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Biomedical subjects

L R Berkowitz

Publications and source records attributed to L R Berkowitz.

28 records · Page 2Linked to original sources

Cetiedil inhibition of calmodulin-stimulated enzyme activity.

Cetiedil, an in vitro anti-sickling agent, inhibited calmodulin-stimulated cyclic 3':5'-nucleotide phosphodiesterase (EC 3.1.4.17) and Ca2+-ATPase (ATP phosphohydrolase, EC 3.6.1.3) activities. The drug had no effect on basal enzyme activities in the absence of calmodulin. The inhibition of phosphodiesterase was competitive with respect to the concentrations of both cAMP and calmodulin. Cetiedil did not inhibit calmodulin-stimulated enzyme activities by acting as a calcium chelator, since increasing the concentration of calcium did not reverse the inhibitory effect.

Antisickling Agents↗

An analysis of the mechanism by which cetiedil inhibits the Gardos phenomenon.

Energy depletion in the human erythrocyte causes a rise in intracellular calcium. This in turn accelerates the transmembrane movement of potassium and chloride, resulting in cell dehydration. This process, known as the Gardos phenomenon, is inhibited by cetiedil. The present study examines the mechanism by which cetiedil inhibits the Gardos phenomenon. The ability of cetiedil to retard the initial step in the Gardos phenomenon, a rise in intracellular calcium, was first tested. Cetiedil did not prevent calcium accumulation. Cetiedil's ability to inhibit anion movement was next evaluated, as cetiedil could appear to be blocking K movement when in fact it was preventing the movement of its accompanying anion. No inhibitory effect on anion movement was seen. Since cetiedil prevented neither calcium accumulation nor anion movement, it must inhibit the Gardos phenomenon by preventing the opening of the K-specific gate in the erythrocyte membrane. The fact that cetiedil's effect on the Gardos phenomenon could not be removed with repeated cell washing indicates that this effect is irreversible.

Adenosine Triphosphate↗

Effects of cetiedil on monovalent cation permeability in the erythrocyte: an explanation for the efficacy of cetiedil in the treatment of sickle cell anemia.

Cetiedil, a drug reported to relieve painful crises in sickle cell anemia, has direct antisickling properties in vitro. However, neither oxygen affinity nor the solubility of deoxyhemoglobin S is altered by cetiedil. Due to the great influence the concentration of hemoglobin S has on the kinetics of gelation, we hypothesized that cetiedil might inhibit sickling by modifying erythrocyte Na+ or K+ movements in a manner which would prevent a rise in the concentration of intracellular hemoglobin. Cetiedil has two such effects: It causes a rise in passive Na+ movements and it inhibits a specific increase in K+ permeability secondary to a rise in cytoplasmic Ca2+ concentration. Cetiedil then may represent an alternate type of antisickling agent, exerting its effect through changes in erythrocyte membrane cation permeability rather than directly modifying hemoglobin S.

Anemia, Sickle Cell↗

Effect of cetiedil, an in vitro antisickling agent, on erythrocyte membrane cation permeability.

Cetiedil has been reported to relieve painful crises in sickle cell anemia and to have antisickling properties in vitro. The drug alters neither oxygen affinity nor the solubility of deoxyhemoglobin S. Because the viscosity of the erythrocyte interior and the kinetics of gelation are dependent on the concentration of hemoglobin, we postulated that cetiedil might inhibit sickling by modifying erythrocyte sodium or potassium movements in a manner that would increase cell water content and thus dilute the cell hemoglobin. The drug has two such effects: it inhibits the specific increase in potassium permeability that follows a rise in cytoplasmic calcium concentration and it causes a rise in passive sodium movements. These effects are further evidence that cell ion and water movements may be important in the process of sickling and suggest a mechanism for the results reported with cetiedil.

Anemia, Sickle Cell↗

Hairy cell leukemia with acquired dyserythropoiesis.

Dyserythropoiesis, a qualitative abnormality of erythrocyte production, is described in a patient with hairy cell leukemia (leukemic reticuloendotheliosis). The development of a second population of circulating RBCs with a mean corpuscular volume of 154 cu mu suggests the emergence of an abnormal clone of marrow erythrocyte precursors.

Erythrocytes↗

Thrombotic thrombocytopenic purpura: a pathology review.

A retrospective analysis of 12 patients with the diagnosis of thrombotic thrombocytopenic purpura was undertaken with a review of pathological material. The gingival biopsy was found to be a poor method of diagnosing thrombotic thrombocytopenic purpura. Pathological review also verified chronicity of disease. The pancreas was found to be the most severely involved organ, although serum amylase values did not always reflect pancreatic disease.

Adrenal Glands↗

Validity of the in-training examination for predicting American Board of Internal Medicine certifying examination scores.

OBJECTIVE: To determine whether the results of the Internal Medicine In-Training Examination (ITE) can predict subsequent performance on the American Board of Internal Medicine certifying examination (ABIMCE). DESIGN: Retrospective data review. SETTING: A mixture of six community hospital and university-based internal medicine training programs in the Eastern United States. SUBJECTS: 109 residents who first took the ABIMCE in 1988 or 1989, and who had also taken at least one ITE. MEASUREMENTS: Scores for the composite and subspecialty sections of the ITE were compared with those for the ABIMCE. An R2 was obtained to relate the scores on the two examinations. A cutoff score was derived to maximize the ability of the ITE to discriminate between residents who were likely to pass and those who were likely to fail the ABIMCE. MAIN RESULTS: ABIMCE scores were available for 109 residents who had also taken the ITE during PGY-2 (19), PGY-3 (50), or both years (40). Composite scores on the ABIMCE were highly correlated with those on the ITE-PGY-2 (R2 = 0.593) and the ITE-PGY-3 (R2 = 0.677) (p less than 0.0001 for each). Most of the subspecialty sections on the two examinations were significantly correlated, although less strongly (range of R2 = 0.041 to 0.32) than were the composite scores. An empirically derived cutoff score of the 35th percentile on the ITE-PGY-2 had a positive predictive value of 89% (probability of passing ABIMCE) and a negative predictive value of 83% (probability of failing ABIMCE). CONCLUSIONS: Performance on the ITE can accurately predict and is highly correlated with performance on the ABIMCE. ITE results may therefore be useful in counseling residents about their educational needs in preparation for the ABIMCE.

Certification↗