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M Biel

Publications and source records attributed to M Biel.

49 records · Page 3Linked to original sources

Tissue-specific expression of high-voltage-activated dihydropyridine-sensitive L-type calcium channels.

The cloning of the cDNA for the alpha 1 subunit of L-type calcium channels revealed that at least two genes (CaCh1 and CaCh2) exist which give rise to several splice variants. The expression of mRNA for these alpha 1 subunits and the skeletal muscle alpha 2/delta, beta and gamma subunits was studied in rabbit tissues and BC3H1 cells. Nucleic-acid-hybridization studies showed that the mRNA of all subunits are expressed in skeletal muscle, brain, heart and aorta. However, the alpha 1-, beta- and gamma-specific transcripts had different sizes in these tissues. Smooth muscle and heart contain different splice variants of the CaCh2 gene. The alpha 1, beta and gamma mRNA are expressed together in differentiated but not in proliferating BC3H1 cells. A probe specific for the skeletal muscle alpha 2/delta subunit did not hybridize to poly(A)-rich RNA from BC3H1 cells. These results suggest that different splice variants of the genes for the alpha 1, beta and gamma subunits exist in tissues containing L-type calcium channels, and that their expression is regulated in a coordinate manner.

Amino Acid Sequence↗

High voltage activated calcium channels: molecular composition and function.

Voltage-activated calcium channels comprise a group of similar yet distinct proteins or protein complexes that differ in electrophysiological properties, modulation by phosphorylation and GTP-binding proteins and in their relative sensitivity to organic calcium channel blockers. Cloning of the cDNA of L-type calcium channels from skeletal muscle, heart and smooth muscle opens the way to understanding the molecular basis of channel function and regulation and provides means of studying calcium channels in other tissues.

Animals↗

Primary structure of the beta subunit of the DHP-sensitive calcium channel from skeletal muscle.

Complementary DNAs for the beta subunit of the dihydropyridine-sensitive calcium channel of rabbit skeletal muscle were isolated on the basis of peptide sequences derived from the purified protein. The deduced primary structure is without homology to other known protein sequences and is consistent with the beta subunit being a peripheral membrane protein associated with the cytoplasmic aspect of the sarcolemma. The protein contains sites that might be expected to be preferentially phosphorylated by protein kinase C and guanosine 3',5'-monophosphate-dependent protein kinase. A messenger RNA for this protein appears to be expressed in brain.

Amino Acid Sequence↗

Neurologists' knowledge of medication costs.

Using mailed questionnaires, neurologists were asked for (1) estimates of retail prices for 39 common drugs, (2) attitudes about drug costs, and (3) implications for clinical practice. Among these practitioners, (1) more product prices were overestimated than underestimated, (2) old products were as unfamiliar as new products, and (3) community practitioners were more aware of prices than academic neurologists and trainees, but still made errors. Future studies should also consider physician prescribing behavior in terms of adherence to recommended laboratory tests and patient inconvenience factors. Neurologists should be aware of alternative prescription outlets for patients.

Drug Prescriptions↗

Maintenance of fetal hemoglobin (HbF) elevations in the baboon by prolonged erythropoietic stress.

We have previously shown that acute erythropoietic (Ep) stress by hemolysis or hypobaric hypoxia causes elevations of HbF in the baboon. The magnitude of these elevations is genetically determined, ranging from 3% to 60% (low, intermediate, and high responders). These genetic differences in HbF levels among animals are mainly due to differences in the number of HbF-containing cells ("F-cells"). The present study was undertaken to study the influence of prolongation and of the severity of Ep stress on HbF levels and the number of F-cells. The packed cell volume (PCV) of the blood of 4 animals, approximately 3 yr old, was maintained at 20% by daily phlebotomies, and the animals were exposed to varying degrees of hypobaric hypoxia for up to 40 days. In these experiments, the number of F-cells increased rapidly and reached individually constant levels ranging from 60% to 80%, when the PCV reached 20%, and no further increase was observed regardless of the subsequent degree of hypoxia. On the other hand, HbF levels, and with it the values for HbF per F-cell, increased proportionally to the severity of the Ep stress and could be maintained at a constant level dependent on the degree of the hypoxia, e.g., at 19,000 feet HbF levels of one animal remained 20%-25% throughout the duration of the exposure of 14 days. These data are indicative of separate control of F-cell numbers and of the levels of HbF per F-cell. It appears that with the increase of Ep stress, those Ep stem cells that have retained the HbF program are mobilized into maturation. A model, attempting to explain this phenomenon is presented.

Anemia, Hemolytic↗

Genetic relationship between fetal Hb levels in normal and erythropoietically stressed baboons.

Previous studies have shown that the magnitude of the fetal haemoglobin (Hb F) response to haemolytic anaemia and hypobaric hypoxia in the baboon is specific to an animal ('high and low Hb F responders'), suggesting that the Hb F response is under genetic control. In this study Hb F levels in 55 adult (over 8 years old) and 23 juvenile unstressed baboons varied between 0.02% and 0.6% ('resting Hb F levels'). Twenty-nine of these animals were subjected to haemolytic stress and the magnitude of their Hb F response was positively correlated with the resting Hb F levels. In addition, the resting levels of Hb F in parents were positively correlated with those of their offspring. In 11 animals, seven adults and four juveniles, subjected to haemopoietic stress the Hb F levels were increased proportionally to the number of F-cells. In juvenile animals the calculated concentration of Hb F per F-cell was markedly higher than in adult animals. These data demonstrate that the resting level of Hb F is predictive of the magnitude of the Hb F response to stress erythropoiesis. The number of F-cells and the concentration of Hb F per cell in erythropoietic stress appear to be modulated by different mechanisms.

Anemia, Hemolytic↗

Differential distribution of four hyperpolarization-activated cation channels in mouse brain.

Hyperpolarization-activated cation currents, termed I(h), are observed in a variety of neurons. Four members of a gene family encoding hyperpolarization-activated cyclic-nucleotide-gated cation channels (HCN1-4) have been cloned. The regional expression and cellular localization of the four HCN channel types in mouse brain was investigated using in situ hybridization. The expression of HCN1 was restricted to the olfactory bulb, cerebral cortex, hippocampus, superior colliculus and cerebellum. In contrast, HCN2 transcripts were found at high levels nearly ubiquitously in the brain, and the strongest signals were seen in the olfactory bulb, hippocampus, thalamus and brain stem. HCN3 was uniformly expressed at very low levels throughout the brain. Finally, HCN4 transcripts were prominently expressed selectively in the thalamus and olfactory bulb. Some neurons expressed two or more HCN channel transcripts including hippocampal pyramidal neurons (HCN1, HCN2 and low levels of HCN 4) and thalamic relay neurons (HCN2 and HCN4). Our results demonstrate that each HCN channel transcript has a unique distribution in the brain. Furthermore, they suggest that the heterogeneity of neuronal I(h) may be, at least in part, due to the differential expression of HCN channel genes.

Amino Acid Sequence↗