcholine↗

Anatomy of the rat albumin promoter.

The sequences preceding the albumin mRNA start site are able to direct efficient transcription only upon introduction into cells expressing the endogenous albumin gene. In transient expression assays, the activity of a reporter gene (CAT) linked to this promoter is 100-fold higher in H4II differentiated hepatoma cells than in H5 dedifferentiated cells which no longer express their albumin gene. This tissue specificity depends on the very proximal promoter region, composed of a CCAAT box, the proximal element and a TATA box. Deletion of the CCAAT box leads to a two- to threefold decrease in activity, deletion of the proximal element (PE) results in loss of activity. The PE is a high-affinity binding site for HNF1/APF, a strictly liver specific trans-acting factor. When the affinity of this factor for PE is decreased by bacterial methylation (PE includes a dam methylase site), by mutation, or by its replacement with the homologous element from the alpha-fetoprotein gene (AFP), the activity of the short promoter (PE plus the TATA box) is abolished. This activity can be rescued in the presence of the more upstream elements: DEII, DEI and the CCAAT box (recognized, respectively, by the NF1/CTF, C/EBP and NFY/ACF factors) which are then absolutely required. Our results suggest that the upstream elements contribute to promoter activity by stabilizing the HNF1-PE complex and not by direct interaction with TFIID or the RNA polymerase. It is probable that these elements, essentially dispensable in already differentiated hepatoma cells, play a crucial role during development or differentiation to activate the promoter in cells that contain a low concentration of HNF1 and/or an HNF1 unable to open inactive chromatin alone.

Animals↗

Recurrent meningitis in a patient with congenital deficiency of the C9 component of complement. First case of C9 deficiency in Europe.

We describe the first cases, to our knowledge, of C9 deficiency in Europe that were detected in a Swiss family, of which two members--one with a complete deficiency and the other with approximately half-normal C9 levels--experienced bacterial meningitis. The index patient, a 56-year-old white man with a history of purulent meningitis at the age of 23 years, presented with an acute meningococcal meningitis. No impairment of cellular immunity or immunoglobulin deficiency could be found. Complement assays showed a complete deficiency of the C9 component, while the other individual component levels were normal and the hemolytic activity (measured using the CH50 assay) was only slightly reduced. A family study revealed complete C9 deficiency in the patient's healthy brother and half-normal C9 concentrations in his sister, his son (who also had experienced an episode of bacterial meningitis), and his niece, consistent with an inherited C9 deficiency. This first case of recurrent meningitis in a white patient with complete C9 deficiency suggests that this complement defect may also be a risk factor for bacterial, especially neisserial, infections.

Complement C9↗

[Characteristics of the work site and their relevance for cardiovascular risk factors; consequences for prevention from an epidemiologic viewpoint].

Although standard risk factors are clearly related to cardiovascular diseases; even taken together they account for about half of the incidence rates in prospective studies. Therefore psychosocial variables - among them work related characteristics - are of increasing significance for research and prevention in CHD. Thus, an enlarged version of the KARASEK-conception was studied in the GDR-MONICA-Population, aged 25 to 64 years. Additional to the original Karasek-questionnaire, the more "objective" work characteristics as well as the scale "Social Interaction at workplace" are implemented. Based on data of this study, the usefulness but also the limitations of the diversified Karasek conception (Job Demands, Decision Latitude, Social Interaction at work) are demonstrated. In spite of the relevance for smoking, blood pressure, cholesterol and overweight of the Karasek-model recommended also the objective work characteristics as well as other mediating variables should be taken into account. As a consequence from our results, the GDR-MONICA-center has started a research programme which uses a complex system of diagnostic methods, among them the following conceptions: --Health knowledge/Attitudes --Social support/social network variables --Vital exhaustion --Life events --mediating personality factors (Type-A behaviour pattern etc.) together with other lifestyle-related factors, for instance physical activity, nutrition and smoking habits. Results from this multifactorial and integrative MONICA-Psychosocial study can be expected in the near future.

Adult↗

[Suicidal digitalis poisoning: considerations concerning treatment strategy with antibodies].

Suicidal digitalis poisoning is life-threatening and often has a fatal outcome. The treatment and clinical course of acute poisoning with 250 mg digitoxin in a depressive male patient aged 48 years are reported. Marked elevation of serum digitoxin level (360 nmol/l 8 hours after ingestion) and initial hyperkalemia (5.7 mmol/l) as well as the history of excessive dose intake, pointed toward severe intoxication. Mainstays of management with favourable outcome were vomiting and gastric lavage, followed by administration of repeated doses of digoxin-specific Fab antibody fragments. Evaluation of severity of poisoning and recommended supportive measures in digitalis overdose suicide victims are summarized and practical features of antibody preparations are discussed.

Digitoxin↗

cDNA cloning demonstrates the expression of pregnancy-specific glycoprotein genes, a subgroup of the carcinoembryonic antigen gene family, in fetal liver.

The pregnancy-specific glycoprotein (PSG) genes constitute a subgroup of the carcinoembryonic antigen (CEA) gene family. Here we report the cloning of four cDNAs coding for different members of the PSG family from a human fetal liver cDNA library. They are derived from three closely related genes (PSG1, PSG4 and PSG6). Two of the cDNA clones represent splice variants of PSG1 (PSG1a, PSG1d) differing in their C-terminal domain and 3'-untranslated regions. All encoded proteins show the same domain arrangement (N-RA1-RA2-RB2-C). Transcripts of the genes PSG1 and PSG4 could be detected in placenta by hybridization with gene-specific oligonucleotides. Expression of cDNA in a mouse and monkey cell line shows that the glycosylated PSG1a protein has a Mr of 65-66 kD and is released from the transfected cells. Sequence comparisons in the C-terminal domain and the 3'-untranslated regions of CEA/PSG-like genes suggests a complex splicing pattern to exist for various gene family members and a common evolutionary origin of these regions.

Amino Acid Sequence↗

Pharmacokinetics of isosorbide dinitrate, isosorbide-2-nitrate and isosorbide-5-nitrate in renal insufficiency after repeated oral dosage.

The pharmacokinetics of isosorbide dinitrate (ISDN) and its two active metabolites isosorbide-2-nitrate (IS-2-N) and isosorbide-5-nitrate (IS-5-N) were studied in 20 patients with normal and impaired renal function after repeated oral doses of standard 20 mg tablets ISDN t.i.d. Blood samples were taken in the steady-state on days 2 and 14, and the plasma concentrations were measured by electron capture capillary gas chromatography. We found a wide variation of pharmacokinetic parameters (AUCss0-8 and t1/2) of ISDN, IS-2-N, and IS-5-N in our patients. No correlation was detected between AUCss0-8 or t1/2 and the degree of renal insufficiency. No drug accumulation was observed after 14 days of administration.

Administration, Oral↗

Comparison of sympatho-adrenergic regulation at rest and of the adrenoceptor system in swimmers, long-distance runners, weight lifters, wrestlers and untrained men.

The effects of different physical training regimes on the plasma catecholamine values at rest and the density and responsiveness of adrenergic receptors at rest were investigated. The changes during well-defined training periods of swimmers, long-distance runners, weight lifters and wrestlers were compared with untrained male volunteers. The training of swimmers and long-distance runners, building up endurance, resulted in a significantly lower basal plasma norepinephrine (NE) concentration and a significantly or possibly lower ratio NE:EPI (epinephrine). Both values indicated reduced sympathetic activity and resulted also in a significantly lower beta-receptor density and a higher alpha 2-receptor sensitivity compared with the other groups investigated. However, swimming-specific characteristics provoked labile hypertensive blood pressure regulation with an unchanged heart rate in swimmers. Static training of weight lifters, building up power, also led to a lower NE concentration compared with untrained subjects, whereas beta-receptor density was unchanged and alpha 2-receptor density and sensitivity were decreased. Elevated blood pressure values were observed in weight lifters and swimmers due to a reduced baroreceptor sensitivity. The dynamic training of wrestlers affected only basal heart rate and alpha 2-receptor sensitivity, both of which were decreased. Different kinds of physical training caused various adaptations of the basal activity of the autonomic nervous system in which adrenergic receptors also became adapted. In this context, the stronger adrenergic circulatory component of overall sympathetic activity at rest in swimmers and long-distance runners resulted in lower beta-receptor density, and the reduced noradrenergic component sensitized alpha 2-receptors.

Adenylyl Cyclases↗

Identification of 5 beta-pregnane and 5 beta-androstane derivatives in adrenal venous and peripheral blood plasma of the female possum (Trichosurus vulpecula).

In the possum a marked sex difference has been found in the steroids in adrenal venous plasma. Four 5 beta-pregnane and four 5 alpha (beta) androstane derivatives together with ten 4-ene-3-keto steroids were isolated from the adrenal venous plasma of the female and definitively identified by gas chromatography-mass spectrometry. The major reduced steroids were: 5 beta-pregnane-3 alpha,17 alpha-diol-20-one and 5 beta-pregnane-3 alpha,17 alpha,20 alpha-triol, at concentrations of 52 +/- 12 micrograms/100 ml and 44 +/- 8 micrograms/100 ml mean +/- SEM respectively. The concentration of cortisol was 198 +/- 47 micrograms/100 ml. The concentration of the 2 reduced steroids in peripheral plasma were approx. 100 times less. In contrast the adrenal venous plasma of a male contained 14 steroids of which only three, found in trace amounts, were reduced. The results confirm previous in vitro observations that reduced steroids are produced by the adrenocortical special zone, which is only present in the female. The physiological significance of the presence of reduced steroids of adrenocortical origin in the circulation of the female possum is discussed.

Adrenal Glands↗