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J Collette

Publications and source records attributed to J Collette.

71 records · Page 4Linked to original sources
PubMedDate not supplied

Thymic expression of insulin-related genes in an animal model of autoimmune type 1 diabetes.

BACKGROUND: Insulin and multiple other autoantigens have been implicated in the pathogenesis of autoimmune type 1 diabetes, but the origin of immunological self-reactivity specifically oriented against insulin-secreting islet beta-cells remains obscure. The primary objective of the present study was to investigate the hypothesis that a defect in thymic central T-cell self-tolerance of the insulin hormone family could contribute to the pathophysiology of type 1 diabetes. This hypothesis was investigated in a classic animal model of type 1 diabetes, the Bio-Breeding (BB) rat. METHODS: The expression of the mammalian insulin-related genes (Ins, Igf1 and Igf2) was analysed in the thymus of inbred Wistar Furth rats (WF), diabetes-resistant BB (BBDR) and diabetes-prone BB (BBDP) rats. RESULTS: RT-PCR analyses of total RNA from WF, BBDP and BBDR thymi revealed that Igf1 and Ins mRNAs are present in 15/15 thymi from 2-day-old, 5-day-old and 5-week-old WF, BBDR and BBDP rats. In contrast, a complete absence of Igf2 mRNA was observed in more than 80% of BBDP thymi. The absence of detectable Igf2 transcripts in the thymus of BBDP rats is tissue-specific, since Igf2 mRNAs were detected in all BBDP brains and livers examined. Using a specific immunoradiometric assay, the concentration of thymic IGF-2 protein was significantly lower in BBDP than in BBDR rats (p<0.01). CONCLUSIONS: The present study suggests an association between the emergence of autoimmune diabetes and a defect in Igf2 expression in the thymus of BBDP rats. This tissue-specific defect in gene expression could contribute both to the lymphopenia of these rats (by impaired T-cell development) and the absence of central T-cell self-tolerance of the insulin hormone family (by defective negative selection of self-reactive T-cells).

Aging↗
PubMedDate not supplied

Prevention of postmenopausal bone loss by tiludronate.

76 healthy women, who had been menopausal for less than 96 months and who had never received any form of treatment to prevent bone loss, were entered into a randomised double-blind study. For the first 6 months, half the patients received tiludronate 100 mg daily, while the others received placebo. During the second 6 months, all patients received placebo. Bone mineral density of the lumbar spine decreased significantly by 2.1% (SE 0.8%) in the placebo group and did not significantly change in the tiludronate group (+1.33 [0.8]%). The difference in response between the groups was significant, as were the differences between values for corrected urinary hydroxyproline and calcium. Treatment with tiludronate was not followed by increased secretion of parathyroid hormone. A 6 month course of oral tiludronate may counteract postmenopausal bone loss for at least a year by decreasing bone resorption.

Absorptiometry, Photon↗
PubMedDate not supplied

IGF-II in primary human colorectal tumors: peptide level, activated promoters, parental imprinting and gene rearrangement.

IGF-II is a polypeptide growth factor with growth and differentiation promoting activities, involved in human development. We have reported previously IGF-II mRNA and peptide overexpression in primary human colon cancers. Here we show that the IGF-II peptide content is increased in six primary colon cancers compared to the corresponding healthy tissues. The IGF-II transcripts in healthy and cancerous colon tissues were identified by Northern blotting and RT-PCR. Promoters P3 and P4 were active in most tissues. Relaxation of parental imprinting was observed in two tumors and one healthy tissue, without any correlation with the IGF-II transcript levels. Rearrangements of the IGF-II gene in two tumors containing very high amounts of IGF-II mRNA are described. Fragments containing the breakpoints were cloned by the vectorette-PCR strategy. In both tumors, the breakpoints occurred in repetitive sequences. In one tumor (T11), the breakpoint was localized 2 kb downstream the end of exon 9. The second tumor (T18) contains two modified alleles. In one rearranged allele the breakpoint is located in exon 9. The exact position of the breakpoint in the second rearranged allele has not been identified. In future experiments, the correlation between the gene rearrangements and IGF-II mRNA overexpression will be studied.

Adenocarcinoma↗
PubMedDate not supplied

Cancer-associated alteration of circadian rhythms in carcinoembryonic antigen (CEA) and alpha-fetoprotein (AFP) in humans.

A circadian rhythm of serum concentrations of two tumor markers (CEA and AFP) was demonstrated in individuals not suffering from cancer. These rhythms exhibited a diurnal peak with a nocturnal dip. They disappeared in cancer groups. However, in some cancer subjects, a circadian activity was still detectable, but with quite different characteristics (time of peak, amplitude) of rhythms when compared to controls. The importance of such findings is discussed with regard to the circadian kinetics of cancer cells, to time scheduled cancer treatments and to the detection of cancer.

Carcinoembryonic Antigen↗
PubMedDate not supplied

[Value of radioimmunological serum levels of carcinoembryonic antigen in the postoperative monitoring of rectocolonic cancer].

Fifty four patients, operated for colorectal cancer have been followed up for 2 to 100 months after surgery by carcino-embryonic antigen (CEA) determinations and classical, clinical, biological, radiological, echographical, isotopical and tomoscanninvestigations. Each new serum sample has been assayed for CEA with previously collected samples within the same patients. This repetition of CEA on the same samples allows to check the good reproducibility of CEA radioimmunoassay (variation coefficient between assay is less than 10%) and to get a complete profile of CEA level evaluation within the same assay. There is a good correlation between clinical evolution and CEA levels. In 42 patients, CEA levels remained or became normal (less than 10 ng ml) after surgical resection of the tumors and no metastasis or local recurrence were detected. In 12 cases, CEA levels remained or became abnormally high (greater than 20 ng ml) at the same time or before clinical and/or paraclinical evidences for metastases or local recurrence. These results showed CEA assay in a quantitative parameter to assess the follow-up of colorectal cancer complementary to clinical, biological, radiological, echographical and isotopical criterias.

Adenocarcinoma↗