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Biomedical subjects

J Martinez

Publications and source records attributed to J Martinez.

At least 469 records · Page 26Linked to original sources

The effect of androgens on DNA synthesis by fetal hemopoietic stromal cells.

Fibroblast-like stromal cells from mid-term fetal bovine liver and bone marrow were grown in liquid culture. The low proliferative activity of these cells is highly increased by serum, after entering a quiescent stage by a serum step-down stimulus. In such condition, androgens stimulate DNA synthesis in stromal cells derived from liver. An inhibitory effect, however, was observed in stromal cells from fetal bone marrow.

Androgens↗

The role of sialic acid in the dysfibrinogenemia associated with liver disease: distribution of sialic acid on the constituent chains.

To further evaluate the role of sialic acid in the dysfibrinogenemia associated with liver disease, we studied the effect of removal of excess sialic acid residues from the fibrinogen of five patients with liver disease on the thrombin time and fibrin monomer aggregation. Patient fibrinogens containing 1.4-3.4 residues of sialic acid per molecule in excess of normal controls, with thrombin times 12-22 sec longer than normal and with abnormal fibrin monomer aggregation, were stripped of their excess sialic acid by incubation with Vibrio cholerae neuraminidase, followed by rapid removal of the enzyme by antineuraminidase antibody affinity chromatography. These partially desialylated patient fibrinogens, with a normal number of sialic acid residues remaining, exhibited normal thrombin times and normal fibrin monomer aggregation. Sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of reduced normal, patient, and partially desialylated patient (sialyl-3H)-fibrinogen exhibited 60% of the radioactivity in the B beta chain and 40% in the gamma chain. There was no radioactivity detectable in the A alpha chain. These studies provide additional evidence that the increased sialic acid content of the acquired dysfibrinogenemia of liver disease is responsible for its functional defect and that the excess sialic acid is distributed on the B beta chain and gamma chains of the fibrinogen.

Afibrinogenemia↗

Activated N-nitrosocarbamates for regioselective synthesis of N-nitrosoureas.

A practical and convenient method for synthesizing antitumor compounds, N-alkyl-N-nitrosoureas, regioselectively nitrosated on the nitrogen atom bearing the alkyl group is proposed. N-Alkyl-N-nitrosocarbamates are interesting intermediates in these syntheses and yield, by reaction with amino compounds, the regioselectively nitrosated N-alkyl-N-nitrosoureas. As an interesting example, N,N'-bis[(2-chloroethyl)nitrosocarbamoyl]cystamine, a new attractive oncostatic derivative, has been prepared. The cytotoxic activity of these various compounds were tested on L1210 leukemia.

Animals↗

Synthesis and some pharmacological properties of Z-Tyr(SO3H)-Met-Gly-Trp-Met-Asp(Phe-NH2)-OH, a 32-beta-aspartyl analogue of cholecystokinin (pancreozymin) 27-33.

The heptapeptide carbobenzoxy-L-tyrosyl(O-sulfate)-L-methionylglycyl-L-tryptophyl-L-methionyl-L- aspartyl-beta-L-phenylalanine amine (Z-32-beta-Asp-CCK-27-33) was synthesized and tested for its ability to stimulate secretion from dispersed pancreatic acini in vitro, to increase protein secretion from cat pancreas in vivo, and to cause contraction of guinea pig gallbladder in situ. In increasing amylase secretion in vitro, the Z-32-beta-Asp-CCK-27-33 was equal in efficacy with but approximatively one-third as potent as the Boc-CCK-27-33, and when tested in vivo its activity is approximately 10 Ivy dog units (Idu)/microgram. In stimulation of the contraction of the gallbladder, it showed an activity lower than 1 Idu/microgram. This analogue has more pancreozyminic activity than cholecystokin-like activity. This seems to indicate different affinities for the two receptors.

Amylases↗

Captopril as treatment for patients with pulmonary hypertension. Problem of variability in assessing chronic drug treatment.

We gave captopril, an angiotensin converting-enzyme inhibitor, to four patients with unexplained pulmonary hypertension to see if it would lower pulmonary arterial pressure or pulmonary vascular resistance. The patients were studied at rest and during supine bicycle exercise, before and after 48 hours of captopril treatment (up to 450 mg/day). During the treatment, each patient was monitored, with systemic and pulmonary pressures measured hourly, and cardiac output every two to four hours. We found no significant effect of captopril, either at rest or with exercise, on the cardiac output, pulmonary artery pressure, or pulmonary vascular resistance, measured at the end of 48 hours treatment. We noted, however, that during the 48 hour period, all patients showed pronounced swings in their pulmonary and systemic artery pressures and cardiac outputs that had no relation to the administration of captopril or time of day. We conclude that captopril appears to be ineffective in causing a sustained reduction in the pulmonary artery pressure or pulmonary vascular resistance in patients with primary pulmonary hypertension. It appears, however, that these patients experience spontaneous variability in their pulmonary resistance from hour to hour which needs to be further studied before a reliable assessment of long-term drug treatment can be made.

Adult↗

Selective modification of the ability of cholecystokinin to cause residual stimulation of pancreatic enzyme secretion.

In the C-terminal heptapeptide of cholecystokinin (-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2), replacing the aspartic acid residue by beta-aspartic acid did not alter the ability of the peptide to cause stimulation, desensitization, or residual stimulation of enzyme secretion from dispersed pancreatic acini. Replacing the tyrosine sulfate residue by hydroxynorleucine sulfate did not alter the ability of the heptapeptide to cause stimulation or desensitization, but caused a 50-fold decrease in the potency with which the peptide caused residual stimulation of enzyme secretion. These findings suggest that a modification of the N-terminal region of cholecystokinin heptapeptide, which does not alter the ability of the peptide to bind to its receptor on pancreatic acini and by so doing cause stimulation and desensitization of enzyme secretion, can increase the rate at which the bound peptide dissociates when the acini are washed and reincubated. This increased dissociation is reflected by a reduction in the potency with which the peptide causes residual stimulation of enzyme secretion.

Amylases↗

The importance of the amino acid in position 32 of cholecystokinin in determining its interaction with cholecystokinin receptors on pancreatic acini.

In the C-terminal heptapeptide of cholecystokinin, replacement of the penultimate residue, aspartic acid, by beta-alanine caused a 300-fold decrease in the potency with which the peptide stimulated enzyme secretions, whereas replacement by glutamic acid caused a 1000-fold decrease in potency. The beta-alanine-substituted peptide was approximately ten times more potent when the n terminus was blocked with t-butyloxycarbonyl than when it was blocked with benzyloxycarbonyl, and the glutamic acid-substituted peptide was approximately twice as potent when the N terminus was blocked with t-butyloxycarbonyl than when it was blocked with benzyloxycarbonyl. Changes in the ability of the peptide to stimulate amylase secretion were accompanied by corresponding changes in the ability of the peptide to inhibit binding of 125I-labeled cholecystokinin. The magnitude of stimulation of enzyme secretion caused by a maximally effective peptide concentration was the same with each analogue as it was with the unaltered peptide. Replacing the aspartyl residue by beta-alanine or glutamic acid or replacing the N-terminal t-butyloxycarbonyl moiety by benzyloxycarbonyl caused an equivalent decrease in the ability of the peptide to stimulate enzyme secretion and its ability to cause residual stimulation of enzyme secretion. In contrast, the N-terminal desamino analogue of cholecystokinin heptapeptide was ten times less potent than the unaltered peptide in stimulating amylase secretion, but 100 times less potent than the unaltered peptide in causing residual stimulation of enzyme secretion.

Alanine↗

Bactericidal activity of tuftsin.

The biological activities of the phagocytosis stimulating tetrapeptide, Thr-Lys-Pro-Arg are discussed. A brief account on the stimulation by tuftsin of phagocytosis of various particles, including bacteria was reported. Stimulation of bactericidal activity by this tetrapeptide was investigated in vitro as well as in vivo. The potency of tuftsin to enhance blood clearing of Staphylococcus aureus, Listeria monocytogenes, Escherichia coli and Serratia marcescens by mouse peritoneal macrophages was demonstrated. Bactericidal activity and effects of tuftsin on this phenomenon were studied in liver and spleen of mice. Tuftsin stimulates these activities. Same experiments were performed in infected leukemic mice by Serratia marcescens or Escherichia coli. Results on blood clearing and bactericidal activities in liver and spleen were reported and compared to those of healthy and leukemic untreated animals. Tuftsin was found to present interesting stimulatory effects on the bactericidal activity of phagocytes.

Animals↗

Prevention of spontaneous tumors of aged mice by immunopharmacologic manipulation: study of immune antitumor mechanisms.

Effects produced by long-term application of three immune modifiers (azimexon, retinoic acid, and tuftsin) on the depressed immune systems of 18-month-old inbred C57BL/6 female mice were investigated. The effect of each agent was examined on four cell types (cytotoxic T-cells, K-cells, NK cells, and macrophages) possibly involved in antitumor defenses and on the spontaneous tumor development that accompanied advancing age. Three substances chosen for this study appeared able to alter immune parameters, and each one displayed its own pattern of activity. Common to all three agents were an increase of age-depressed tumoricidal activity of peritoneal macrophages and no effect on the depressed NK activity of spleen cells. Retinoic acid increased splenic K-cell activity, already elevated in aged mice and unaffected by the other two agents. Cytotoxic T-cell activity, diminished by age, was stimulated considerably by retinoic acid and by tuftsin but only slightly by azimexon. Histopathologic studies revealed a decrease in the incidence of spontaneous tumors in the 3 treated groups. This decrease was statistically significant in the retinoic acid- and tuftsin-treated groups when compared with the incidence in untreated mice of the same age. Correlation of drug-induced modifications of the immune system with tumor incidence in aged mice was attempted.

Adjuvants, Immunologic↗

Regulation of catalase biosynthesis in Saccharomyces cerevisiae: factor repressing catalase biosynthesis.

A factor which represses the catalase biosynthesis in yeast has been demonstrated in Saccharomyces cerevisiae. This factor can be obtained from yeast cells having both low and normal catalase levels, and is unable to enter the intact cytoplasmic membrane. Moreover, the factor-containing cell extracts obtained either from acatalasemic mutants or normal strains grown in catalase repressive conditions showed higher activity than those obtained from normal strains after being cultured in permissive conditions.

Catalase↗

The importance of the amino acid in position 27 of cholecystokinin in determining its biological activity on pancreatic acini.

We tested the synthetic C-terminal heptapeptide of cholecystokinin, which has the same biologic activity as cholecystokinin, and various synthetic analogs of the C-terminal heptapeptide for their abilities to increase amylase secretion from dispersed acini prepared from guinea-pig pancreas. We found that altering the chemical character of the amino acid in position 27 altered the potency with which the peptide stimulated amylase secretion but did not alter the efficacy of the peptide. We also found that, in the amino acid in position 27, the major function of the side-chain seems to be to position to the sulfate ester group at a proper distance from the backbone of the peptide chain, whereas the chemical structure of the side-chain per se seems to be of relatively minor importance.

Amino Acid Sequence↗

Upbeat nystagmus and internuclear ophthalmoplegia with brainstem glioma.

We describe the unusual association of two ocular motor abnormalities: upbeat nystagmus and internuclear ophthalmoplegia in a young woman originally believed to have demyelinating disease. Quantitative eye movement recordings documented a unidirectional defect in upward visual pursuit with preservation of the vertical vestibulo-ocular reflexes. The ocular oscillation was characterized as a type of "pursuit defect" nystagmus. An enhancing lesion of the upper brainstem seen on computerized tomography was primarily localized to the midbrain on pneumoencephalography. Biosy of the lesion disclosed a malignant glial tumor. The patient's course initally progressed but became stable following radiotherapy and chemotherapy during the next eight months. We believe the association of upbeat nystagmus and internuclear ophthalmoglegia should prompt a detailed search for a structural lesion.

Adolescent↗