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Biomedical subjects

C Gilbert

Publications and source records attributed to C Gilbert.

9 recordsLinked to original sources

Evidence for the involvement of tyrosine kinases in the locomotory responses of human neutrophils.

Erbstatin, a recently described inhibitor of tyrosine kinases, has been used to examine the potential role of tyrosine phosphorylation in human neutrophil locomotion. Preincubation of human neutrophils with erbstatin inhibited both spontaneous and directed migration induced by chemotactic factors such as formylmethionylleucylphenylalanine (fMet-Leu-Phe) and leukotriene B4. The decreased migratory responses were correlated with an inhibition of adherence of neutrophils to serum-coated surfaces. Erbstatin did not, however, affect the adherence of human neutrophils to uncoated surfaces. These results indicated that the inhibitory effects of erbstatin were specific and not due to a generalized alteration of the surface of human neutrophils. To elucidate the mechanism of the inhibitory effect of erbstatin on adherence properties, the expression of the leukocyte integrin Mo1 was studied. Erbstatin induced a small but significant increase in the expression of Mo1, but decreased the stimulation of the expression of Mo1 elicited by fMet-Leu-Phe. These results suggest that mechanisms in addition to alteration of the number of surface integrins are involved in the inhibition of neutrophil adherence and locomotion by erbstatin.

Cell Adhesion

Rapid priming of calcium mobilization and superoxide anion production in human neutrophils by substimulatory concentrations of phorbol esters: a novel role for protein kinase C and tyrosine phosphorylation in the up-modulation of signal transduction.

The modulatory influences of phorbol esters on the functional responsiveness of human peripheral blood neutrophils have been investigated. These studies focused on measurements of the levels of cytoplasmic free calcium and of tyrosine phosphorylation as well as on their ability to mount an oxidative response. Short incubation times (< 1 min) with low concentrations of phorbol esters (5-50 nM) were shown to enhance the above indices of neutrophil responsiveness to chemotactic factors such as fMet-Leu-Phe and leukotriene B4. On the other hand, a time- and concentration-dependent inhibition of calcium mobilization and superoxide production was also observed. The effects of the phorbol esters were stereo-specific and were antagonized by a novel protein kinase C inhibitor (RO 318220) but were not affected by the oxidative burst inhibitor diphenyleneiodonium. Pre-incubation of the cells with phorbol 12,13-dibutyrate (PDBu) altered in a concentration-dependent manner the tyrosine phosphorylation pattern stimulated by fMet-Leu-Phe. In addition, the tyrosine kinase inhibitor erbstatin inhibited the priming of the mobilization of calcium induced by PDBu. These data demonstrate the rapidity of the effects of the activation of protein kinase C, their potential to modulate positively the early events of the excitation-response coupling sequence and the complexity of the functional interrelationships among the various cellular activation pathways available to human neutrophils and other non-muscle cells.

Adult

Cell-wall-associated proteinase of Lactobacillus delbrueckii subsp. bulgaricus CNRZ 397: differential extraction, purification and properties of the enzyme.

Whole cells of Lactobacillus delbrueckii subsp. bulgaricus CNRZ 397 were able to hydrolyse alpha- and beta-caseins. Irrespective of the growth medium used, milk or De Man-Rogosa-Sharpe (MRS) broth, identical patterns of alpha- and beta-casein hydrolytic products, respectively, were visualized by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. A soluble proteinase present in cell-wall extracts was active on caseins and displayed the same hydrolytic patterns as whole cells. It was purified from cell-wall extract to homogeneity by ultrafiltration and ion exchange chromatography. The enzyme is a monomer with a molecular mass of 170 kDa, an optimum temperature of 42 degrees C and an optimum pH of 5.5. It was strongly activated by dithiothreitol and partially inhibited by E-64. These properties indicate that cysteine residues play an important role in the enzyme mechanism. The purified proteinase was not able to hydrolyse di- or tripeptides.

Amino Acid Sequence

Reentry within the His-Purkinje system. Elucidation of reentrant circuit using right bundle branch and His bundle recordings.

Routes of impulse propagation during reentry in the His-Purkinje system (Re-HPS) in 13 patients were studied using the right ventricular extra stimulus (V2) method and right bundle branch (RBB) recordings in addition to the conventional His (H) bundle recordings. The H-V and RB-V intervals during sinus rhythm averaged 44.2 and 27.6 msec respectively, with the average antegrade H-RB interval 16.6 msec. All 13 patients demonstrated Re-HPS in the form of V3 showing a left bundle branch block (LBBB) pattern, and two of the 13 patients also manifested V3 with a right bundle branch block (RBBB) pattern. During Re-HPS showing a LBBB pattern, the retrograde activation of the His bundle (H2) in response to V2 occurred via the left bundle branch (LBB), as indicated by inscription of retrograde H2 prior to RB2 in nine of 13 cases (average H2-RB2 = 9.4 msec), and simultaneous incription of retrograde H2 and RB2 in the remaining four. When V3 showed a RBBB pattern the retrograde RB2 preceded H2, suggesting H2 activation via the RBB. These findings suggest that circuit of Re-HPS incorporates both bundle branches and the bundle of His. The H-RB recordings were also useful in distinguishing sustained Re-HPS from atrioventricular nodal reentry when in both instances the QRS complex showed a LBBB pattern.

Adult

Acupuncture tonification: adjunct in psychiatric rehabilitation.

Our aim was to "tonify" chronic psychiatric patients, i.e., restore their physiological homeostasis and sense of well-being by using standardized acupuncture. In eighteen subjects, eleven diagnosed as schizophrenic, feelings of well-being lasting no longer than three days were obtained in over 60% of the treatments. In more than two-thirds of the cases normalization of blood pressure values tending to 120/80 was evident. Degree of physiological change did not appear to be associated with overall psychological improvement; neither was the number of treatments associated with long-term improvement. For future studies, increased treatment frequency and less rigidly controlled procedures are suggested.

Acupuncture Therapy