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Biomedical subjects

A Cornet

Publications and source records attributed to A Cornet.

At least 19 recordsLinked to original sources
PubMed2001

Enterocolitis induced by autoimmune targeting of enteric glial cells: a possible mechanism in Crohn's disease?

Early pathological manifestations of Crohn's disease (CD) include vascular disruption, T cell infiltration of nerve plexi, neuronal degeneration, and induction of T helper 1 cytokine responses. This study demonstrates that disruption of the enteric glial cell network in CD patients represents another early pathological feature that may be modeled after CD8(+) T cell-mediated autoimmune targeting of enteric glia in double transgenic mice. Mice expressing a viral neoself antigen in astrocytes and enteric glia were crossed with specific T cell receptor transgenic mice, resulting in apoptotic depletion of enteric glia to levels comparable in CD patients. Intestinal and mesenteric T cell infiltration, vasculitis, T helper 1 cytokine production, and fulminant bowel inflammation were characteristic hallmarks of disease progression. Immune-mediated damage to enteric glia therefore may participate in the initiation and/or the progression of human inflammatory bowel disease.

Adolescent↗
PubMed2000

Role of astrocytes in antigen presentation and naive T-cell activation.

Astrocytes may have a role in antigen presentation in inflammatory diseases of the central nervous system (CNS) such as MS and EAE. In this study, we have assessed whether purified astrocyte cultures could stimulate naive CD4(+) or CD8(+) T-cells from TCR transgenic mice. As previously described, astrocytes sustained antigen-specific CD4(+) T-cell proliferation only in the presence of IFN-gamma, which promotes expression of both MHC class II and B7 molecules on astrocytes. In addition, we show that astrocytes also have the capacity to present antigens to naive CD8(+) T-cell and promote their proliferation. In one system, this CD8(+) T-cell proliferation was dependent on IFN-gamma-induced upregulation of B7 molecules on astrocytes. However, in a second TCR transgenic system, astrocytes could induce naive CD8(+) T-cell proliferation even in the absence of IFN-gamma. The possible implications of these findings for the pathophysiology of CNS inflammatory diseases are discussed.

Animals↗
PubMed2000

The experimental (in vitro) and clinical (in vivo) immunosuppressive effects of a rat IgG2b anti-human CD2 mAb, LO-CD2a/BTI-322.

BACKGROUND: CD2 is a cell surface glycoprotein expressed on most human T cells and natural killer (NK) cells, working as a cell adhesion and costimulatory molecule. The aim of this paper is to analyze the mechanism of action of a rat IgG2b anti-human CD2 monoclonal antibody (mAb) (LO-CD2a/BTI-322 mAb), which is a potent immunosuppressive agent and inducer of cell death. In vivo, this mAb is able to prevent or treat kidney allograft rejection. METHODS: The mechanisms by which the LO-CD2a/BTI-322 mAb is able to induce inhibition of cell activation and cell death were analyzed by mixed lymphocyte reactions and by flow cytometry. After in vivo treatment, levels of circulating mAb were measured by ELISA as well as anti-rat immunization and cytokine release. RESULTS: We show that the inhibition of cell activation induced by LO-CD2a/BTI-322 mAb after allogeneic or OKT3 stimulation is due to an Fcgamma receptor-dependent CD2 down-modulation and to T-cell depletion through an antibody-dependent cell-mediated cytotoxicity mechanism mediated by NK cells or activated monocytes. Peripheral T- and NK-cell depletion was observed after in vivo treatment with LO-CD2a/BTI322. Cytokine release (TNFalpha) was correlated with some side effects, but only after the first injection, and the effects were never severe or life threatening. CONCLUSION: The correlation between the in vitro and in vivo data suggests that T-cell depletion, especially of activated cells, and inhibition of cell activation after CD2 down-modulation are the main mechanisms of action of the LO-CD2a/BTI-322 mAb.

Animals↗
PubMed2000

Genes upregulated during castration-induced rat prostatic apoptosis: cloning and characterization of new cDNAs.

OBJECTIVE: To isolate new cDNAs corresponding to genes whose expression is increased during castration-induced rat prostate apoptosis. MATERIALS AND METHODS: Differential display of mRNAs from 3-day castrated and normal rat ventral prostates was used to identify differentially expressed clones. Northern blots were hybridized to confirm the positive regulation of the candidates and to follow the change in their expression in the involuting rat prostate, and in thymocytes of dexamethazone-treated rats. RESULTS: Five cDNAs were cloned: one encoding ribosomal protein L7, one coding for the insulin-like growth factor binding protein-3 (IGFBP-3), and three whose products are unknown. After castration, all five genes had expression kinetics that closely paralleled the proportion of prostatic epithelial cells undergoing apoptosis. The gene encoding L7 and two of the unknown genes were also upregulated in glucocorticoid-induced programmed death in thymocytes. In addition to the IGFBP-3 gene, those coding for proteins IGFBP-4, -5 and -6 were also overexpressed in the involuting prostate of androgen-deprived rats. CONCLUSION: Five new genes were identified that are up-regulated during castration-induced rat prostate apoptosis, three of which are potentially involved in the common intracellular pathway leading to programmed cell death.

Animals↗
PubMed2000

A novel messenger ribonucleic acid homologous to human MAGE-D is strongly expressed in rat Sertoli cells and weakly in Leydig cells and is regulated by follitropin, lutropin, and prolactin.

We have cloned a novel complementary DNA whose expression was decreased in rat Sertoli cell cultures after treatment with FSH. This complementary DNA encodes a protein of 570 amino acids and shares 92% homology with the human MAGE-D protein. In contrast to other MAGE genes (A, B, or C), we have shown that MAGE-D expression was ubiquitous in healthy rat tissues. In the seminiferous tubules, the MAGE-D was expressed in Sertoli cells but not in germ cells as demonstrated by RT-PCR and in situ hybridization, whereas for the other MAGE genes, expression has been shown to be restricted to germ cells. Interestingly, MAGE-D was also detected for the first time in the female gonad by Northern blotting. In MLTC-1 cells (mouse Leydig tumor cell line-1), LH and PRL stimulated MAGE-D expression. Using hypophysectomized rats, it was confirmed that FSH decreased MAGE-D expression, whereas LH and PRL increased MAGE-D messenger RNA level in the whole testis most probably through a direct action on Leydig cells. As MAGE-D is present in both the seminiferous compartment and interstitium and hormonally regulated in each, it is possible that it has specific functions in each compartment during the development and the maintenance of the testis.

Amino Acid Sequence↗
PubMed1999

Effects of pituitary hormones on the prostate.

BACKGROUND: Although essential, androgens alone are not sufficient to induce normal growth and functionality of the prostate. Nonandrogenic hormones must also be involved in the proliferation of the prostate cancer cells which do not respond to antiandrogenic therapy and which thus become androgen-independent. Prolactin, but also growth hormone and luteinizing hormone, are potentially able to act on both normal and abnormal prostatic cells. METHODS: In this review we summarize data from the literature concerning the physiological and pathological implications of prolactin, growth hormone, and luteinizing hormone on the prostate. RESULTS: In rodent prostates, prolactin and growth hormone can induce a variety of effects independently of androgens (e.g., transactivation of certain genes, or synthesis of the major secretion products). Moreover, hyperprolactinemia is responsible for inflammation and dysplasia of the gland, while growth hormone promotes the development of prostate tumors in vivo in the mouse and rat. Growth hormone acts on the gland directly, through prostatic growth hormone receptors, and/or indirectly via the stimulation of insulin-like growth factor-I (IGF-I) synthesis in the liver. Luteinizing hormone receptor is expressed in rat and human prostates. Luteinizing hormone increases the amount of various transcripts in the rat prostate through an androgen-independent pathway. CONCLUSIONS: Prolactin, growth hormone, and luteinizing hormone, alone or synergistically with androgens, play physiologically significant roles in the normal prostate. The involvement of these hormones in the development of benign prostatic hyperplasia and prostatic carcinoma is an issue that needs to be addressed.

Animals↗
PubMed1999

Role of autoreactive CD8+ T cells in organ-specific autoimmune diseases: insight from transgenic mouse models.

There is now convincing evidence that autoreactive CD8+ T cells can contribute to the pathogenesis of organ-specific autoimmune diseases. In the non-obese diabetic mouse, there is direct evidence that beta-islet cell-specific CD8+ cytotoxic T cells have a pathogenic effect. In human diseases such as autoimmune diabetes and multiple sclerosis, indirect evidence also suggests a role for CD8+ T cells in tissue damage, although their antigen specificity is unknown. Transgenic mouse models as well as the use of knockout mice have been instrumental in the identification of the role of autoreactive CD8+ T cells. Spontaneous models of CD8+ T-cell-mediated autoimmunity generated through transgenesis should help delineate the effector mechanisms leading to tissue destruction. The study of autoreactive CD8+ T cells and the characterization of their antigenic specificity should help unravel the pathophysiology of organ-specific autoimmune diseases, help identify exacerbating foreign antigens, and allow the design of antigen-specific immunotherapy targeting the pathogenic autoreactive T cells.

Animals↗
PubMed1999

A novel gene overexpressed in the prostate of castrated rats: hormonal regulation, relationship to apoptosis and to acquired prostatic cell androgen independence.

We have identified a novel complementary DNA (cDNA) corresponding to a gene overexpressed in the rat ventral prostate after castration. This cDNA displays 89.4% identity with 453 bp of a mouse EST and 81.5% identity with 157 bp of a human EST and was named PARM-1 for prostatic androgen-repressed message-1. The complete cDNA is 1187 bp long and codes for a protein of 298 amino acids that contains four potential glycosylation sites and three half cystinyl residues. The PARM-1 gene was found to be expressed at quite low levels in most rat tissues including those of the urogenital tract. The kinetic of induction of PARM-1 gene in the prostate was highly correlated to the development of apoptosis in the whole organ. Supplementation of castrated animals with androgens reversed both the process of apoptosis and the overexpression of PARM-1 gene. Supplementation with estrogens did not result in an increase in the PARM-1 messenger RNA levels when compared with the castration alone. However, the treatment resulted in a more rapid return to intact levels in the castrated plus estrogen group. When apoptosis of testis and prostate was induced in vivo by hypophysectomy, it was found that PARM-1 was only overexpressed in the prostate. Therefore, PARM-1 seems to be regulated by androgens only in the prostate. Using in situ hybridization and immunohistological techniques, we have shown that PARM-1 gene product is found exclusively in the epithelial cells of involuting prostate. Analysis by flow cytometry of MAT LyLu epithelial cells transiently expressing PARM-1 protein did not allow us to demonstrate a direct effect of PARM-1 gene overexpression on the programmed death of the transfected cells. Treatment of MAT LyLu cells by transforming growth factor-beta induced apoptosis but had no effect on PARM-1 production. However PARM-1 protein has been detected by Western blotting in various cell lines such as MAT LyLu, MAT Lu, and PIF, which are androgen independent. This would suggest that PARM-1 gene product would be a marker for acquired androgen-independence of these tumor cells.

Amino Acid Sequence↗
PubMed1998

1,25-Dihydroxyvitamin D3 regulates the expression of VDR and NGF gene in Schwann cells in vitro.

The vitamin D receptor (VDR) is a nuclear receptor that mediates the effect of the active metabolite of vitamin D3, the 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3). To investigate the potential role of this hormone in the peripheral nervous system, we have studied the VDR expression in Schwann cells. The VDR mRNA was detected by Northern blot analysis in rat primary cultures of Schwann cells, and its levels were strongly increased in the presence of 1,25-(OH)2D3. Using the mouse Schwann cell line, MSC80, we showed that concentrations as low as 10(-10) M of hormone stimulated the expression of the VDR gene and strongly increased the amounts of activated VDR, capable of binding to the specific vitamin D responsive element (VDRE). We also found that 1,25-(OH)2D3 stimulated the expression of the nerve growth factor gene in MSC80. These data suggest a role for the hormone in the peripheral nervous system, possibly as a mediator active in trauma.

Animals↗
PubMed1998

[Experimental autoimmune encephalomyelitis].

Experimental autoimmune encephalomyelitis is an induced inflammatory and demyelinating disease of the central nervous system widely used as an animal model for multiple sclerosis. New insights into its pathophysiology have been possible due to recent immunological concepts. New therapeutical approaches have been designed and tested in experimental autoimmune encephalomyelitis and are now entering the clinical setting.

Animals↗
PubMed1997

Luteinizing hormone increases the abundance of various transcripts, independently of the androgens, in the rat prostate.

Differential display analysis was carried out to find, in the rat prostate, genes that could be regulated by Luteinizing Hormone (LH), independently of the androgens. Hypophysectomized and castrated adult rats were treated with either LH, testosterone or saline. Regulated discrete bands have been eluted and reamplified. After Northern blotting, the levels of mRNA corresponding to 8 PCR fragments were significantly increased by LH treatment. None of these inserts were found to be induced by testosterone. One insert was subcloned, sequenced and identified as the ribosomial protein S 23. A competitive RT-PCR assay was carried out on the full length S 23 cDNA and confirmed that its mRNA levels were stimulated by LH but not by testosterone. These results strongly suggest that the LH membrane receptor, previously shown to be expressed in the rat prostate, has a physiological significance in this organ. Moreover, it appears that the effect of LH on the rat prostate are independent of the androgens.

Animals↗
PubMed1996

Prophylactic immunosuppression with anti-interleukin-2 receptor monoclonal antibody LO-Tact-1 versus OKT3 in liver allografting. A two-year follow-up study.

A prospective trial was conducted in 129 recipients of primary liver transplantation, to compare induction immunosuppression using triple drug therapy (cyclosporine, steroids, and azathioprine; group 1, n = 42), versus triple drug therapy with a 10-day course of OKT3 (group 2, n = 44) or of the anti-interleukin-2 receptor monoclonal antibody LO-Tact-1 (group 3, n = 43). Two-year actual patient survival rates were 64%, 79%, and 93% in groups 1, 2, and 3, respectively (1 vs. 2, NS; I vs. III, P = 0.003; 2 vs. 3, NS). Up to 2 years after transplantation, 18%, 44%, and 53% of the grafts in groups 1, 2, and 3, respectively, had not experienced steroid-resistant acute rejection (1 vs. 2, P = 0.002; 1 vs. 3, P = 0.007; 2 vs. 3, NS). The overall incidence of chronic rejection was 4%. OKT3 therapy, but not LO-Tact-1, significantly increased the incidence of cytomegalovirus infections (P = 0.019). In conclusion, immunoprophylaxis with LO-Tact-1 seemed to provide a liver graft acceptance rate at least as satisfactory as that with OKT3, without an increase in the incidence of infections.

Antibodies, Monoclonal↗
PubMed1996

An anti-CD2 mAb induces immunosuppression and hyporesponsiveness of CD2+ human T cells in vitro.

We describe here the potent specific immunosuppression obtained in vitro by LO-CD2a, a rat mAb directed against the human CD2 molecule. Addition of low dose LO-CD2a (40 ng/ml) at the time of mixed lymphocyte culture (MLC) initiation inhibits 80% of the proliferation and, more impressive, addition of the mAb 4 days after culture initiation at a similar concentration still suppresses 50% of the MLC. When responder T cells previously treated with LO-CD2a are challenged a second time by the same donor or third party allogeneic cells, hyporesponsiveness occurs in both cases, although reactivity to T cell mitogenic stimulation persists. Finally, the low production of cytokines such as tumor necrosis factor-alpha and IFN-gamma after incubation of human T cells with LO-CD2a suggests the absence of T cell activation. These results demonstrate that LO-CD2a mAb has a significant immunosuppressive effect and induces hyporesponsiveness in vitro, thereby suggesting potential efficacy in vivo for the treatment of acute rejection and for the induction of tolerance in allotransplantation.

Antibodies, Monoclonal↗
PubMed1996

[Gastroduodenal arterial aneurysm and chronic pancreatitis. A case and review of the literature].

A case of pseudoaneurysm of the gastroduodenal artery due to chronic pancreatitis is reported. Pancreatitis causing splanchnic arterial aneurysm is more likely to affect the splenic artery than the gastroduodenal artery. Ten percent of cases of chronic pancreatitis are associated with splanchnic aneurysm. Hemorrhage occurs in 50% of cases. Color Doppler ultrasound is the best diagnostic tool, indicating the need for coeliac arteriography. In our case report, transcatheter embolization was performed with stainless steel coils and the pseudoaneurysm was successfully occluded.

Adult↗
PubMed1995

[A press campaign during the last century in order to help women students of medicine as candidates for the "Internat des Hôpitaux de Paris"].

In 1885, towards the end of the last century, young female French medical students were given the right to be "externes des Hôpitaux de Paris" (non-resident students) on a par with male students. Nevertheless they were still denied places at the "Internat des Hôpitaux" entrance examination (houseman or intern resident). Two years afterwards the feminist movement, putting their trust in public opinion, took hold of an opportunity to further their demands and had them published in several daily French newspapers. This successful campaign finally enabled female medical students to sit an open "Internat des Hôpitaux" entrance examination. An American, Augusta Klumpke, became the first graduate in 1886 and went on to be recognised as one of the best neurologists in France a few years later.

Education, Medical↗
PubMed1995

Prophylaxis of graft-versus-host disease in identical sibling donor bone marrow transplant by anti-IL-2 receptor monoclonal antibody LO-Tact-1.

The efficacy of the rat monoclonal IgG2b antibody LO-Tact-1 specific for the human interleukin-2 (IL-2) receptor was evaluated for prophylaxis of graft-versus-host disease (GVHD) in patients who received transplants of marrow from HLA-matched sibling donors. Fifteen patients received cyclosporine (CsA) + antibody LO-Tact-1, 0.2 mg/kg/day from day +7 to day +28. Twelve additional patients were administered methotrexate (MTX) + CsA+antibody LO-Tact-1, 0.4 mg/kg/day from day -1 to day +28. The antibody was well tolerated. Engraftment was not affected. GVHD grade > or = II occurred in six of 15 and eight of 12 patients receiving CsA+LO-Tact-1 and MTX+CsA+LO-Tact-1, respectively (P = 0.52). GVHD grade > or = II developed in patients at a median of 32 and 34 days with CsA+LO-Tact-1 and MTX+CsA+LO-Tact-1, respectively (log-rank test, P = 0.57). GVHD contributed to death in four patients who were administered CsA+LO-Tact-1 and in one patient who was administered MTX+CsA+LO-Tact-1. Chronic GVHD occurred in two patients who were treated with CsA+LO-Tact-1 and in two patients treated with MTX+CsA+LO-Tact-1. Throughout therapy, serum levels of LO-Tact-1 ranged from 2 to 10 mg/l. There was no correlation between serum levels of LO-Tact-1 and the occurrence of GVHD. GVHD occurred in 10 patients during LO-Tact-1 prophylaxis. There was no significant difference between relapse or survival rates among the patient groups. We conclude that, while free of adverse effects, monoclonal anti-IL-2 receptor antibody LO-Tact-1 does not improve prophylaxis of GVHD in HLA-matched sibling BMT.

Adolescent↗