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Biomedical subjects

A Schwartz

Publications and source records attributed to A Schwartz.

At least 307 records · Page 17Linked to original sources
PubMed1990

Structural and developmental differences between three types of Na channels in dorsal root ganglion cells of newborn rats.

The changes in Na current during development were studied in the dorsal root ganglion (DRG) cells using the whole-cell patch-clamp technique. Cells obtained from rats 1-3 and 5-8 days after birth were cultured and their Na currents were compared. On top of the two types of Na currents reported in these cells (fast-FA current and slow-S current) a new fast current was found (FN). The main characteristics of the three currents are: (i) The voltages of activation are -37, -36 and -23 mV for the FN, FA and S currents, respectively. (ii) The activation and inactivation kinetics of FN and FA currents are about five times faster than those of the S current. (iii) The voltages at which inactivation reaches 50% are -139, -75 and -23 mV for the FN, FA and S currents, respectively. The kinetics and voltage-dependent parameters of the three currents and their density do not change during the first eight days after birth. However, their relative frequency in the cells changes. In the 1-3 day-old rats the percent of cells with S, FA, and mixed S + FN currents is 22, 18, and 60% of the cells, respectively. In the 5-8 day-old, the percent of cells with S, FA, and FN + S is 10, 66 and 22%. The relative increase in the frequency of cells with FA current during development can contribute to the ease of action potential generation compared with cells with FN currents, which are almost completely inactivated under physiological conditions. The predominance of FA cells also results in a significant decrease in the relative frequency of cells with the high-threshold, slow current. Antibodies directed against a part of the S4 region of internal repeat I of the sodium channel (C1+, amino acids 210-223, eel channel numbering) were found to shift the voltage dependence of FA current inactivation (but not of FN or S currents) to more negative potentials. The effect was found only when the antibodies were applied externally. The results suggest that FN, FA and S types of Na currents are generated by channels, which are different in the topography of the C1+ region in the membrane.

Action Potentials↗
PubMed1990

Doppler color flow imaging of common carotid artery dissection.

Sonographic findings are reported in a case of common carotid artery dissection assessed by Doppler color flow imaging and confirmed by angiography. Advantages and clinical relevance of this new ultrasound method for this diagnosis are discussed.

Aortic Dissection↗
PubMed1989

Photoaffinity labeling of the purified skeletal muscle calcium antagonist receptor by a novel benzothiazepine, [3H]azidobutyryl diltiazem.

Previous photoaffinity-labeling studies with [3H]azidopine, (+) [3H]PN200-110, and [3H]LU 49888 have demonstrated that 1,4-dihydropyridines (nifedipine-like drugs) and phenylalkylamines (verapamil-like drugs) bind exclusively to the 165-kDa alpha 1 subunit of skeletal muscle calcium channels. However, it has not been conclusively determined whether benzothiazepines (diltiazem-like drugs), which represent the third group of calcium antagonists, also bind to the alpha 1 subunit. Here we report data obtained with a newly developed benzothiazepine photoaffinity probe, [3H]azidobutyryl diltiazem. This drug competes with diltiazem for the benzothiazepine-binding site and, in purified calcium channel preparations, specifically labels the 165-kDa polypeptide which does not change its electrophoretic mobility upon disulfide reduction. These data show that benzothiazepines, just like 1,4-dihydropyridines and phenylalkylamines, bind to the alpha 1 subunit of the skeletal muscle calcium channels.

Affinity Labels↗
PubMed1989

Conformation of DNA modified at a d(GG) or a d(AG) site by the antitumor drug cis-diamminedichloroplatinum(II).

The purpose of this work was the comparison of the conformational changes induced in the double helix by the adducts formed at d(GG) and d(AG) sites in the reaction between the antitumor drug cis-diamminedichloroplatinum(II) (cis-DDP) and DNA. Two duplexes (20-mer) containing either a single d(A*G*) or a single d(G*G) adduct were studied by means of gel electrophoresis and artificial nuclease and chemical probes. It is shown that the d(G*G*) and the d(A*G*) adducts bend DNA similarly, but at the nucleotide level they distort differently the double helix. We suggest that the weaker interactions between platinated A residues and the other nucleotides, as compared to the interactions between platinated G residues and the other nucleotides, are largely responsible for the differences in the distortions induced in DNA by the d(A*G) and d(G*G*) adducts. This suggestion is supported by the study of the distortions induced in duplexes by the d(G*G*) adducts, one of the platinated G residues being paired with a T residue.

Adenine↗
PubMed1989

Characterization of cDNA clones encoding two putative isoforms of the alpha 1 subunit of the dihydropyridine-sensitive voltage-dependent calcium channel isolated from rat brain and rat aorta.

cDNA clones encoding rat brain and rat aorta isoforms of the alpha 1 subunit of the dihydropyridine-sensitive, voltage-dependent calcium channel were isolated and sequenced. These tissue-specific cDNA clones share significant amino acid similarity with the rabbit skeletal muscle calcium channel alpha 1 subunit (75% and 66% amino acid identity for rat brain and rat aorta isoforms, respectively). Northern analysis revealed transcript sizes of 6.5 and 8.6 kb in aorta and 8.6 kb in brain.

Amino Acid Sequence↗
PubMed1989

Evidence for the existence of a cardiac specific isoform of the alpha 1 subunit of the voltage dependent calcium channel.

Biochemical, pharmacological and electrophysiological evidence implies the existence of tissue specific isoforms of the L-type VDCC. The alpha 1 and alpha 2 subunits of the skeletal muscle calcium channel have been previously cloned and their amino acid sequence deduced. Here we report the isolation and sequencing of a partial cDNA that encodes a heart specific isoform of the alpha 1 subunit. The amino acid sequence deduced from this part cDNA clone shows 64.7% similarity with the skeletal muscle alpha 1 subunit. Northern analysis reveals 2 hybridizing bands, 8.5 and 13 kb, in contrast to one 6.5 kb band in the skeletal muscle. Selective inhibition of mRNA expression in Xenopus oocytes by complementary oligodeoxy-nucleotides derived from the heart clone provides further evidence that the cDNA corresponds to an essential component of the VDCC. These data further support the existence of tissue-specific isoforms of the L-type VDCC.

Amino Acid Sequence↗
PubMed1989

Developmental regulation of expression of the alpha 1 and alpha 2 subunits mRNAs of the voltage-dependent calcium channel in a differentiating myogenic cell line.

The voltage-dependent calcium channel (VDCC) in skeletal muscle probably plays a key role in transducing membrane charge movement to the calcium release channel. We report here that the expression of VDCC alpha 1 and alpha 2 mRNAs is developmentally regulated in differentiating C2C12 myogenic cells. The alpha 1 mRNA is not detectable in the myoblast form of C2C12 cells while its expression is induced 20-fold in differentiated myotubes. In contrast, the alpha 2 mRNA is weakly expressed in myoblasts but is also induced upon myogenic differentiation.

Animals↗
PubMed1989

Rate-dependent electrophysiological effects of OPC-8212: comparison to sotalol.

The rate-dependent effects of OPC-8212 (6 microM), a new positive inotropic drug which lengthens cardiac action potential duration were studied in dog cardiac Purkinje fibers and compared to the effects of sotalol (30 microM), a class III antiarrhythmic using conventional microelectrode technique. Both OPC-8212 and sotalol lengthened action potential duration in a frequency-dependent manner. Both had a greater effect at slower pacing frequencies than at fast. The maximum rising velocity of the action potential upstroke was not affected by either compound at any of the pacing cycle lengths applied (300-2000 ms). The effects of OPC-8212 and sotalol on action potential duration and maximum rising velocity were also compared following abrupt changes in pacing cycle length (i.e. coupling intervals ranging between approximately 250-3000 ms). The effects of both OPC-8212 and sotalol following abrupt changes in pacing cycle length were similar to one another. Neither OPC-8212 nor sotalol altered the time constants for restitution of action potential duration or the kinetics for recovery of the maximum rising velocity of the action potential upstroke. These results indicate that the rate-dependent electrophysiological effects of OPC-8212 closely mimic those of sotalol and suggest that OPC-8212 may be an effective class III antiarrhythmic in addition to being a positive inotropic compound.

Action Potentials↗
PubMed1989

The DNA bending by acetylaminofluorene residues and by apurinic sites.

We have studied the distortions induced in double-stranded oligonucleotides by covalently bound acetylaminofluorene residues and by apurinic sites. Within the acetylaminofluorene-modified oligonucleotide three base-pairs are unpaired as detected by the chemical probes chloroacetaldehyde and osmium tetroxide. These two probes reveal that the bases adjacent to the apurinic site are paired. In both the modified double-stranded oligonucleotides, the backbone on the 5' side of the modification is more reactive with 1,10-phenanthroline copper than the backbone on the 3' side. On polyacrylamide gels, the ligated multimers of acetylaminofluorene or apurinic site-modified oligonucleotides migrate slower than the multimers of the unmodified oligonucleotides. It is suggested that the acetylaminofluorene-modified guanine residues and the apurinic sites behave more as hinge joints than as the centres of directed bends.

2-Acetylaminofluorene↗
PubMed1989

The scintigraphic characteristics of ventricular pre-excitation through Mahaim fibers with the use of phase analysis.

The phase image pattern of blood pool scintigrams was blindly assessed in 11 patients exhibiting conduction through Mahaim pathways, including 6 nodoventricular and 5 fasciculoventricular. These patterns were compared with the phase image findings in normal subjects, patients with left and right bundle branch block in the absence of pre-excitation and patients with pre-excitation through atrioventricular (AV) connections. In all patients with a Mahaim pathway, the site of earliest phase angle was septal or paraseptal. Phase progression was asymmetric and the pre-excited ventricle demonstrated the earliest mean ventricular phase angle in 10 of 11 patients. This pattern, and the associated ventricular phase difference, appeared to vary from that in normal subjects and in those with a septal AV connection, in whom phase progression is generally symmetric. Scintigraphic phase analysis provided localizing information and presented patterns consistent with Mahaim pathways. Although not able to differentiate among Mahaim pathway subtypes, these phase patterns differed from those in normal subjects, those with right and left lateral free wall pathways and most patients with a septal AV pathway. However, the phase pattern of patients with a Mahaim pathway may not differ from that of patients with a septal AV connection displaying an asymmetric pattern of phase progression, or those with left and right bundle branch block in the absence of pre-excitation. Objective, yet imperfect phase measurements supported these differences. Such image findings may complement the often complex electrophysiologic evaluation of patients presenting with pre-excitation.

Adult↗
PubMed1989

The validity and reliability of photographic documentation of proliferative vitreoretinopathy.

The Silicone Study is a multicentered, randomized surgical trial designed to compare the tamponade effectiveness of silicone oil versus long-acting gas in the treatment of proliferative vitreoretinopathy (PVR) by vitrectomy and associated techniques. Fundus photographs are taken to provide documentation of the anatomic status of eyes proposed for entry and are graded at an independent Reading Center. This article describes the protocol for photographic documentation of PVR as a continuum of increasing pathology, in which the pathology may only be present in the anterior retina, and the retina is usually highly elevated. In a validity and reliability study, agreement between photographic and clinical observation within one step was obtained for 88% of the eyes; intra- and inter-observer agreement within one step was 85 and 80%, respectively. Differences between the surgeon's grade and the Reading Center's were caused about equally by disagreement regarding extent of fixed folds and width of the funnel. Rarely did peripheral folds not visible in the photographs appear to be the sole explanation of the disagreement. Differences among readers were concerned mainly with differentiation of true full-thickness fixed folds from folds due to simple redundancy of the detached retina. These results demonstrate that complicated retinal detachment (RD) can be photographically documented and independently assessed.

Clinical Trials as Topic↗
PubMed1989

Cytomegaloviral and cryptosporidial cholecystitis in two patients with AIDS.

We report two cases of acalculous cholecystitis due to infection with cytomegalovirus (CMV) and cryptosporidium. Both involved homosexual men who presented with right upper quadrant pain and elevations of serum alkaline phosphatase and bilirubin. Cholecystectomy specimens showed a thickened gallbladder wall and ulcerated mucosa. There were no stones. CMV inclusion bodies were found in granulation tissue at the base of ulcers and intact mucosa surrounding ulcers. Cryptosporidia were aligned along the luminal surface of intact mucosal epithelial cells. Both organisms have a patchy distribution; hence the diagnosis requires a high degree of suspicion. The prognosis is poor. Following cholecystectomy, both patients pursued a downhill course with development of pancreatitis and cholangitis. Both patients are now dead.

Acquired Immunodeficiency Syndrome↗
PubMed1989

New positive inotropic agent OPC-8212 modulates single Ca2+ channels in ventricular myocytes of guinea pig.

The effects of a new positive inotropic drug, OPC-8212 (a quinolinone derivative, 3,4-dihydro-6-[4-(3,4-dimethoxybenzoyl)-1 -piperazinyl]-2(1H)-quinolinone), on whole-cell and single-channel calcium currents of guinea pig ventricular myocytes were studied by the patch-clamp method. OPC-8212 increased whole-cell calcium currents in a concentration-dependent manner. The concentration-response curve was fitted by a single binding site model that has an ED50 of 2.7 microM. At the single-channel level, OPC-8212 increased calcium currents mainly by increasing the probability of channel opening on depolarization; the open times were slightly increased, but single-channel conductance did not change. The actions of OPC-8212 on single calcium channel currents were compared with those of forskolin, isoproterenol, and caffeine, agents that cause positive inotropic effects associated with an increase in cytoplasmic cyclic AMP level, and with those of the dihydropyridine calcium channel agonist (-)Bay K 8644, an agent that has a positive inotropic effect but does not act through cyclic AMP. OPC-8212 increased calcium currents in a manner that resembled the actions of forskolin, isoproterenol, and caffeine rather than the actions of (-)Bay K 8644. We suggest that activation of calcium currents by OPC-8212 is mediated by an elevation of intracellular cyclic AMP. Since OPC-8212 produces bradycardia and antitachycardiac effects in animals and humans, unlike agents that increase cyclic AMP, additional effects on other currents are likely.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Changing patterns of neuroleptic dosage over a decade.

A study of patterns of neuroleptic dosage for 206 schizophrenic inpatients showed significant differences over time and among three centers--a general hospital psychiatric unit, a community mental health center, and a state hospital. In 1982 patients' mean dose at discharge was higher than the peak mean daily dose in 1973, and high-potency neuroleptics were being used almost exclusively. The mean length of stay decreased from 49 days in 1973 to 34 days in 1982. The possible relationship, if any, between increasing dosage, decreased length of stay, and the switch from low-potency to high-potency neuroleptics remains undetermined.

Adolescent↗