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Biomedical subjects

A David

Publications and source records attributed to A David.

At least 37 records · Page 2Linked to original sources
PubMed1997

Adenovirus-mediated gene transfer into isolated mouse adult pancreatic islets: normal beta-cell function despite induction of an anti-adenovirus immune response.

The in vitro purification of pancreatic islets offers an opportunity for their modification by ex vivo gene transfer. We investigated the efficiency and functional consequences of adenovirus-mediated gene transfer into adult murine pancreatic islets with a recombinant adenovirus encoding for the beta-galactosidase (beta-Gal) reporter gene. At 10(6) pfu/islet, almost all of the islets were transduced, but maximal transduction was obtained at 10(7) pfu/islet. Histochemical analysis of frozen islet sections showed that transduced cells were only located at the periphery of islets. Transduced islets showed normal insulin secretion in vitro, and were able to normalize in vivo the glycemia of streptozotocin-induced diabetes in syngeneic and allogeneic mice. beta-Gal expression in transduced islets was observed for at least 6 weeks in naive normal recipients and in immunodeficient mice, but was shortened in mice preimmunized to adenovirus. Nevertheless, islets maintained normal control of glycemia in all mice. An early leukocyte infiltrate was observed in syngeneic grafts of transduced islets, but no acceleration in rejection of fully MHC-incompatible islet grafts occurred. In summary, adenovirus-mediated gene transfer in adult mouse islets, although sparing most of the beta-cells, was highly efficient and did not impair insulin secretion by islets. The immune response to the adenovirus and/or to the transgene might be only partially responsible for the decreased expression over time of the transduced gene. Accordingly, adenovirus-mediated gene transfer might allow efficient expression of vectorized sequences with potential immunosuppressive effects in the islet microenvironment.

Adenoviridae↗
PubMed1997

Adenovirus-mediated gene transfer in rat liver of interleukin 4 but not interleukin 10 produces severe acute hepatitis.

Several immune responses are either limited to or concentrated in a given organ. Cytokines produced during ongoing immune responses have organ-localized effects that can be only partially mimicked upon their systemic delivery. Recombinant adenoviruses are efficient vectors to induce transient organ-localized cytokine expression. This allows in vivo analysis of the effects of cytokines produced spatially and temporally in a manner comparable to that observed during immune responses. The authors generated recombinant adenovirus for rat IL-4 (AdIL-4) and IL-10 (AdIL-10) to analyse the in vivo effects of these two important immunoregulatory molecules after gene transfer in the liver. It was first established that AdIL-4 and AdIL-10 were able to direct the production of biologically active cytokines by different rat cell types in vitro. Intraportal injection of doses of up to 10(10) pfu of AdIL-10 or control non-coding recombinant adenovirus were well tolerated, and hepatic histology showed only mild alterations. Conversely, animals receiving more than 2.5 x 10(9) pfu of AdIL-4 showed dose-dependent mortality, with clinical signs of hepatic dysfunction. Liver histology in animals receiving 2.5 x 10(9) pfu of AdIL-4 showed severe acute hepatitis with maximal lesions between day 7 and 14 and almost complete normalization by day 28 after gene transfer. The leukocyte infiltrate was composed primarily of mononuclear cells, but eosinophils and mast cells were significantly increased as compared to control animals. Hepatic function was also altered in animals that received AdIL-4, with kinetics similar to that of histological lesions. Our study describes a model for investigating cytokine function in vivo through liver-localized transgene expression mediated by adenoviral vectors and demonstrates that liver production of IL-4 but not IL-10 results in acute severe hepatitis.

Acute Disease↗
PubMed1997

Serum testosterone, DHEAS, and prolactin levels in patients with a Bartholin's abscess.

This study examines Prolactin and Androgen concentrations in 15 women with a Bartholin's gland abscess and in 15 matched normal controls. The Dehydroepiandrosterone sulfate concentrations were higher in the Bartholin's abscess group as compared to the concentrations in the control group [7.0 +/- 3.1 mmol/l versus 4.3 +/- 1.3 mmol/l (p < 0.05), respectively]. The Prolactin and the Testosterone levels did not differ statistically between the two groups.

Abscess↗
PubMed1997

[Hepatoportal sclerosis: apropos of a familial case].

BACKGROUND: Hepatoportal sclerosis is uncommon in European countries and its diagnosis is difficult. The etiology remains unknown; its familial origin is probably exceptional. CASE REPORT: An 18-month-old girl born to a mother with hepatoportal sclerosis had hepatomegaly. She also had a moderate splenomegaly and mild increase transaminase and gamma GT activities. Ultrasound examination failed to show portal hypertension. Histological study of liver showed changes quite similar to those seen in her mother. Two members of the mother's family had portal hypertension. DISCUSSION: Familial forms of portal hypertension have been reported: a familial form of incomplete septal cirrhosis and a familial occurrence of cavernous transformation of the portal vein. Obstruction of the portal vessels was not found in our patient, the youngest in whom hepatoportal sclerosis is documented.

Biopsy↗
PubMed1997

cDNA sequence, genomic organization and differential expression of three Arabidopsis genes for germin/oxalate oxidase-like proteins.

Wheat germin is a protein expressed during germination which possesses an oxalate oxidase activity. Germin-type oxalate oxidases have been extensively studied in monocotyledons (wheat and barley) where they are thought to have important functions for development, stress response and defence against pathogens. In contrast, almost nothing is known about the germin-like proteins found in dicotyledons, gymnosperms and myxomycetes. In this work, cDNA clones for three genes (ATGER1, ATGER2 and ATGER3) encoding germin-like proteins, initially characterized as expressed sequence tags (ESTs), from Arabidopsis thaliana cDNA libraries were further characterized. In addition, we isolated and sequenced a Brassica napus cDNA which was strongly homologous to the cDNA for ATGER1. Sequence analysis and secondary structure predictions of the proteins encoded by these cDNAs showed that they possess all the characteristic features of members of the germin family and of the germin/seed globulins/sucrose binding protein superfamily. Sequence comparisons and mapping demonstrated the existence of at least two different gene families in the A. thaliana genome encoding a minimum of three genes for germins. These three genes have been mapped in three different location on the Arabidopsis genome. By northern blot hybridizations we found that these genes are differentially regulated. ATGER1 was expressed during germination, like wheat germin, but also in leaves whereas ATGER2 transcripts were exclusively found in developing embryos, like wheat pseudo-germin. ATGER3 mRNAs were found in leaves and flowers and their abundance was shown to vary during the circadian cycle.

Amino Acid Sequence↗
PubMed1997

Distribution of mutations in the PEX gene in families with X-linked hypophosphataemic rickets (HYP).

Mutations in the PEX gene at Xp22.1 (phosphate-regulating gene with homologies to endopeptidases, on the X-chromosome), are responsible for X-linked hypophosphataemic rickets (HYP). Homology of PEX to the M13 family of Zn2+ metallopeptidases which include neprilysin (NEP) as prototype, has raised important questions regarding PEX function at the molecular level. The aim of this study was to analyse 99 HYP families for PEX gene mutations, and to correlate predicted changes in the protein structure with Zn2+ metallopeptidase gene function. Primers flanking 22 characterised exons were used to amplify DNA by PCR, and SSCP was then used to screen for mutations. Deletions, insertions, nonsense mutations, stop codons and splice mutations occurred in 83% of families screened for in all 22 exons, and 51% of a separate set of families screened in 17 PEX gene exons. Missense mutations in four regions of the gene were informative regarding function, with one mutation in the Zn2+-binding site predicted to alter substrate enzyme interaction and catalysis. Computer analysis of the remaining mutations predicted changes in secondary structure, N-glycosylation, protein phosphorylation and catalytic site molecular structure. The wide range of mutations that align with regions required for protease activity in NEP suggests that PEX also functions as a protease, and may act by processing factor(s) involved in bone mineral metabolism.

Amino Acid Sequence↗
PubMed1997

Novel COL4A5/COL4A6 deletions and further characterization of the diffuse leiomyomatosis-Alport syndrome (DL-AS) locus define the DL critical region.

Diffuse leiomyomatosis (DL) with Alport syndrome (AS) has been shown to be associated with contiguous gene deletions of the COL4A5 and COL4A6 genes, with the COL4A6 breakpoint of the deletions invariably located in the large intron 2 of the gene. We describe four YAC clones covering the locus and a refined restriction map of the entire COL4A6 gene. These resources have allowed us to make a precise estimate of the size of COL4A6 introns 2 and 3, as well as the size of the gene itself. We also describe five novel deletions which, in conjunction with previous reports, allow the definition of a 90-kb critical region in which to search for a gene or other entity involved in the pathogenesis of DL.

Adult↗
PubMed1997

Reasoning and delusions.

BACKGROUND: Delusions are assumed to reflect disordered reasoning. but with little empirical support. We attempted to study this in 16 relatively intelligent deluded patients and 16 normal volunteers. METHOD: Standard tests were used which required subjects to choose between logically fallacious and valid responses, both of which were plausible. The tests were: (a) conditional statements (if...then), (b) syllogisms (e.g. no A are C, some B are C, some C are not A), and (c) judgements of probability. All three tasks incorporated neutral and emotive content. RESULTS: Both normal and deluded subjects frequently made logical errors. With conditionals, deluded subjects tended to endorse fallacies more often than normal controls and this was accentuated when the content was emotive. Similarity, with syllogisms, the effect of emotional content on the endorsement of unbelievable responses was increased slightly in the deluded group. Finally, the deluded patients showed a trend to be less prone to the conjunction fallacy than normals, suggesting less reliance on existing schema. conclusions: Differences in reasoning between deluded patients and controls are surprisingly small. Patients are somewhat more prone to endorse invalid or fallacious responses, especially when emotive themes are involved.

Adult↗
PubMed1996

Child with manifestations of Nager acrofacial dysostosis, and the MURCS, VACTERL, and pulmonary agenesis associations: complex defect of blastogenesis?

Nager acrofacial dysostosis (NAFD) combines the facial anomalies of mandibulofacial dysostosis (Treacher-Collins-Francescetti) with hypoplastic/aplastic or triphangeal thumbs. The MURCS association consists of Müllerian duct aplasia, renal aplasia, cervicothoracic somite dysostosis with Klippel-Feil anomaly, and often defects of the facio-auriculo-vertebral (Goldenhar) spectrum. We describe a child with NAFD, MURCS anomaly (Klippel-Feil anomaly, vertebral synostoses, left renal agenesis), and left pulmonary agenesis. Our proband appears to express a unique anomaly of blastogenesis, simultaneously affecting the acrorenal, the mandibulofacial, and the cervicothoracic developmental fields, combining clinical manifestations of the MURCS, NAFD, VACTERL, and pulmonary agenesis associations. All anomalies may be traced back to abnormal blastogenesis, occurring during the third or the fourth week of embryonic development, and show that NAFD is a polytopic developmental field defect.

Abnormalities, Multiple↗
PubMed1996

Compliance therapy in psychotic patients: randomised controlled trial.

OBJECTIVE: To determine whether compliance therapy, a cognitive-behavioural intervention, could improve compliance with treatment and hence social adjustment in acutely psychotic inpatients, and if so, whether the effect persisted six months later. DESIGN: Randomised controlled trial of compliance therapy and non-specific counselling, each comprising 4-6 sessions lasting 10-60 minutes. SETTING: Acute psychiatric admissions ward serving an inner London catchment area. SUBJECTS: 47 patients with psychosis. MAIN OUTCOME MEASURES: Informant and observer reported measure of compliance; observer assessed global functioning after intervention and three and six months later; self-rated attitudes to drug treatment after the intervention and one month later; symptom scores after intervention and six months later. RESULTS: 25 patients received compliance therapy and showed significantly greater improvements in their attitudes to drug treatment and in their insight into illness and compliance with treatment compared with the control group. These gains persisted for six months. The intervention group was 5.2 times more likely than the control group to reach a criterion level of compliance (95% confidence interval 1.5 to 18.3). Global functioning showed a tendency to improve more in the intervention group after a delay (odds ratio 3.0 (0.8 to 11.5) to reach the criterion level at six months). Four subjects given compliance therapy and six in the control group were readmitted during follow up (odds ratio 2.0 (0.48 to 8.2)). CONCLUSIONS: Compliance therapy is a pragmatic method for improving compliance with drug treatment in psychotic inpatients and its gains persist for at least six months. Overall functioning may also be enhanced.

Acute Disease↗
PubMed1996

Rothmund-Thomson syndrome and osteosarcoma.

The Rothmund-Thomson syndrome (RTS), also called poikiloderma congenitale is a rare autosomal recessive disease first described in 1868. This syndrome includes most frequently seen skin lesions (atrophy, telangiectases, pigmentation), cataracts and bone defects (dysostosis, dysplasia). Some authors describe an association with malignancy. We report three cases of Rothmund-Thomson syndrome associated with osteosarcoma. After cutaneous epithelioma, osteosarcoma is the most frequent malignancy. Thus, patients with RTS need a careful survey. The treatment did not differ from sporadic osteosarcoma. Chemosensitivity and toxicity are also not different.

Bone Neoplasms↗