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Biomedical subjects

A Camus

Publications and source records attributed to A Camus.

34 records · Page 2Linked to original sources
PubMed1995

Increased T-cell apoptosis and terminal B-cell differentiation induced by inactivation of the Ets-1 proto-oncogene.

The Ets-1 proto-oncogene is a member of a transcription factor family characterized by homology to the v-ets oncogene. In adult mice, Ets-1 is expressed predominantly in lymphoid cells where it has been implicated in regulating transcription of lymphocyte-specific genes. Following T-cell activation, the specific DNA binding activity of Ets-1 is inactivated by transient phosphorylation, suggesting a function in the transition from the resting to activated state. Ets-1 has also been suggested to cooperate with the AP-1 transcription factor complex to mediate cellular growth factor responses. Here we show, by using RAG-2-deficient blastocyst complementation, that Ets-1 deficiency has dramatic, but different, effects on development and function of T- and B-lineage cells. Ets-1-deficient T cells were present in reduced numbers and were highly susceptible to cell death in vitro. In contrast, Ets-1-deficient B cells were present in normal numbers but a large proportion were IgM plasma cells. Our data demonstrate that Ets-1 is essential for maintenance of the normal pool of resting T- and B-lineage cells.

Animals↗
PubMed1995

Megakaryoblastic leukemia in a dog.

A 7-year-old spayed Louisiana Catahoula Leopard dog was examined to determine the cause of shifting forelimb lameness, anorexia, and lethargy. The dog was pyrectic and had splenomegaly, thrombocytopenia, and nonregenerative anemia. Examination of a bone marrow aspirate revealed hypocellularity with normal maturation of erythroid and granulocytic cell lines; however, approximately half of the cells were large undifferentiated blast cells. These cells were identified as megakaryoblasts, using immunohistochemical techniques to detect reactivity for Factor VIII-related antigen and platelet glycoprotein IIIa. Necropsy revealed diffuse neoplastic involvement of the spleen, liver, lungs, bone marrow, and lymph nodes. Cellular infiltrate was characterized by a mixture of megakaryoblasts and typical megakaryocytes. Megakaryoblastic leukemia (M7) is the designation proposed by the Animal Leukemia Study Group for myeloproliferative neoplasms of megakaryocytic lineage.

Animals↗
PubMed1994

Modified technique for efficient detection of microsporidia.

Changes in temperature (from room temperature to 50 degrees C) and staining time (from 90 to 10 min) were evaluated as a means of improving the detection of microsporidia from stool specimens. A blinded and independent comparison of 50 known positive matched-specimen pairs by three technologists resulted in consistently easier microscopic detection. The background is clearer, and spores stain more intensely. Staining time is reduced by 80 min.

AIDS-Related Opportunistic Infections↗
PubMed1989

Molecular determinants of receptor affinity and selectivity of the natural delta-opioid agonist, dermenkephalin.

Processing of the polyprotein precursor pro-dermorphin generates two distantly related D-amino acid-containing peptides, dermorphin and dermenkephalin, which are among the most selective high affinity agonists described, respectively, for the mu- and delta-opioid receptors. Dermenkephalin, Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2, is a linear, potentially flexible peptide devoid of structural homology with either enkephalins, endorphins, or dynorphins and, as such, represents a useful tool for identifying determinants of high affinity and selective binding of opioids to the delta-receptor. A series of selected dermenkephalin analogs and homologs was investigated for affinity at the mu- and delta-sites in the brain. Whereas dermenkephalin has high affinity and specificity for the delta-opioid receptors, its tetrapeptide amino end, dermenkephalin-[1-4]-NH2 binds almost exclusively at the mu-receptors. Dermorphin, Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2, is only marginally more selective for the u-sites than is dermenkephalin-[1-4]-NH2. Using dermorphin-dermenkephalin peptide hybrids and C-terminal deletion analogs of dermenkephalin, we showed the critical role that the C-terminal residues Met6 and Asp7 play in specifying correct addressing of dermenkephalin toward delta-receptors. The potent mu-deteminant located within the amino end of dermenkephalin is over-whelmed by the powerful delta-directing ability of the carboxy end. The negatively charged side chain of Asp7 makes a significant contribution to the delta-addressing ability of the C-terminal region, a finding consistent with Schwyzer's membrane selection model (Schwyzer, R. (1986) Biochemistry 25, 6335-6342). The Leu residue in position 5 and D-configuration about the alpha-carbon of Met2 were found to be of crucial importance for high affinity binding to delta-receptors. Whereas the Met residue in position 6 in dermenkephalin could safely be oxidized or replaced with D-Met, oxidation of Met2 led to deleterious effects, this analog being 1/100 as potent as dermenkephalin at delta-sites. Overall, the data collected demonstrate that highest levels of selectivity and affinity for the delta-opioid receptors can be achieved with small-sized, potentially flexible, linear peptides and further support the model according to which, in addition to optimum accommodation at the receptor, selection for delta-receptors is reduced by the effective positive charge of the molecule. Dermenkephalin may provide a starting point for the design of agonists and antagonists with nearly total specificity for the delta-sites. Such pharmacological agents could be used to explore the ill-defined physiological role and behavioral actions conveyed by delta-opioid receptors.

Amino Acid Sequence↗
PubMed1989

Differential contribution of C-terminal regions of dermorphin and dermenkephalin to opioid-sites selection and binding potency.

Dermorphin and dermenkephalin are D-aminoacid containing peptides generated from processing of the plurifonctional biosynthetic precursor pro-dermorphin. Dermorphin, Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2 (DRM) and dermenkephalin, Tyr-D-Met-Phe-His-Leu-Met-Asp-NH2 (DREK), are among the most selective and potent agonists described respectively for the mu- and delta-opioid receptors. In order to identify determinants of selectivity and high-affinity receptor binding of dermorphin and dermenkephalin, a series of analogs was investigated for their affinity at the mu- and delta-receptors in the brain. The tetrapeptide amino end of both DRM and DREK were found to display high affinity and selectivity towards mu-receptors. Substitution of the C-terminal tripeptide of DREK with that of DRM reversed the receptor selectivity of DREK from delta to mu. Replacement of the C-terminal tripeptide of DRM with the C-terminal counterpart of DREK shifted the selectivity of DRM from mu to delta. These data emphasize the critical contribution of the carboxy end of DREK to delta-selectivity. They further suggest that the potent mu-address lying in the N terminus of DREK is overwhelmed by the powerful delta-directing ability of the carboxy end. Unlike DREK, the C-terminus of DRM is not involved in opioid receptor sites selection but is important insofar as it serves to stabilize interactions of DRM with the mu-receptor binding site.

Animals↗
PubMed1989

Protection by serine peptidase inhibitors of endogenous cholecystokinin released from brain slices.

Endogenous cholecystokinin immunoreactivity released by depolarization of slices of rat cerebral cortex undergoes extensive degradation (85% of released immunoreactivity) before reaching the incubation medium. In order to identify the responsible peptidases, a large number of inhibitors of the four catalytic classes were tested for their protective effects. Inhibitors of metallopeptidases (bestatin, amastatin, puromycin, Thiorphan, captopril, o-phenantroline), thiol-peptidases, (leupeptin, antipain, p-hydroxymercuribenzoate) or carboxyl-peptidases (pepstatin) had generally low if any protective effect. By contrast, several serine peptidase inhibitors, i.e. diisopropyl-fluorophosphate, phenylmethylsulphonylfluoride or the chloromethylketone Ala-Ala-Pro-Val-CH2Cl, doubled the recovery of cholecystokinin immunoreactivity and the effect was amplified in the co-presence of bestatin, an aminopeptidase inhibitor and/or Thiorphan, an enkephalinase inhibitor. High-performance liquid chromatographic analysis of the cholecystokinin immunoreactivity recovered in medium in the absence of any inhibitor showed cholecystokinin-8 to be the major peak, representing 8% of the released immunoreactive material. Non-sulphated cholecystokinin-8 represented less than 1%, indicating that desulphation does not constitute a major inactivation pathway for the endogenous octapeptide. Cholecystokinin-5 was the major clearly identifiable immunoreactive fragment, representing 9% of released immunoreactivity in the absence of inhibitors. Its formation was decreased by about 50% in the presence of either diisopropyl-fluorophosphate or bestatin and Thiorphan and abolished when they were associated, suggesting that it resulted from the actions of a serine peptidase(s) and an aminopeptidase(s). Cholecystokinin-6 (or cholecystokinin-7) was less abundant, representing 4% of the released immunoreactivity, and its level was augmented in the presence of diisopropyl-fluorophosphate. Hence a serine endopeptidase cleaving the Met3-Gly4 bond of cholecystokinin-8 may represent a major inactivating peptidase for the endogenous neuropeptide. Additional metabolic pathways not blocked by serine peptidase inhibitors and resulting in the formation of cholecystokinin-6 (or cholecystokinin-7) and, possibly, cholecystokinin-4, are also suggested by the present approach.

Animals↗
PubMed1989

Role of a serine endopeptidase in the hydrolysis of exogenous cholecystokinin by brain slices.

The participation of a serine endopeptidase, previously shown to be involved in endogenous cholecystokinin inactivation [Rose, Camus and Schwartz (1989) Neuroscience 29, 583-594], in the hydrolysis of various exogenous cholecystokinin peptides was studied with slices from rat cerebral cortex. In order to protect intermediate fragments from further degradation and mimick experimental conditions in this previous study, most experiments were performed in the presence of Thiorphan, an enkephalinase inhibitor, and bestatin, an aminopeptidase inhibitor, which did not significantly affect the rate of cholecystokinin-8 hydrolysis. All peptide fragments formed after incubation of cholecystokinin-8, non-sulphated cholecystokinin-8, cholecystokinin-6, cholecystokinin-5, cholecystokinin-4 or Asp-Tyr-Met-Gly-Trp were identified by isocratic high-performance liquid chromatography in several systems, fluorescence spectra and/or amino acid analysis. When identified, the appearing fragments were quantified by u.v. spectrophotometry and found to fully account for the substrate disappearance. The hydrolysis rate was higher for short cholecystokinin peptides than for the octapeptide and was, in all cases, diminished by 30-50% in the presence of diisopropyl fluorophosphate, a serine peptidase inhibitor. One of the main hydrolysis products of cholecystokinin-8, or its non-sulphated analogue, was cholecystokinin-5, whose formation was impaired in the presence of diisopropyl fluorophosphate. Cholecystokinin-5 itself was apparently a substrate for a serine peptidase leading to the formation of the tripeptide Gly-Trp-Met, later cleaved into Trp-Met and Trp. Hence a serine endopeptidase(s) appears to be responsible for cleavage of the two peptides bonds of the cholecystokinin-8 molecule where the carboxyl group is donated by a methionine residue.2+n addition,

Animals↗
PubMed1988

A serine peptidase responsible for the inactivation of endogenous cholecystokinin in brain.

A serine endopeptidase was characterized as a major inactivating enzyme for endogenous cholecystokinin (CCK) in brain. CCK-8 released by depolarization of slices of rat cerebral cortex, as measured by its immunoreactivity (CCK-ir), undergoes extensive degradation (approximately 85% of the amount released) before reaching the incubation medium. However, recovery of CCK-ir is enhanced up to 3-fold in the presence of serine-alkylating reagents (i.e., phenylmethylsulfonyl fluoride) as well as selected active site-directed inactivators (i.e., peptide chloromethyl ketones) or transition-state inhibitors (i.e., peptide boronic acids) of serine peptidases. Among these compounds, elastase inhibitors were the most potent protecting agents, whereas trypsin or chymotrypsin inhibitors were ineffective. HPLC analysis of endogenous CCK-ir recovered in media of depolarized slices indicated that endogenous CCK-5 [CCK-(29-33)-pentapeptide] was the most abundant fragment and that its formation was strongly decreased in the presence of an elastase inhibitor. HPLC analysis of fragments formed upon incubation of exogenous CCK-8 [CCK-(26-33)-octapeptide] with brain slices showed CCK-5, Gly-Trp-Met, and Trp-Met to be major metabolites of CCK-8 whose formation was prevented or at least diminished in the presence of the elastase inhibitor. It is concluded that there is an elastase-like serine endopeptidase in brain that cleaves the two peptide bonds of CCK-8 where the carboxyl group is donated by a methionine residue and constitutes a major inactivation ectoenzyme for the neuropeptide.

Animals↗
PubMed1986

Autoradiographic localization and quantification of dopamine D2 receptors in normal human brain with [3H]N-n-propylnorapomorphine.

The precise distribution of dopamine receptors has been studied autoradiographically in the normal human brain using [3H]N-n-propylnorapomorphine ([3H]NPA) as a ligand. Preliminary experiments aimed at optimizing the binding assay conditions revealed that preincubation washing of caudate nucleus sections was a prerequisite to obtain a good ratio of specific to non-specific binding. The binding of [3H]NPA to caudate-putamen sections was saturable, stereospecific, reversible, of high affinity (Kd = 0.27-0.35 nM) and occurred at a single population of sites. Competition experiments with various drugs indicated that in the caudate-putamen the specific [3H]NPA binding sites possess the pharmacological features of the dopamine D2 receptor. The highest levels of [3H]NPA binding sites were found in the caudate nucleus, putamen, globus pallidus and nucleus accumbens. There were also intermediate to low concentrations of the 3H-ligand in the hippocampus, the insular and cingular cortices and in the occipito-temporal gyrus, while almost undetectable levels of binding were found in the anterior frontal cortex. Thorough examination of the subregional distribution of [3H]NPA binding sites in the caudate-putamen-pallidum complex revealed heterogeneous patterns of radioactivity. In these brain regions, the distribution of autoradiographic grains was punctate and islands of high and low densities were observed. Moreover, in the caudate nucleus, there was a subtle high lateral to low medial gradient in the topography of the [3H]NPA binding sites and a more pronounced gradient along the rostrocaudal axis; the highest levels of binding being located at the midbody of the nucleus. No gradients of [3H]NPA binding were observed in the putamen. The present data indicate that [3H]NPA is a suitable ligand for accurate autoradiographic labeling of dopamine D2 receptors in human postmortem brain tissue and that dopamine receptors are heterogeneously distributed and topographically organized in patches and gradients in the basal ganglia regions.

Aged↗
PubMed1984

Autoradiographic localization of muscarinic cholinergic receptors at various segmental levels of the human spinal cord.

Muscarinic cholinergic receptors were localized autoradiographically at different segmental levels of the normal human spinal cord after in vitro labelling using [3H]quinuclidinylbenzilate. The highest densities of muscarinic receptors were found in laminae II (substantia gelatinosa) and IX (motor neurons) of the gray matter. Lower densities of receptors were present in the other laminae and no binding sites were found in the white matter. This pattern of distribution of muscarinic receptors was similar at the cervical, thoracic, lumbar and sacral levels of the cord. These data suggest that muscarinic receptors may not only take part in motor function but also in the processing of sensory information.

Anterior Horn Cells↗
PubMed1984

Interaction of the human leukocyte proteinases elastase and cathepsin G with gold, silver and copper compounds.

Gold thiomalate and the corresponding silver and copper derivatives were investigated as inhibitors of the human leukocyte proteinases elastase and cathepsin G. The kinetic inhibition mechanism for gold- and silver thiomalate is of the hyperbolic non-competitive type with both enzymes and the inhibitory efficiency of the metals increases in the order Cu less than Ag less than Au. On the contrary, D-penicillamine derivatives of the three metals do not influence at all the activity of the two proteinases. Although gold thiomalate is the most efficient of the investigated metal compounds (Ki = 33 microM and 25 microM for elastase and cathepsin G, respectively), the hyperbolic nature of the inhibition imposes a serious limit to its practical usefulness since the maximum inhibitory action on both enzymes is about 40%. We suggest that, in order to act as inhibitor, a copper, silver or gold compound must be able to easily transfer the metal to the enzyme.

Cathepsin G↗
PubMed1976

Mutagenicity of beta-oxidized N,N,-di-n-propylnitrosamine derivatives in S. typhimurium mediated by rat and hamster tissues.

The relative abilities of liver, kidney and lung fractions from untreated or phenobarbitone-pretreated rats and hamsters to convert N,N-di-n-propylnitrosamine and several beta-oxidized synthetic putative intermediates into mutagens was quantitatively compared in a tissue-mediated mutagenicity assay with S. typhimurium TA 1530 in vitro. With one exception, namely, N,N-di(2-acetoxy-n-propyl)nitrosamine, liver was the most active tissue from hamsters; in rats also, only liver fractions were able to activate some nitroso-compounds to mutagens. The highest enzyme-mediated mutagenicities were observed with N-2-hydroxy-n-propyl-N-n-propylnitrosamine, N,N-di-n-propylnitrosamine and N,N-di(2-acetoxy-n-propyl)nitrosamine. Hamster lung tissue converted N,N-di-n-propylnitrosamine, N-2-hydroxy-n-propyl-N-n-propylnitrosamine and N,N-di(2-acetoxy-n-propyl)nitrosamine into mutagens; activity with the latter compound was greater with lung tissue than with liver tissue when untreated animals were used. N-methyl-N-n-propylnitrosamine was mutagenic in the presence of hamster liver fraction but less so than N,N-di-n-propylnitrosamine. The results of the mutagenicity assays using various tissues are qualitatively compared to sites of tumour formation in rats and hamsters by these N-nitrosamines.

Animals↗
PubMed1976

Comparative mutagenicity of N-nitrosamines in a semi-solid and in a liquid incubation system in the presence of rat or human tissue fractions.

The rat liver microsome-mediated mutagenicities of a series of N-nitrosodialkylamines and heterocyclic N-nitrosamines were determined in a liquid incubation system using Salmonella typhimurium TA1530. The influence on mutation frequency of the concentration of co-factors for mixed-function oxidase and composition and molarity of the buffer was investigated, using N-nitrosomorpholine as substrate. The mutagenicity of the N-nitroso compounds in the liquid incubation system under optimal reaction conditions at equimolar concentration was compared quantitatively with that obtained in a soft-agar incorporation assay. N-Nitrosodi-n-pentylamine and N-nitrosodi-n-butylamine showed no enzyme-mediated mutagenicity in the liquid incubation system, and metabolically activated N-nitroso-dimethylamine and N-nitroso-diethylamine showed negligible mutagenic activity in the soft-agar assays. In contrast with these results with the N-nitrosodialkylamines, the mutagenic effects of heterocyclic N-nitrosamines were similar in the liquid incubation system and in soft-agar incorporation assays. The heterocyclic N-nitrosamines showed rat-liver microsome-mediated mutagenicity in the following descending order: N-nitrosomorpholine greater than N-nitrosopyrrolidine greater than N-nitrosopiperidine greater than N-nitroso-N'-methylpiperazine. Seven human liver specimens converted all heterocyclic N-nitrosamines into mutagens; this activity was similar to that of rat liver, except that for N-nitroso-N'-methylpiperazine, fractions from three human liver biopsies were three to 30 times more active than those from untreated rats. The specific reversion of S. typhimurium TA1530 to histidine prototrophy provides experimental evidence that all the N-nitrosamines studied were converted by liver microsomal enzymes into monofunctional alkylating agents.

Animals↗
PubMedDate not supplied

Psychomotor desadaptation syndrome.

This article constitutes a description of a clinical entity that has been observed and that we have described in French literature for over 10 years. This syndrome has been named 'la Régression Psychomotrice' in the french language and is termed here 'psychomotor desadaptation syndrome' (PDS). Postural impairments, neurological signs and psychological features have been found to be associated with PDS. Postural and neurological disorders were characterized by retropulsion, muscle tone modification, and the loss of reactive and protective postural reactions. Psychological features consisted of slowness of cognitive processing, often associated with anxiety and a fear of falling. PDS may be considered as a functional disorder, and clinicians must identify not only predisposing factors, but also etiological ones. The medical treatment of these factors and specific readaptation approaches must be associated with the management of PDS. PDS appears to be a reversible syndrome if a multidisciplinary approach and early management are undertaken.

Journal Article↗
PubMedDate not supplied

Tuberculosis in commercial emus (Dromaius novaehollandiae).

Extensive granuloma formation typical of tuberculosis was observed in a mature female emu. The diagnosis was confirmed by demonstration of acid-fast bacilli in lesions and culture of a Mycobacterium with growth characteristics resembling M. avium from liver tissue. Individual emus on the affected farm and an epidemiologically related unit gave a positive skin reaction to intradermal M. avium tuberculin. The implication of tuberculosis in commercial emus is noted in relation to the growth of the industry in North America and to management and commercial practices that encourage dissemination of infection within the species and to other exotic and domestic animals.

Animals↗