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Biomedical subjects

A Stern

Publications and source records attributed to A Stern.

At least 163 records · Page 9Linked to original sources

Binding of iron to human red blood cell membranes.

The binding of Fe3+ to red cell membranes was studied in a system in which lipid peroxidation was proportional to Fe3+ concentration. Binding of Fe3+ was evaluated by labeling with 59FeCl3 and measurement of NMR water-proton relaxation times. Labeling with 59Fe showed that 95% of the Fe3+ was membrane bound at 100 microM FeCl3 in a 1.5 mg protein/ml membrane suspension. Both spin-lattice (T1) and spin-spin (T2) relaxation times decreased with increasing Fe3+ concentration. Addition of red cell membrane suspensions largely prevents the Fe3+ effect on relaxation times. Charge transfer to Fe3+ may occur at the membrane binding site with resultant decrease in the Fe3+ effect on water-proton relaxation times. These studies support the hypothesis that Fe3+ binds to the membrane and generates free radicals at the binding site.

Adult↗

Accidental overdose of multiple chemotherapeutic agents.

A 35-year-old man with refractory low grade diffuse centroblastic centrocytic non-Hodgkin's lymphoma was treated accidentally with an overdose of multiple chemotherapeutic agents. He was given adriamycin 50 mg/m2 and cyclophosphamide 350 mg/m2 for 6 days followed by 4 days of vincristine 1 mg/m2 and bleomycin 10 mg/m2. He was transferred when he developed pancytopenia, fever, severe mucositis, ileus and peripheral neuropathy. He was treated with broad spectrum antibiotics, red cell and single donor platelet transfusions and strict parenteral nutrition. In addition, he was given a continuous infusion of 400 micrograms daily human recombinant granulocyte macrophage-colony stimulating factor (rh GM-CSF) for 17 days. Intractable severe bleeding from his oral mucositis necessitated treatment with a continuous infusion of 8-ornithine-vasopressin for 8 days. He recovered and could be discharged home after 36 days of hospitalization with normal blood counts and without severe sequelae.

Adult↗

Transient cyclic neutropenia following GM-CSF in a patient with chronic granulocytic leukemia transplanted with HLA-identical T cell-depleted donor bone marrow.

Treatment with GM-CSF or G-CSF is becoming widely used in patients with chronic neutropenia, or who are aplastic following chemotherapy or autologous or allogeneic bone marrow transplantation. Recently, some authors have described a phenomenon analogous to cyclic agranulocytosis following treatment with G-CSF in a patient with chronic neutropenia. We wish to describe the same phenomenon in a patient with chronic granulocytic leukemia who received GM-CSF (Sandoz) after T cell depletion in order to accelerate hematological reconstitution.

Agranulocytosis↗

Autoimmune endotheliopathy and chronic herpetic conjunctivitis.

A migrating endothelial line of keratic precipitates associated with overlying corneal edema suggests an immune attack on the corneal endothelium. This is seen most commonly in corneal allotransplantation rejection. The etiology of such lines in the absence of this condition is unclear. We document the presence of an intranuclear virus compatible with herpesvirus in this condition.

Conjunctivitis↗

NMR water-proton spin-lattice relaxation time of human red blood cells and red blood cell suspensions.

NMR water-proton spin-lattice relaxation times were studied as probes of water structure in human red blood cells and red blood cell suspensions. Normal saline had a relaxation time of about 3000 ms while packed red blood cells had a relaxation time of about 500 ms. The relaxation time of a red cell suspension at 50% hematocrit was about 750 ms showing that surface charges and polar groups of the red cell membrane effectively structure extracellular water. Incubation of red cells in hypotonic saline increases relaxation time whereas hypertonic saline decreases relaxation time. Relaxation times varied independently of mean corpuscular volume and mean corpuscular hemoglobin concentration in a sample population. Studies with lysates and resealed membrane ghosts show that hemoglobin is very effective in lowering water-proton relaxation time whereas resealed membrane ghosts in the absence of hemoglobin are less effective than intact red cells.

Adult↗

Unusual cough related stress injuries.

Two cases of unusual cough related stress injuries of the ribs are described. Both were detected on a 2 h delay bone scan. To our knowledge, cough stress injuries have been not previously described scintigraphically.

Adult↗

Screening devices for diminished cognitive capacity.

This study compares three commonly used tests to detect organic mental disorders: the Mini-Mental State (MMS), Cognitive Capacity Screening Examination (CCSE), and Tachistoscope (T-Scope). Ninety-seven medical-surgical inpatients at the Mount Sinai Hospital referred for psychiatric consultation had a Missouri Mental Status Examination performed by a psychiatrist who also rated the patients' organic mental disorder as "none," "mild," "moderate," or "severe." The CCSE, MMS, and T-Scope, respectively, showed: sensitivity--0.54, 0.52, 0.68; specificity--0.85, 0.76, 0.79; and positive predictive value--0.83, 0.74, 0.79. False negatives occurred more often among those patients with mild organic mental disorders with all instruments (p = 0.05), while the T-Scope could not be administered in 27% of the patients. Screening instruments with increased acceptability, sensitivity, and specificity need to be developed to identify a potentially life-threatening disorder.

Adult↗

The Arthus reaction in domestic cats.

A classic Arthus reaction was elicited in normal domestic cats using chicken red blood cells as antigen. The response was quantitated grossly by measuring the area of the resulting skin bleb at several set time intervals and by microscopic examination of biopsies taken at the conclusion of each of the trials. This method produced an intense Arthus reaction in each of the cats tested.

Animals↗

Evaluation of right and left ventricular function in hard metal workers.

Ingested cobalt has previously been associated with the development of a congestive cardiomyopathy. Despite occasional reports of cardiomyopathy after industrial exposure to cobalt, this association remains controversial. In a study of 30 cemented tungsten carbide workers with a mean duration of exposure to cobalt of 9.9 +/- 5.3 years radionuclide ventriculography was performed to study right and left ventricular ejection fractions at rest and exercise. For the entire group, rest and exercise biventricular function was normal. There was, however, a weak but significant inverse correlation between duration of exposure and resting left ventricular function (r = -0.40, p less than 0.03). Workers with abnormal chest x ray findings (9/30) had relatively lower exercise right ventricular ejection fractions (45% +/- 6 v 52% +/- 7, p less than 0.02). An inverse relation was also found between rest and exercise right ventricular ejection fraction and severity of parenchymal abnormalities on x ray examination (r = -0.44, p less than 0.01 and r = -0.41, p less than 0.02). Diminished right ventricular reserve was probably due to fibrotic lung disease and early cor pulmonale. Although overt left ventricular dysfunction was not present, prolonged exposure to industrial cobalt may be a weak cardiomyopathic agent with unknown long term significance.

Adult↗

Influence of exogenous iron and ascorbate on H2O2-induced glutathione oxidation in red cells.

The effective fall in cytosolic reduced glutathione levels in intact red cells exposed to exogenous oxidant stress in the form of Fe2+, H2O2 and ascorbate was caused by H2O2 alone. Relatively high concentrations of Fe2+ had no contributory effect on the oxidizing capacity of H2O2. Ascorbate, at physiological levels, showed no protection whereas glucose was totally protective. Since glucose, via hexose monophosphate shunt, is the only source of reducing equivalent in red cells, the NADPH/NADP+ redox role in the diminution of intracellular reduced glutathione.

Ascorbic Acid↗

Inhibition of mammalian fatty acid synthetase activity by NADP involves decreased mobility of the 4'-phosphopantetheine prosthetic group.

Mammalian fatty acid synthetase carrying a 3-keto, 3-hydroxy, or 2-enoyl acyl-enzyme intermediate on the 4'-phosphopantetheine thiol is reversibly inhibited by binding of NADP to the enoyl reductase domain. Acyl moieties which can normally leave the enzyme by thioester hydrolysis or by transfer to a CoA acceptor cannot readily be removed from the NADP-inhibited enzyme; in addition, 3-keto or 2-enoyl moieties attached to the enzyme 4'-phosphopantetheine cannot readily be reduced when NADP is replaced by NADPH, even though model substrates can be reduced immediately. Reactivation of the NADP-inhibited 3-ketoacyl-enzyme, by exposure to NADPH, is paralleled by reduction and dehydration of the 3-ketoacyl moiety to a saturated acyl moiety without accumulation of either the 3-hydroxy or 2-enoyl acyl-enzyme intermediates, indicating that once the 4'-phosphopantetheine engages the ketoacyl moiety in the ketoreductase domain, subsequent reactions occur very rapidly. The results are consistent with a hypothesis which proposes that NADP binding to the enoyl reductase domain of fatty acid synthetase carrying an acyl intermediate other than a saturated moiety induces a conformational change in the enzyme that results in decreased mobility of the 4'-phosphopantetheine prosthetic group. Normal mobility of the prosthetic group, essential for transfer of acyl-enzyme intermediates through the active sites of the various functional domains, is restored relatively slowly when NADP is replaced by NADPH. It remains to be determined whether this modulation by pyridine nucleotides observed in vitro plays a role in the regulation of fatty acid synthetase activity in vivo.

Animals↗

Fluorescent properties of merocyanine 540 in solutions of sialogangliosides.

The spectral modifications in the absorption and emission properties of merocyanine 540 have been evaluated in solvents of varying dielectric constants. The fluorescence behavior of dye in solutions of low dielectric constant has offered a possibility for monitoring the micropolarity of sialoganglioside micelles in aqueous solutions. Our results demonstrate that sialic acid residues markedly influence the aggregation properties of gangliosides in solution as well as the nature of dye binding to the micellar structures.

Electrochemistry↗

Oxidative reactivity of the tryptophan metabolites 3-hydroxyanthranilate, cinnabarinate, quinolinate and picolinate.

The oxidative reactivities of four tryptophan metabolites in the kynurenine pathway were examined as a potential mechanism for their reported neurotoxicities and carcinogenicities. Neither quinolinic acid, a neurotoxin, nor its monocarboxylic analogue, picolinic acid, auto-oxidized over a wide pH range. However, 3-hydroxyanthranilic acid (3-HAT), a carcinogen, readily auto-oxidized and the reaction rate increased exponentially with increasing pH. 3-HAT auto-oxidation likely involves two steps: auto-oxidation of 3-HAT to the semiquinoneimine (anthranilyl radical) which oxidizes to the quinoneimine, followed by condensation and oxidation reactions to yield a second carcinogen, cinnabarinic acid. 3-HAT auto-oxidation to cinnabarinate required molecular oxygen and generated superoxide radicals and H2O2. Superoxide dismutase (SOD) accelerated 3-HAT auto-oxidation 4-fold, probably by preventing back reactions between superoxide and either the anthranilyl radical or the quinoneimine formed during the initial step of auto-oxidation. Catalase did not accelerate 3-HAT auto-oxidation, but it did prevent destruction of cinnabarinate by H2O2. Interconversion between oxyhemoglobin and methemoglobin occurred during 3-HAT auto-oxidation, although neither form of hemoglobin altered rates of 3-HAT auto-oxidation. Mn2+, Mn3+ and Fe3+-EDTA did not directly catalyze cinnabarinate formation in the absence of O2, but they did accelerate cinnabarinate formation under aerobic conditions.

3-Hydroxyanthranilic Acid↗