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Biomedical subjects

A Schwartz

Publications and source records attributed to A Schwartz.

At least 343 records · Page 19Linked to original sources
PubMed1988

Vasodilatory action of amlodipine on rat aorta, pig coronary artery, human coronary artery, and on isolated Langendorff rat heart preparations.

Amlodipine inhibited contractions of rat aortic rings induced by 40 mM KCl (IC50 = 7.5 x 10(-9) M). The time to attain the maximum inhibitory effect of KCl-induced contractions was long (hours) and dependent on the concentration of amlodipine. After 6 h of washing in drug-free normal Krebs-Ringer solution the contractions recovered only partially. The KCl-induced contractions appeared to be more sensitive to inhibition by amlodipine than were norepinephrine-induced contractions. CaCl2-induced contraction of KCl-depolarized aortic rings was inhibited by amlodipine in a complex manner. Amlodipine not only increased ED50 but also inhibited the maximal tension induced by CaCl2. Amlodipine also inhibited 35 mM KCl-induced contractions of pig coronary artery rings (IC50 = 2.2 x 10(-8) M) and human coronary artery rings (IC50 = 2.1 x 10(-8) M). In Langendorff rat heart preparations, low concentrations of amlodipine increased coronary flow (ED50, 10(-9) M) whereas higher concentrations (greater than 10(-7) M) decreased coronary flow. Amlodipine also decreased the rate of contraction (+ dP/dt, IC50 = 3 x 10(-7) M) and the rate of relaxation (-dP/dt, IC50 = 1.2 x 10(-7) M). Amlodipine decreased heart rate but only at high concentrations (greater than 300 nM). The results of this study indicate that amlodipine is a potent vasodilator with similar cardiovascular actions to other dihydropyridines except that its effects are slower in onset and longer lasting.

Amlodipine↗
PubMed1988

A clinical diagnostic model for the assessment of asbestosis: a new algorithmic approach.

Asbestosis, one of the pneumoconioses that is defined by a set of clinical, radiographic, and pathologic findings, occurs as a result of exposure to asbestos fibers. Several approaches have attempted to describe the presence, progression, or extent of asbestosis. However, these approaches have attempted to describe the presence, progression, or extent of asbestosis. However, these approaches have limitations or lack correlations with other diagnostic modalities. We propose a comprehensive clinical diagnostic model that uses the sensitivities and specificities of the various clinical, radiographic, and pathologic findings to generate a set of "likelihood numbers." These likelihood numbers, contribute to the calculation of a value that can indicate the probability of asbestosis. The clinical diagnostic model is heuristic in that a specific feature supportive of the diagnosis of asbestosis may be tested as to its sensitivity and specificity, and new features may be added to the model. The model also indicates how probabilistic a given set of findings is in the diagnosis of asbestosis and suggests what additional data may make the diagnosis more or less statistically probable. Regarding the radiologic considerations of asbestosis, the strength of the clinical diagnostic model is that it is capable of supporting a diagnosis of asbestosis in the presence of a normal chest radiograph and, conversely, may reject the diagnosis of asbestosis despite the radiographic finding of pulmonary fibrosis.

Algorithms↗
PubMed1988

Calcium Effects on Stomatal Movement in Commelina communis L. : Use of EGTA to Modulate Stomatal Response to Light, KCl and CO(2).

Stomatal movements depend on both ion influx and efflux; attainment of steady state apertures reflects modulation of either or both processes. The role of Ca(2+) in those two processes was investigated in isolated epidermal strips of Commelina communis, using the Ca(2+) chelator EGTA to reduce apoplastic [Ca(2+)]. The results suggest that a certain concentration of Ca(2+) is an absolute requirement for salt efflux and stomatal closure. EGTA (2 millimolar) increased KCl-dependent stomatal opening in darkness and completely inhibited the dark-induced closure of initially open stomata. Closure was inhibited even in a KCl-free medium. Thus, maintenance of stomata in the open state does not necessarily depend on continued K(+) influx but on the inhibition of salt efflux. Opening in the dark was stimulated by IAA in a concentration-dependent manner, up to 15.4 micrometer without reaching saturation, while the response to EGTA leveled off at 9.2 micrometer. IAA did not inhibit stomatal closure to the extent it stimulated opening. The response to IAA is thus consistent with a primary stimulation of opening, while EGTA can be considered a specific inhibitor of stomatal closing since it inhibits closure to a much larger degree than it stimulates opening. CO(2) causes concentration-dependent reduction in the steady state stomatal aperture. EGTA completely reversed CO(2)-induced closing of open stomata but only partially prevented the inhibition of opening.

Journal Article↗
PubMed1988

Roentgenographic underestimation of early asbestosis by International Labor Organization classification. Analysis of data and probabilities.

We analyzed the limitations of the International Labor Organization (ILO) classification of chest roentgenograms in predicting the presence of histologically determined early asbestosis. The ILO system is arbitrary, without histologic correlates, and does not consider the asbestos exposure history or clinical and laboratory information. We present data from the literature and our own work which demonstrate that the application of the ILO classification to an asbestos-exposed individual can result in a 10 to 20 percent probability of a "normal" roentgenographic interpretation in the presence of significant asbestosis at the histologic level, leading to an inappropriate conclusion regarding the presence of asbestosis. In view of the data and statistical analysis presented, we suggest that sole reliance upon the ILO classified chest roentgenogram for determination of the presence of early pulmonary asbestosis in individual cases is inappropriate.

Asbestosis↗
PubMed1988

Action of diltiazem on excitation-contraction coupling in bullfrog skeletal muscle fibers.

In this study the calcium antagonist drug diltiazem was found to produce twitch potentiation, lower the mechanical threshold potential and block inward calcium currents in bullfrog skeletal muscle fibers. Under tonic conditions (stimulation either every 1 or 2 min) high concentrations of diltiazem were required to enhance twitch tension (ED50 = 249 microM) and block calcium currents (IC50 = 190 microM). In addition, 100 microM diltiazem lowered the mechanical threshold rheobase potential from -49.3 to -57.0 mV. At higher rates of stimulation, concentrations of diltiazem as low as 1 and 10 microM, which had no tonic action, were found to produce twitch potentiation and calcium channel block, respectively. Onset and washout of tonic and frequency-dependent actions of diltiazem on twitch and current amplitude occurred over a similar time course. It is proposed that the mechanical potentiation, as well as the calcium channel block produced by diltiazem, result from the interaction of diltiazem with the same or similar receptor site(s).

Animals↗
PubMed1988

Stereoselective effect of diltiazem on endothelium-dependent relaxations in canine femoral arteries.

Experiments were designed to analyze potential interactions between voltage-dependent calcium channel blockers and endothelium-dependent vascular responses. Rings of canine femoral artery were suspended for isometric force recording in organ chambers and contracted with prostaglandin F2 alpha. Removal of the endothelium had no effect on relaxations induced by d-cis-diltiazem (active stereoisomer), verapamil or nimodipine. When rings with endothelium were first partially relaxed with acetylcholine or the calcium ionophore A23187 the concentration-relaxation curve to d-cis-diltiazem (but not to verapamil or nimodipine) was significantly shifted to the right. Partial relaxation of femoral arterial rings without endothelium by sodium nitroprusside had no effect on relaxations evoked by diltiazem. Pretreatment with diltiazem (10(-6) M) had no effect on endothelium-dependent relaxations to acetylcholine in femoral artery rings. D-cis-Diltiazem partially reversed the relaxation induced by acetylcholine in a bioassay system, in which a ring of canine coronary artery without endothelium was superfused by solution passing through a segment of femoral artery with endothelium. D-cis-Diltiazem relaxed the bioassay ring when infused downstream of the perfused femoral artery with, or upstream of a femoral artery without endothelium. The effect of diltiazem was stereoselective (the less active l-cis-diltiazem had no effect). Verapamil did not reverse the relaxation induced by acetylcholine and did not affect the reversal induced by diltiazem. These findings indicate that diltiazem specifically antagonizes the production and/or the release of endothelium-derived relaxing factor(s) stimulated by acetylcholine or A23187 in canine femoral arteries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Functional evidence in diseased human heart fibers for multiple sensitivities of the inotropic ouabain receptor Na+,K+-ATPase (NKA).

Through contributions of many investigators from our group at the University of Cincinnati Medical Center, several facts emerged. It is clear that the rat ventricle has 2 inotropic sensitivities to ouabain (Grupp et al., 1981), related to high and low affinity ouabain binding sites (Adams et al., 1982) and the presence of an appropriate abundance of alpha and alpha + catalytic subunits of NKA (Young and Lingrel, 1987). The rat atria which demonstrate only the low affinity inotropic response (Grupp et al., 1981) also show the alpha catalytic subunit in vast predominance, with little or no alpha + (Young and Lingrel, 1987). This scheme has now also been confirmed in the ferret (Ng and Akera, 1987). By analogy, we suggest that the possibility exists that in diseased hearts part of the normally prevailing alpha catalytic subunit (sensitivity in normal human fibers about 140 nM ouabain) is converted to a more sensitive alpha + catalytic subunit leading to an increase of the ouabain sensitivity to about 50 nM. There is also an earlier occurrence of toxic effects and a reduction of the number of low affinity (alpha) ouabain binding sites, resulting in a decrease of the maximally achievable contractile force effect of ouabain. This hypothesis is presently being tested in the genetics laboratory of the University of Cincinnati Medical Center where the relative abundance of the alpha, alpha + and perhaps other isoforms of the NKA are being determined in the tissues of the same hearts from which the trabeculae used in this study were obtained.

Heart Atria↗
PubMed1988

The calcium dependence of the biphasic inotropic response to ouabain in the isolated rat heart.

From the results of this study the following significant conclusions can be drawn. First, there are two separate inotropic responses to ouabain in the rat ventricle and the isolated rat heart resulting in a biphasic dose-response curve. Second, both the "low dose" and "high dose" inotropic responses of ouabain in the rat heart result from the inhibition of NKA, i.e., NKA is the binding site of ouabain for both "low" and "high" dose effects. Third, biphasic inotropic effects (rat ventricle) go together with alpha + and alpha (high and low affinity) isoforms of NKA, monophasic (rat atrium) with the alpha isoform (low affinity). Fourth, high extracellular calcium concentrations inhibit NKA and mask the full expression of the "low-dos" effect.

Animals↗
PubMed1988

Role of the Na+K+-ATPase in the cardiotonic action of cardiac glycosides.

In terms of evolution, the Na+,K+-ATPase is one of the oldest proteins. It is intriguing that this membrane-based enzyme has become biologically consistent with a multifunctional protein. One of the most interesting aspects of the Na+,K+-ATPase is that it contains a specific receptor domain for the oldest plant origin cardiotonic drug and that it is involved in the regulation of myocardial contractility.

Animals↗
PubMed1988

A study of androgen-resistant subjects indicates that the 6.7 pI/56 kDa protein in genital skin fibroblasts is related to the androgen receptor.

Two-dimensional gel electrophoresis of cultured human skin fibroblast lysates reveals a silver-stained "spot" of molecular mass 56 kilodaltons (kDa) and isoelectric point (pI) 6.7, occasionally as part of a doublet with a minor pI 6.5 partner. Its presence in each of 23 genital skin fibroblast strains (6 labium majus, 17 prepuce) and its absence in 30 of 32 control non-genital skin fibroblast strains accords with the 3-fold greater concentration of androgen-receptor activity in the former. However, the size and intensity of the spot do not change when cells are preincubated for 48 hours with 3 nM methyltrienolone (MT, a non-metabolizable androgen), and it is pulse-labeled with [35S]methionine to an autoradiographically equal extent, with or without incubation in 3 nM MT for 2 or 16 hours. Furthermore, the protein identified by the spot is found in the labium majus skin fibroblast strains from 2 of 12 unrelated subjects with complete androgen resistance due to negligible androgen-receptor activity, but it is absent from those of 2 others who have the same phenotype despite a normal level of qualitatively abnormal androgen-receptor activity. Hence, it is very unlikely to be an androgen-induced protein, and it cannot be a functional version of the androgen receptor itself. Its absence in 12 of 14 labium majus strains of subjects with complete androgen resistance, regardless of 5 alpha-reductase activities, indicates that it is neither a constitutive cytotypic marker of genital skin fibroblast differentiation nor a reflection of that enzyme. When intact prepuce fibroblasts are covalently labeled by photolysis with 50 nM [3H]MT, the only specific labeling detectable after two-dimensional electrophoresis is in the 6.7 and 6.5 pI doublet of the 56 kDa protein. Considering the sensitivity of silver staining and the incomplete concordance between the androgen-receptor activity of a strain and the size/intensity of its 6.7 pI/56 kDa spot on the gels, we postulate the latter to be a comparatively abundant androgen-binding protein that is causally related to the androgen receptor. The precise nature of this relation remains to be elucidated by use of novel immunologic and/or nucleic acid probes for this protein and for the mature androgen receptor. In any event, the presence or absence of the 6.7 pI/56 kDa protein in genital skin fibroblast lysates is a new marker of genetic heterogeneity within the class of complete androgen resistance.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1987

[Lipid myopathy: a heterogenic familial case].

A case is reported of lipid storage myopathy in a 24-year-old patient and her family. In the patient and an aunt, muscle biopsy disclosed intrafibrillar lipid depositions, and electron microscopy revealed lipid vesicles in the sarcolemma border. In the father, no lipid depositions were observed but electron microscopy showed alterations to mitochondria compatible with a mitochondrial myopathy. In the patient muscular biochemistry revealed a major reduction in NADH oxydase activity and in the aunt a diminished level of carnitin compatible with carnitin deficiency. The heterogeneity of these lipidic myopathies is discussed.

Adult↗
PubMed1987

Calcium channel activity in a purified dihydropyridine-receptor preparation of skeletal muscle.

A purified dihydropyridine-receptor complex (DHPR) of skeletal muscle consisting of a major polypeptide of Mr 150K under reducing conditions induces divalent cation selective channels when incorporated into planar lipid bilayers. Channels were inserted into preformed planar bilayers by two techniques: (i) direct dilution of detergent-solubilized DHPR into the aqueous chambers adjacent to the bilayer membrane or (ii) reconstitution of DHPR into phospholipid vesicles followed by fusion of the preformed vesicles to the planar bilayer membrane. Unlike native membrane preparations of t-tubules, which only have one major Ca channel type of slope conductance of 12 pS in symmetrical 100 mM Ba, the purified DHPR complex induced at least two channel types with conductances of 12-14 and 22 pS. Some recordings suggest that these two channels are statistically coupled in time, i.e., that they may correspond to substrates of the same DHPR channel. Activity was found to occur spontaneously in the absence of the Ca channel agonist Bay k 8644. The 12-14-pS channel from DHPR exhibits voltage-dependent kinetics, is highly selective for barium ions, and was inhibited by micromolar nitrendipine. The 12-14-pS DHPR channel appears to be identical with functional Ca channels previously described in native t-tubules.

Animals↗
PubMed1987

Identification of a novel 1,4-dihydropyridine- and phenylalkylamine-binding polypeptide in calcium channel preparations.

A 1,4-dihydropyridine- and phenylalkylamine-binding polypeptide has been identified by photoaffinity labeling of purified rabbit and guinea pig skeletal muscle calcium channel preparations. The arylazide ligands (-)-[3H]azidopine and (-)-5-[(3-azidophenethyl)[N-methyl-3H]methylamino]-2-(3,4,5- trimethoxyphenyl)-2-isopropylvaleronitrile [( N-methyl-3H]LU 49888) were used to label 1,4-dihydropyridine- and phenylalkylamine-binding sites, respectively. A single, 155 to 170-kDa polypeptide was specifically labeled by both ligands in rabbit and guinea pig preparations provided that the skeletal muscle membranes used for purification were derived from fresh and not previously frozen and thawed tissue. The photoaffinity labeled polypeptide (termed here alpha 1) is different from the previously described alpha subunit in that it has the identical electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels irrespective of pretreatment either with N-ethylmaleimide or with dithiothreitol. The use of transverse tubular membranes isolated from previously frozen and thawed skeletal muscle results in a purified calcium channel preparation devoid of the alpha 1 subunit. In these preparations proteolytic degradation products of alpha 1 are labeled with both (-)-[3H]azidopine and [N-methyl-3H]LU 49888. Another large molecular weight polypeptide (termed here alpha 2) was also present in every purified calcium channel preparation studied. alpha 2 is distinct from alpha 1 in that reduction with dithiothreitol changes its apparent mass from 160-190 to 130-150 kDa. The alpha 2 subunit is not photoaffinity labeled either with (-)-[3H]azidopine or [N-methyl-3H]LU 49888. These data suggest that two distinct high molecular weight polypeptides (termed alpha 1 and alpha 2) are putative subunits of skeletal muscle calcium channels. Only the alpha 1 subunit contains both 1,4-dihydropyridine and phenylalkylamine receptors. alpha 2 is the same as the previously described alpha subunit (Curtis, B. M., and Catterall, W. A. (1984) Biochemistry 23, 2113-2118), but is neither a 1,4-dihydropyridine- nor a phenylalkylamine-binding protein.

Animals↗
PubMed1987

Paradoxical augmentation of (-)Bay K 8644-induced calcium influx by nitrendipine.

(-)Bay K 8644 produced a concentration-dependent contraction of porcine coronary artery rings with the maximal contraction at 10(-6) M. Pretreatment of the rings with 10(-6) M nitrendipine inhibited (-)Bay K 8644-induced contraction, while pretreatment with 10(-8) M nitrendipine potentiated the contraction elicited by (-)Bay K 8644. (-)Bay K 8644 (10(-6) M) significantly stimulated Ca2+ influx. Although 10(-8) M nitrendipine never stimulated Ca2+ influx, Ca2+ influx induced by (-)Bay K 8644 was significantly potentiated by pretreatment with 10(-8) M nitrendipine. Pretreatment with 10(-6) M nitrendipine significantly decreased Ca2+ influx in tissues treated with (-)Bay K 8644. Our results suggest that the increased Ca2+ influx might be involved in the mechanisms by which (-)Bay K 8644-induced contraction was potentiated by pretreatment with nitrendipine.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1987

Purification of putative Ca2+ channel protein from rabbit skeletal muscle. Determination of the amino-terminal sequence.

A putative Ca2+ channel protein was purified from rabbit skeletal muscle transverse tubules with the combined use of lectin affinity chromatography and ion-exchange chromatography, followed by sucrose density gradient centrifugation. The major component of the purified preparation detected by sodium dodecyl sulfate-gel electrophoresis was a protein of 150 kDa when reduced with 20 mM dithiothreitol and a 191-kDa protein when treated with 20 mM N-ethylmaleimide. Therefore, this protein appears to be identical with the alpha subunit previously described (Curtis, B. M., and Catterall, W. A. (1984) Biochemistry 23, 2113-2118). This protein was purified by preparative sodium dodecyl sulfate-gel electrophoresis, followed by electroelution and/or electroblotting, and its amino acid composition and NH2-terminal sequence were determined. The NH2-terminal sequence is: NH2-Glu-Pro-Phe-Pro-Ser-Ala-Val-X-Ile-Lys-Ser-X-Val-X-Lys-Met-Gln-.

Amino Acid Sequence↗