Search PubMed⌕ Search

Biomedical subjects

A Schwartz

Publications and source records attributed to A Schwartz.

At least 289 records · Page 16Linked to original sources

Molecular cloning of multiple subtypes of a novel rat brain isoform of the alpha 1 subunit of the voltage-dependent calcium channel.

Several cDNAs encoding an isoform of the alpha 1 subunit of the voltage-dependent calcium channel were isolated from rat brain cDNA libraries. The complete nucleotide sequence of 6975 bp encodes a protein of 1634 amino acids, which corresponds to an Mr of 186,968. The protein exhibits 71% and 76% homology to skeletal and cardiac alpha 1 subunits, respectively. When compared with skeletal and cardiac alpha 1 isoforms, the rat brain protein is intermediate in size at the amino terminus and shorter at the carboxyl terminus. Multiple subtypes of this alpha 1 isoform cDNA were characterized. These are indicative of alternative splicing of a primary transcript and encode three variants between motif I and motif II and two within the S3 region of motif IV. Thus, multiple isoforms of this rat brain alpha 1 subunit are possible.

Amino Acid Sequence↗

Chromosomal anomaly and malformation syndrome with abdominal polyorchidism.

We describe a neonate who presented with multiple severe malformations including polyorchidism. To our knowledge this is the second case reported with ipsilateral testes located intra-abdominally. Chromosomal studies in cases of polyorchidism have been reported previously only once and the patient exhibited a normal karyotype. Our patient had a chromosome 21 long arm deletion. Interestingly, a trisomy 21 patient has been reported with agonadism. We suggest that genes on chromosome 21 may have some role in gonadal development.

Abnormalities, Multiple↗

Rate and concentration-dependent effects of UK-68,798, a potent new class III antiarrhythmic, on canine Purkinje fibre action potential duration and Vmax.

1. The frequency-dependent electrophysiological effects of UK-68,798 in concentrations of 1, 3, 10 and 30 nM were examined in isolated cardiac Purkinje fibres of the dog at both a number of constant rates of stimulation and following abrupt changes in pacing cycle length. 2. In all concentrations evaluated, UK-68,798 lengthened action potential duration in a concentration- and rate-dependent manner (e.g., at a cycle length = 500 ms, control APD90 = 234.0 +/- 3.3 ms, while after 10 nM UK-68,798, APD90 = 315.0 +/- 5.9 ms). 3. The duration of action potentials evoked following abrupt changes in pacing rate were also increased in a concentration-dependent manner at all diastolic intervals tested. 4. The fast and slow time constants for restitution of APD were not altered by UK-68,798. However, the amplitude terms for this relation were increased. 5. In addition, the maximum upstroke velocity (Vmax) was not significantly affected by exposure to UK-68,798 at any concentration or diastolic interval. The kinetics for recovery of Vmax were thus unaffected. 6. These findings are similar to those previously reported for recognized class III antiarrhythmic agents (e.g., bretylium, clofilium, and sotalol); however, UK-68,798 was 1,000 to 10,000 times more potent. 7. The combined potency and selectivity of this agent seem to make it an ideal tool for the investigation of cardiac potassium channels believed responsible for controlling the duration of the action potential. 8. This potent and highly selective compound may prove extremely useful in the control of cardiac arrhythmias.

Action Potentials↗

Acute posterior multifocal placoid pigment epitheliopathy with cerebral involvement.

In a patient with angiographically proven cerebral vasculitis five months after acute posterior multifocal placoid pigment epitheliopathy (APMPPE) neurological symptoms promptly responded to steroid treatment. Cerebrospinal fluid (CSF) showed a lymphocytic pleocytosis. Magnetic resonance imaging (MRI) revealed multifocal white matter lesions in the hemispheres and the brain stem suggesting a diffuse subcortical vasculitis.

Cerebral Arterial Diseases↗

Expression of HLA class I and class II in gastric carcinoma in relation to pathologic stage.

The expression of HLA class I and II antigens was studied in 41 patients with gastric cancer and in 2 normal stomachs. The normal gastric epithelia were diffusely stained for class I antigens. No staining was observed for class II. In gastric cancer an overall reduction in staining was observed, which was related to the degree of tumor penetration through the gastric wall. In tumors which penetrated the mucosa and submucosa only, 80-90% of tumor cells were stained for class I, as well as the normal areas surrounding the tumor. On the other hand, in tumors which penetrated through the organ to the fat, only 10-20% of cells were stained. Staining for class II was observed in only 12 cases, all of them advanced, with penetration to muscle or fat. No staining was observed in the normal areas surrounding the tumor. The importance of HLA antigens in immune surveillance is discussed.

Gastric Mucosa↗

A new approach to dose reduction in chronic schizophrenia.

The bromocriptine growth hormone test (BGHT) was used to monitor D2 receptor activity in a group of 16 chronic schizophrenics who during the baseline phase were receiving greater than or equal to 20 mg/day haloperidol. In all subjects at baseline, the rise in plasma GH in response to the oral administration of bromocriptine (50 micrograms/kg) was blocked. The dose of haloperidol was then gradually reduced; the BGHT was repeated as each new dose was established. No escape from blockade of the GH response was observed until the dose of haloperidol was lowered to 10 mg/day (3 of 16 subjects escaped from blockade). At this dose the average plasma haloperidol level was 4 ng/ml. Two additional subjects escaped as the dose was reduced to 5 mg/day and six more escaped as the dose was reduced to 2.5 mg/day. The average haloperidol plasma level at 5 and 2.5 mg/day was 1.6 and 1.2 ng/ml respectively. The remaining five subjects escaped from blockade as the dose was reduced to 0 mg/day. In five subjects, escape from blockade was associated with a significant decrease in positive psychotic symptoms; in these subjects reestablishing the "just" blockade dose of haloperidol did not increase psychotic symptoms. In nine subjects escape from blockade was associated with an increase of positive psychotic symptoms; in six of these patients, reestablishing the "just" blockade dose of haloperidol attenuated psychotic symptoms to near baseline levels. We conclude that the GH challenge test is a useful adjunct to dose-reduction in the chronic patient. Furthermore, for some patients the "just" blockade dose appears to be near the minimum dose with the maximum therapeutic effect.

Adult↗

[Glomerulonephritis--morphologic study. I].

The submitted paper contains the morphological description of different types of isolated glomerulonephritis. From the methodical aspect the author emphasizes the importance of comprehensive examination and application of the RF and EM method and histological classification. He emphasizes the great importance of morphological diagnosis which provides most information, an accurate classification and an accurate answer on the activity of the process and prognosis of the disease. Thus it makes the most adequate therapy possible. In the morphological diagnosis we cannot omit the importance of the case-history and clinical course. The author emphasizes the method of needle biopsy which is relatively sparing, and if performed by an experienced specialist, it is associated with a minimal risk. In children biopsy by the lumbotomic route is most suitable.

Glomerulonephritis↗

Vascular actions of TA 3090, a novel analog of diltiazem: interaction with endothelium-dependent relaxation in canine femoral and coronary arteries.

The effects of a new 1,5-benzothiazepine calcium antagonist, TA 3090 (an analog of diltiazem), were analyzed in isolated canine femoral and coronary arteries suspended in organ chambers or studied in a bioassay system. TA 3090 (10(-9) to 10(-4) M) caused comparable relaxations in arterial rings with and without endothelium contracted by prostaglandin F2 alpha. Coronary arteries were more sensitive to the Ca++ antagonist. In both preparations, TA 3090 was more potent than diltiazem. In femoral (but not coronary) artery rings with endothelium, acetylcholine (10(-8) M) inhibited relaxations to TA 3090. Previous treatment of femoral or coronary arteries with TA 3090 (10(-6) M) had no effect on endothelium-dependent relaxations to acetylcholine. In a bioassay system, TA 3090 (2 x 10(-7) M) caused partial reversal of acetylcholine-induced relaxation in perfused femoral arteries and superfused coronary arterial rings. The dihydropyridine enantiomer (-)-202,791 did not affect acetylcholine-induced relaxations and did not prevent the reversal by TA 3090. These data indicate that, in addition to a direct action on vascular smooth muscle, this novel benzothiazepine Ca(++)-antagonist interferes with the synthesis/release of endothelium-derived relaxing factor stimulated by acetylcholine in canine femoral arteries. These findings, which are similar to those obtained with d-cis-diltiazem, support the hypothesis that a specific benzothiazepine-dependent mechanism(s) can suppress the production of endothelium-derived relaxing factor in endothelial cells.

Acetylcholine↗

cDNA cloning of a dihydropyridine-sensitive calcium channel from rat aorta. Evidence for the existence of alternatively spliced forms.

Several complementary DNAs have been isolated from rat aorta cDNA libraries that encode the alpha 1 subunit of the L-type dihydropyridine-sensitive voltage-dependent calcium channel (VDCC). The clones were isolated using previously cloned rabbit skeletal and cardiac VDCC cDNAs as well as newly isolated rat aorta cDNA clones as probes. The complete nucleotide sequence of the 8305-base pair aortic alpha 1 cDNA codes for a protein of 2169 amino acids, which corresponds to an Mr of 243,615. The deduced amino acid sequence exhibits 93 and 65% amino acid identity with previously cloned rabbit cardiac and rabbit skeletal muscle dihydropyridine-sensitive VDCCs, respectively. The close identity of the aortic alpha 1 cDNA with cardiac alpha 1 cDNAs suggests that they arise from the same gene. Specific divergent areas of the aortic cDNA suggest that this cDNA represents an alternatively spliced form. We report the existence of two forms of a specific region within this aortic cDNA which also exists in cardiac tissue. This evidence supports the existence of alternative splicing for calcium channel cDNAs, a mechanism which provides diversity and potential tissue-specific isoforms of the L-type VDCC. The rat aorta alpha 1 isoform has a message size of 8.6 kilobases (kb). Rat aorta also contains additional transcripts of 12.0 and 6.5 kb. Northern blot analysis of poly(A)+ RNA from several rat tissues including heart, brain, and several smooth muscles reveals the co-existence of the 8.6- and 12.0-kb mRNA species but not the 6.5-kb species. Southern analysis of rat genomic DNA reveals a low copy number of the gene encoding this type of calcium channel.

Amino Acid Sequence↗

Molecular cloning and functional expression of a potassium channel cDNA isolated from a rat cardiac library.

A full-length K+ channel cDNA (RHK1) was isolated from a rat cardiac library using the polymerase chain reaction (PCR) method and degenerate oligonucleotide primers derived from K+ channel sequences conserved between Drosophila Shaker H4 and mouse brain MBK1. Although RHK1 was isolated from heart, its expression was found in both heart and brain. The RHK1-encoded protein, when expressed in Xenopus oocytes, gated a 4-aminopyridine (4-AP)-sensitive transient outward current. This current is similar to the transient outward current measured in rat ventricular myocytes with respect to voltage-dependence of activation and inactivation, time course of activation and inactivation, and pharmacology.

Amino Acid Sequence↗

Serous papillary adenocarcinoma of the endometrium. Analysis of proto-oncogene amplification, flow cytometry, estrogen and progesterone receptors, and immunohistochemistry.

Primary and metastatic tumor tissues of serous papillary adenocarcinoma of the endometrium were examined for the following: (1) amplification of int-2, c-erbB-2 and c-myc proto-oncogenes by Southern blot hybridization; (2) DNA ploidy by flow cytometric study; (3) and expression of specific proteins, such as estrogen and progesterone receptors, keratin, vimentin, and carcinoembryonic antigen (CEA) using immunohistochemical and biochemical techniques. Amplification of c-myc was observed in the specimens from the endometrium (ten-fold) and from omental metastasis (five-fold). Both int-2 and c-erbB-2 amplification were not observed. The tumor showed aneuploidy, with the specimens from the endometrium and omental metastasis exhibiting multiple populations of aneuploid tumor cells. Estrogen and progesterone receptors could not be detected biochemically; however, immunohistochemically, estrogen receptors were observed in tumor cells forming papillary structures but not in the tumor cells of the solid, more poorly differentiated areas. A similar distribution was observed for both low and high molecular weight keratin. The findings of c-myc amplification and aneuploidy in the serous papillary adenocarcinoma of the endometrium are consistent with its aggressive behavior observed clinically and emphasize the importance of distinguishing this lesion from other types of endometrial carcinoma.

Blotting, Southern↗

Toward an understanding of the dihydropyridine-sensitive calcium channel.

The dihydropyridine-sensitive calcium channel continues to fascinate scientific investigators. Each new discovery leads to more complexity. Further work elucidating the molecular structures and functions of the various isoforms of the channel will lead us to a better understanding of its nature. We are well on our way towards understanding the molecular structure and mechanisms involved in calcium permeability, and the coming decade promises to reveal numerous breakthroughs in our understanding of this channel.

Amino Acid Sequence↗

Free proximal trisomy 21 in the mother and malformation syndrome in the son.

We report on a new case of duplication of the proximal part of the long arm of chromosome 21. The proposita presents normal mental development, no trisomy 21 manifestations; on the contrary, she had a few monosomy 21-like stigmata. She gave birth to a severely malformed infant with a pattern of malformations suggesting a partial 21-monosomy syndrome, but with a 46,XY normal karyotype in his peripheral blood lymphocytes. The findings are explained in the following way: the infant probably had originally a 47,XY,+21q- karyotype like his mother. Post zygotic nondisjunctional events produced a prevalent 46,XY,21q- line responsible for the severe malformations and the normal 46,XY line found in his blood lymphocytes.

Abnormalities, Multiple↗

Altered rheological properties of blood following administrations of tissue plasminogen activator and streptokinase in patients with acute myocardial infarction.

Tissue blood flow is determined by rheological properties of blood as well as by vascular resistance. In acute myocardial infarction patients who participated in the TIMI I trial, we compared the effects of recombinant tissue plasminogen activator (rt-PA) and streptokinase (SK) on blood rheological properties and plasma fibrinogen concentration. Blood viscosity was determined by using a coaxial cylinder viscometer at shear rates, gamma, of 0.01-200 sec-1. Red blood cell (RBC) deformability was studied by filtration through polycarbonate microsieves with pore size of 3 and 5 microns. Therapy with rt-PA resulted in slight decreases but statistically significant in blood viscosity from 5.2 +/- 0.5 to 4.9 +/- 0.4 cP (gamma = 52 sec-1), plasma viscosity from 1.36 +/- 0.09 to 1.32 +/- 0.06 cP, and plasma fibrinogen from 0.26 +/- 0.04 to 0.21 +/- 0.03 g/dl. SK therapy resulted in reductions in blood viscosity from 5.1 +/- 0.5 to 4.6 +/- 0.3 cP, plasma viscosity from 1.26 +/- 0.10 to 1.16 +/- 0.03 cP, and fibrinogen from 0.26 +/- 0.06 to 0.10 +/- 0.05 g/dl. Changes observed with SK were significantly greater than those observed with rt-PA (all p less than 0.05), and the differences persisted at 10 days after thrombolytic therapy. RBC deformability was similar in the two groups. The greater reduction of blood viscosity after SK than rt-PA suggests that, for a given degree of arterial patency, myocardial blood flow may be better maintained with SK than rt-PA in patients with acute myocardial infarction.

Blood Proteins↗