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Biomedical subjects

M S Segal

Publications and source records attributed to M S Segal.

At least 19 recordsLinked to original sources

Effect of pH, ionic charge, and osmolality on cytochrome c-mediated caspase-3 activity.

Cytochrome c-mediated activation of caspase-3 is the final common pathway for most signals that induce apoptosis. Before release of cytochrome c from mitochondria, K(+) and Cl(-) efflux and intracellular acidification must occur. We have utilized an in vitro assay to examine the role of pH, cations, anions, and uncharged molecules on the process of cytochrome c-mediated activation of procaspase-3. In this cell-free system, a pH above 7.4 severely suppressed the activation of procaspase-3 but not the activity of caspase-3. KCl, NaCl, and other salts all inhibited caspase activation, but uncharged molecules did not. Comparison of the inhibitory capacity of various salts suggests that the crucial element in causing suppression is the cation. The inhibition of alkaline pH could be overcome by increasing concentrations of cytochrome c, whereas the inhibition of ionic charge could not, suggesting that pH and salts affect the activation of caspase-3 by different mechanisms.

Apoptosis↗

Disulfide bond formation during the folding of influenza virus hemagglutinin.

To study the importance of individual sulfhydryl residues during the folding and assembly in vivo of influenza virus hemagglutinin (HA), we have constructed and expressed a series of mutant HA proteins in which cysteines involved in three disulfide bonds have been substituted by serine residues. Investigations of the structure and intracellular transport of the mutant proteins indicate that (a) cysteine residues in the ectodomain are essential both for efficient folding of HA and for stabilization of the folded molecule; (b) cysteine residues in the globular portion of the ectodomain are likely to form native disulfide bonds rapidly and directly, without involvement of intermediate, nonnative linkages; and (c) cysteine residues in the stalk portion of the ectodomain also appear not to form intermediate disulfide bonds, even though they have the opportunity to do so, being separated from their correct partners by hundreds of amino acids including two or more other sulfhydryl residues. We propose a role for the cellular protein BiP in shielding the cysteine residues of the stalk domain during the folding process, thus preventing them from forming intermediate, nonnative disulfide bonds.

Amino Acid Sequence↗

Clinical use of non-invasive method for determining oxygen saturation: ear oximetry.

Oxygen saturation can be estimated by measuring the absorption properties of the arterialized blood perfusing the ear. Simultaneous determination of oxygen saturation by blood gas and ear oximetry showed no statistical difference. This non-invasive method allows rapid and accurate monitoring of the oxygenation status of patients with respiratory insufficiency.

Cough↗

Gas exchange and arterial blood gas tensions to terbutaline sulfate in older patients with reversible airway obstruction.

Ten patients 55 years and older, known to have chronic obstructive airway disease with reversible component and who had required daily sympathomimetics for many years, were studied. At a clinically stable state in a sitting position, spirometry, ventilation, gas exchange, diffusion and arterial blood gas determinations were performed before and 10, 30, 60 and 120 minutes after administration of 0.5 mg of terbutaline sulfate by inhalation. Although changes were small, significant improvement in FEV1 remained even two hours after inhaling terbutaline. Increase of conducting airways reflected an increase of dead space for 120 minutes. Early rise of alveolar-arterial oxygen tension (PAO2-PaO2) with decreased arterial oxygen tension was observed. This was a transient phenomenon and not severe enough to warrant immediate therapy. No significant EKG or blood pressure changes were noted throughout the study. It appears that terbutaline, an effective long acting bronchodilator, can be safely administered to older patients with bronchospasms.

Aged↗

Sudden disappearance of electrocardiographic pattern of anteroseptal myocardial infarction. Result of superimposed acute posterior myocardial infarction.

In a 76-year-old man an electrocardiographic pattern of acute anteroseptal myocardial infarction disappeared suudenly. At necropsy, a more recent posterior myocardial infarct was found, in addition to an acute anteroseptal infarct. "Normalization" of the electrocardiogram from the pattern of anteroseptal myocardial infarction in this case resulted from the loss of opposing electromotive forces in the posterior wall because of posterior infarction.

Aged↗

Isoproterenol aerosols.

Notable acute improvement in pulmonary function in the majority of 32 patients with known bronchial asthma followed two inhalations of Isoproterenol. No deleterious clinical or cardiovascular effects of EKG changes (after one-half hour) were observed. A slight drop in blood pressure was noted in previously hypertensive patients. Isoproterenol's short duration of effects is ideal and one or two inhalations spaced four hours apart may be safely recommended for the relief of the acute asthma paroxysm.

Adolescent↗