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Biomedical subjects

E Schwartz

Publications and source records attributed to E Schwartz.

At least 289 records · Page 16Linked to original sources
PubMed1984

Detection of a novel DNA polymorphism in the beta-globin gene cluster.

Analysis of DNA from the beta-globin gene cluster in an Albanian family identified a novel RsaI site approximately 550 base pairs 5' to the beta-globin gene. In this family, two chromosomes carrying otherwise identical beta-globin haplotypes were found to differ at the RsaI site. Population screening demonstrated the presence and absence of the site in DNA from individuals of northern European, Mediterranean, Middle Eastern, Southeast Asian, African, and Asian Indian descent, indicating that this site is a DNA polymorphism common in many ethnic groups. The polymorphism is also present in DNA from individuals carrying different beta-globin alleles. Additional nucleotide sequence changes identified in an RsaI (+) genomic clone in the region immediately 3' to the RsaI site suggest a mechanism for the randomization of the site with respect to haplotype.

Alleles↗
PubMed1984

Tapetal changes in beagle dogs. I. Ocular changes after oral administration of a beta-adrenergic blocking agent--SCH 19927.

SCH 19927 [R,R)-(-)-2-Hydroxy-5-[1-hydroxy-2-[(1-methyl -3-phenylpropyl)amino]ethyl]benzamide hydrochloride) is a beta-adrenergic blocking agent which has vasodilating properties. In a subchronic oral toxicity study in beagle dogs, SCH 19927 was given by gavage at doses of 30, 60, and 90 mg/kg. Lesions were observed at weeks 13 and 19 in the tapetum lucidum, a light reflecting structure of the eye. The lesions consisted of focal to multifocal areas of discoloration of the tapetal portion of the ocular fundus, pigmentation in the tapetal area, and, in one dog, subretinal edema resulting in a focal retinal detachment. Light and electron microscopic examination of the ocular lesions demonstrated tapetal cell degeneration and necrosis with macrophages, lymphocytes, and occasional plasma cells in the tapetum and adjacent choroid. Local cellular infiltrates within the retina internal to the pigmented epithelium were observed in one dog (60 mg/kg) which was demonstrated to have focal retinal edema during the study. In a repeat study the lesion again occurred in tapetal beagle dogs but not in atapetal beagle dogs (90 mg/kg) or cynomolgous monkeys (360 mg/kg). The lesion had not occurred in a previous subchronic study in albino rats. These results demonstrated that the tapetum lucidum was a target organ of toxicity for SCH 19927 and indicated that the finding was without observable toxicological significance in animals, including man, whose eyes do not have this structure.

Animals↗
PubMed1984

Tapetal changes in beagle dogs. II. Ocular changes after intravenous administration of a macrolide antibiotic--rosaramicin.

Two studies were conducted to assess the toxicity of rosaramicin (a macrolide antibiotic) when given intravenously for 30 consecutive days to beagle dogs with and without a tapetum lucidum (a light reflecting structure within the choroid of the eye). In the initial study, groups of three tapetal dogs/sex were given 20, 40, or 80 mg of rosaramicin/kg, twice daily. Ophthalmoscopic examination during Week 4 revealed dose-related, bilateral ocular changes characterized by a brown-tan discoloration and general pallor or loss of reflectivity of the normally blue-purple or yellow-green, highly reflective tapetum lucidum. These findings were restricted to the tapetal fundus; recovery occurred between Weeks 4 and 10 of the postdose period. To further investigate these changes, a second study was conducted in which groups of three tapetal dogs were given rosaramicin or erythromycin lactobionate (comparative macrolide antibiotic) at 80 mg/kg, twice daily. A third group of atapetal dogs was given 80 mg of rosaramicin/kg, twice daily. A similar change was observed in tapetal dogs given 80 mg of rosaramicin/kg, twice daily, in the follow-up study, but not in the other two groups. No other compound-related changes were observed in either study. The ocular changes observed in dogs given rosaramicin were reversible and structure-specific, occurring only in animals possessing a tapetum lucidum.

Animals↗
PubMed1984

The silent carrier allele: beta thalassemia without a mutation in the beta-globin gene or its immediate flanking regions.

A molecular genetic analysis has been performed using as subjects an Albanian family in which the father is a silent carrier, the mother has high Hb A2-beta thalassemia trait, and both children have beta thalassemia. Nucleotide sequence analysis of the daughter's paternal beta-globin gene and its flanking regions failed to reveal any base changes of known functional significance. When introduced into HeLa cells the gene was expressed at normal levels with proper processing of RNA. Haplotype analysis revealed that the affected son and daughter inherited different epsilon gamma delta beta-globin gene clusters from the father. The silent carrier allele is not due to a mutation within the beta-globin structural gene or its flanking regions and as such represents a novel form of beta+ thalassemia.

Alleles↗
PubMed1984

Clinical trial of young red cell transfusions.

The lower mean cell age and prolonged 51Cr-labeled red cell survival of the top layer of centrifuged red blood cells suggest that this product may reduce blood requirements in patients with transfusion-dependent anemias. In a prospective clinical trial, we compared the effect of regular administration of young red cells with that associated with use of conventional frozen cells. Six patients with thalassemia major received 192 units of young red cells prepared from single donor units of whole blood using the IBM 2991 Cell Processor. The mean transfusion requirement to maintain the hemoglobin level greater than 9.0 gm/dl was 110 +/- 17 ml RBC/kg during the year of young cell transfusions, in comparison with 130 +/- 20 and 131 +/- 23 ml RBC/kg when conventional frozen cells were administered in the years before and after the young cell trial, respectively. Blood requirements in individual patients were reduced by 8% to 24% (mean 15.8%); the hemoglobin level remained constant. Although young cells of consistent quality can be prepared regularly in a clinical setting with little difficulty, the cost of the product is high and the effect on transfusion requirements is less than predicted from studies in vitro and from labeling experiments.

Blood Transfusion↗
PubMed1984

Depletion of excessive liver iron stores with desferrioxamine.

To determine the therapeutic effect of long-term, intensive iron chelation therapy, we studied liver iron content and histology in four children with thalassaemia major during 52-83 months of intensive therapy with desferrioxamine. The initial biopsies obtained prior to or within 21 months after beginning chelation therapy had Grade IV iron staining, with heavy iron deposition present in parenchymal and reticuloendothelial cells. Subsequent biopsies, obtained when serum ferritin levels had fallen to 71-246 micrograms/l, contained Grade 0 or Grade I stainable iron. Little or no iron was present in parenchymal or reticuloendothelial cells. The liver iron concentration, measured by magnetic susceptibility, returned to normal or nearly normal levels. Hepatic fibrosis did not progress during treatment with desferrioxamine. These findings demonstrate that intensive and sustained chelation therapy with desferrioxamine will remove excessive liver iron and preserve hepatocellular structure.

Adolescent↗
PubMed1984

Thalassemia.

Explore the source record for details and available documents.

Blood Transfusion↗
PubMed1984

Effect of transfusion therapy on arteriographic abnormalities and on recurrence of stroke in sickle cell disease.

Stroke is a relatively frequent and severe complication of sickle cell disease. We performed cerebral arteriograms in 30 patients with sickle cell disease to evaluate the cause of acute neurologic deficits and to assess the effects of transfusion therapy given for a year or more after the acute episode. Twenty-three patients with motor and speech deficits had multiple abnormalities of major cerebral arteries. The internal carotid and anterior and middle cerebral arteries showed stenosis and/or occlusion at their common junction. Irregular luminal surfaces suggested that endothelial damage and intimal hyperplasia were the basis of stroke. Prolonged transfusion therapy nearly stopped progression of stenosis and markedly decreased the irregularity of the luminal surfaces; in 4 untransfused patients, the degree of stenosis doubled and the luminal abnormalities persisted. Prior to transfusion, 90% of patients had recurrence of stroke. With transfusion therapy, only 10% of patients had recurrence despite persistent arterial abnormalities. Clinical recurrences per patient-month decreased 75-fold. The patients tolerated prolonged transfusion therapy well, despite progressive iron accumulation. Seven patients with smooth abnormalities of a single artery, nonocclusive changes, or with normal arteriograms did not receive transfusions. Only one of this group had recurrence of symptoms.

Acute Disease↗
PubMed1983

Nucleotide sequence analysis of the delta beta-globin gene region in humans.

The continuous DNA sequence of a 16.5-kilobase pair region encompassing the linked delta beta-globin gene cluster in humans is presented with a detailed restriction endonuclease map. There are 38 differences (0.5%) in comparison with published sequence data, corrected for errors in sequencing, resulting in polymorphic rates of 0.2% in exons and 0.76% in 5'-gene flanking regions. Fifteen changes result in the generation or elimination of restriction sites which may be useful in linkage disequilibrium studies. Two pairs of inverted Alu repeats, a pyrimidine-rich region 5' to delta, and (TG)n, (Pu/Py)n, and (ATTTT)n tracts 5' to beta are described. Dinucleotide frequencies and deviation from expected values approximated those found in total human genomic DNA. Regions of less than 50% A + T content were found associated with Alu sequences, a 150-base pair region immediately 5' to the beta gene, exon regions from both genes, and an area 3' to the beta gene. These regions also contained significantly lower than expected CpG levels compared to other regions, suggesting a possible relationship between DNA organizational patterns and functionally important regions. In addition, strand asymmetries in base composition in this region differ from those associated with the fetal globin genes.

Base Composition↗
PubMed1983

The infrastructure of aortic elastic fibers.

Elastic fibers are composed of a central core of elastin that is amorphous and electron-lucent in conventional transmission electron micrographs and peripheral microfibrils. A complex infrastructure within the amorphous elastin of mature rat aorta is made visible by fixation and staining with a glutaraldehyde-ruthenium red mixture in phosphate buffer or osmium-ruthenium red in cacodylate buffer. The infrastructure is composed of at least two interlacing but distinct elastic structural components; a framework of circumferentially orientated microfibrils and a three-dimensional meshwork of filaments that permeate the fiber. The latter resembles a reticulum that has previously been observed in freeze-fractured and negatively stained elastin and attributed to the supramolecular organization of elastin. Microfibrils also extend from the core of the elastic fiber into the surrounding matrix where they appear to function as anchoring fibers. These observations indicate that the elastic properties of the arterial wall are an integrated function of both elastin and microfibrils.

Animals↗
PubMed1983

Trial of low doses of aspirin as prophylaxis in sickle cell disease.

The effects of low doses of aspirin on the frequency and severity of painful vaso-occlusive crises were evaluated in children with sickle hemoglobinopathies. Aspirin was compared with placebo in 49 patients in a double-blind crossover study. Careful monitoring of patients revealed an average of 1.1 painful crises per patient year. During the 21 months of study, 70% of patients had a maximum of two painful crises, and 25% experienced four or more. The frequency and severity of crises were not affected by aspirin therapy. In view of aspirin's demonstrated effect on platelet function, we suggest that platelets do not contribute to the initiation or progression of the vaso-occlusive process.

Adolescent↗