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J Picard

Publications and source records attributed to J Picard.

At least 19 recordsLinked to original sources

Awake or asleep.

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Analgesia, Epidural↗

The use of liposomal amphotericin B in the management of Xylohypha bantiana mycosis in a dog.

Xylohypha bantiana is a rare neurotropic fungal infection reported in humans, dogs and cats. In dogs it has only been identified on post mortem examination and thus no successful treatments have previously been reported. Amphotericin B is a potent antifungal drug with a low therapeutic index because of its nephrotoxicity. Liposomal encapsulation of the drug has resulted in much safer use in humans. This article reports a case of Xylohypha bantiana infection in a dog that was diagnosed antemortally and managed with liposomal amphotericin B, which resulted in the prolongation of quality of life for an infection that invariably results in rapid death.

Amphotericin B↗

Differential and opposed transcriptional effects of protein fusions containing the VP16 activation domain.

Overexpression of strong transcriptional activators like herpes simplex virion protein 16 (VP16) may lead to non-specific inhibition of gene expression as a result of the titration of transcription factors. Here we report that a fusion between the homeoprotein Hoxa2 and the VP16 activation domain inhibits transcription from the strong promoter/enhancers of cytomegalovirus (CMV) and Rous sarcoma virus (RSV). A similar fusion involving a Hoxa2 mutant protein that is defective in DNA binding has no effect on the CMV promoter but increases, rather than inhibits, the RSV promoter activity. This suggests that depending on its ability to bind DNA, the VP16 activator can interact with different sets of cofactors, giving rise to distinct transcriptional effects.

Animals↗

Immune reactivity to glutamic acid decarboxylase 65 in stiffman syndrome and type 1 diabetes mellitus.

BACKGROUND: The immune response to an isoform of glutamic acid decarboxylase (GAD), GAD65, is associated with two clinically distinct diseases, stiff-man syndrome (SMS) and type 1 (insulin-dependent) diabetes mellitus. We sought to identify differences in the cellular and humoral immune responses to GAD in these two diseases. METHODS: We compared T-cell responses in 14 SMS patients with axial disease and 17 patients with type 1 diabetes. FINDINGS: Peripheral blood T cells of eight SMS patients recognised different immunodominant epitopes of GAD65 compared with T cells from 17 patients with type 1 diabetes. GAD regions 81-171 and 313-403 induced a dominant T-cell response in six of eight patients with SMS but in only one of 17 patients with type 1 diabetes (p=0.001). No SMS patients responded dominantly to GAD fragments 161-243 and 473-555 compared with ten patients with type 1 diabetes (p=0.008). GAD antibodies were detected in 11 of 14 SMS patients (seven with diabetes) and 11 of 17 patients with type 1 diabetes; IgG1 was dominant in both groups. SMS patients, however, were more likely than patients with diabetes to have isotypes other than IgG1 (p=0.03), in particular, IgG4 or IgE isotypes, which were not detected in patients with type 1 diabetes (p=0.012). INTERPRETATION: Our findings indicate differences between patients with SMS and type 1 diabetes in cellular (epitope recognition) and humoral (isotype pattern) responses to GAD65. Thus the same autoantigen can elicit distinct immune responses in patients with SMS, even when associated with diabetes, compared with patients with type 1 diabetes.

Adolescent↗

A susceptibility region for myasthenia gravis extending into the HLA-class I sector telomeric to HLA-C.

We have analyzed a series of HLA region markers in 207 UK Caucasoids with early-onset myasthenia gravis (EOMG, onset before age 40), where there is a strong female bias. The well known associations with HLA-DR3 and -B8 have now proved to be significantly stronger in the 165 females than in the 42 males. In patients (of either sex) lacking -DR3, there was also a significant increase in HLA-DR2. Although the muscle weakness in EOMG is clearly mediated by autoantibodies, the associations are consistently stronger with HLA-B8 (in class I) than with HLADR3 (in class II), as confirmed here. We therefore typed 87-137 cases for polymorphisms at four loci in the intervening class III region, and also at three in the adjacent stretch of class I. At each locus, one allele tended to co-occur with HLA-B8 and showed strong and highly significant associations in the patients. There appeared to be a region of maximal susceptibility extending from HSP70 (in class III) past HLA-B and HLA-C at least 600 kb telomerically into the class I region, which is now being mapped in detail. Any candidate genes here that act shortly after puberty may allow more precise localization of susceptibility.

Adult↗

Chlamydia-induced septic polyarthritis in a dog.

A systemic disease associated with pyrexia, lymphadenopathy, and arthropathy of several joints of the appendicular skeleton in a dog is described. Chlamydia-like organisms were detected on light-microscopic examination of a smear made from joint fluid aspirated from one of the affected joints. A group-specific lipopolysaccharide antigen shared by all Chlamydia spp. was demonstrated by direct fluorescent antibody staining of joint fluid, which also proved positive for chlamydia by means of the relevant polymerase chain reaction test. An indirect fluorescent antibody test on serum was also positive, although the complement fixation test was negative. Attempts to grow the organism from joint aspirates in the yolk sac of embryonating hens' eggs and on appropriate tissue cultures, however, failed. Chlamydia spp. are considered to have played an aetiological role in this case, making it the first substantiated case of naturally-occurring arthropathy in a dog due to chlamydiosis. The origin of the infection could not be traced.

Animals↗

Prevalence of helicobacteriosis and gastritis in semicaptive cheetahs (Acinonyx jubatus).

Endoscopic biopsy specimens were obtained from the cardiac, fundic, and pyloric stomach regions of 28 semicaptive cheetahs (Acinonyx jubatus) to look for signs of helicobacteriosis and gastritis. Impression smear cytology and urease tests were positive in 23 and 26 of the cheetahs, respectively. Histopathology showed mild or no lesions in 27 cheetahs; only one cheetah had moderate gastritis. Gastritis was uncommon in these semicaptive cheetahs, and stress could play a major role in the development of helicobacteriosis-associated gastritis in the captive cheetah.

Acinonyx↗

Characterization of a recent retroposon insertion on mouse chromosome 2 and localization of the cognate parental gene to chromosome 11.

The genomic sequence on mouse Chromosome (Chr) 2 corresponding to a previously identified novel cDNA has been characterized. The genomic organization of this locus, adjacent to the beta 2 microglobulin gene, has the properties of a processed gene or retroposon including the presence of a short flanking direct repeat, a polyadenylation signal/poly A tract, and the absence of introns. Analysis of inbred and wild-derived Mus DNAs reveals the retroposon to be a feature only of M. m. domesticus subspecies, suggesting that the insertion event is relatively recent. This notion is supported by the presence of an open reading frame and the lack of sequence divergence in the flanking direct repeats. The complex chromatin configuration characteristic of this region in mouse and human is not, therefore, related to this cDNA. The cognate parental gene encoding the cDNA was mapped to Chr 11. A further, more ancient retroposon present in many Mus species localizes to Chr 17.

Animals↗

Role for PKC alpha and PKC epsilon in down-regulation of CFTR mRNA in a human epithelial liver cell line.

BACKGROUND/AIMS: In the liver, intrahepatic biliary cells are the sole site of expression of the cystic fibrosis transmembrane conductance regulator, the product of the cystic fibrosis gene. We examined the regulation of cystic fibrosis transmembrane conductance regulator gene expression by protein kinase C in the recently characterized human liver epithelial BC1 cell line which expresses, at early confluence, both biliary (cystic fibrosis transmembrane conductance regulator, cytokeratin 19) and hepatocytic (albumin) specific markers. METHODS: Expression of the cystic fibrosis transmembrane conductance regulator was examined at the mRNA level by Northern blot, reverse transcription-polymerase chain reaction and nuclear run-on assays and at the protein level by Western blotting. The functionality of this protein was tested by measurement of chloride efflux. Protein kinase C isotype expression and cytosol-to-membrane translocation were analysed by Western blotting. RESULTS: 1) Phorbol ester down-regulated cystic fibrosis transmembrane conductance regulator mRNA expression in a time- and dose-dependent manner through a post-transcriptional mechanism with concomitant inhibition of stimulated chloride efflux. 2) Phorbol ester also activated protein kinase C as indicated by the cytosol-to-membrane translocation of both protein kinase C alpha and epsilon the two major protein kinase C isotypes expressed by BC1 cells. 3) Further, maximal down-regulation of the cystic fibrosis transmembrane conductance regulator mRNA by the phorbol ester was inhibited by H7 and by GF 109203X, two known protein kinase C inhibitors. CONCLUSIONS: These findings provide the first evidence for phorbol ester-induced down-regulation of cystic fibrosis transmembrane conductance regulator mRNA expression in a human liver epithelial cell line and point to a role for the classical protein kinase C alpha and the novel protein kinase C epsilon in this process.

Cell Line↗

Intrinsic differences in hearing performances between ears revealed by the asymmetrical shooting posture in the army.

Left ear noise-induced hearing losses are dominant in the army. The common explanation is the asymmetrical effect of the shooting posture. However, firm evidence to support this possibility is still lacking. In the French army shooters, eye preference rather than hand preference for shooting determines the side of shooting and hence the ear more exposed to noise. To test whether left-right asymmetry of hearing thresholds really relates to the shooting posture, we analyzed audiograms from 644 officers of the infantry and artillery branches. The interaural differences reached 7 dB for right-eyed subjects, and less, about 5 dB, for left-eyed subjects at 6-7 kHz, both with disadvantage for the left ear. In contrast, hearing thresholds of both groups in the low frequency range were significantly better for left ears. Our results suggest each ear has different intrinsic characteristics. The right cochlea might be a less sensitive but more robust sensor than the left cochlea, which might be a finer sensor but more sensitive to noise.

Adult↗

Caffeine-induced disturbances of early neurogenesis in whole mouse embryo cultures.

In toto mouse embryos were cultivated at embryonic day 8.5 for 26 h with 105, 310 or 620 microM caffeine; 105-310 microM correspond to concentrations transferred by the placenta of heavy caffeine consumers. Failure of neural tube closure, excessive proliferation of neuroepithelial cells and premature evagination of telencephalic vesicles were present in 50% of treated embryos. When reaching the embryonic neural tube before neuronal migration, caffeine regionally modifies the schedule and/or rate of neural cell proliferation.

Abnormalities, Drug-Induced↗

Chronic episodic diarrhoea associated with apparent intestinal colonisation by the yeasts Saccharomyces cerevisiae and Candida famata in a German shepherd dog.

A 3-year-old German shepherd dog was presented with a history of lifelong episodic diarrhoea. An adverse reaction to food was considered the most likely cause of the diarrhoea. The dog had received prolonged antibiotic therapy for most of its life as well as receiving probiotics containing the yeast Saccharomyces cerevisiae (syn. S. boulardi) for a year before referral. The probiotic was discontinued 2 months before to referral. Examination and culture of faecal samples identified yeast-like organisms, S. cerevisiae and Candida famata. S. cerevisiae has been isolated from humans in association with predisposing conditions such as prolonged sojourns in hospital, immunosuppression, broad-spectrum antibiotic therapy and prosthetic devices, but is regarded as non-pathogenic in humans and is rarely associated with disease in animals. C. famata has been isolated from animals, humans and the environment, but is regarded as a very rare pathogen. No evidence of immunosuppression was found in the dog. The presence of yeasts in the faecal isolates and the history of prolonged use of antibiotics and probiotics with a concurrent adverse reaction to food, suggest that conditions may have occurred within the bowel that made it possible for the yeasts to colonise parts of it. This has apparently not been reported before.

Animals↗

VISAUDIO: a Windows software application for Bekesy audiogram analysis and hearing research.

A Windows software system has been designed to facilitate hearing research programs and decision aid for epidemiological surveys in a military context. VISAUDIO provides graphical displays of audiograms with the results of various processing (smoothing, pathological patterns detection and classification), audiograms with pathological patterns like scotoms and recruitments are described (number, impaired frequencies, severity of loss for scotoms). Classical French ORL indexes are calculated (Index 42 which is the French legal index in occupational medicine, PAM or Lafon's index, IPA from the French norm NF S31-013 and IRB, a new occupational medicine index). An audiometric pattern classification is done for each audiogram using discriminant factorial analysis. The program allows audiogram comparisons on the same screen. The processing and analysis results can also be copied to any Windows software package via a PC clipboard. This prototype software is to be tested in a quasi real-time audiological information system comprising audiogram acquisition, processing, analysis and storage in a database. VISAUDIO software functions are illustrated with examples of screen displays.

Adult↗

Hyaluronic acid and dermatan sulfate are selectively stimulated by retinoic acid in irradiated and nonirradiated hairless mouse skin.

All-trans retinoic acid (RA) has been shown to enhance subepidermal repair in photoaged hairless mice. The current study assesses the effects of RA on the glycosaminoglycan (GAG) content in irradiated and nonirradiated mouse skin. Mice were exposed to ultraviolet B (UVB) for 10 wk, after which they were treated either with 0.05% RA or with an ethanolpolyethylene glycol 400 vehicle three times a week for 10 or 20 wk. When assessed at the end of 10 wk of UVB irradiation, the GAG content had doubled, without a change in the hyaluronic acid (HA) to dermatan sulfate (DS) ratio. When irradiation was discontinued, the GAG content decreased progressively until the end of the experimental period. This decline was totally inhibited by RA treatment and could be ascribed to a marked increase in hyaluronic acid (78%), whereas no significant change in DS was observed. In nonirradiated skin, however, topical RA increased GAG levels mainly by a pronounced increase in the content (50%) and the synthesis (40%) of DS. In untreated mice, the HA/DS ratio decreased significantly with age in both irradiated and nonirradiated mice. Interestingly, RA maintained this ratio only in animals exposed to UVB. In addition, there was a marked stimulation in the heparin content, up to approximately 20-fold, after irradiation, whereas the amount of heparin in both irradiated and nonirradiated skin increased about 2- to 3-fold with RA treatment. In summary, the alterations induced in HA and DS contents in irradiated and nonirradiated skin indicate the specificity of the RA-induced effects for the various GAGs.

Animals↗

Aspartate at position 57 of nonobese diabetic I-Ag7 beta-chain diminishes the spontaneous incidence of insulin-dependent diabetes mellitus.

MHC class II genes have been shown to influence the development of the autoimmune disease insulin-dependent diabetes mellitus (IDDM) in the nonobese diabetic (NOD) mouse. In human IDDM it has been suggested that the presence of an aspartate at position 57 of the DQ beta-chain might be important in determining resistance to development of IDDM. The involvement of MHC class II genes in IDDM was investigated through the introduction of MHC encoding transgenes. We show that introduction of a mutated I-Ag7 Ab gene which encodes an aspartate at position 57 reduces the incidence of IDDM but does not prevent insulitis, sialadenitis, or the development of insulin and nuclear autoantibodies.

Amino Acid Sequence↗