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Biomedical subjects

A Schwartz

Publications and source records attributed to A Schwartz.

At least 271 records · Page 15Linked to original sources

The beta subunit controls the gating and dihydropyridine sensitivity of the skeletal muscle Ca2+ channel.

The skeletal muscle (SKM) L-type Ca2+ channel is composed of a central subunit designated alpha 1, which contains the pore and the dihydropyridine (DHP) binding domains and three associated subunits, alpha 2/delta, beta, and gamma, which influence the activity of the SKM alpha 1. Coexpression of SKM alpha 1 and SKM beta in stably transfected mouse L cells results in a dramatic increase in DHP binding accompanied by fast gated Ba2+ currents. We report here that this "SKM alpha 1 beta-related phenotype" can be converted upon intracellular trypsin treatment into a slowly inactivating, DHP sensitive "SKM alpha 1 phenotype." These observations indicate that current amplitude, fast inactivation, and DHP sensitivity are modulated by an interaction of SKM alpha 1 and SKM beta on the internal side of the membrane.

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

[MR angiography of the vertebrobasilar circulatory area: the potential uses of the saturation technic to determine the direction of the flow].

MR angiography (MRA) combined with selective saturation techniques has proved to be a reliable method for the determination of flow direction and vascular supply at the level of the circle of Willis. We describe its application to the vertebrobasilar system (VBS) in ten volunteers and five patients with abnormal findings. In one patient with postsurgical stenosis of the brachiocephalic artery, reverse flow of the vertebral artery (VA) was demonstrated. Collateral blood flow from the anterior circulation over the posterior communicating arteries was shown in three patients with bilateral vertebral or proximal basilar artery occlusion. Due to increase of pressure during contrast injection into the contralateral VA, DSA showed reverse flow of a dissected VA in one patient. MR flow determination as well as TCD proved antegrade flow. All results correlated with both DSA and transcranial Doppler (TCD). The technique is little time consuming and is a promising add-on examination to conventional and MRA imaging of the VBS.

Adult↗

Dehydroepiandrosterone (DHEA) and synthetic DHEA analogs are modest inhibitors of HIV-1 IIIB replication.

Down-regulation of Epstein-Barr virus (EBV) induced transformation of human lymphocytes in vitro by dehydroepiandrosterone (DHEA), a naturally occurring human steroid secreted by the adrenal gland has been demonstrated. This article reports on the effects of DHEA and its novel synthetic analogs 16 alpha-fluoro-5-androsten-17-one (8354) and 3 beta-hydroxy-16 alpha-fluoro-5 alpha-androstan-17-one (OH8356) on human immunodeficiency virus (HIV-1) replication. Treatment with DHEA, 8354, or OH8356 resulted in a modest down-regulation of HIV-1 replication in phytohemagglutinin-stimulated peripheral blood lymphocytes as measured by syncytia formation, release of p24 antigen, and accumulation of reverse transcriptase activity. DHEA and 8354 also reduced syncytia formation in HIV-1-infected SupT1 lymphoblasts. DHEA and synthetic analogs of DHEA, which have been shown previously to have antiproliferative effects, now are shown to reduce HIV-1 replication. DHEA or synthetic analogs of DHEA could provide an alternative and/or adjuvant for HIV-1 infection.

Androstenes↗

Diminished in vitro production of interleukin-1 and tumor necrosis factor-alpha during acute visceral leishmaniasis and recovery after therapy.

Disturbance of T cell-mediated immunity has been reported in acute visceral leishmaniasis (AVL). In a study of 16 patients with AVL, defective production of interleukin-1 (IL-1) by peripheral blood mononuclear cells was demonstrated in response to leishmania antigens, heat-killed Listeria organisms, and lipopolysaccharide when compared to posttherapy values or controls. This global defect in IL-1 production was corrected after successful therapy. Twelve of 16 patients responded with a greater than or equal to 2.5-fold increase in IL-1 production that correlated with clinical cure, P less than .01. Depressed production of tumor necrosis factor (TNF) was leishmania antigen-specific and similarly recovered after therapy. In vitro TNF production during the follow-up period did not correlate with clinical status but high serum levels were associated with AVL. Since T cells are activated by processed antigens presented on class II major histocompatibility molecules and by newly synthesized IL-1, defective IL-1 production may contribute to the immunosuppression observed in AVL.

Acute Disease↗

Synergistic effect of light and fusicoccin on stomatal opening : epidermal peel and patch clamp experiments.

Upon incubation of epidermal peels of Commelina communis in 1 millimolar KCl, a synergistic effect of light and low fusicoccin (FC) concentrations on stomatal opening is observed. In 1 millimolar KCl, stomata remain closed even in the light. However, addition of 0.1 micromolar FC results in opening up to 12 micrometers. The same FC concentration stimulates less than 5 micrometers of opening in darkness. The synergistic effect (a) decreases with increasing FC or KCl concentrations; (b) is dark-reversible; (c) like stomatal opening in high KCl concentrations (120 millimolar) is partially inhibited by the K(+) channel blocker, tetraethyl-ammonium(+) (20 millimolar). In whole-cell patch-clamp experiments with guard cell protoplasts of Vicia faba, FC (1 or 10 micromolar) stimulates an increase in outward current that is essentially voltage independent between - 100 and +60 millivolts, and occurs even when the membrane potential is held at a voltage (-60 millivolts) at which K(+) channels are inactivated. These results are indicative of FC activation of a H(+) pump. FC effects on the magnitude of inward and outward K(+) currents are not observed. Epidermal peel and patch clamp data are both consistent with the hypothesis that the plasma membrane H(+) ATPase of guard cells is a primary locus for the FC effect on stomatal apertures.

Journal Article↗

Active and passive electrical properties of isolated canine cardiac Purkinje fibers under conditions simulating ischaemia: effect of diltiazem.

The effect of a calcium channel blocker diltiazem on the electrical properties of canine Purkinje fibers superfused in a milieu similar to that occurring in acute myocardial ischaemia was studied. Action potential parameters, passive electrical properties, and conduction velocity were measured using conventional microelectrode techniques. Superfusion with glucose-free Tyrode's solution containing 9 mM K+, gassed with 100% N2 at pH = 6.5 ('ischemic solution') significantly reduced the maximal diastolic potential, action potential duration, maximal upstroke velocity, conduction velocity and length constant, while input resistance and longitudinal resistance were elevated and membrane resistance remained unchanged. Diltiazem (1 microM) alone reduced only the action potential duration, while all other parameters were unaffected. Pretreatment with diltiazem did not fully prevent the effects of ischemic superfusion; however, the ischaemia-induced decrease in length constant was not significant in the presence of diltiazem. In addition, the increase in longitudinal resistance during ischaemia was significantly reduced following diltiazem pretreatment. This decrease in longitudinal resistance may contribute to the improvement of ischaemia-induced conduction delay observed in intact animals and may be related to a reduction of ischaemia-induced increase in intracellular free Ca2+.

Action Potentials↗

Molecular biology of the calcium antagonist receptor.

The calcium channel plays a key role in controlling many physiological processes in the body. Drugs that block the calcium channel have proven clinically effective for the treatment of a multitude of cardiovascular disorders. The elucidation of the precise mechanism of action of these drugs involves cloning the calcium channels on which they act. Genetic manipulation of these cloned channels is beginning to reveal the binding sites for the calcium channel blocking drugs and may lead to the development of more specific agents.

Animals↗

Spontaneous vertebral artery dissection initially mimicking myocardial infarction.

BACKGROUND AND PURPOSE: Vertebral and carotid artery dissections may present with very different signs and symptoms, making early recognition difficult. However, diagnosis should be established as soon as possible to prevent unnecessary diagnostic investigations and to institute adequate treatment. CASE DESCRIPTION: A 46-year-old man presented with severe intermittent pain of his left upper arm and general discomfort. During extensive cardiological evaluation for suspected myocardial infarction, a severe brain stem syndrome occurred. Ultrasound Doppler studies detected vertebral artery dissection, which was confirmed by angiography. CONCLUSIONS: The unusual initial presentation of vertebral artery dissection delayed an early diagnosis and adequate treatment. Because noninvasive methods are available today, their applications are recommended in similarly uncharacteristic circumstances.

Aortic Dissection↗

Facial and trigeminal neural dysfunction by a primary cutaneous squamous cell carcinoma: MRI and clinicopathologic correlates.

Carcinomatous neural infiltration and subsequent neural dysfunction are phenomena associated with the facial nerve and parotid gland tumors, particularly adenoid cystic carcinoma. The association of primary cutaneous squamous cell carcinoma (PCSCC) with these phenomena is not as well recognized, especially with respect to the involvement of the trigeminal nerve. By presenting the case history of a man who successively developed facial and trigeminal neural dysfunction after Mohs chemosurgery of a PCSCC, this paper documents histologically the occurrence of such neural invasion, and illustrates the utility of gadolinium-enhanced magnetic resonance scanning in patient management.

Carcinoma, Squamous Cell↗

[Pleuro-pulmonary manifestation of pancreatic diseases].

Non-neoplastic pancreatic disorders may cause pleuro-pulmonary signs. In acute pancreatitis respiratory disorders are very frequent and may cause simply an hypoxia or the adult respiratory distress syndrome (SDRA). There is no single mechanism: mechanical hypoventilation, alteration of the vessel walls and interstitial oedema, stasis of leucocytes, alterations in surfactant and intravascular coagulation may all contribute. These disturbances may be made by direct action of enzymes or by the intermediary of the activation of the kinine system, of complement activation and of coagulation mechanisms. In chronic pancreatitis the problem is to diagnose the cause of the pleural effusion which may often appear to be primary. The cause is suggested by a raised pleural amylase, type P. Although neoplastic pleural effusions may sometimes be rich in amylase it is of type S. The diagnosis rests on echos, computerised scans and retrograde cholangeopancreatography. The pathophysiology of these effusions is through the passage on the enzymes by the lymphatic route, by the oesophageal and aortic route or by a pancreatico-pleural fistula.

Acute Disease↗

[Sclerosing intravascular bronchiolo-alveolar tumor].

We report the case of a 56 year old female who was admitted to hospital in 1980 for assessment of disseminated nodular pulmonary opacities. The histological examination of a prescalene node biopsy showed features which were compatible with sarcoidosis. No treatment was given. In 1987 a discrete increase in the pulmonary nodules was noted. In 1989 effort dyspnoea occurred and there were pains in the right lower chest and an evening fever. The chest X-ray showed a right sided pleurisy and an increase in the size of the nodules with mediastinal lymphadenopathy. A histological examination of a pulmonary nodule, which was taken at an open lung biopsy enabled the diagnosis of a broncho-alveolar sclerosing intravascular tumour to be established. This is a rare tumour which has a slow evolution occurring most often in middle aged females. In 50% of cases the discovery is fortuitous. Besides patients present with non-specific symptoms. The radiological examination reveals multiple nodular opacities which are diffuse and 0.5 to 1.5 cm in diameter. Currently these tumours do not benefit from any particular therapy.

Diagnosis, Differential↗

Spinal cord infarction: MRI and MEP findings in three cases.

We report findings of magnetic resonance imaging (MRI) in three patients with spinal cord ischemia. While myelography was normal in all three patients, MRI found pathological signal increase on the T2-weighted images in each case. Signal changes in T1-weighted images of hemorrhagic infarction were seen in one patient, and gadolinium-DTPA enhancement because of a disturbed blood-tissue barrier was noted in another. Motor evoked potentials after transcortical magnetic stimulation showed normal latencies with very low amplitudes as a sign of axonal loss in ischemia of the spinal cord.

Aged↗

Acceleration of activation and inactivation by the beta subunit of the skeletal muscle calcium channel.

The L-type voltage-dependent calcium channel is an important link in excitation-contraction coupling of muscle cells (reviewed in refs 2 and 3). The channel has two functional characteristics: calcium permeation and receptor sites for calcium antagonists. In skeletal muscle the channel is a complex of five subunits, alpha 1, alpha 2, beta, gamma and delta. Complementary DNAs to these subunits have been cloned and their amino-acid sequences deduced. The skeletal muscle alpha 1 subunit cDNA expressed in L cells manifests as specific calcium-ion permeation, as well as sensitivity to the three classes of organic calcium-channel blockers. We report here that coexpression of the alpha 1 subunit with other subunits results in significant changes in dihydropyridine binding and gating properties. The available number of drug receptor sites increases 10-fold with an alpha 1 beta combination, whereas the affinity of the dihydropyridine binding site remains unchanged. Also, the presence of the beta subunit accelerates activation and inactivation kinetics of the calcium-channel current.

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

Interstrand cross-links are preferentially formed at the d(GC) sites in the reaction between cis-diamminedichloroplatinum (II) and DNA.

A DNA restriction fragment with convergent SP6 and T7 promoters has undergone reaction with cis-diamminedichloroplatinum(II) (cis-DDP) and was then used as a template for RNA synthesis in vitro. The T7 and SP6 RNA polymerases generate fragments of defined sizes. Analysis of the RNA fragments shows that the polymerases are mainly blocked at the level of the d(GG) and d(AG) sites and to a lesser extent at the level of the d(GC) sites. The adducts at the d(GC) sites are more resistant to cyanide ion attack than those at the major sites and are identified as interstrand cross-links. The formation of an interstrand cross-link between the N-7 atoms of two guanine residues at the d(GC) sites was further confirmed by chemical modifications.

Azides↗

Calcium channels from Cyprinus carpio skeletal muscle.

The complete amino acid sequence of the L-type calcium channel alpha 1 subunit from the carp (Cyprinus carpio) white skeletal muscle was deduced by cDNA cloning and sequence analysis. The open reading frame encodes 1852 amino acids (Mr 210,060). A 155-amino acid COOH-terminal sequence (after the fourth internal repeat) is evolutionarily preserved (90% homology) and may represent an important functional domain of L-type calcium channels. The photolabeled, membrane-bound, and purified carp alpha 1 subunits have masses of 211 and 190 kDa. The purified channel could not be phosphorylated by cAMP-dependent protein kinase. Two glycoproteins (alpha 2 subunits) are associated with the alpha 1 subunit and change their apparent masses from 235 and 220 kDa to 159 kDa upon reduction of disulfide bonds. Nucleic acid hybridization with alpha 2 cDNA revealed an 8.0-kilobase transcript in carp skeletal muscle. Evidence for a copurification of subunits similar in size to mammalian beta or gamma subunits was not obtained.

Affinity Labels↗

Dihydropyridine receptor binding sites in the cardiomyopathic hamster heart are unchanged from control.

An increase in the number of voltage dependent calcium channels has been implicated in the overload of calcium found in cardiac tissue of the cardiomyopathic hamster. We examined the binding of [3H]-(+)PN200110 to dihydropyridine receptors in cardiac muscle membranes from TO cardiomyopathic hamsters. When compared to random bred controls, there were no differences in either the Bmax or the KD for [3H]-(+)PN200110 binding using homogenates from 35 to 41-day-old TO cardiomyopathic hearts. In 8 to 9-month-old myopathic animals there were only small decreases in Bmax with no change in KD. We suggest that the calcium overload observed in cardiomyopathic hamster heart may not be due to an increased density of calcium channels as estimated by high affinity dihydropyridine receptor binding sites.

Animals↗