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Biomedical subjects

J Marquez

Publications and source records attributed to J Marquez.

At least 19 recordsLinked to original sources

Repeated dose administration of desmopressin acetate in uncomplicated cardiac surgery: a prospective, blinded, randomized study.

The effects of single or repeated doses of desmopressin on blood loss were examined in uncomplicated cardiac surgery, while assessing the potential for thrombogenic side effects. Seventy patients undergoing elective coronary artery bypass grafting (CABG) were studied. Patients were randomized into three blinded groups: Group I received DDAVP (0.3 micrograms/kg), IV, after cardiopulmonary bypass (CPB) and 12 hours later in the Intensive Care Unit (ICU); Group II, DDAVP (0.3 micrograms/kg), IV, after termination of CPB and saline (placebo) 12 hours later in the ICU; Group III, saline (placebo) IV after CPB and 12 hours later in the ICU. Blood loss and bleeding time decreased for Group I at 24 hours (P < 0.04) when compared to Group III; however, blood product replacement, as well as intraoperative and total blood loss at 36 hours, were not different among treatment and control groups. There were four myocardial infarctions recorded in Group I, two in Group II, and one in Group III. These differences were not found to be statistically significant. It is concluded that in routine CABG the prophylactic use of single or repeat dose DDAVP does not effectively decrease blood loss or blood product replacement.

Bleeding Time

Sch 42137, a novel antifungal antibiotic from an Actinoplanes sp. Fermentation, isolation, structure and biological properties.

A novel polycyclic xanthone, Sch 42137, related to the albofungin family of compounds was isolated from culture broth. Its structure was determined by detailed spectroscopic studies and comparison of circular dichroic studies to related compounds albofungin and simaomicin. Sch 42137 exhibited MIC values less than 0.125 micrograms/ml against yeasts and dermatophytes. Details are presented herein.

Actinomyces

Macrolactams: a novel class of antifungal antibiotics produced by Actinomadura spp. SCC 1776 and SCC 1777.

Three novel antifungal antibiotics, Sch 38518, Sch 39185 and Sch 38516 were isolated from the fermentation broths of two actinomycetes identified by chemical, morphological and physiological analysis as a new species of Actinomadura. The compounds were isolated from broth by solvent extraction and purified by silica gel chromatography. Physico-chemical properties, mass spectral analysis, IR and UV suggested the compounds were similar. Sch 38518 and Sch 39185 have a molecular formula of C25H48N2O5. 1H NMR, 13C NMR and hydrolysis indicated the aglycones were identical, however the compounds differed in containing isomeric sugar moieties. Sch 38518 contains mycosamine while Sch 39185 contains 3,6-dideoxy-3-amino-L-talopyranose. Sch 38516 has a molecular formula of C24H46N2O5 and is a lower homolog of Sch 39185. The three compounds, Sch 38518 (1), Sch 39185 (2), and Sch 38516 (3) exhibit similar activity against Candida spp. with geometric mean MICs of 1.81, 2.00 and 0.91 micrograms/ml, respectively.

Actinomycetales

Macrolactams: two novel homologous series of compounds produced by Actinomadura sp. SCC 1778.

Eight antifungal compounds were identified from the fermentation of Actinomadura sp. SCC 1778. This culture produces four homologous compounds (C22H42N2O5 approximately C25H48N2O5) containing the sugar, mycosamine, and four homologous compounds (C22H42N2O5 approximately C25H48N2O5) containing the sugar, 3,6-dideoxy-3-amino-L-talopyranose. Five of the compounds identified were novel macrolactams. All these compounds exhibit antifungal activity against Candida spp. with geometric mean MICs ranging from approximately 1.0 micrograms/ml for the higher homologs to 30 micrograms/ml for the lower homologs.

Actinomycetales

Hemodynamic performance and histamine levels after desmopressin acetate administration following cardiopulmonary bypass in adult patients.

Sixteen patients undergoing cardiac surgical procedures were prospectively randomized into two groups to study the hemodynamic and histamine-releasing effects of desmopressin acetate (DDAVP) administration after cardiopulmonary bypass. Ten minutes after administration of protamine for reversal of heparin, DDAVP, 0.3 microgram/kg, was infused intravenously over 5 seconds in group 1, and the same dose of DDAVP was administered over 5 minutes as an infusion in group 2. There were no statistical differences between baseline values in groups 1 and 2. DDAVP decreased mean arterial pressure by 30% and 25% in groups 1 and 2 (69 +/- 5 mm Hg to 52 +/- 8 mm Hg, P less than 0.005, and 79 +/- 20 mm Hg to 55 +/- 8 mm Hg, P less than 0.005), respectively. The hypotension in both groups was related to decreases in systemic vascular resistance (1,616 +/- 262 dyne.s.cm-5 to 1,073 +/- 199 dyne.s.cm-5, P less than 0.005, and 1,850 +/- 541 dyne.s.cm-5 to 1,144 +/- 214 dyne.s.cm-5, P less than 0.005). Phenylephrine infusion successfully treated the DDAVP-induced hypotension in all patients. Arterial histamine levels at 3 and 5 minutes after infusion of DDAVP did not differ significantly from baseline values. It is concluded that DDAVP at 0.3 microgram/kg is a potent vasodilator when administered intravenously and that histamine is not involved in producing its hypotensive effects.

Anesthesia, Intravenous

Covalent modification of a critical sulfhydryl group in the acetylcholine receptor: cysteine-222 of the alpha-subunit.

Chemical modification of the Torpedo californica acetylcholine receptor (AcChR) by the fluorescent agent N-(1-pyrenyl)maleimide (PM) under nonreducing conditions resulted in the labeling of cysteine residues in all subunits and marked inhibition of the AcChR ion channel opening [Clarke, J. H., & Martinez-Carrion, M. (1986) J. Biol. Chem. 261, 10063-10072]. The PM alkylation kinetics are not affected by the presence of agonists or a competitive antagonist. The PM-labeled alpha-subunit has been purified and digested with both CNBr and trypsin. The resulting fragments from both cleavages were fractionated by high-performance liquid chromatography. The amino acid analysis and sequencing data of the PM-labeled peptides identified cysteine-222 as the only residue labeled by PM on the alpha-subunit primary structure. Cysteine-222 is located in the middle of a hydrophobic domain designated M1, which contains a homologous class of cysteines (Cys-241 in the aligned sequences) conserved in the four subunits of the AcChR. Because of its reactivity and fluorescent properties of the bound probe, alpha Cys-222 seems to be free sulfhydryl group accessible through a hydrophobic pocket, and these properties should be incorporated into proposed folding models for the alpha-subunit.

Amino Acid Sequence

Interaction of nicotinic acetylcholine receptor with two monoclonal antibodies recognizing different epitopes.

The interactions of nicotinic acetylcholine receptor (nAChR) with two monoclonal antibodies (mAb370A and mAb371A) which block the agonist-induced ion flux into nicotinic acetylcholine receptor vesicles [Donnelly, D., Mihovilovic, M., Gonzalez-Ros, J. M., Ferragut, J. A., Richman, D., & Martinez-Carrion, M. (1984) Proc. Natl. Acad. Sci. U.S.A. 81, 7999] have been studied by a combination of immunochemical and spectroscopic techniques. Both mAbs are specific for the alpha-subunit of the receptor, but they recognize different epitopes. We have detected specific binding of the mAb370A to a synthetic peptide corresponding to residues alpha 187-205, a sequence known to contain the alpha-bungarotoxin binding site. By contrast, mAb371A seems to recognize an epitope which is largely silent after proteolytic digestion of the subunit. Binding of mAb370A to the receptor is inhibited by cholinergic agonist and alpha-neurotoxins but not by competitive antagonists or local anesthetics. By contrast, none of these ligands interferes with binding of mAb371A. The spectroscopic properties of the fluorescent probe ethidium have been used to investigate the effect of the mAbs on the interaction of the agonist carbamylcholine with nAChR in membranes. mAb370A, but not mAb371A, blocks both the agonist-induced increase in the fluorescence intensity of receptor-bound ethidium and the agonist-induced increase in the polarization value of the probe. In addition, measurements of ethidium binding followed by stopped-flow techniques showed that mAb370A, but not mAb371A, blocked the agonist-induced association of the probe to nAChR membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Hemichorea-hemiballismus associated with acquired immune deficiency syndrome and cerebral toxoplasmosis.

A young woman had hemichorea-hemiballismus subsequently found to be secondary to a cerebral toxoplasmosis infection complicating human immunodeficiency virus infection. This patient had the sixth reported case of acquired immune deficiency syndrome (AIDS) with hemichorea-hemiballismus, and each has been secondary to cerebral toxoplasmosis. The presence of hemichorea-hemiballismus in a young patient should suggest a diagnosis of AIDS and in particular the diagnosis of secondary cerebral toxoplasmosis. Other movement disorders that occur in AIDS are discussed.

Acquired Immunodeficiency Syndrome

Sch 38519, a novel platelet aggregation inhibitor produced by a Thermomonospora sp. Taxonomy, fermentation, isolation, physico-chemical properties, structure and biological properties.

The complex containing a new platelet aggregation inhibitor, Sch 38519, was recovered from the fermentation filtrate of Thermomonospora sp. SCC 1793. A chemically defined medium was developed which favored the production of Sch 38519. The antibiotic was isolated from the fermentation filtrate by absorption on macroreticular resin and further purified by ion exchange chromatography and reverse phase HPLC. Sch 38519 is an isochromanequinone structurally related to medermycin, lactoquinomycin and granaticin. It inhibits thrombin-induced aggregation of human platelets with an IC50 of 68 micrograms/ml. Sch 38519 is also active against Gram-positive and Gram-negative bacteria.

Actinomycetales

Purification of phosphate-dependent glutaminase from isolated mitochondria of Ehrlich ascites-tumour cells.

Phosphate-dependent glutaminase was purified to homogeneity from isolated mitochondria of Ehrlich ascites-tumour cells. The enzyme had an Mr of 135,000 as judged by chromatography on Sephacryl S-300. SDS/polyacrylamide-gel electrophoresis displayed two protein bands, with Mr values of 64,000 and 56,000. Two major immunoreactive peptides of Mr values of 65,000 and 57,000 were found by immunoblot analysis using anti-(rat kidney glutaminase) antibodies. The concentration-dependences for both glutamine and phosphate were sigmoidal, with S0.5 values of 7.6 mM and 48 mM, and Hill coefficients of 1.5 and 1.6, respectively. The glutaminase pH optimum was 9. The activation energy of the enzymic reaction was 58 kJ/mol. The enzyme showed a high specificity towards glutamine. A possible explanation for the different kinetic behaviour found for purified enzyme and for isolated mitochondria [Kovacević (1974) Cancer Res. 34, 3403-3407] should be that a conformational change occurs when the enzyme is extracted from the mitochondrial inner membrane.

Animals

Sch 37137, a novel antifungal compound produced by a Micromonospora sp. Taxonomy, fermentation, isolation, structure and biological properties.

A new antifungal compound, Sch 37137, was isolated from the cultured broth of a Micromonospora sp., SCC 1792. Sch 37137 is structurally related to A 19009, a dipeptide previously discovered from a Streptomyces sp. The compound was weakly active against species of Candida and dermatophytes (mean MICs greater than or equal to 128 micrograms/ml) in Sabouraud dextrose, yeast-nitrogen and modified Eagles minimum essential media; however activity against Candida sp. (mean MICs greater than or equal to 12 micrograms/ml) and dermatophytes (mean MICs greater than or equal to 0.8 microgram/ml) significantly improved in MA medium.

Amino Acids, Diamino

Sch 36605, a novel anti-inflammatory compound. Taxonomy, fermentation, isolation and biological properties.

A novel anti-inflammatory compound, Sch 36605, belonging to the blasticidin family of nucleoside compounds was isolated from the fermentation filtrate of a Streptomyces sp. Sch 36605, as well as blasticidin S, demonstrated anti-inflammatory activity in the reverse passive Arthus reaction and the adjuvant arthritic rat at doses ranging between 1-10 mg/kg and 0.3-6.0 mg/kg, respectively. A minor component, Sch 366606, co-produced in the in the fermentation was isolated and identified as a known compound in the blasticidin family of compounds.

Animals

Treatment of leiomyomata uteri with D-Trp6-luteinizing hormone-releasing hormone.

Suppression of the secretion of gonadal steroids by chronic administration of a superactive agonist of luteinizing hormone-releasing hormone (LH-RH) was used for treatment of leiomyomata uteri. Ten menstruating women, presenting with a total of 20 uterine leiomyomas, were treated for 3 months with daily subcutaneous injections of D-Trp6-LH-RH. Serum estradiol (E2) levels were suppressed rapidly in five patients and were decreased in other patients. At the end of therapy, leiomyomas regressed completely in three patients, while five patients showed a decrease of more than 40% in the volume of leiomyomas. The reduction in tumor size was correlated with the rapidity of the fall in serum E2 levels. In one patient, the leiomyomata increased in size during treatment, and one woman had a poor clinical response. The agonist was well tolerated and few side effects were observed. Therapy with LH-RH agonists offers an alternative in the management of some uterine leiomyomas.

Adult

Ventricular assist by cardiac cycle-specific increases in intrathoracic pressure.

Changes in intrathoracic pressure can influence cardiac performance by altering ventricular loading conditions. Since ventricular loading, both from systemic venous return (preload) and from left ventricular wall stress (afterload), varies during the cardiac cycle, we reasoned that appropriately placed, phasic, cardiac cycle-specific (synchronous) increases in intrathoracic pressure might augment ventricular ejection in acute ventricular failure. Recent studies in animals suggest that synchronous increases in intrathoracic pressure during systole increase ejection. We compared the hemodynamic effect of synchronous increases in intrathoracic pressure with similar increases delivered at random in the cardiac cycle in patients with congestive cardiomyopathy (n = 9). Intrathoracic pressure was estimated by measuring esophageal pressure. High-frequency jet ventilation (HFJV) synchronized with the electrocardiogram (synchronous HFJV) was compared with HFJV at a fixed frequency within 15 percent of the heart rate (asynchronous HFJV) and with intermittent positive-pressure breathing (IPPB) (tidal volume = 10 ml/kg; f = 15). All forms of ventilation resulted in the same mean airway pressure and esophageal pressure. Mean pulmonary arterial occlusion pressure and arterial pressure were constant in all conditions. Cardiac output was greater with synchronous HFJV than with either IPPB or asynchronous HFJV (4.5 +/- 0.7 L/min compared with 3.5 +/- 0.7 and 3.4 +/- 0.6 L/min [mean +/- SE], respectively; p less than 0.05). Mixed venous oxygen saturation covaried with cardiac output (p less than 0.05), such that calculated oxygen consumption remained constant for all conditions. We conclude that synchronous HFJV augments cardiac output more efficiently than do similar increases in intrathoracic pressure delivered randomly in the cardiac cycle.

Adult