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Biomedical subjects

W Lewis

Publications and source records attributed to W Lewis.

At least 91 records · Page 5Linked to original sources
PubMed1986

Anthracycline effects on actin and actin-containing thin filaments in cultured neonatal rat myocardial cells.

Adriamycin (ADR, Doxorubicin) effects on actin and other proteins in cultured neonatal rat cardiac myocytes were investigated. Heart cells were exposed to ADR in doses of 10(-8) M to 10(-5) M for 24 hours. Cells were harvested in 2 mM of Tris buffer containing Triton X-100, homogenized and centrifuged in a microfuge. Parallel dishes of cultured cardiac myocytes were washed in buffered saline and were fixed at 4 degrees C in Karnovsky's fixative. The supernatant solutions were dialyzed and then incubated with pancreatic DNAase I to quantify actin by enzyme inhibition. In parallel studies, both cell supernatant solutions and pellets were subjected to sodium dodecyl sulfate polyacrylamide gel electrophoresis and the stained polypeptide bands were quantified by densitometry. Results showed that heart cells exposed to 10(-6) M of ADR for 24 hours had unpolymerized actin levels reduced to 7.7 micrograms/10(6) cells (as measured by DNAase I inhibition or by sodium dodecyl sulfate polyacrylamide gel electrophoresis along with densitometry) compared to 11.0 micrograms/10(6) cells in untreated culture heart cells. When ADR concentration was 10(-7) or 10(-8) M, unpolymerized actin levels were similar to the levels of untreated heart cells. Protein content of extract solutions of untreated and ADR-treated myocytes were 1.2 mg/ml and 0.8 mg/ml, respectively. Gel densitometry of electrophoretograms showed actin to account for 12 to 16% of total density of bands on sodium dodecyl sulfate polyacrylamide gel electrophoresis. Comparative densitometry of ADR-treated cells treated with 10(-6) M of ADR show depolymerized actin to account for 77% of total actin. Ultrastructural results show a large clear cytoplasmic zone of disorganized 12 to 14-nm filaments in cultured myocytes exposed to 10(-6) M ADR. Little change in myocyte ultrastructure was seen at 10(-7) M or 10(-8) M ADR exposure. Data support ADR as a cellular disruptor with toxic effects on cardiac cytoplasmic and contractile proteins and filaments. This ADR effect on heart cells in culture is dose-related.

Actins↗
PubMed1985

Doxorubicin and covalently crosslinked doxorubicin derivatives binding to purified cardiac thin-filament proteins in vitro.

The binding of cardiac actin and tropomyosin to a cardiotoxic antineoplastic agent, doxorubicin, and its covalently crosslinked derivatives was investigated. The primary amino group of the daunosamine moiety of doxorubicin was blocked with fluorescein isothiocyanate. This doxorubicin derivative did not bind to Sepharose which was conjugated with cardiac actin. A doxorubicin dimer was made by covalently crosslinking one doxorubicin molecule to another identical doxorubicin molecule through the free amino group of each daunosamine moiety. This derivative demonstrated mobility different from parent doxorubicin on thin-layer chromatography, different elution pattern by column chromatography, and did not show binding affinity for actin. Exploring other purified thin-filament proteins, it was found that doxorubicin did bind to tropomyosin when gel filtration was performed on the protein drug mixture. The ability of tropomyosin to form paracrystal in vitro was not disturbed by a variety of concentrations of doxorubicin. These data support the concept that the doxorubicin solitary free amino group is the site which is responsible for this ligand to bind to actin and may relate to its cardiotoxic effects.

Actins↗
PubMed1985

Cardiac lesions in acquired immune deficiency syndrome (AIDS).

Autopsy findings in 41 patients with acquired immune deficiency syndrome (AIDS) were reviewed. Major pathologic findings in the heart were demonstrated in 10 cases, and metastatic Kaposi's sarcoma in either the epicardium or myocardium was revealed in 4 cases, including 1 with additional fibrinous pericarditis. Nonbacterial thrombotic endocarditis with embolization to major organs was found in three cases, isolated fibrinous pericarditis of unknown origin was found in two and Cryptococcus neoformans myocarditis was found in one case. The primary cause of death in eight cases was pulmonary or systemic infection. Two patients died of thromboembolic disease. These findings suggest that cardiac lesions in AIDS relate to both morbidity and mortality.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Adherence of Candida to corneal surface.

In the pathogenesis of mycotic infections, adherence of the microbes to surface structures prior to invasion appears to be the initial and essential step in a susceptible host. Adherence and inhibition of adherence of Candida albicans to rabbit corneal surface was investigated in vitro by light and scanning electron microscopic examinations. The results indicate that blastospores of Candida albicans rarely bind to intact corneal epithelium, but consistently adhere to stroma denuded of epithelium. Such adherence was inhibited by concanavalin A. With its strong affinity for the yeast cell wall carbohydrate mannan, concanavalin A may block the site of attachment of yeast cells to the corneal surface.

Animals↗
PubMed1985

Dilated cardiomyopathy associated with Friedreich's ataxia.

Friedreich's ataxia (FA) is a progressive, spinocerebellar, degenerative, neuromuscular disease that is frequently associated with hypertrophic cardiomyopathy as part of the clinical illness. Hypertrophic cardiomyopathy associated with FA can be seen with or without obstruction to the left ventricle outflow tract. We present the postmortem findings in a case of FA with dilated (congestive) cardiomyopathy. At autopsy, the heart was enlarged with all four chambers dilated; no ventricular hypertrophy or aortic outflow obstruction was present. Microscopic sections of myocardium revealed myocyte hypertrophy, atrophy, and focal interstitial fibrosis. Findings of dilated cardiomyopathy at necropsy supported the antemortem clinical impression. Although FA has been reported to be associated rarely with dilated cardiomyopathy, postmortem documentation of dilated cardiomyopathy with FA has not been shown previously, to our knowledge. The mechanism of either form of myocardial disease in patients with FA is presently speculative.

Adolescent↗
PubMed1983

Compartmentalization of adriamycin and daunomycin in cultured chick cardiac myocytes. Effects on synthesis of contractile and cytoplasmic proteins.

The affinity of two anthracycline antineoplastics [( 14C]adriamycin and [14C]daunomycin) for cultured embryonic chick heart cells was determined by measuring their uptake, compartmentalization into subcellular fractions, and effects on the synthesis of cytoplasmic and cytoskeletal proteins. Both drugs, at micromolar concentrations, were readily uptaken by myocytes and found to be concentrated in a light-buoyant-density fraction containing no lysosomes. Nuclear 14C drug content accounted for 20-25% of the drug incorporated. Binding of adriamycin was saturable within 90 minutes of drug exposure, and the uptake of [14C]adriamycin was inhibited 50% by verapamil and adenosine triphosphate. Uptake of [14C]daunomycin was not influenced by these compounds. Cytosolic and contractile protein synthesis measured by [35S]methionine incorporation into proteins was blocked 70% overall in each fraction after 6 hours of incubation with 2 microM adriamycin. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis followed by autoradiography and quantitative densitometry, revealed that actin synthesis was the least affected of the major proteins. Cardiac myocytes incubated for short periods of time with 2 microM adriamycin revealed subtle cytoplasmic changes in their organelles with the appearance of clear zones of cytoplasm containing short unorganized microfilaments. The deleterious effects of anthracyclines in heart cells are manifested early by rapid drug incorporation into myocytes and inhibition of cytoplasmic protein synthesis.

Animals↗
PubMed1982

The distribution of the glycosaminoglycans in the anatomic components of the lung and the changes in concentration of these macromolecules during development and aging.

The glycosaminoglycans of the normal human and bovine lungs and of the major structural components of these organs (pleura, 'alveoli', peripheral and central bronchi, arteries and veins) were investigated. To carry out this study, a micromethod for the separation and quantitative determination of these macromolecules, namely two-dimensional electrophoresis on cellulose acetate plates, was employed. This procedure made it possible to measure the content of each glycosaminoglycan present in the mentioned anatomic components. In the human lung the distribution of the glycosaminoglycans varies considerably from one component to another: dermatan sulfate was the predominant mucopolysaccharide of the pleura, chondroitin 6-sulfate that of the central bronchi, and heparan sulfate and chondroitin sulfate those of the alveoli. Heparin and keratan sulfate were not detected in any of the structural components. Significant changes in the mucopolysaccharide levels were found during maturation and aging. Further age-related changes were noted between 22 and 39 years. In the bovine lung significant changes in the glycosaminoglycan levels were also observed during growth and aging. Heparin appeared in the lung at an age between 1 and 16 months. Similarities and differences in the total contents and compositions of the glycosaminoglycans between the human and bovine lung were noted.

Adolescent↗
PubMed1982

Lack of cytotoxicity of ticrynafen in primary cultures of rat liver cells.

Primary cultures of hepatocytes obtained from neonatal Sprague-Dawley rats were grown in arginine-deficient, ornithine-supplemented medium to inhibit fibroblastic overgrowth and to selectively isolate relatively pure cultures of parenchymal hepatocytes. This system of primary hepatocytes was used to study the potential cytotoxicity of ticrynafen by measuring cytoplasmic enzyme leakage, cell viability,, and total protein per culture dish. Hepatic cultures were treated with the drug in concentrations ranging from 10(-3)M to 10(-6)M and for durations from 2 to 8 h. The results of the study indicate that ticrynafen was minimally toxic to the hepatocytes.

Animals↗
PubMed1982

Interaction of adriamycin in vitro with cardiac myofibrillar proteins.

Binding of the anthracycline antibiotic doxorubicin [Adriamycin (ADR)] to selected cardiac muscle contractile proteins was determined in purified canine heart actin and alpha-actinin. Adriamycin binding to these proteins in solution was measured by equilibrium dialysis and gel filtration with [14C]-labeled ADR. Adriamycin did not bind when its primary amino group was blocked. Adriamycin binding did not affect actin polymerization as detected by viscometry. Viewed under the electron microscope, however, ADR promoted formation of distinct actin filaments in the presence of microM amounts of ATP without K+ and MG++. Adriamycin-induced actin microfilaments were thicker (120 A) than those of F-actin controls (70 A) and stimulated myosin-ATPase to higher levels than the F-actin controls. It appears that ADR has a direct effect on the biophysical and biochemical properties of heart myofibril proteins in vitro.

Actinin↗
PubMed1975

Bacteremia on an obstetric-gynecologic service.

In a one-year evaluation of the Obstetric-Gynecologic Services of the Los Angeles County University of Southern California Medical Center, bacteremia was confirmed on 144 occasions in 139 patients. This represented an over-all incidence of 7/1,000 admissions with gram-negative bacteremia observed in 3.1/1,000 admissions. There were four deaths in this series. The most frequently recovered aerobes were Escherichia coli, enterococci, and beta hemolytic streptococci, not Group A or D, while the most commonly isolated anaerobes were peptostreptococci, peptococci, and Bacteroides. These patterns of bacterial isolation should be acknowledged in antibiotic strategies for septic patients. There is a positive correlation between the incidence of intrapartum maternal and fetal monitoring and postpartum maternal bacteremia. The oncology patients were the most seriously ill women with bacteremia.

Adolescent↗