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Biomedical subjects

E Schwartz

Publications and source records attributed to E Schwartz.

At least 307 records · Page 17Linked to original sources
PubMed1983

Ultrastructure and staining properties of aortic microfibrils (oxytalan).

Microfibrils are the insoluble, 10- to 12-nm components of the extracellular matrix that are involved in elastogenesis. Reports of their ultrastructure vary: they have been described as tubular and beaded and as nontubular filaments that are devoid of any periodicity. Ultrastructurally, microfibrils resemble oxytalan fibers that have been observed in peridontal membranes, skin, and other locations. Whether microfibrils have the staining characteristics of oxytalan is difficult to determine in tissues because available light microscopic stains also stain elastin. Calf aortic smooth muscle cells grown in media without added ascorbate provide a unique model for examining the ultrastructure and staining characteristics of chemically defined microfibrils. Microfibrils are the predominant insoluble extracellular protein in such cultures, which do not deposit collagen or elastin. These studies demonstrate that microfibrils are tubular structures with 10- and 12-nm striations and have the same staining characteristics as oxytalan, reacting with aldehyde fuchsin and orcein after oxidation. Microfibrillar protein is enriched in glutamic and aspartic acids and the electron density of microfibrils is enhanced by fixation in the presence of cationic dyes. In such preparation, microfibrils are made visible within the core of amorphous elastin as well as in regions that are free of elastin. The widespread distribution of microfibrils (oxytalan) indicates that their function extends beyond elastogenesis. Their localization within tissues suggests that they serve as an elastic attachment protein in sites that are subject to mechanical stress.

Animals↗
PubMed1982

RBC destruction caused by a micropore blood filter.

Two infants who received whole blood filtered through commercially available woven stainless steel micropore filters experienced a sudden onset of hemoglobinuria. The plasma hemoglobin level in one child was 200 mg/dL. To investigate whether filters might lead to RBC destruction, we experimentally quantitated filter-induced hemolysis using standard conditions. Our studies in vitro show that hemolysis decreases with increased speed to transfusion. Hemolysis is particularly extensive with blood stored more than 14 days, but measurable hemolysis occurs with blood stored for as little as one day.

Blood↗
PubMed1982

beta-Thalassemia in a Kurdish Jew. Single base changes in the T-A-T-A box.

We recently described a "non-random" sequencing procedure for DNA inserts in bacteriophage M13 using Bal 3 nuclease and the dideoxy chain termination method (Poncz, M., Solowiejczyk, D., Ballantine, M., Schwartz, E., and Surrey, S. (1982) Proc. Natl. Acad. Sci. U. S. A., in press). Using this procedure, we have determined the nucleotide sequence of a cloned human beta-globin gene from a Kurdish Jew with beta +-thalassemia major. Comparison with the previously reported human beta-globin gene sequences (1-3) reveals a change in the "T-A-T-A" box. This region 5' to the capping site was previously demonstrated to be critical for the proper transcription in vitro of several different eukaryotic genes (4-7). This is the first report of a T-A-T-A box modification found in association with a spontaneously occurring human genetic disorder. In addition to this mutation, other base changes, an insertion, and a deletion in the cloned gene were found in the 5' and 3' flanking regions.

Base Sequence↗
PubMed1982

"Nonrandom" DNA sequence analysis in bacteriophage M13 by the dideoxy chain-termination method.

We describe a rapid "nonrandom" DNA sequence analysis procedure that facilitates the nucleotide sequence determination of large contiguous regions of DNA. The method consists of cloning a restriction endonuclease fragment of interest into bacteriophage M13 followed by construction of a series of nuclease BAL-31 deletion mutants originating from a single site in M13 that is close to the DNA insert. Determination of the size of the deletion mutant is accomplished by hybridization to a complementary single-stranded probe derived from M13 containing that total insert followed by nuclease S1 treatment. Single-stranded M13-insert DNAs of progressively smaller sizes are isolated and analyzed by using a site-specific M13 DNA primer and the dideoxy chain-termination method. In this way, analysis of the DNA sequence proceeds from one end of the total insert to the other in a nonrandom fashion due to generation of a controlled overlapping set of deletion mutants.

Base Sequence↗
PubMed1982

Changes in the components of extracellular matrix and in growth properties of cultured aortic smooth muscle cells upon ascorbate feeding.

Culture conditions can modify the composition of the extracellular matrix of cultured calf aortas smooth muscle cells. In the absence of ascorbate the major components of the matrix are microfibrillar proteins; deposition of collagen occurs upon ascorbate supplementation and, with increased time of exposure of cells to ascorbate, collagen becomes the dominant protein of the extracellular matrix (greater than 80%). Collagen accumulation follows a sigmoidal time-course, suggesting that it is a cooperative phenomenon. Covalent crosslinks are not required for collagen accumulation in the matrix. Microfibrillar proteins and increased amounts of proteoglycans and fibronectin accumulate concurrently with collagen but elastin deposition was not observed either with or without ascorbate feeding. Addition of ascorbate leads to a general stimulation of incorporation of [14C]proline into cellular protein and to changes in cell growth parameters and morphology: cell-doubling time decreases from 62 to 47 h and plating efficiency increases approximately fourfold. We conclude that the composition of the extracellular matrix assembled by cultured cells is subject to experimental manipulation and that changes in endogenously deposited matrix may have significant effects on cellular functions.

Animals↗
PubMed1982

Effect of cetiedil on cation and water movements in erythrocytes.

Cetiedil is a potential antisickling agent whose major effect appears to be at the erythrocyte membrane. To test the hypothesis that cetiedil alters cation transport, we studied the effect of the drug in promoting changes in cell water (Wc), cell sodium (Nac), and cell potassium (Kc). Results are quite different depending on the presence or near absence of intracellular ATP. With fresh cells, 100 microM cetiedil causes little in the net cation or water movements compared with control cells incubated for 2 h. At cetiedil concentrations greater than 100 microM, however, net movements of sodium and potassium increase considerably, and cell swelling results from a net Nac gain that exceeds a net Kc loss. All water movements can be accounted for by cetiedil-induced net cation movements. When 100 microM ouabain is added along with cetiedil, net Nac gain, net Kc loss, and net Wc gain are all increased compared with results obtained with cetiedil alone. External calcium inhibits cetiedil-induced changes in cation transport. With cells depleted of their ATP, cetiedil inhibits the typical potassium loss that occurs in the presence of external calcium; net sodium uptake changes little under these conditions, regardless of the presence or absence of external calcium. Our findings indicate a complex mode of action for cetiedil on the erythrocyte membrane, and support the hypothesis that the erythrocyte membrane, and support the hypothesis that the antisickling effect of the drug observed in vitro results from dilution of intracellular hemoglobin secondary to net salt and water gain.

Adenosine Triphosphate↗
PubMed1982

Construction of human gene libraries from small amounts of peripheral blood: analysis of beta-like globin genes.

We describe a rapid procedure for constructing cloned human genomic libraries from small amounts of peripheral blood. High molecular weight DNA is isolated from 5-20 ml peripheral blood, partially cleaved with Eco R1, and 8-22 kb fragments are cloned using bacteriophage Charon 4A and suitable E. coli host. Using the approach we have isolated and characterized several non-alpha globin clones from a Kurdish Jew with homozygous beta thalassemia. The ability to isolate suitable amounts of high molecular weight DNA from peripheral blood provides a relatively simple means of constructing human gene libraries representing a variety of hemoglobin disorders.

Base Sequence↗
PubMed1982

An outbreak of pyomyositis in a large refugee camp in Thailand.

During a 2-month period, 17 cases of pyomyositis were seen in the hospital population of a large refugee camp for Cambodians in Thailand. The temporal clustering of the cases suggests an epidemic pattern. Patients in this series were generally young and otherwise healthy. All had gram-positive cocci demonstrated in abscess pus, and all responded to surgical drainage. Fourteen (82%) of the cases were initially misdiagnosed by volunteer physicians who were unfamiliar with the disease. The authors suggest that a mosquito-borne virus predisposes to the development of the pyomyositis abscess.

Abscess↗
PubMed1982

The gamma-delta-beta-globin gene region in G gamma-beta +-hereditary persistence of fetal hemoglobin.

We report restriction endonuclease analysis of the gamma-delta-beta-globin gene region in a mother and child heterozygous for G gamma-beta +-hereditary persistence of fetal hemoglobin (HPFH). The affected chromosome in these persons directs the production of G gamma-chains and beta-chains but not A gamma-chains. DNA was digested with several restriction enzymes and was examined for gamma, delta, beta sequences by blot hybridization. Only normal digestion fragments were present. By sensitive methods, we were unable to detect a deletion in the entire gamma-delta-beta-globin gene region of the affected chromosome, indicating that in this family, G gamma-beta +-HPFH is not due to a large deletion.

Adult↗
PubMed1982

A simple technique for preparation of young red cells for transfusion from ordinary blood units.

We have developed a rapid and simple method for the isolation of relatively young cells from ordinary fresh or previously frozen blood units, using the IBM-2991 Blood Cell Processor. Based on in vitro measurements of red cell pyruvate kinase activity, the resolution of the method is excellent, comparable to that of the stractan discontinuous gradient system. In splenectomized patients with thalassemia major, the administration of the "youngest" 50% of blood units yielded 51Cr survival times of 40 and 42 days for fresh packed red cells and 41 and 43 days for previously frozen red cells.

Blood Transfusion↗
PubMed1982

Theophyllines three times daily - when are the doses actually taken? - Pharmacokinetic ideals versus clinical practice.

We asked patients "At what times of the day do you usually take your medicine?" In contrast to compliance interviews dealing with missed doses, this question was previously shown to give valid information. Here we present results from 126 patients on theophyllines three times daily, the most common dosage schedule for these drugs in Sweden in 1978. Only 2% of the patients stated the ideal 8-h intervals between all doses, while 72% had confined all their doses within 12 h. The first and second intervals ranged from 0 to 11 h with a mean of 5.5 and 6.1 h respectively. The third interval varied from 7 to 18 h with a mean of 12.4 h. Patients might benefit more from their therapy by even-spacing of their intake of theophylline.

Adolescent↗
PubMed1982

The effect of cetiedil on red cell membrane permeability.

We report the effects of cetiedil, a new antisickling agent, on red cell membrane permeability. With fresh red cells containing normal levels of intracellular ATP, cetiedil increases membrane permeability to both sodium and potassium. With drug concentrations from 100 to 500 microM, net sodium gain exceeds net potassium loss, and the cells quickly swell. Changes are identical with normal and sickle red cells. Membrane permeability returns to normal after washing the cells in buffer free of cetiedil. In the absence of phosphate, ouabain potentiates the cetiedil effect. With external phosphate present, the effect of cetiedil is also enhanced, but ouabain is without effect. Our findings support the idea that the antisickling effect of cetiedil observed in vitro is secondary to cell swelling.

Adenosine Triphosphate↗
PubMed1981

Effect of piracetam on sickle erythrocytes and sickle hemoglobin.

Piracetam, 2-oxo-1-pyrrolidine acetamide, inhibits sickling of red cells containing sickle hemoglobin (Hb S). The concentration required for 50% inhibition is about 300 mM. Addition of piracetam into the supersaturated Hb S solution in concentrated phosphate buffer prolongs the delay time prior to gelation. Piracetam shifts the oxygen equilibrium curves of blood toward the right, with a stronger effect at higher piracetam concentrations. Piracetam increases the viscosity of oxygenated cells but reduces the relative viscosity of deoxygenated sickle cells. The mechanism for the antisickling effect of piracetam will be discussed.

Anemia, Sickle Cell↗