[Diagnostic models. I. Preparation of split models].
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Biomedical subjects
Publications and source records attributed to M Vincent.
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The tryptophan (Trp) rotational dynamics and the secondary structure of the peptide hormones adrenocorticotropin-(1-24) [ACTH(1-24)]--the fully active N-terminal fragment of adrenocorticotropin-(1-39)--and glucagon were studied in aqueous solutions and in reverse micelles of sodium bis(2-ethylhexyl) sulfosuccinate (AOT)/water/isooctane, a system selected to mimic the membrane-water interface. In aqueous solutions, the total fluorescence intensity decays of their single Trp residue [Trp-9 and Trp-25 for ACTH(1-24) and glucagon, respectively] are multiexponential. This is also the case for ACTH(5-10), a fragment of the adrenocorticotropin "message" region. Time-resolved fluorescence anisotropy data evidence a high degree of rotational freedom of the single Trp residue. Transfer of these peptides from water to the aqueous core of reverse micelles induces severe restrictions of the Trp internal motion and of its local environment. The results indicate that the Trp-9 residue in ACTH(1-24 is maintained in the close neighborhood of the water-AOT molecular interface where the water molecules are strongly immobilized. By contrast, the Trp residues in ACTH(5-10) and glucagon are likely to be located closer to the center of the micellar aqueous core where the water molecules are in a more mobile state. Furthermore, the above location of Trp can be extended to the peptide chains themselves as evidenced by the overall correlation time values of the peptide-containing micelles. Nevertheless, in all peptides, the indole ring remains susceptible to oxidation by N-bromosuccinimide. Circular dichroism measurements evidence the induction in glucagon of alpha-helices remaining unaffected by the micellar water content. Conversely, beta-sheet structures are favored in ACTH(1-24) at low water-to-surfactant molar ratios (w0) but are disrupted by subsequent additions of water. These results are discussed in terms of the possible role of the micellar interfaces in selecting the preferred peptide dynamical conformation(s)
Monoclonal antibody A7H2 has been selected from a library of monoclonals raised against the branchial arch cells of 3-day-old chicken embryos, and its histological distribution was examined at different embryonic stages and levels. The immunoreactivity appeared during neurulation and was almost general in extraembryonic areas. As the embryo formed, A7H2-fluorescence disappeared from most tissues, but was concentrated in the splanchnomesoderm-derived smooth muscle lineages and epithelial linings of the coelomic cavity. A strong and durable reactivity was also observed in the myogenic condensations constituting the axis of the branchial arches, whereas myotomal cells of the differentiating somites were labelled more weakly and for a shorter time. Interestingly, non-mesodermal fluorescence was restricted to the branchial arch epithelium and some ectodermal placodes, to the thinning-out zones of the neural tube destined to form the choroid plexus, and to the pharyngeal and cloacal extremities of the digestive tract.
A computer-assisted morphometrical and microdensitometrical analysis has been performed on cardiovascular noradrenaline (NA), adrenaline (A) and neuropeptide (Y (NPY) neurons in adult and 24-month-old male rats and on hypotensive (LL), normotensive (LN) and hypertensive (LH) male rats of the Lyon strain using the indirect immunoperoxidase procedures. It was found that in NPY/phenylethanolamine-N-methyltransferase (PNMT) costoring neurons of the CI area of the rostral medulla oblongata NPY-like immunoreactivity showed a more marked reduction than the PNMT immunoreactivity. Furthermore, within the parvocellular part of the paraventricular hypothalamic nucleus. NPY immunoreactive nerve terminal profiles were much more affected than the PNMT immunoreactive profiles during aging as revealed by a marked reduction in the number of profiles and by a marked reduction of absorbency values in the microdensitometrical analysis. Thus, in the NPY/PNMT costoring neurons of the A C1 group of the ventrolateral medulla projecting, for example, to the hypothalamus, the peptide transmission line may have a special vulnerability to the aging processes which may contribute to the development of hypertension in old people in view of a vasodepressor role of many central NPY/PNMT neurons. An extensive morphometrical and microdensitometrical analysis of the various catecholamine (CA) cell groups of the medulla oblongata of the LL, LN and LH rats of the Lyon strain was performed. In a comparison between LL and LH rats the A2 cell group of the LH strain showed a trend for an increase in the mean tyrosine hydroxylase (TH) immunoreactive cell body area and the C3 group showed a significant increase in the number of PNMT immunoreactive profiles.(ABSTRACT TRUNCATED AT 250 WORDS)
Punch biopsies of skin were taken from allogeneic marrow recipients routinely before transplantation, at 14-22 and 90-107 d after grafting and in the event of a clinical rash. Three histological appearances were encountered: graft versus host disease (GvHD), epidermal abnormalities, and normal. Graft versus host disease was characterized by epidermal basal vacuolation, spongiosis and individual cell necrosis associated with mononuclear cell infiltration of the upper dermis and lower epidermis, while epidermal abnormalities were identical to GvHD but without the mononuclear cell infiltrate. Graft versus host disease occurred only in patients receiving marrow unpurged of T-cells while epidermal abnormalities occurred with equal frequency in recipients of purged and unpurged marrow and were also noted in a high proportion of pre-transplant biopsies. Patients whose skin biopsies exhibited epidermal abnormalities showed no greater incidence of subsequent clinical or histological GvHD than those with normal biopsies. For these reasons, we conclude that epidermal abnormalities cannot be regarded as a minor manifestation of GvHD as has often been previously assumed. We also conclude that they cannot be regarded as the cause of a rash as, unlike GvHD, the incidence was not significantly different in patients with and without rashes. The cause of epidermal abnormalities is not entirely clear; cytotoxic drugs and irradiation appear to play a part but their occurrence in patients with previously normal post-transplant biopsies suggests that other factors may also be important. Some patients with strong clinical evidence of GvHD had negative biopsies; these should be regarded with caution especially within the first 24 h after the onset of a rash as the diagnostic histological picture may take time to develop. In some cases, GvHD was confined to pilosebaceous units; this seems to represent a minor form of the disease with only a limited capacity for progression. Dysplastic epidermal changes which have previously been attributed to the use of cyclosporin A were found with equal frequency in patients who did not receive this drug and must therefore have some other cause.
To determine precisely the influence of high blood pressure and age on the baroreflex sensitivity (BRS), we measured it in conscious genetically hypertensive (LH), normotensive (LN) and low-blood pressure (LL) rats of the Lyon strains. Groups of male rats were studied at the age of 5, 9, 13, 21 and 40 weeks. Using our previously described technique, their blood pressure (BP) and heart period (HP) were recorded beat by beat, in the conscious unrestrained state. Each animal received 2 or 3 i.v. injections of phenylephrine (PHE, 5 micrograms/kg) and nitroglycerin (NG, 100 micrograms/kg). The BRS (msec/mmHg) was computed as the slope of the closest relationship found between systolic BP (SBP) and HP changes. Otherwise, in the 13-week-old rats, BRS had been measured in basal conditions, after vagal blockade (atropine: 2 mg/kg i.v.) and after beta-adrenergic blockade (propranolol: 2 mg/kg) so as to determine the relative importance of vagal and sympathetic components of the baroreflex. In LN and LL rats, the BRS measured with PHE and NG increased markedly between 5 and 9 weeks of age and then remained stable in LN rats or decreased between 21 and 40 weeks of age in LL rats. In LH rats, BRS remained stable between 5 and 9 weeks of age and increased slightly up to 21 weeks of age. Significant differences between LH and LN rats were observed starting from 9 weeks of age when BRS was measured with PHE and only at 9 weeks of age when it was measured with NG injections. In 13-week-old rats, the cardiac baroreflex response was estimated to depend for 82 p. 100 and 18 p. 100 upon vagal and sympathetic components respectively when BRS was measured with PHE injections and of 68 p. 100 and 32 p. 100 when it was measured with NG injections.(ABSTRACT TRUNCATED AT 250 WORDS)
Graft versus host reaction (GVH) is a major complication of allogenic marrow transplants. The GVH present is a pluri-visceral syndrome in which certain pulmonary disorders are recognised. Amongst these respiratory failure by bronchiolitis is not an exceptional presentation. The case reported here is of an 18 year old man who developed, immediately following a marrow graft for acute lymphoblastic leukaemia, a lethal obstructive respiratory failure after progression for 2 1/2 years. The respiratory function data (TVO with elevated residual volume (VR) and VR/Total lung capacity (CT) hypoxia which corrected on exercise with normocapnia then hypoxic hypercapnia; compliance normal at low frequency but fell at high frequency and inspiratory and expiratory resistance was raised: DLCO/VA was normal) allowed the confirmation of obstructive respiratory failure by disease of the small airways. The pathogenesis of CVH is equivocal. Recurring infections seem to play a role, favoured by iatrogenic factors such as chemotherapy and total body irradiation. In the case reported here the first pulmonary signs followed an episode of influenza with sero-conversion.
We report a case of lipoid pneumonia complicated by supra-infection with Mycobacterium fortuitum. The diagnosis of a lipoid pneumonia was suggested by the CT Scanner which showed a negative density in the pneumonic tissue. The supra-infection by the mycobacterium dit not change the radiological opacities which stayed the same following a cure of the mycobacterial infection. A histo-pathological study showed evidence of macrophages with voluminous lipid inclusions but equally the atypical mycobacteria were associated with a giant cell-epithelioid reaction. In patients with a lipoid pneumonia the possibility of an infection should be considered and a supra-infection with an atypical mycobacterium should be looked for. At the same time, when a bacteriological study of sputum or fibreoptic aspiration of a rapidly growing mycobacterium is obtained this should raise the possibility of oil inhalations. Alveolar lavage seems to be a technique which seems to be entirely appropriate to obtain the diagnosis of the two concomitant disorders.
The purpose of this study was to investigate coital behavior, contraceptive practices, and attitudinal and knowledge differences between "early coital initiators" (subjects having initial coitus at 16 years or younger) and "late coital initiators" (subjects having initial coitus from 17 to 20 years of age). Data were compiled from the results of a questionnaire administered to 929 students enrolled in personal health courses at 14 colleges and universities. The sample used for analysis included only the never-married coitally experienced males and females aged 20 and older (N = 396). The results suggested that late coital initiators: were more effective contraceptors during initial coitus; had more committed relationships with their initial sex partners; engaged in more discussion about and planning for contraceptive use; and used more authoritative and reliable sources for contraceptive information than their younger counterparts. Both groups scored very low on basic knowledge questions concerning fertility, contraception, and sexually transmitted diseases. These results mandate greater public concern and involvement to delay early coital experiences and prevent unprotected sexual intercourse.
The potency of cholesterol to affect the acyl chain order and dynamics of cardiolipin membranes in the liquid-crystalline state was monitored by steady-state and time-resolved fluorescence anisotropy as well as excited-state lifetime measurements with cis- and trans-parinaric acids as probes. Up to a cholesterol mole fraction (mean chl) of congruent to 0.20, no measurable effect on any of the fluorescence parameters of either probe in cardiolipin bilayers was evidenced. This was in striking contrast to the situation in dioleoylphosphatidylcholine (DOPC), for which a cholesterol mole fraction of 0.20 corresponded to the half-maximal effect on the fluorescence parameters, reflecting the classical ordering effect of cholesterol observed in lecithin systems in the liquid-crystalline phase. Whereas in DOPC bilayers this order effect plateaued at mean chl = 0.50, in cardiolipins the increase in acyl chain order was observable up to a mole fraction as high as 0.80. This indicated that cardiolipins were able to incorporate about 4 mol of cholesterol/mol of cardiolipin (i.e., 1 mol of cholesterol per fatty acyl chain). Besides, 31P NMR spectra of multilamellar liposomes obtained from pure cardiolipins and cardiolipin--cholesterol mixtures evidenced a line shape characteristic of lamellar structures. These results clearly indicate that the presence of high levels of cardiolipins in inner mitochondrial membrane does not impede cholesterol uptake by these membranes. However, the absence of an effect of cholesterol in the physiological range of the cholesterol mole fraction (congruent to 0.20) would signify weaker sterol-cardiolipin interactions than with lecithins and in turn would explain the relative dearth of cholesterol in these membranes.
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The purpose of this study was to investigate the main renal and hormonal responses to head-down bed rest, which is currently considered a reliable experimental model for the simulation of weightlessness. Urinary output and electrolytes, plasma renin activity (PRA), aldosterone (PA), antidiuretic hormone (ADH) and immunoreactive neurophysin-I (Np) were measured in eight adult volunteers submitted to a 4-day head-down bed rest (-6 degrees) after a 24-h control period in the horizontal position (day 0). Four of the eight subjects were submitted to two 1-h periods of controlled muscular exercise (50% VO2max) from day 1 to day 4. Throughout the head-down bed rest period, urinary output remained stable, although lower than in the control period (day 0), but the urinary Na/K ratio decreased. Plasma electrolytes and osmolality, and creatinine clearance remained unchanged. There was no significant difference between exercising and non-exercising subjects. At the hormonal level, PRA and PA increased during the head-down bed rest. This increase was more pronounced in the group with exercise. At the end of the tilt period, PRA and PA were about 3 times higher than on day 1. No significant changes could be observed for ADH and Np. It is concluded that a 4-day head-down bed rest results in no apparent changes in neurohypophyseal secretory activity, and in a progressive secondary hyperaldosteronism.
We studied the effects of training by forced swimming on plasma lipid and lipoprotein concentrations in the Lyon genetically hypertensive rats (LH), its normotensive (LN) and low blood pressure (LL) controls. Training was carried out 5 days a week for 5 weeks. The duration of daily training sessions was increased 15 min per day, from 2 to 6 h/day. Following training low density lipoprotein-cholesterol (LDL-C) was significantly lower (P less than 0.01) in LL, and the very low density lipoprotein (VLDL-C) was also lower in LN (P less than 0.01) and LH (P less than 0.05) rats compared with their sedentary controls. High density lipoprotein-cholesterol (HDL-C) was not significantly increased after training in all strains. Compared with controls, plasma total cholesterol, plasma triglycerides and phospholipids were not modified by training. The reduction of LDL-C, VLDL-C as well as the increase of the HDL-C:VLDL-C ratio suggest a beneficial effect of training on atherosclerosis and perhaps coronary heart disease risk.
The evolution with age of blood pressure (BP), heart rate (HR), and baroreflex sensitivity was studied in hypertensive (LH), normotensive (LN), and low blood pressure (LL) male rats of the Lyon strains. Intra-arterial BP was continuously recorded for 48 h in freely moving animals. On-line computer analysis of the BP curve allowed calculation of systolic (SBP), mean (MAP), and diastolic (DBP) blood pressure, HR, and their variability. At 5 wk of age, LH rats exhibited a higher BP than LN and LL controls, which, at 21 wk of age, was associated with significant bradycardia and a greater variability in DBP and HR. LL rats had a MAP similar to LN, which confirms that both strains are, in terms of BP, valid controls for LH animals. The baroreflex sensitivity measured after phenylephrine injections increased with age more markedly in LN and LL than in LH rats, whereas in the latter, it was significantly lower at the age of 9 and 21 wk. When measured after nitroglycerin injections, the baroreflex sensitivity was higher and more stable than that observed after phenylephrine administration. In addition, the baroreflex sensitivity in the different strains was inversely related to the level and the variability of DBP but not of HR.
A retrospective study of 166 cases of renovascular hypertension was performed. Before 1979, 114 patients were treated for renovascular hypertension. Forty underwent surgery. In this group, therapy resulted in cure or improvement in 45% of the patients. Seventy-four patients underwent medical therapy: 88% of these patients had improvement of blood pressure when beta-blockers were used, but only 41% when they were not. More recently (from 1979 to 1983), 52 patients were treated for renovascular hypertension, of which 31 patients have been operated for fibromuscular renal artery stenosis (62%) or atherosclerotic renal artery stenosis (32%). In this group, 90% of the patients were considered to be cured or improved with a mean follow-up of 36 months. Eighteen of thirty-one patients underwent autotransplantation with satisfactory results on blood pressure control. Twenty-one patients were treated by antihypertensive drugs: 86% of the patients were improved or cured (71.5% of the patients had atherosclerotic lesions) with a mean follow-up of 46.8 months.