Biomedical subjects

A Schlein

Publications and source records attributed to A Schlein.

3 recordsLinked to original sources

PubMed1992

Enterobacter endocarditis.

Endocarditis due to Enterobacter species is very rare. We recently cared for a patient who developed E. cloacae endocarditis following mitral valve replacement with a porcine heterograft, and was successfully treated with antibiotic therapy alone. A review of the literature disclosed an additional 17 well-described cases of enterobacter endocarditis. Two-thirds of the patients had underlying cardiac disease. The mitral valve was most frequently involved (10/16 cases) with 4 of the patients having concomitant aortic valve involvement. The overall mortality rate was 44.4%. Antibiotic therapy of enterobacter endocarditis should consist of the combination of a beta-lactam antibiotic and an aminoglycoside with careful monitoring of blood cultures to assure the adequacy of therapy. Resistance of enterobacter to previously susceptible antibiotics may occur during therapy due to induction of a chromosomally-mediated beta-lactamase, necessitating a change in antimicrobial therapy. Valvular surgery is indicated for patients failing medical management.

Endocarditis, Bacterial↗

PubMed1988

Relationship of pseudopod extension to chemotactic hormone-induced actin polymerization in amoeboid cells.

Aggregation-competent amoeboid cells of Dictyostelium discoideum are chemotactic toward cAMP. Video microscopy and scanning electron microscopy were used to quantitate changes in cell morphology and locomotion during uniform upshifts in the concentration of cAMP. These studies demonstrate that morphological and motile responses to cAMP are sufficiently synchronous within a cell population to allow relevant biochemical analyses to be performed on large numbers of cells. Changes in cell behavior were correlated with F-actin content by using an NBD-phallacidin binding assay. These studies demonstrate that actin polymerization occurs in two stages in response to stimulation of cells with extracellular cAMP and involves the addition of monomers to the cytochalasin D-sensitive (barbed) ends of actin filaments. The second stage of actin assembly, which peaks at 60 sec following an upshift in cAMP concentration, is temporally correlated with the growth of new pseudopods. The F-actin assembled by 60 sec is localized in these new pseudopods. These results indicate that actin polymerization may constitute one of the driving forces for pseudopod extension in amoeboid cells and that nucleation sites regulating polymerization are under the control of chemotaxis receptors.

Actins↗

PubMed1985

Animal models for evaluating the myelosuppressive effects of cancer chemotherapeutic agents.

An important objective of new anticancer drug discovery programs is identification of agents that are less myelosuppressive than those currently available. We have developed several animal models to evaluate these drugs for myelosuppression. Our screening model measures changes in neutrophil counts in mice as an indicator of myelosuppression. This model correctly predicted the myelosuppressive effects of 13 (76%) of 17 known agents. Cisplatin, carboplatin, spiroplatin, and marcellomycin caused no reduction in the neutrophil counts, representing four (24%) of 17 false negatives. Our secondary evaluation system is the more labor-intensive murine CFU-C assay on femoral bone marrow cells from drug-treated mice. Known myelosuppressive drugs such as mitomycin C, doxorubicin, and BCNU, as well as the false negatives from the mouse neutropenia model (cisplatin, carboplatin, spiroplatin, and marcellomycin) caused marked inhibition of colony formation 24 h after dosing; bleomycin was inactive. Advanced evaluations are performed using ferrets in which neutrophil counts can be monitored in the same animal for 28 days after treatment. Mitomycin C, doxorubicin, and BCNU caused significant reductions in the neutrophil counts whereas bleomycin had no effect. Importantly, cisplatin and marcellomycin also caused significant reductions in the neutrophil counts. Although the mouse neutropenia model is a rapid assay, there is potential for false-negative predictions. It is important that other test systems be used for more advanced evaluation of drugs identified by this model as being less myelosuppressive than reference drugs. The mouse CFU-C and ferret hematology models are suitable for this purpose in that they can identify the false-negative predictions as well as identify less myelosuppressive drugs such as bleomycin.

Agranulocytosis↗