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J P Nicolas

Publications and source records attributed to J P Nicolas.

At least 19 recordsLinked to original sources
PubMed1995

Identification of the binding domain for secretory phospholipases A2 on their M-type 180-kDa membrane receptor.

The rabbit muscle (M)-type receptor for secretory phospholipases A2 (sPLA2s) has a large extracellular domain of 1394 amino acids, composed of an N-terminal cysteine-rich domain, a fibronectin-like type II domain, and eight carbohydrate recognition domains (CRDs). It is thought to mediate some of the physiological effects of mammalian sPLA2s, including vascular smooth muscle contraction and cell proliferation, and is able to internalize sPLA2s. Here, we show by site-directed mutagenesis that OS1, a snake venom sPLA2, binds to the receptor via its CRDs and that deletion of CRD 5 completely abolishes the binding of sPLA2s. Moreover, a receptor lacking all CRDs but CRD 5 was still able to bind OS1 although with a lower affinity. Deletion of CRDs 4 and 6, surrounding the CRD 5, slightly reduced the affinity for OS1, thus suggesting that these CRDs are also involved in the binding of OS1. The M-type sPLA2 receptor and the macrophage mannose receptor are homologous and are predicted to share the same tertiary structure. p-Aminophenyl-alpha-D-mannopyranoside bovine serum albumin, a known ligand of the macrophage mannose receptor, binds to the M-type sPLA2 receptor essentially via CRDs 3-6.

Animals↗
PubMed1995

In vitro colonization ability of human colon mucosa by exogenous Lactobacillus strains.

We have tested five Lactobacillus strains for their in vitro colonization ability in a human colon epithelium culture model. Positive colonization occurred in different degrees in the presence of four Lactobacillus strains. We have found that L. casei GG and L. acidophilus NCFB 1748 induce an intermediate colonization. These two strains, largely investigated by others, have been reported to be beneficial to humans. The use of human intestinal tissue in our study partially reconstitutes the complex architectural specificity of human epithelium with the mucus layer and more closely simulates the in vivo situation.

Colon↗
PubMed1995

Structural elements of secretory phospholipases A2 involved in the binding to M-type receptors.

Specific membrane receptors for secretory phospholipases A2 (sPLA2s) have been initially identified with novel snake venom sPLA2s called OS1 and OS2. One of these sPLA2 receptors (muscle (M)-type, 180 kDa) has a very high affinity for OS1 and OS2 and a high affinity for pancreatic and inflammatory-type mammalian sPLA2s, which might be the natural endogenous ligands of PLA2 receptors. Primary structures of OS1 and OS2 were determined and compared with sequences of other sPLA2s that bind less tightly or do not bind to the M-type receptor. In addition, the binding properties of pancreatic sPLA2 mutants to the M-type receptor have been analyzed. Residues within or close to the Ca(2+)-binding loop of pancreatic sPLA2 are crucially involved in the binding step, although the presence of Ca2+ that is essential for the enzymatic activity is not required for binding to the receptor. These residues include Gly-30 and Asp-49, which are conserved in all sPLA2s. Leu-31 is also essential for binding of pancreatic sPLA2 to its receptor. Many other mutations have been considered. Those occurring in the N-terminal alpha helices and the pancreatic loop do not change binding to the M-type receptor. Conversion of pancreatic prophospholipase to phospholipase is essential for the acquisition of binding properties to the M-type receptor.

Amino Acid Sequence↗
PubMed1995

Neurotensin decreases with fasting in the ventromedian nucleus of obese Zucker rats.

Neurotensin (NT) inhibits food intake when injected either in brain ventricles or in hypothalamic nuclei such as the ventromedian nucleus (VMN). NT concentrations are lower in obese than in lean Zucker rats in several hypothalamic nuclei, including the VMN. In this experiment, we studied the influence of the feeding state on NT concentrations in different brain areas of 10-week-old lean (n = 27) and obese (n = 27) Zucker rats that were fasted for 48 hours and then refed for 6 hours. NT level was measured in the microdissected areas by radioimmunoassay. Obese rats ingested approximately 50% more food than lean rats in the ad libitum (ad lib) condition (P < .001) and 12% more during the refeeding time (NS). NT concentrations in the median eminence (ME) were 50% lower in obese than in lean rats (P < .001). This decrease could be related to a 20% decrease in the arcuate nucleus (ARC) of the obese rats (P < .04). NT concentrations in the ME and ARC, which are important for the control of pituitary hormone secretion by NT, were not changed by the feeding state in both genotypes. NT varied with the feeding state in the VMN only (P < .04). Concentrations were 45% lower in fasted (FD) obese rats than in ad lib or refed (RF) obese rats (1.09 +/- 0.25 ng/mg protein v 1.98 +/- 0.36 ad lib and 1.62 +/- 0.11 RF, P < .05). They remained unchanged in lean rats. NT variations in the VMN of obese rats could contribute synergistically with other neuropeptides to the abnormal feeding behavior of these rats.

3-Hydroxybutyric Acid↗
PubMed1995

The immunological impairment of arcuate neuropeptide Y neurons by ricin A chain produces persistent decrease of food intake and body weight.

Neuropeptide Y is demonstrated as a potent orexigenic peptide when injected into the rat hypothalamic paraventricular nuclei. The neuropeptide Y innervation of paraventricular nuclei originates from both hypothalamic arcuate nuclei and brainstem neurons, whose specific role in the control of food intake is still under discussion. To assess the role of the arcuate neuropeptide Y in the regulation of food intake, we propose a new method for immunologically impairing the neuronal secretion of neuropeptide Y from a unique brain site. The monoclonal antibody to the neuropeptide Y precursor epitope, the C-flanking peptide, was microinjected with two cellular toxins (the ricin A chain and the monensin) into the hypothalamic arcuate nuclei or paraventricular nuclei. One microinjection into the arcuate nuclei reduced the food intake and body weight gain for 10 days. It prevented the food intake stimulation usually induced by a 12 h food deprivation. This decrease of food intake was not due to the aversive properties of monoclonal antibody or cellular toxins, or the immunoneutralization of the biologically active neuropeptide Y, because (i) the acute effect of the microinjection into the arcuate nuclei promoted a transient increase of the food intake likely induced by a strong release of neuropeptide Y from the arcuate neurons which were immunologically damaged, and (ii) the C-flanking peptide monoclonal antibody binds neither neuropeptide Y nor its receptors. The microinjection was inefficient when C-flanking peptide monoclonal antibody was replaced by non-specific rat immunoglobulins or when the C-flanking peptide monoclonal antibody/toxins mixture was injected into the paraventricular nuclei. The data bring further arguments in two domains.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

A decreased metabolic clearance of glucose is involved in the hyperglycemic effect of a serum temperature induced factor (TIF).

We have studied the effects of a hyperglycemic temperature induced factor (TIF) on glucose metabolism, in 3 groups of Wistar rats: 10 rats injected with non-heated serum, 10 rats injected with heated serum and 10 rats injected with semi-purified TIF. Seric levels of insulin and glucagon were not modified in rats injected with heated serum. The injection of heated serum induced hyperglycemia (p < 0.0001), a decrease of lactate (p < 0.001) and pyruvate (p < 0.05) levels, and an increase of acetoacetate level (p < 0.001). The levels of beta hydroxybutyrate and amino acids (alanine and glutamine) were not changed. Glucose turn over rate (12.3 +/- 1.3 g/min/kg) and metabolic clearance of glucose (10.0 +/- 0.8 ml/min/kg) were significantly lower in rats treated with heated serum and purified TIF than in controls (respectively, p < 0.05 and p < 0.001). These data suggested that the hyperglycemic effect of heated serum and isolated TIF could correspond to an impaired metabolic clearance of glucose and to an increased gluconeogenesis.

Animals↗
PubMed1995

Gastric intrinsic factor and its receptor.

Cbl metabolism has been the subject of many studies since the existence of Cbl was suspected in the first decades of the twentieth century. These studies have confirmed the high complexity of the assimilation of Cbl by the organism. During absorption, Cbl is bound to two glycoproteins, Hc and IF, in a consecutive manner. Over the last few years, it has been demonstrated that Cbl bound to Hc in the stomach is only transferred to IF after the action of pancreatic trypsin. It is also possible that Hc-bound biliary Cbl is transferred to IF in this way and that the Cbl in the Cbl-IF complex is absorbed in the terminal ileum, thus constituting an enterohepatic cycle. Knowledge concerning the sites of synthesis and secretion of IF is becoming more detailed due to the use of immunocytochemistry and in situ hybridization techniques. It is now certain that in man, IF is not only localized in gastric parietal cells, but also in other foregut-derived cells. This observation may explain the multiple physiological stimuli involved in mediating IF secretion. Determination of the molecular structure of purified Cbl binders can be added to the significant progress made due to the application of molecular biology techniques to the field of isolation and structural characterization of cDNA encoding Cbl binders, and particularly IF. Studies of IF, Hc and TC in different species and those into the properties of acceptor fragments have allowed the distinction between the Cbl binding site on IF and the IF-Cbl binding site on the IFCR. The absence of experimental models cause difficulties in studying transcytosis of Cbl through the enterocyte. There are also problems in determining the structure of IFCR as it is difficult to obtain a large quantity of a molecule which denatures very quickly. Studies into IFCR expression in polarized cancerous cells of intestinal or renal origin, including the effects of different pharmacological agents, along with the results of immunochemical investigations are beginning to clarify the pathway involved in the transport of Cbl through the enterocyte.

Adult↗
PubMed1995

Anaphylaxis to mustard as a masked allergen in "chicken dips".

BACKGROUND: Masked allergens in processed foods are sometimes responsible for "idiopathic" anaphylaxis because of the lack of full ingredient labeling. Patients, even if they are aware of a specific hypersensitivity, may be unaware of trace amounts of the offending allergen(s) that are present in these products. METHODS: We report a case of severe anaphylaxis to mustard masked in "chicken dips." A 38-year-old woman had an anaphylactic reaction beginning 20 minutes after eating "chicken dips" in a fast food restaurant. She was treated successfully in an emergency room and then referred to us for evaluation. We performed skin prick tests, IgE antibody, and inhibition assays to identify allergens in foods eaten just prior to the anaphylactic reaction. RESULTS: She had a history of allergy to mustard. Skin prick tests revealed sensitivity to mustard, coriander, and curry powder, which contains mustard. She had 56.3 KU/L mustard-specific serum IgE antibody in a Phadebas CAP RAST assay (Pharmacia, Sweden). The mustard RAST was inhibited with an extract of "chicken dips," confirming the presence of mustard in "chicken dips." CONCLUSIONS: This case points out the risk of masked allergens in modern food products and the value of the RAST inhibition assay for the identification of such hidden allergens.

Adult↗
PubMed1995

The use of two multitests fx5 and fx10 in the diagnosis of food allergy in children: regarding 42 cases.

The multitests Cap RAST fx5 and fx10 (Pharmacia, Cap System) are used for a rapid biological diagnosis of food allergy. These tests were assessed in 29 children who presented 42 food allergies (FA) documented by prick tests, specific IgE and labial or oral provocation tests (single blind placebo controlled food challenges). When the multitests were positive, the search for specific IgE to the corresponding allergens was performed (Cap RAST, Pharmacia). The theoretical coverage of FA could be estimated according to the frequency of food allergens involved in the children. It reaches 85% for Cap RAST fx5 and 29% for Cap RAST fx10. The sensitivity of Cap RAST fx5 is 89% and 50% for Cap RAST fx10. Even in the case when the child had a single food allergy, the detail of specific IgE showed multiple positivities to several allergens included in the multitest. Consequently, the positive predictive value of Cap RAST was only 32%. Prick tests to the same allergens were more rarely positive, gaining thus a better positive predictive value. The authors propose the use of Cap RAST fx5, eventually completed by a Cap RAST to beef for the first approach of food allergy in children. They stress the point that prick tests have to be carried on subsequently, in order to select properly allergens responsible for food allergy.

Adolescent↗
PubMed1994

Putative neuropeptide Y antagonist failed to decrease overeating in obese Zucker rats.

A central dysregulation of several neuropeptides could be at the origin of the marked hyperphagia of the obese Zucker rat, a well-known animal model used for the study of obesity. Neuropeptide Y (NPY), which stimulates food intake and increases early in life in obese rats, plays a major role in the development of this hyperphagia. The aim of our experiment was to test a proposed NPY antagonist namely PYX-2 in obese hyperphagic Zucker rats in order to know if it could be an interesting drug for limiting their food intakes. Four doses of PYX-2 (50-1000 pmol) were injected in a counterbalanced order in the lateral brain ventricles of 10 adult male Zucker rats. Food intake was recorded 0.5, 1, 2, 3, 6, and 23 h after PYX-2 injection and compared either to the rat's spontaneous food intake or to the food intake following injection of artificial CSF (vehicle) only. It was not modified by any dose of PYX-2 whatever the time considered (1 h after injection: 4.3 +/- 0.5 (1000 pmol) vs 4.6 +/- 0.8 (CSF) g; 23 h period: 27.0 +/- 1.9 (1000 pmol) vs 26.6 +/- 2.9 (CSF) g; N.S.). Thus, PYX-2, the putative NPY antagonist, totally failed to inhibit food intake in the obese rats. The absence of effect of PYX-2 on food intake can be explained by the structure of PYX-2, a modified 27-36 amino acid sequence that may not be recognized by the Y1-type NPY receptors which are involved in the regulation of feeding behavior.

Amino Acid Sequence↗
PubMed1994

Increased threshold concentrations of neuropeptide Y for a stimulatory effect on food intake in obese Zucker rats--changes in the microstructure of the feeding behavior.

A central dysregulation of several neuropeptides could be at the origin of the marked hyperphagia of the obese Zucker rat, a well-known animal model used for the study of obesity. Neuropeptide Y (NPY), which strongly stimulates food intake and increases early in life in obese rats, plays a major role in the development of this hyperphagia. The aim of our experiment was to measure the feeding responses of lean (n = 8) and obese (n = 17) male Zucker rats to several doses of exogenous NPY injected in the lateral brain ventricle. We analyzed the microstructure of the rats' feeding behavior with an automatic device for 8 h post-injection. NPY stimulated food intake both in the lean and obese rats in a dose-dependent manner (P < 0.001). However, the minimal effective dose was always 3-4 times greater in the obese rats than in the lean ones (range: 0.43-0.53 vs. 0.12-0.18 microgram/brain; P < 0.001). Meal size, meal duration and time spent eating significantly increased in the lean rats (P < 0.05 or less). The last two parameters also increased in the obese rats but with the highest dose (5 micrograms) only. The obese Zucker rats were therefore less sensitive to NPY than the lean ones, probably because of their already high endogenous NPY levels. The modifications in the eating behavior indicate that NPY could overcome the satiety signals.

Animals↗
PubMed1994

Hypothalamic neuropeptides could mediate the anorectic effects of fenfluramine.

Oxytocin, vasopressin and corticotrophin releasing factor have anorectic properties when injected centrally. We studied the kinetics of these neuropeptides by injecting fenfluramine, a drug which reduces food intake, in Long Evans rats. The drug was injected daily through a double chronic cannula implanted above the paraventricular nucleus of the hypothalamus; the rats had free access to pure macronutrients. The rats lost weight during the treatment. Their total caloric intake decreased mostly because the carbohydrate intake decreased, while the protein intake increased slightly. The synthesis and release of brain oxytocin and vasopressin were increased and the release of corticotrophin releasing factor was stimulated. The neuropeptides could be involved in fenfluramine-triggered mechanisms.

Animals↗
PubMed1994

Macronutrient type independently of energy intake modulates hypothalamic neuropeptide Y in Long-Evans rats.

Neuropeptide Y (NPY) induces a robust feeding response when it is injected in the hypothalamus. It stimulates both carbohydrate and fat intakes. Diets rich in either macronutrient are known to induce obesity and to modify feeding behavior. The aim of the present study was to determine the effects of long-term ingestion of these diets on hypothalamic NPY in relation with food intake and body weight gain and composition. For this purpose, three groups of weanling Long-Evans rats were fed either a well-balanced diet, a high-carbohydrate (HC) diet (high starch plus 25% sucrose solution), or a high-fat (HF) diet during 14 weeks. Body weight and food intake were recorded during this period. At the end of the experiment, NPY was measured in several microdissected brain areas, and some adipose tissues (AT) depots were sampled. HF rats weighed significantly more than the two other groups (p < 0.02). They were also fattier (+ 30-50% in AT weights; p < 0.01). Energy intake (EI) of the HC rats was significantly greater than that of the control (+ 15%; p < 0.02) and HF rats (+ 34%; p < 0.01) during the week preceding killing. EI of HF rats over the whole experiment was lower than that of the two groups (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Thymoma with immunodeficiency (Good's syndrome) associated with selective cobalamin malabsorption and benign IgM-kappa gammopathy.

We have described the first case, to our knowledge, in which recurrent respiratory tract infections were the primary manifestation of thymoma with immunodeficiency (Good's syndrome) associated with cobalamin malabsorption and immunoglobulin M-kappa (IgM-kappa) M component. The intrinsic factor receptor activity was dramatically decreased in a mucosal homogenate prepared from ileal biopsies. This decreased activity could be the principal cause of the malabsorption of labelled cobalamin which was observed in the presence of intrinsic factor. However, it could be the consequence of the cobalamin deficiency, as it is known that a cobalamin deficiency can affect the assimilation of cobalamin, even in presence of exogenous intrinsic factor.

Aged↗
PubMed1994

Surimi and native codfish contain a common allergen identified as a 63-kDa protein.

We have compared the allergenicity of codfish and surimi (prepared from codfish) by skin testing, specific IgE-RIA, and leukocyte histamine release (LHR) in six fish-allergic patients. Prick tests were positive for codfish and, to a lesser extent, surimi. The percentages of labeled anti-IgE bound to surimi-Sepharose were 1.55 +/- 0.19% and 3-6% with control and patient sera, respectively. Inhibition of the surimi protein-Sepharose IgE-RIA was greatest (80%) at protein concentrations of 13.4 and 408.5 micrograms/ml for codfish and surimi extract, respectively. The allergenic protein was isolated by gel filtration and subjected to SDS-PAGE. The eluate from codfish contained several proteins ranging from 13 to 63 kDa, while the eluate from surimi contained a single 63-kDa protein. It was concluded that surimi contained a single allergenic protein.

Adolescent↗
PubMed1994

[Corticotropin-releasing factor and anorexia nervosa: reactions of the hypothalamus-pituitary-adrenal axis to neurotropic stress].

The aim of this study is to obtain CRF (Corticotropin Releasing Factor) stimulation at a suprahypothalamic level with a psychological stressor and to evaluate its response in anorexia nervosa. CRF plays a major role in the mechanisms underlying the hypothalamo-pituitary-adrenal (HPA) system's response to stress. Animal studies clearly showed that CRF is involved both in the adaptation to a novel environment and the regulation of eating behaviour. CRF's staietogenic effect is mediated via the paraventricular nucleus. Three groups of age matched young women were studied: 8 patients meeting the DSM III-R criteria for anorexia nervosa, 8 underweight healthy volunteers and 10 normal weight volunteers. All subjects were submitted to an auditory stimulation test ("psychosocial stress test") consisting of an intellectual task in which maximal performance is impossible to achieve, the subjects being permanently disturbed by various meaningful noises. Subjects were asked to answer self-rating scales for anxiety and tension prior to and after the test. CRF reactivity was measured by salivary cortisol (RIA). After the test, anorexia nervosa patients exhibit a significantly higher salivary cortisol response compared to the normal weight volunteers. In most of cases, salivary cortisol response was not correlated with the psychological variables. The range of the response is very explosive in two anorectic patients. Our data are consistent with the hyperactivity of the corticotropic axis stress response in anorexia nervosa, but request further investigations to prove that.

Acoustic Stimulation↗
PubMed1994

[Absorption, distribution and excretion of vitamin B12].

In our first communication, the complexity of vitamin B12 digestive transport was considered. This second presentation demonstrates the route of the vitamin in the body. As cobalamin or vitamin B12 has existed for Four Billion Years, they figure without any doubt amongst those molecules which have the most complex structure. The rarity of an architecture organised around a cobalt atom confirms their high level of originality. Their exceptional character is reflected in their cycle such as for mammals and for man where the intervention of binders, such as intrinsic factor, transcobalamin and haptocorrin is necessary for transporting them. As far as cellular metabolism is concerned, it is especially loaded sometimes with folates in the transfer of the methyl group. The Molecules are spiked with hydrophobic sites. Their membrane transfer is facilitated by several types of receptors. The intestinal absorption, which appears to require the presence of two receptors and two transporters, remains for the moment a unique assimilation model. The very probable existence of an enterohepatic cycle as well as a renal reabsorption saves this molecule, itself synthesised by microorganisms only.

Humans↗