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Biomedical subjects

E Sanchez

Publications and source records attributed to E Sanchez.

At least 73 records · Page 4Linked to original sources

Cytokine-induced respiratory burst of human neutrophils: dependence on extracellular matrix proteins and CD11/CD18 integrins.

Human polymorphonuclear leukocytes (PMN) released large quantities of hydrogen peroxide in response to tumor necrosis factor, but only when the cells were adherent to surfaces coated with extracellular matrix proteins. The PMN did not respond when exposed to cytokines and matrix proteins in suspension, or when exposed to cytokines while adherent to surfaces coated with stearic acid. PMN from children with genetic deficiency of the CD11/CD18 integrins underwent a normal respiratory burst upon adherence to uncoated polystyrene, but not in response to tumor necrosis factor when tested on polystyrene that was coated with serum, fibronectin, vitronectin, fibrinogen, thrombospondin, or laminin. Anti-CD18 antibodies, alone of sixteen antibodies tested, induced a similar defect in PMN from normal donors, when the PMN were tested on surfaces coated with serum, fibrinogen, thrombospondin, or laminin; no defect was induced by the anti-CD18 monoclonal antibody IB4 in normal PMN tested on surfaces coated with fibronectin or vitronectin. Thus, for cytokines to induce a respiratory burst in PMN, the cells must be able to use CD11/CD18 integrins and must interact with matrix proteins in the solid phase. CD11/CD18, which is already known to serve as a receptor for fibrinogen, may also be a receptor for thrombospondin and laminin. Finally, receptor(s) exist on PMN for fibronectin and vitronectin which are not blocked by the anti-CD18 antibody IB4 but which are nonetheless CD11/CD18 dependent.

Antibodies↗

Perceiver bias in the processing of human faces: neuropsychological mechanisms.

Previous research has suggested that in face-to-face contexts perceivers are biased to judge the side of the poser's face to their left as more similar to the full face than the side to their right. Traditional explanations of the perceiver bias have presumed that it is a visual field effect, with the side of the poser's face falling within the perceiver's left visual field dominating impressions of the full face. In this study, five experiments are reported. In the first experiment, the validity of the perceiver bias phenomenon was supported. The remaining experiments examined three alternative accounts of the neuropsychological processes that underlie the perceiver bias. No support was obtained for the visual field explanation, nor for an account of the bias as due to asymmetry in gaze patterns. Support was obtained for an account emphasizing a hemispatial bias in central processing. Despite equivalent intake of information from both sides of space, the brain may differentially weight information as a function of hemispatial origin. Practical and theoretical implications are discussed.

Adult↗

Neuropsychologic symptoms in the migraine syndrome.

Twenty patients with complex neuropsychologic symptoms associated with classic migraine were selected from a group of 200 patients with vascular headache. Twenty types of symptoms were found and grouped into six categories (language, visual symptoms, cognitive-dysmnesic symptoms, olfactory-gustatory hallucinations, automatisms, and somatosensory symptoms). Some of the symptoms found have apparently not been reported previously. The importance of the analysis of this complex neuropsychologic set of symptoms and of the possible consequences of complicated, frequent vascular headache is emphasized.

Adult↗

Inhibition and activation of UDP-glucuronyltransferase in alloxanic-diabetic rats.

Short or long term alloxan diabetes produced activation of oestrone and morphine glucuronidation and inhibition of p-nitrophenol glucuronidation in rat liver microsomes. Insulin treatment restored decreased glucuronyltransferase (GT) activity for p-nitrophenol and it did not abolish diabetes activation on oestrone glucuronidation. Triton X-100 detergent activation reduced differences between normal, diabetic and insulin treated rats in the glucuronidation rates of the substrates assayed. 1,4-Benzodiazepines inhibited morphine GT activity and stimulated oestrone GT activity in normal, diabetic and insulin treated diabetic rats. Activation and inhibition of GT activities for oestrone and xenobiotics in diabetes mellitus appears to be related with membrane perturbations of liver microsomes.

Animals↗

Prediction of the optimal timing of bone marrow reinfusion after high dose chemotherapy.

Autologous bone marrow transplantation allows the use of high dose chemotherapy by obviating dose limiting myelosuppression. The pharmacology of high dose chemotherapy has been inadequately explored, yet this information is critical to determine the timing of marrow infusion and assure that engraftment is not compromised. We have used the Salmonella mutagenesis test (SMT) and colony forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte assay to evaluate the optimal time for marrow infusion after therapy with high dose combinations of alkylating agents (Solid Tumor Autologous Marrow Support Program) in seven patients. The SMT is sensitive, rapidly performed, and has been used to detect mutagenic activity in urine following administration of cyclophosphamide, cisplatin, and 1,3-bis(2-chloroethyl)-1-nitrosourea. In parallel, determination of colony forming ability of the patients own bone marrow (colony forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte assay), when cocultured with autologous serum obtained before and after treatment, provided an assay for circulating marrow toxic drugs or metabolites. The onset of mutagenic activity in the SMT and the in vitro appearance of myelotoxicity by autologous serum in the colony forming unit-granulocyte, erythrocyte, monocyte, megakaryocyte assay were concurrent, and these activities returned to base line at the time of marrow infusion (72 h posttreatment). One patient of the seven was excreting mutagens (TA100 strain only) at the time of marrow reinfusion; he developed hepatic venoocclusive disease, and delayed engraftment. These observations suggest that as high dose regimens evolve the SMT may serve as a rapid, sensitive indicator of the circulation and excretion of toxic compounds, and thereby assist in predicting the optimum time of bone marrow reinfusion.

Alkylating Agents↗

Increased activity of testosterone hydroxylases in liver microsomes of diabetic rats treated with insulin.

Liver microsomes from alloxan diabetic rats displayed decreased activity to hydroxylate testosterone only at the 2-alpha and 6-beta positions. Diabetic insulin-treated rats showed higher hydroxylase activities than diabetic and control rats in the formation of all testosterone metabolites analyzed. The sodium dodecylsulfate electrophoretic profile of liver microsomal proteins from each group of rats exhibited distinct increases as well as decreases in the cytochrome P-450 region. Stimulation of testosterone metabolism by insulin may be associated with a higher synthesis of certain cytochrome P-450 isozymes.

Animals↗

Drug tolerance and detoxicating enzymes in Octodon degus and Wistar rats. A comparative study.

Octodon degus shows greater tolerance to pentobarbital as compared with the Wistar rat. Mixed function oxidase activities in liver microsomes were higher in Octodon degus than in the Wistar rat. The reactions assayed were: aminopyrine N-demethylation, aniline and naphthalene hydroxylation and p-nitroanisole O-demethylation. These higher activities seem to be due mainly to the greater cytochrome P-450 content of liver microsomes of Octodon degus. Glutathione S-transferase activity towards 1-chloro-2,4-dinitrobenzene was 30 times higher in Octodon degus than in the Wistar rat. These results may explain the tolerance of Octodon degus to pentobarbital and other drugs.

Animals↗

Structure-activity relationship in the effect of 1,4-benzodiazepines on morphine, aminopyrine and oestrone metabolism.

The influence of a number of 1,4-Benzodiazepines was investigated on morphine and aminopyrine metabolism and on oestrone and p-nitrophenol glucuronidation, in rat liver microsomes. Benzodiazepines inhibited in a differential degree the N-demethylase activities for morphine and aminopyrine N-demethylation as well as glucuronyltransferase activity for morphine. Oestrone glucuronyltransferase activity was markedly stimulated by certain benzodiazepines whereas p-nitrophenol glucuronidation was not altered. A structure activity relationship in the inhibition of morphine and aminopyrine metabolism by benzodiazepines was observed. In fact, the presence of halogens at C-2, a methyl group at N-1 and a methylene substituent instead of a keto group at C-3 in the benzodiazepine structure increased the inhibitory effect. The possible role of these metabolic pathways of other substituents in the benzodiazepines, is discussed.

Aminopyrine↗

[The fuzzy set theory as a biomedical diagnostic aid (author's transl)].

In this paper, the theory of fuzzy sets and fuzzy logic is approached as a diagnostic aid for practitioners and biologists. A few theoretical considerations are followed by two practical applications. The first is a modification of the WHO-Fredrickson classification of hyperlipoproteinemias, with the introduction of secondary or minor types corresponding to everyday medical practice. The other is an attempt at classifying the four most prevalent anemias encountered in internal medicine. Recent studies have shown that the various parameters should be grouped on a hierarchical basis.

Anemia↗

Differential inhibition by diazepam and nitrazepam of UDP-glucuronyltransferase activities in rats.

To assess the role of the N-alkyl group in the interaction of N-alkylated compounds on UDP-glucuronyltransferases, the effect of diazepam and nitrazepam, an N-desmethyl derivative of the diazepam class was studied on morphine, p-nitrophenol and testosterone glucuronidation in rats. Diazepam competitively inhibited the UDP-glucuroyltransferase activity for morphine in hepatic microsomes. The k value for morphine was 0.3 mM and the Ki for diazepam was about 0.23 mM. Also, diazepam administration to male rats reduced the glucuronyltransferase activity for morphine in rat hepatic microsomes in a dose effect relationship. Nitrazepam had no significant effect on morphine UDP-glucuronyltransferase activity in vitro or in in vivo experiments. Neither diazepam nor nitrazepam produced any effect on p-nitrophenol or testosterone glucuronidation in liver microsomal preparations. Single or repeated doses of these benzodiazepines did not change cytochrome P-450, RNA or protein contents of hepatic microsomes. It is suggested that morphine glucuronyltransferase contains an active site for binding of the N-methyl group present in the substrate. Such a binding site would be absent or in effective in p-nitrophenol and testosterone glucuronyltransferases. The reported inhibition of morphine metabolism by diazepam may account for an enhancement of morphine pharmacological effects.

Animals↗

Immuno-overlay: a method for identification of hepatoma cell colonies that secrete albumin.

A screening technique was developed for the identification of clones of hepatoma cells that secrete albumin. The technique employs the overlay of a 1% agarose solution containing antiserum to albumin onto clones of hepatoma cells. A distinct immunoprecipitation complex is formed in the immuno-overlay that corresponds directly to the position of each secreting clone. Clones deficient in albumin secretion do not form an immunoprecipitate. Thus comparison of the immuno-overlay and the cell colonies results in identification of variant clones as well as those capable of secretion. Biochemical characterization of the region of agarose overlay from secreting and nonsecreting clones demonstrates the specificity of the method and its potential for selection of colonies that are secreting other hepatic or cellular proteins.

Albumins↗

Structural requirements in the reaction of morphine uridine diphosphate glucuronyltransferase with opioid substances.

The influence of the 3-hydroxyl and N-alkyl groups in the reactivity of narcotic compounds with morphine UDP-glucuronyltransferase was studied. Opioids possessing both, one or none of these groups were tested for inhibition of morphine glucuronidation in rabbit liver microsomal preparations. Compounds with only a 3-hydroxyl group (normorphine) or an N-methyl group (codeine, ethylmorphine) were less potent competitive inhibitors than those containing both groups (dextrorphan). Norcodeine, with neither of these groups, had no inhibitory effect. The synthetic narcotics (+)- and (-)-methadone, (-)-alpha-acetylmethadol and meperidine, with only an N-alkyl group, were effective competitive inhibitors. No stereoselectivity of the morphine glucuronyltransferase for opioid isomers was observed, and [methionine]enkephalin does not react with morphine glucuronyltransferase. Differences of pKa values and water/lipid solubility of narcotics could not explain the effects. Results indicate that the N-alkyl group plays a critical role in the interaction of narcotics with the morphine UDP-glucuronyltransferase.

Animals↗