Biomedical subjects
A Schmid
Publications and source records attributed to A Schmid.
The nitrendipine-sensitive Ca2+ channel in chick muscle cells and its appearance during myogenesis in vitro and in vivo.
The nitrendipine-sensitive Ca2+ channel of chick skeletal myotubes in culture has been studied using both the 45Ca2+ flux technique and [3H]nitrendipine binding experiments. Ca2+ uptake is insensitive to nitrendipine when chick myotubes in culture are polarized. Whereas depolarization reveals a new component of 45Ca2+ influx which is inhibited by nitrendipine. Half-maximal inhibition occurs at a nitrendipine concentration of 0.7 nM. This value is similar to the dissociation constant Kd = 0.4 nM found in [3H]nitrendipine binding experiments. During myogenesis in vitro the nitrendipine receptor is absent in myoblasts and appears in parallel with the fusion process. Two stages of increased binding have been observed in vivo. The first one, which occurs during embryonic life, has the same properties as in the in vitro development. The second stage occurs near hatching and corresponds to a large increase in the number of nitrendipine receptors. This increase is accompanied by a decrease of affinity of nitrendipine for its receptor by a factor of 4 to 10. Chronic denervation produces a further increase in the number of nitrendipine receptors which reaches a factor of about 2 at 15 days of denervation. Results are discussed in relation to the particular localization of these channels in transverse tubules and with the innervation.
Comparative changes of levels of nitrendipine Ca2+ channels, of tetrodotoxin-sensitive Na+ channels and of ouabain-sensitive (Na+ + K+)-ATPase following denervation of rat and chick skeletal muscle.
Three major ion transport systems, the nitrendipine-sensitive Ca2+ channels, the tetrodotoxin-sensitive Na+ channel and the ouabain-sensitive (Na+ + K+)-ATPase, have been studied in skeletal muscle from rat and chick after chronic denervation. It is shown that the situation found for the Ca2+ channel differs dramatically from that found for the Na+ channel and the (Na+ + K+)-ATPase and that regulation of the nitrendipine-sensitive Ca2+ channel in denervated muscle also differs widely from that of the tetrodotoxin-sensitive Na+ channel and the ouabain-sensitive (Na+ + K+)-ATPase which show a quite similar evolution.
[Ultrastructure of diabetic autonomic neuropathy of the gastrointestinal tract].
Gastrointestinal motility disorders induced by diabetes mellitus are most commonly manifested in the colon, and are considered to be an expression of diabetic autonomic polyneuropathy. In this study, for the first time, the intrinsic nervous system of the bowel has been subjected to an ultrastructural and morphometric examination in rectal biopsy material obtained from diabetics with and without diabetic enteropathy. In patients with diabetic enteropathy, the nerves of the submucous plexus (Meissner's plexus) revealed significant swelling of the axons, as an expression of neural degeneration. Furthermore, in about a half of these patients, thickening of the basal membrane of Schwann's cells was also detected. Additional, although unspecific, changes found in the diabetics were a quantitative increase in the lysosomes, lipofuscin and glycogen in the Schwann cells. The ultrastructural findings represent evidence for the presence of an intrinsic autonomic polyneuropathy in diabetics with diabetic enteropathy. At the same time, they indicate that the diagnosis of diabetic enteropathy is no longer merely an "exclusion" diagnosis.
Differentiation of receptor sites for [3H]nitrendipine in chick hearts and physiological relation to the slow Ca2+ channel and to excitation-contraction coupling.
The properties of interaction of the Ca2+ channel antagonist [3H]nitrendipine have been investigated in chick hearts at various stages of in ovo and post-natal development and in cultured cells. The dissociation constant of the [3H]nitrendipine-receptor complex is between 0.4 nM and 0.5 nM for intact ventricle and cultured cells. [3H]Nitrendipine binding is antagonized by nitrendipine analogs. The order of efficacy of the different dihydropyridine molecules is nitrendipine greater than nimodipine greater than nifedipine greater than nisoldipine with Kd values ranging from 0.5 to 4 nM. Inhibition of [3H]nitrendipine binding by other antiarrhythmic molecules like amiodarone, F13004 and bepridil was observed. Half-maximum inhibitions (K0.5) were found for verapamil and D600 at concentrations between 0.23 and 0.26 microM. The potency of organic Ca2+ blockers to depress by 50% the maximum amplitude of spontaneous beating of heart cells is closely related to K0.5 values obtained from [3H]nitrendipine binding experiments. Electrophysiological results indicate that the slow channel is insensitive to nitrendipine at the younger stage of development (3-day-old) whereas, in adult like cells, nitrendipine (50 nM) abolished both slow action potential due to the slow Ca2+ channel and contraction. The maximum binding capacity for [3H]nitrendipine is found to increase during development of the embryonic heart from 40 fmol/mg protein at day 3 to 100 fmol/mg protein at day 14, to stay relatively stable until day 18. Then the number of sites increases rapidly to reach a second plateau at 210 fmol/mg protein on day 4 after hatching. Treatment with 6-hydroxydopamine results in 35% increase in [3H]nitrendipine binding, whereas reserpine treatment is without effect. Developmental properties of nitrendipine-sensitive Ca2+ channels have been compared with those of tetrodotoxin-sensitive Na+ channels and muscarinic receptors. These results indicate that nitrendipine receptors exist at the early stage of development (3-day-old-hearts) but that they do not correspond to functional slow Ca2+ channels, that in ovo development corresponds both to an increase of the number of [3H]nitrendipine receptors and to the transformation of silent Ca2+ channels into functional Ca2+ channels, and that there is a regulation of the level nitrendipine-sensitive Ca2+ channels by innervation.
Cloning of DNA corresponding to four different measles virus genomic regions.
Hybrid plasmids containing sequences corresponding to four different regions of the measles virus genome inserted in pBR322 were obtained by use of polyadenylated 50 S viral RNA as template for reverse transcription. One class of plasmids contains inserts corresponding to the 3' terminal region of the virus genome. The sequence of one of these inserts (605 nucleotides) partially overlaps with the cloned cDNA sequence corresponding to a part of the nucleocapsid protein (N) mRNA (M. Gorecki and S. Rozenblatt (1980). Proc. Natl. Acad. Sci. USA 77, 3686-3690). This insert region shows only one long open reading frame defining the N-terminal part of the nucleocapsid protein. The nucleocapsid protein mRNA starts at about 60 nucleotides from the genome end as revealed by nuclease S1 mapping. Three other classes of plasmid clones contain inserts derived from unidentified regions of the viral genome; they hybridize with viral mRNA species less abundant than those from which cDNA clones have been isolated so far (S. Rozenblatt, C. Gesang, V. Lavie, and F. S. Neumann (1982) J. Virol. 42, 790-797.
Linear electrical properties of isolated cardiac cells.
A frequency domain equivalent circuit analysis of isolated ventricular cells indicated the presence of an internal membrane structure which has a total capacitance four- to sixfold larger than the surface membrane. The internal membrane was mainly attributed to the sarcoplasmic reticulum since other morphological studies have shown that its area is many-fold larger than that of the surface membrane. Corresponding estimates from the transverse tubular system indicate an area less than that of the surface; thus this structure is not a likely candidate for the observed internal capacitance. Measurements in hypertonic solutions showed that the access resistance to the internal membrane reversibly increased as the tonicity was elevated. Freeze-fractured electron microscopic studies confirmed that hypertonic solutions increased the volume of transverse tubular system, which thus appears to have little relation to the access resistance. The most probable source of the access resistance is the diadic junction to the sarcoplasmic reticulum, which therefore would electrically couple it to the surface membrane.
[Clinical experiences with the short-acting opioid alfentanil (Rapifen)].
Alfentanil (R 39 209, Rapifen), a new short-acting narcotic analgesic, has been used in five modifications of routine anaesthesia. The results of these observations are discussed, as well as the haemodynamic and pharmacokinetic data reported in literature. Rapid onset and short duration of action due to a short elimination half-life time and a low distribution volume offer new possibilities in anaesthesiology. In premedicated patients the drug provides analgesia for very short lasting procedures and can supplement hypnotics like etomidate, short-acting barbiturates and benzodiazepines, e.g. midazolam. Thus it becomes possible to obtain a very pleasant anaesthesia under controlled or assisted ventilation with nitrous oxide/oxygen for procedures of a short or mean duration without further need for volatile anaesthetics.
Ontogenic appearance of Ca2+ channels characterized as binding sites for nitrendipine during development of nervous, skeletal and cardiac muscle systems in the rat.
The appearance of specific receptors for the Ca2+ channel antagonist nitrendipine has been followed during the fetal and post-natal development of rat brain without cerebellum, cerebellum, skeletal muscle and cardiac muscle. The number of nitrendipine receptors is low at the fetal stage and increases drastically during post-natal development of brain, cerebellum, skeletal muscle and cardiac muscle. The time course of this increase is different for each type of tissue studied. No significant change in receptor ligand dissociation constant (Kd) can be detected over the development period studied. The results are discussed in relation with the known properties of the differentiation process in the four types of excitable tissues studied.
[Chloramphenicol residues in foods of animal origin as a potential cause of aplastic anemia in man].
The essential features of aplastic anemia by chloramphenicol are outlined. Then a detailed evaluation of possible chloramphenicol residues in foods of animal origin is given, showing that these residues may be either original chloramphenicol and/or numerous, partly radical, metabolites of chloramphenicol. Further discussion of the pathogenesis of aplastic anemia by chloramphenicol reveals that this anemia is the result of an inhibition of DNA synthesis in bone marrow by covalently bound chloramphenicol metabolites. The aromatic nitro group of chloramphenicol is but of indirect importance and does not take part in the binding of the molecule. The final critical examination of chloramphenicol residues demonstrates, that these residues amy potentially cause aplastic anemia only insofar as unchanged chloramphenicol or metabolites capable of being retransformed to it are present; the persistent, covalently bound residues occurring in animals and eventually in foods of animal origin are insignificant in this respect.
[Residues of chloramphenicol in food of animal origin as a possible cause of aplastic anemia in man].
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[Metabolic radical formation from halothane and enflurane and their modification by enzyme induction and inhibition].
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Molecular size of different neurotoxin receptors on the voltage-sensitive Na+ channel.
Measurements were made of the molecular sizes of two distinct receptors on the Na+ channel in rat brain synaptosomes that are specific for different neurotoxins. Radiation inactivation of the binding of radiolabeled derivatives of the toxins was consistent with Mr = 260,000 for the tetrodotoxin receptor and Mr = 266,000 for the receptor specific for two scorpion toxins, toxin II from Centruroides suffusus suffusus and toxin gamma from Tityus serrulatus serrulatus. Covalent cross-linking of the latter to its receptor similarly indicated Mr = 270,000. It seems most likely that these two distinct receptors reside on the same molecule.
[Pharmacological and toxicological evaluation of arsanilic acid and sodium arsanilate].
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Purification of binding protein for Tityus gamma toxin identified with the gating component of the voltage-sensitive Na+ channel.
The gating component associated with the voltage-sensitive Na+ channel from electroplax membranes of Electrophorus electricus has been purified by using toxin gamma from the venom of the scorpion Tityus serrulatus serrulatus. The toxin-binding site was efficiently solubilized with Lubrol PX, resulting in an extract of high initial specific activity. Purification was achieved by adsorption of the toxin-binding component to DEAE-Sephadex A-25 followed by desorption at high ionic strength and chromatography on either wheat germ agglutinin-Ultrogel or Sepharose 6B. Maximal final specific activities were at least 42% of the specific activity expected for a pure toxin-binding component. The purified material exhibited a Stokes radius of 85 A, and sodium dodecyl sulfate/polyacrylamide gel electrophoresis demonstrated a single polypeptide component of Mr 270,000. Furthermore, tetrodotoxin binding activity and Tityus gamma toxin binding activity copurified, suggesting that the selectivity filter and the gating component of the Na+ channel are carried by the same polypeptide chain.
[Mechanism of action of S-(dichlorovinyl)-L-cysteine].
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Tityus serrulatus venom contains two classes of toxins. Tityus gamma toxin is a new tool with a very high affinity for studying the Na+ channel.
The interaction of TiTx gamma, the major toxin in the venom of the scorpion Tityus serrulatus, with its receptor in excitable membranes was studied with the use of 125I-TiTx gamma. This derivative retains biological activity, and its specific binding to both brain synaptosomes and electroplaque membranes from Electrophorus electricus is characterized by a dissociation constant equal to that of the native toxin-receptor complex, about 2 to 5 pM. This very high affinity results mainly from a very slow rate of dissociation, equivalent to a half-life longer than 10 h at 4 degrees C. There is a 1:1 stoichiometry between TiTx gamma binding and tetrodotoxin binding to the membranes, but neither tetrodotoxin nor any of 7 other neurotoxins that are representative of 4 different classes of effectors of the Na+ channel interfere with TiTx gamma binding. Similarly, local anesthetics and other molecules that affect other types of ionic channels or neurotransmitter receptors have no effect on TiTx gamma binding. However, toxin II from Centruroides suffusus suffusus does compete with TiTx gamma, though its affinity for the receptor is much lower. Since the Centruroides toxin II is known to affect Na+ channel function, these two scorpion toxins must be put into a fifth class of Na+ channel effectors.
[Clinico-pathologic conference: anemia and kidney insufficiency in a 70-year-old female patient].
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