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Biomedical subjects

M Vincent

Publications and source records attributed to M Vincent.

At least 235 records · Page 13Linked to original sources

Nanosecond dynamics of horse heart apocytochrome c in aqueous solution as studied by time-resolved fluorescence of the single tryptophan residue (Trp-59).

The time-resolved fluorescence emission characteristics of the single tryptophan residue (Trp-59) of horse heart apocytochrome c--the precursor of the intramitochondrial cytochrome c--were studied in aqueous solution. The total fluorescence intensity decay measured over the whole emission spectrum was analyzed as a sum of three or four exponentials by the nonlinear least-squares method, the last model always providing a slight but significant decrease in the chi 2 values. Maximum entropy analysis, recently developed for time-resolved fluorometry (Livesey et al., 1987; Livesey & Brochon, 1987), strongly suggests the existence of a distribution including at least four separate classes of lifetimes. The center values were around 0.1-0.2, 1, 3, and 5 ns, in agreement with the lifetime values obtained by nonlinear least-squares regression analysis. As a function of the emission wavelength, these values remained constant within the experimental error, whereas a redistribution of the fractional amplitudes was observed: the contributions of the short components increased in the blue edge region of the emission spectrum. Temperature increase led essentially to a redistribution of the fractional amplitudes, affecting mostly that of the 5-ns component, which almost totally disappeared at high temperature (35-40 degrees C). The lifetime values were not significantly affected except for the 3-ns component, which decreased by about 15% in the temperature range studied. Such observations strongly suggest that the protein exists under different conformational substates in thermal equilibrium. Time-resolved fluorescence anisotropy measurements evidenced the existence of fast internal rotation of the Trp residue. An average maximum restricted angle of rotation of around 55 degrees was calculated. A second internal motion, slower by 1 order of magnitude, corresponding likely to a local motion of the peptide chain involving the Trp-59 residue, was detected on the anisotropy decay curve. Finally, the longest correlation time (5 ns) should correspond to the average rotation of the overall protein. Its value doubled as a function of the protein concentration, revealing an association process leading most likely to a dimer in the concentration range studied (2-139 microM). The flexibility of the peptide chain was more restrained in the associated than in the monomeric form, but the fast internal rotation of the Trp residue was not.

Animals↗

Therapy for neutropenia in hairy cell leukemia with recombinant human granulocyte colony-stimulating factor.

STUDY OBJECTIVE: To determine whether recombinant human granulocyte colony-stimulating factor (G-CSF) is effective in increasing neutrophil counts in patients with hairy cell leukemia and neutropenia. DESIGN: Open label, phase I/II study of G-CSF, given by daily subcutaneous injection for up to 7 weeks. SETTING: Outpatient oncology clinic of a university medical center. PATIENTS: A consecutive sample of four patients with hairy cell leukemia complicated by severe neutropenia. Three patients completed the study; one patient was removed after 2 weeks of therapy. INTERVENTIONS: Granulocyte colony-stimulating factor was given by daily subcutaneous injection. Each patient began therapy with 1 microgram/kg body weight.d; after 1 week the dose was increased to 3 micrograms/kg.d, and 1 week later to 6 micrograms/kg.d. Therapy was continued for 5 to 6 weeks. Patients were taught self-injection, and administered treatment at home. MEASUREMENTS AND MAIN RESULTS: In three patients, an increase in absolute neutrophil counts from less than 0.9 X 10(9)/L to greater than 4.0 X 10(9)/L was noted within 2 weeks of beginning G-CSF therapy. In two patients, infections resolved during therapy. One patient developed acute neutrophilic dermatosis (the Sweet syndrome) while receiving 3 micrograms/kg.d of G-CSF, and drug therapy was discontinued. CONCLUSIONS: Granulocyte colony-stimulating factor may increase neutrophil counts within 2 weeks in patients with hairy cell leukemia and neutropenia. This therapy may be a useful adjunct to definitive treatment of hairy cell leukemia with interferon or pentostatin.

Agranulocytosis↗

First-line chemotherapy rechallenge after relapse in small cell lung cancer.

Response to second-line therapy in relapsing patients with small cell lung carcinoma (SCLC) is often claimed to be evidence in favour of non-cross resistance. Fifteen patients with SCLC who had relapsed off treatment after responding to initial first-line chemotherapy were retreated with the same regimen at relapse. Ten (67%) achieved a further partial response. Median response duration was only 3 months (range 2-4 months), but similar poor results have been reported for most studies using second-line chemotherapy. Relapse in SCLC does not necessarily imply complete clinical resistance to first-line chemotherapy, and strict clinical criteria are required to demonstrate true non-cross resistance.

Aged↗

Correlation between the synergistic effect of liposomes and endotoxins on the activation of macrophage tumoricidal activity and the effect of liposomes on the rough endoplasmic reticulum of macrophages.

Treatment of resident peritoneal macrophages of rats with small unilamellar vesicles of dipalmitoylphosphatidylcholine (DPPC SUV) potentiated their activation for tumor cell lysis by endotoxins. The fluorescence polarization of diphenylhexatriene (DPH) embedded in rough endoplasmic reticulum membranes isolated from DPPC SUV-treated macrophages was enhanced. The average fluorescence lifetime of DPH and the rotational correlation time deduced from anisotropy decay were unchanged, whereas the residual anisotropy and hence the order parameter were increased. The measurement of the fluorescence anisotropy of DPH as a function of the temperature showed a phase transition. No phase transition was observed in the rough endoplasmic reticulum membranes of macrophages either treated or not treated with cholesterol/DPPC SUV (1/1; mol/mol). The synergistic effect of DPPC SUV on the tumoricidal activity of macrophages induced by endotoxins appears to be correlated with the changes in the properties of the rough endoplasmic reticulum membranes. Both effects were transient; they had the same kinetics of induction and reversion, and they were both inhibited by cholesterol.

1,2-Dipalmitoylphosphatidylcholine↗

Noradrenaline content and adrenergic receptors in kidney and heart of the prehypertensive and hypertensive Lyon rat strain.

Sympathetic activity modulates the blood pressure in part by activation of cardiac and renal adrenergic receptors. Thus an alteration of tissue noradrenaline content and/or adrenergic receptors in heart and kidney might be involved in the pathogenesis of hypertension. In order to verify this possibility, we studied tissue noradrenaline content and alpha and beta adrenergic receptors in the heart and kidney of Lyon hypertensive (LH), normotensive (LN), and low-pressure (LL) rats. Density and affinity of receptors were determined using the specific radioligands [3H]-prazosin (alpha 1), [3H]-rauwolscine (alpha 2), and [3H]-dihydroalprenolol (beta) in prehypertensive (5-week-old) and hypertensive (21-week-old) rats. In the prehypertensive period, no differences concerning renal and cardiac noradrenaline content and adrenergic receptor densities and affinities were observed. In the hypertensive period, an age-related decrease of renal alpha 1 and beta receptors was observed in LN and LL (P less than 0.01) but not in LH rats. Consequently, at this time, density of renal alpha 1 and beta receptors was higher in LH than in LN and LL (P less than 0.01). In contrast, the density and affinity of renal alpha 2 and cardiac alpha 1 and beta receptors and tissue noradrenaline content were similar in the three rat strains. Because renal alpha 1 and beta receptors mediate various functions involved in the control of blood pressure such as tubular sodium reabsorption, renin secretion, and glomerular filtration, the different density of these receptors in LH rats might be involved in the development or maintenance of hypertension.

Aging↗

Mineralocorticoids are not involved in the antihypertensive effect of neonatal thymectomy in the genetically hypertensive LH rat.

1. In order to determine whether the antihypertensive effect of neonatal thymectomy in genetically hypertensive rats could be mediated through altered adrenal function, systolic blood pressure (SBP) and urinary excretion of deoxycorticosterone (DOC), corticosterone (B) and aldosterone were measured in thymectomized hypertensive (LH), normotensive (LN) and low-blood pressure (LL) rats of the Lyon strain. Sham-operated animals served as controls. 2. Neonatal thymectomy prevented the spontaneous increase of SBP in LH rats while it slightly decreased the SBP of LN and did not change that of LL rats. 3. Five week old sham-operated LH rats exhibited an increased urinary excretion of DOC and a decreased excretion of B compared with both LN and LL controls. Thymectomy did not alter the urinary excretion of adrenal steroids in LN and LL rats. The urinary excretion of B was markedly enhanced in thymectomized LH rats whereas that of DOC remained unmodified. 4. These data suggested that the thymus could be involved in the development of hypertension in LH rats. 5. The antihypertensive effect of thymectomy did not seem to be mediated by a decreased mineralocorticoid production in the genetically hypertensive rat of the Lyon strain.

Aldosterone↗

Cardiovascular response to emotional stress and spontaneous blood pressure variability in genetically hypertensive rats of the Lyon strain.

1. Intra-aortic blood pressure (BP) was continuously recorded in freely moving genetically hypertensive (LH), normotensive (LN) and low BP (LL) rats of the Lyon strains under basal conditions and during aversive stimulation (a jet of air for 20 min). Rats were studied when 5 and 14 weeks old. 2. The 24 h standard deviation (i.e., variability) of diastolic BP was significantly greater in LH rats of both ages than in LN and LL control rats. 3. In response to the stressor, LH rats showed larger increases in BP than age-matched controls. 4. The BP variability was related to the BP responses to stress in the whole series of rats. 5. It is concluded that the spontaneous BP variability and the BP responses to an experimental stressor rely upon a common regulatory mechanism in rats and that an increased lability of diastolic BP is a primary characteristic of Lyon hypertensive rats.

Aging↗

Identification of a developmentally modulated, intermediate filament associated protein in the chick embryo.

We report here the detection of a high molecular weight (greater than 400,000) cytoskeletal protein in the myogenic and neural tube derived structures of the chick embryo using a monoclonal antibody, F51H2. Immunohistological analysis reveals that this protein is concentrated in the myotome part of the somites, in the heart primordium, and in the neural tube at the end of the 2nd day of incubation. In cultured fibroblasts, the antibody appeared to decorate a filamentous network, although immunoreactivity was not detected on mesenchymal cells in situ. This network was also observed in cultured myoblasts where it has been demonstrated to be coincident to that of desmin. In colchicine-treated cells the immunoreactivity coincided with the perinuclear cap formed by the collapse of intermediate filaments (IFs). Immunoblot experiments confirmed the early distribution of F51H2 antigen in muscle and nerve tissues and its concentration in a salt-resistant IF-rich fraction of muscle tissues. In addition, there is a progressive loss of immunoreactivity during development. The immunoreactive band on sodium dodecyl sulfate gels was faint in tissues from newly hatched chickens and absent in adult tissues. It is suggested that the monoclonal antibody observed herein reacts with an embryo specific high molecular weight protein that is associated with IFs.

Animals↗

NE turnover in genetically hypertensive rats of Lyon strain. I. Brain nuclei.

Several indirect evidences of alterations in the central catecholaminergic structures were obtained in genetically hypertensive rats. Because they could be of pathogenetic value, we measured, in the present work, the in vivo turnover (TO) of norepinephrine (NE) in brain areas of 5- and 22-wk-old genetically hypertensive (LH) rats of the Lyon strain, and their simultaneously selected normotensive (LN) and low blood pressure (LL) controls. Among the changes observed, the increased TO of NE in the A2 and A6 regions of 5-wk-old LH rats and its decrease in the posteroventral hypothalamic nucleus of 22-wk-old LH animals appeared likely to compensate for hypertension. On the contrary, the decreased TO of NE in the anterior hypothalamic nucleus observed at 5 wk and in the A6 and A1 areas at 22 wk of age in LH rats could participate in the development or the maintenance of hypertension. Above all, it was postulated that the increased TO of NE found in the A7 region of 5-wk-old LH rats could play a primary role in the pathogenesis of hypertension in the Lyon model.

Aging↗

NE turnover in genetically hypertensive rats of Lyon strain. II. Peripheral organs.

The peripheral sympathetic nervous system (SNS) is a major determinant of blood pressure and is likely to be involved in the pathophysiology of hypertension. Because SNS activity varies among organs, we measured the in vivo turnover (TO) of norepinephrine (NE) in seven organs of 5- and 22-wk-old genetically hypertensive (LH), normotensive (LN), and low blood pressure (LL) rats of the Lyon strains. The TO of NE was found normal in the superior cervical ganglia and decreased in the heart of 5-wk-old LH rats compared with both LL and LN controls. This suggests that sympathetic cardiac innervation may not be involved in the development of hypertension. On the contrary, an increased TO of NE in the kidney cortex and an elevated TO of dopamine associated with an increased epinephrine content in the adrenal medulla were observed in 5-wk-old LH rats, which could participate in the development of hypertension in the Lyon model.

Adrenal Medulla↗

Multiple personality disorder in childhood.

Multiple Personality Disorder (M.P.D.) has been diagnosed in adults and adolescents at an almost exponential rate over the last 10 years in contrast to the previous 100 years. Childhood M.P.D., a more recently recognized entity, has been identified both by retrospective patient reports and actual child case reports, of which we were able to note 12 in total, 4 of which may be more accurately described as "incipient M.P.D." Given the apparently rapid response to treatment compared to adults and the high morbidity caused by the adult form of the disorder, the authors recommend a "high index of suspicion" and the use of screening questionnaires to detect cases of M.P.D. in high risk populations of children. Although the natural history of M.P.D. is not known, early identification and treatment could lower the number of cases of childhood M.P.D. that become established as adult cases and decrease the associated morbidity of the disorder in both children and adults. More research is needed to establish prevalence, etiology and effective treatment methods.

Abreaction↗

Brain and peripheral noradrenergic neuron activity in developing genetically hypertensive rats of the Lyon strain.

In order to estimate the alterations in the activity of noradrenergic brain areas and peripheral nerves in relation to genetic hypertension, the concentration and the in-vivo turnover (TO) of norepinephrine (NE) were measured in various brain and peripheral structures of 5 and 22 week-old genetically hypertensive (LH), normotensive (LN) and low blood pressure (LL) male rats of the Lyon strains. LH rats significantly differed from both LN and LL age-matched controls by: i) at 5 weeks, a lowered TO of NE in the anterior hypothalamic region and the median eminence; an elevated TO of NE in the A6 and A7 areas, and in the kidney cortex, and an elevated TO of dopamine in the adrenal medulla, ii) at 22 weeks, a decreased TO of NE in A1 and A6 regions and an increased TO of NE in the thoracic spinal cord. These data suggest that an increased activity of the renal nerves and of the adrenal medulla, possibly originating in central alterations of noradrenergic neurons, could be involved in the development of hypertension in the Lyon strain.

Animals↗

[Qualitative and quantitative variations in carotenoid pigments in the ovary and hepatopancreas of Penaeus schmitti during ovarian maturation].

Carotenoid pigments of Penaeus schmitti were investigated and identified in the ovaries and hepatopancreas. Their individual variations were measured in these two organs. The relative concentrations of zeaxanthin in hepatopancreas and astaxanthin in ovaries increased during the sexual development. The role of zeaxanthin monoester in carotenoids transfer from hepatopancreas to ovaries during this sexual development is discussed.

Animals↗

[Influence of hypertension and age on the sympathetic and parasympathetic components of cardiac baroreflex in the conscious rat].

The influence of blood pressure (BP) level and age on the baroreflex sensitivity (BRS) and its autonomic nervous components was studied in genetically hypertensive (LH), normotensive (LN) and low blood pressure (LL) rats of the Lyon strains at 5, 9, 13 and 70 weeks of age. BRS was computed as the slope of the closest relationship, according to the cardiac response delay, between systolic blood pressure (SBP) and heart period changes induced by phenylephrine injections (3 micrograms/kg, i.v.) BRS and the relative importance of vagal and sympathetic components were determined in 4 conditions: 1) basal; 2) after beta-adrenergic blockade (propranolol, 2 mg/kg i.v.); 3) after vagal blockade (atropine, 2 mg/kg i.v.); 4) after vagal and beta-adrenergic blockade (atropine and propranolol, 2 mg/kg, i.v. each). At 5 weeks of age, BRS did not differ between the 3 strains (0.50 +/- 0.05, 0.69 +/- 0.10 and 0.62 +/- 0.09 ms/mmHg in LH, LN and LL rats respectively). In LN rats, BRS increased sharply between 5 and 9 weeks (1.25 +/- 0.12 ms/mmHg) and then remained stable until 70 weeks of age (1.19 +/- 0.14 ms/mmHg). Such an increase did not occur in LH rats and their BRS value was lower than that of LN and LL controls starting from 9 weeks of age. The vagal component of BRS was found to be more important than the sympathetic one in adult rats whatever the strain (80 p. 100 vs 20 p. 100).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗