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Biomedical subjects

R Benoit

Publications and source records attributed to R Benoit.

At least 37 records · Page 2Linked to original sources

Preparation and biological properties of native and recombinant ciliary neurotrophic factor.

CNTF (ciliary neurotrophic factor), purified from rabbit sciatic nerves by a relatively simple procedure, is bioactive in tissue culture at low picomolar concentration and appears as a doublet on polyacrylamide gel electrophoresis (PAGE). In these nerves, CNTF accounts for more than one-half of the survival-promoting activity on ciliary neurons. The concentration of CNTF in rabbit sciatic nerves is estimated to be 5 nmol/kg, more than 1000 times higher than would seem to be required to support neurons if the neurotrophic factor were homogeneously distributed. With recombinant DNA technology, rat CNTF has been synthesized in Escherichia coli, purified without denaturating agents, and found to be bioactive at a slightly lower concentration than CNTF extracted from rabbit sciatic nerves. After radioiodination, CNTF retains biological activity but is not specifically internalized and retrogradely transported in motor and sensory axons. In peripheral nerves, ciliary neurotrophic factor differs biologically from nerve growth factor (NGF) by its much higher tissue concentration and apparent lack of internalization by peripheral nerve axons.

Amino Acid Sequence↗

Comparison of cord purine metabolites to maternal and neonatal variables of hypoxia.

Umbilical arterial concentrations of purine metabolites were evaluated prospectively as markers of hypoxia. The results suggest that hypoxanthine accumulates in association with fetal acidosis and reduced levels of buffer base (P less than .01). Acute hypoxemia defined by umbilical arterial oxygen pressure was accompanied by elevation of uric acid concentrations (P less than .01). Fetal heart rate tracings with characteristics classically associated with fetal stress correlated with increased concentrations of hypoxanthine and xanthine (P less than .01). Therefore, intrapartum events may occur that are not documented by standard markers of perinatal hypoxia at delivery.

Asphyxia Neonatorum↗

[Post-antibiotic diarrheas: role of Klebsiella oxytoca].

From May 1989 to January 1991, 20 patients were investigated for antibiotic-associated acute diarrhea. Colonoscopy or rectosigmoidoscopy was performed in each patient. Cultures of colonic mucosal biopsies were carried out using conventional culture grounds (cystine-lactose-electrolyte-deficient). The aim of this study was to investigate the role of a gram negative bacillus: Klebsiella oxytoca. Among the 20 patients with antibiotic-associated acute diarrhea, 11 had bloody and mucus diarrhea and colitis ranging from a right-sided hemorrhagic to diffuse acute ulcerative or erosive colitis, 7 had a grossly normal colonic appearance, while 2 had mucus diarrhea and pseudomembranous colitis. Of colonic biopsies cultures obtained from 36 control patients, 15 had a normal colonic appearance, 15 had ulcerative or crohn's colitis, 6 had well-tolerated amoxicillin therapy. Klebsiella oxytoca was never found in the 36 control patients; Klebsiella oxytoca was noted among 8/11 patients with mucus-discharging and bloody diarrhea. These results suggest that antibiotic-associated, non pseudomembranous colitis is frequently associated with Klebsiella oxytoca infection, which may be the cause of this type of colitis.

Adult↗

[Traveller's thromboembolic disease. The economy-class syndrome].

Economy class syndrome refers to a thrombo-embolic disease occurring generally after a long air flight, but it may follow long car trips or even simply abnormally long or uncomfortable sitting position such as in war shelters. So the term traveller thrombo-embolic disease would preferably be used. On the basis of 12 personal cases and literature review, it appears that the disease often begins on disembarkation, that pulmonary embolus is frequently the only and first sign, that the victims tend to be over 40 years, and that more than 50% of the patients present a risk factor such as previous venous thrombosis, cardiac insufficiency, hemostasis abnormality ... Although exact frequency of the disease is unknown, our patients should be aware of respecting some preventive rules. Frequent feet flexion-extension motions and correct hydratation are recommended. Elastic contention must be proposed to patients with history of venous stasis. Finally patients with previous thromboembolism must be anticoagulated with preventive heparin dose.

Adult↗

BCNU stability as a function of ethanol concentration and temperature.

BCNU is increasingly used in low ethanol (ETOH) concentrations, 5% dextrose-water (D5W), or normal saline (NS) solutions, especially for intra-arterial and prolonged (e.g., 3 day) intravenous (IV) infusions. Little work, however, has been done to evaluate BCNU decomposition rates in concentrations, diluents, and temperatures similar to those employed clinically. This study examined BCNU solutions in ETOH, NS, and D5W to evaluate, conclusively, initial recovery and decomposition rates in these three diluents. Initial BCNU recovery rates were: 95.6 +/- 0.3% (100% D5W), 89.6 +/- 0.5% (15% ETOH), and 85.2 +/- 0.5% (NS) (P less than 0.001). Study of all solutions revealed no measurable BCNU decomposition over 24 hrs (0 degrees C) and no significant difference in decomposition rates between any of the diluents (19.5 degrees C). At 37 degrees C, the solutions showed different half-lives: 14.3 +/- 0.19 hrs (15% ETOH), 10.6 +/- 0.02 hrs (10% ETOH), 8.2 +/- 0.21 hrs (5% ETOH), 7.3 +/- 0.06 hrs (NS), and 6.8 +/- 0.07 hrs (D5W) (P less than 0.001). Decomposition rates between all three temperatures (19.5 degrees C, 37 degrees C, and 50 degrees C) were significantly different (P less than 0.01) for each diluent. Dissolving BCNU powder into either D5W or NS required only 5 min when hand-shaken at body temperature. This study of initial recovery and decomposition rates suggests that, although BCNU decomposition rates were significantly increased at body temperature (37 degrees C), it was quite low and essentially unaffected by different diluents at room temperature (i.e., 19.5 degrees C).(ABSTRACT TRUNCATED AT 250 WORDS)

Carmustine↗

Potential role of endothelin-1 in normal and hypertensive pregnancies.

Endothelins are the most potent naturally occurring vasoconstrictors yet discovered. Both normal and abnormal pregnancies are associated with significant changes in vascular smooth muscle; therefore the potential role of endothelin in pregnancy was investigated. Plasma immunoreactive endothelin-1 concentration was measured by radioimmunoassay in blood from women with normal pregnancy and preeclampsia and in cord blood from normal pregnancies. Endothelin-1 levels were elevated in pregnant women during labor when compared with levels in nonpregnant women and patients with normal pregnancies before labor. Preeclampsia in nonlaboring women before treatment was associated with higher endothelin values when compared with values in normal nonlaboring patients and women with preeclampsia after magnesium sulfate infusion. The umbilical venous concentration of endothelin was 10 times higher than normal pregnant levels and four times higher than levels in laboring patients.

Adult↗

The effects of chronic central administration of corticotropin-releasing factor on food intake, body weight, and hypothalamic-pituitary-adrenocortical hormones.

The effects of chronic central administration of corticotropin-releasing factor (CRF) on food intake, body weight, and hypothalamic-pituitary-adrenocortical hormones were investigated in rats. The infusion of ovine CRF at doses of 0.3 and 1.0 microgram/h continuously induced decrease in food intake and a suppression of body-weight gain for 7 days. The inhibition of body weight gain induced by CRF could not be accounted for solely by a decreased food intake since the suppression of body-weight gain in CRF-infused rats was significantly greater than that observed in rats which received the same amount of food as the CRF-infused rats. The content of proopiomelanocortin (POMC) -derived peptides in the anterior lobe of the pituitary as well as the plasma levels of ACTH and corticosterone (B) were significantly elevated in CRF-treated rats, and the CRF content in the hypothalamus was significantly decreased. These results suggest that chronic intracerebroventricular (icv) administration of CRF stimulates the synthesis and secretion of POMC-related peptides in the pituitary and suppresses food intake accompanied by inhibition of body weight gain. The results are similar to clinical and laboratory findings observed in patients with stress-induced anorexia.

Adrenocorticotropic Hormone↗

Coexistence of muscarinic acetylcholine receptors and somatostatin in nonpyramidal neurons of the rat dorsal hippocampus.

This study describes the colocalization of muscarinic acetylcholine receptors (mAChRs) and the neuropeptide somatostatin (SOM) in nonpyramidal neurons of the rat dorsal hippocampus. SOM and mAChRs were identified by immunocytochemistry employing antibody S309 and M35, respectively. Half of the SOMergic cell population is found to be immunoreactive for muscarinic receptor protein as obtained by fluorescent double-labeling techniques. These findings provide additional evidence for a direct cholinergic influence upon SOMergic, nonpyramidal neurons, and defines the anatomical distribution of SOMergic, cholinoceptive neurons in the dorsal hippocampus. Concerning the muscarinic cholinoceptive, nonpyramidal neuron population of the dorsal hippocampus, a considerable number (approximately one-third) was found to be colocalized with somatostatin. These results indicate that a significant part of the cholinergic influence upon hippocampal nonpyramidal neurons is relayed via SOMergic neurons.

Animals↗

Processing of prosomatostatin.

Several peptides are generated from prosomatostatin (proSS) in addition to somatostatin-14 (SS-14) and somatostatin-28 (SS-28). These are SS-28(1-12), proSS(1-76) and, as shown more recently, proSS(1-63) and antrin. Important variations in the proportion of these molecular forms are seen among different tissues and among different species. Processing of the precursor in the human brain yields minimal quantities of SS-28(1-12) and high levels of proSS(1-76), namely in cortical areas and in the bed nucleus of the stria terminalis. This is in contrast with findings in rat brain, where SS-28(1-12) is a predominant molecular form. Antrin, which corresponds to proSS(1-10), reaches its highest concentration in the antral portion of the stomach (117 +/- 13 pmol/g wet weight), where it is found in secretory granules of delta cells. We observed an inverse relationship between levels of antrin and proSS(1-63) after chromatography of various tissue extracts. This suggests a precursor-product relationship between these two peptides.

Amino Acid Sequence↗

The effect of magnesium sulfate infusion on systemic and renal prostacyclin production.

Recent in vitro studies have suggested that magnesium sulfate (MgSO4) infusions may increase prostacyclin production. We studied the effect of MgSO4 infusion on prostacyclin (PGI2) metabolite excretion in women with either pregnancy induced hypertension or preterm labor. Excretion of renal and systemic metabolites of PGI2 was measured prior to and following the start of MgSO4 infusion in the two groups. An increased in renal PGI2 metabolite preterm labor excretion was noted in the hypertension group but no change was noted in systemic PGI2 excretion in either group. These data fail to support a generalized, short term increase in endothelial cell PGI2 production as the basis for the beneficial effect of MgSO4.

Adult↗

Subpopulations of somatostatin 28-immunoreactive neurons display different vulnerability in senile dementia of the Alzheimer type.

We tested whether the vulnerability of somatostatin (SST) neurons in senile dementia of the Alzheimer type (SDAT) depended upon their co-localization with neuropeptide Y (NPY). Density estimates of SST28- and NPY-immunoreactive neurons and percentage of double-labeled SST-NPY neurons were obtained in the cortex (areas 9 and 25) and the bed nucleus of stria terminalis (BST), in 6 SDAT and 5 control cases. Counts of senile plaques (SP) and neurofibrillary tangles (NFT) were done on thioflavin S stains. In both cortical areas, a decrease in the density of SST28-IR neurons was found in SDAT cases (-60% in area 25 and -80% in area 9), whereas density of NPY-IR neurons was unchanged. Accordingly, the proportion of single-labeled SST neurons decreased; this decrease was significantly correlated with SP (r = -0.89, P less than 0.001). We conclude that single SST-IR neurons, in cortical layers II-III, and V, are preferentially lost relative to co-localized SST-NPY neurons. In the BST, no significant reduction of SST-IR, NPY-IR neurons nor of the percentage of single labeled SST neurons was found, despite the presence of SP. Thus one subpopulation of SST neurons, defined by associated neurochemical characters (not co-localized with NPY nor with NADPH diaphorase) and by topography (cortical layers III and V) appears to be particularly vulnerable in SDAT. The potential importance of their position in neural circuitry is emphasized.

Aged↗

Distribution of somatostatin-like immunoreactivity in the monkey amygdala.

The distribution of somatostatin-like immunoreactivity was studied in the macaque monkey (Macaca fascicularis) by using primary antisera that recognize somatostatin-28 (S309) or somatostatin-28(1-12) (S320). Somatostatin-immunoreactive neuronal cell bodies were observed in all amygdaloid nuclei and cortical regions. The density of labeled cells varied substantially, however, both within and across the various amygdaloid subdivisions. The highest densities of labeled neurons were observed in layer III of the periamygdaloid cortex, in layers II and III of the medial nucleus, in the magnocellular division of the accessory basal nucleus, and in the medial portion of the lateral nucleus. Many labeled cells were also consistently observed in the caudoventral portion of the lateral division of the central nucleus. Labeled cells were heterogeneous in size and shape ranging from small and spherical to large and multipolar. The density of somatostatin-immunoreactive fibers also varied greatly from region to region and was often inversely related to the density of immunoreactive cells. Highest densities of immunoreactive fibers were observed in the periamygdaloid cortex, medial nucleus, parvicellular division of the accessory basal nucleus, paralaminar nucleus, ventrolateral portion of the lateral nucleus, parvicellular division of the basal nucleus, and the lateral division of the central nucleus. Fibers and terminals in the central nucleus had a coarsely varicose appearance and this pattern of staining was continuous along the trajectory of the central nucleus projection to the bed nucleus of the stria terminalis. The large, immunoreactive varicosities located in this area often appeared to outline dendritic or vascular profiles within the substantia innominata. The lowest levels of somatostatin-immunoreactive fibers were observed in the magnocellular division of the basal nucleus and in the ventromedial portion of the accessory basal nucleus.

Amygdala↗

Distribution of somatostatin receptors in the brain of the frog Rana ridibunda: correlation with the localization of somatostatin-containing neurons.

The biochemical characterization and anatomical distribution of somatostatin binding sites were examined in the brain of the frog Rana ridibunda, and the distribution of the receptors was compared with the location of somatostatin immunoreactive neurons. The pharmacological profile of somatostatin receptors was determined in the frog brain by means of an iodinated superagonist of somatostatin, [125I-Tyr0,DTrp8]S-14. Membrane-enriched preparations from frog brain homogenates were shown to contain high-affinity receptors (KD = 0.78 +/- 0.34 nM; Bmax = 103 + 12.7 fmoles/mg protein) with pharmacological specificity for [DTrp] substituted S14 and S28 analogs. The distribution of somatostatin-binding sites was studied by autoradiography on coronal sections of frog brain. Various densities of somatostatin receptors were detected in discrete areas of the brain. The highest concentration of binding sites was observed in the olfactory bulb, in the pallium, and in the superficial tectum. Moderate binding was observed in the striatum, amygdaloid complex, preoptic area, and cerebellum. Immunocytochemical studies of the distribution of somatostatin-28 (S28) related peptides were also conducted in the frog brain. Two antisera that recognize distinct epitopes of the somatostatin molecule have been used for immunohistochemical mapping of the peptide. Antiserum SS9 recognizes both S28 and somatostatin-14 (S14) and allowed the labelling of perikarya. Antiserum S320 recognizes the N-terminal fragment (1-12) resulting from enzymatic cleavage of S28. This latter antiserum, which does not cross-react with S28, stained mainly neuronal processes. At the infundibular level, however, both antisera stained cell bodies and fibers. Immunoreactive somatostatin-related peptides were detected in many areas of the frog brain. In the diencephalon, a heavy accumulation of perikarya and fibers was seen in the preoptic nucleus, the dorsal and ventral infundibular nuclei, and the median eminence. Immunoreactive perikarya were also observed in the telencephalon, especially in the pallium and in thalamic nuclei. Immunostained processes were detected in many telencephalic areas and in the tectum. There was good correlation between the distribution of somatostatin-immunoreactive elements and the location of somatostatin-binding sites in several areas of the brain, in particular in the median pallium, the tectum, and the interpeduncular nucleus.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Histochemical characterization of sensory neurons with high-affinity receptors for nerve growth factor.

Approximately one half of the neurons in the lumbar dorsal root ganglion of adult rats display high-affinity receptors for nerve growth factor (NGF). To ascertain which types of sensory neurons are potentially responsive to NGF, adjacent cryostat sections of rat dorsal root ganglia were processed either for NGF-receptor using radioautography or by one of four histochemical procedures. Histograms of the densities of neuronal labelling by radioiodinated NGF were examined for subpopulations of lumbar sensory neurons with thiamine monophosphatase enzyme activity or with immunoreactivity for calcitonin gene-related peptide (CGRP), substance P, or somatostatin. Virtually all neurons with strong CGRP immunoreactivity had high-affinity NGF binding sites, although some neurons with faintly positive CGRP immunoreactivity lacked such NGF binding. A subpopulation of large neurons, approximately 5% of the total, had dense labelling by 125I-NGF but were not stained by this immunohistochemical technique for CGRP. Of the three major populations of small neurons those with substance P immunoreactivity were consistently and heavily labelled by radioiodinated NGF whereas those with somatostatin immunoreactivity or thiamine monophosphatase activity were not specifically labelled by radioautography. For these primary sensory neurons in mature rats the genes for substance P and CGRP seem to be strongly expressed only in neurons capable of responding to NGF. On the other hand, neurons containing somatostatin and thiamine monophosphatase invariably lack high-affinity NGF receptors.

Animals↗

The association between apolipoprotein A-I and prostacyclin binding in human serum.

The stability of Prostacyclin in human blood is dependent upon binding to circulating proteins. Although this binding has been considered to be primarily due to albumin, a recent report has suggested that apolipoprotein A-I is responsible. We compared prostacyclin binding to the concentration of albumin and apolipoprotein A-I in several groups of sera with known differences in the ability to bind prostacyclin. Our results indicate a strong correlation with albumin concentration but no correlation between binding and the concentration of apolipoprotein A-I. It appears that in the human circulation albumin concentration is the most important determinant of prostacyclin binding.

Apolipoprotein A-I↗