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J Tousignant

Publications and source records attributed to J Tousignant.

At least 19 recordsLinked to original sources

Anti-apoptotic effect of insulin on normal hepatocytes in vitro and in vivo.

Liver growth factors are known to be anti-apoptotic for hepatocytes. The potential of insulin, a liver co-mitogen, has not been thoroughly evaluated. We studied the anti-apoptotic role of insulin on primary cultures of rat hepatocytes exposed to transforming growth factor-beta (TGF-beta) as the apoptotic agent and in the left portal vein ligation model (LVPL) of liver atrophy. Results show that insulin decreases apoptosis of TGF-beta-treated hepatocyte cultures by 43% (P < 0.002) and the alanine amino transferase (ALT) release by 49% (P < 0.001). Left lobes of LPVL animals displayed a significant increase in the levels of TGF-beta mRNA. In LPVL rats receiving continuous infusion of insulin in the left lobes, the weight of the atrophic lobes was higher over a 7-day period in comparison to control animals. This was associated with lower levels of serum ALT and with a five-fold decrease in the apoptotic index in the left lobes (P < 0.0001). Induction of Akt phosphorylation and increased expression of Bcl-xl were observed in the left lobes of insulin-treated animals. In conclusion, these results show that insulin is anti-apoptotic for normal hepatocytes both in vitro and in vivo and that the action of insulin is associated with increased Bcl-xl expression and Akt activation.

Animals↗

Tacrolimus in dermatology.

BACKGROUND: Tacrolimus (FK 506), a metabolite of the fungus Streptomyces tsukubaensis, is an anti-T-cell drug. It acts by inhibiting the production of IL-2, IL-3, IL-4, TNFa, and GM-CSF. More potent and with slightly less secondary effects than cyclosporine, it has been the object of considerable interest, especially in conditions that could benefit from the latter. OBJECTIVE: In psoriasis, a placebo-controlled double-blind study has shown oral tacrolimus at 0.1 mg/kg/day to be effective in controlling recalcitrant lesions. In human, small studies have reported tacrolimus ointment to be effective in controlling acute contact dermatitis. Short-term trials of topical tacrolimus in the treatment of atopic dermatitis have recently shown excellent results in both adults and children. In animal studies of hair growth disorders, topical tacrolimus induces anagen and protects from chemotherapy-induced alopecia. Animal studies with the ointment for the prevention of skin graft rejection, lupus dermatoses, and skin papilloma formation have also shown to be promising. CONCLUSIONS: There are case reports of pyoderma gangrenosum, Sezary's syndrome, and Behcet's disease successfully treated with oral tacrolimus but, because of their small number, they remain anecdotal at this point.

Administration, Oral↗

The role of Apligraf in the treatment of venous leg ulcers.

A cultured, allogeneic, bi-layered human skin equivalent has recently become available to help clinicians manage difficult-to-heal venous ulcers. This skin equivalent has an epidermis and dermis similar to human skin. Its living keratinocytes and fibroblasts are from cultured cell banks derived from human neonatal foreskin. Because the skin equivalent is made up of viable human cells, it cannot be terminally sterilized. Safety concerns, which have been addressed, include the risk of possible transmission of infection, immunogenicity, immunological graft rejection, and tumor formation. However, the maternal blood of the neonatal donor and the master cell banks are screened for infectious agents. Additionally, the human skin equivalent is produced under strict aseptic control, with sterility continuously monitored by the Good Manufacturing Processes. This paper reviews the characteristics of this human skin equivalent and provides practice guidelines.

Algorithms↗

[Hypertrichosis and gingival hypertrophy regression in renal transplants following the substitution of cyclosporin by tacrolimus].

Gingival Hyperplasia (GH) and hypertrichosis (HT) are two sides effects associated with the usage of cyclosporine (CyA) but not with tacrolimus (FK 506). The aim of this study is to evaluate the efficacy and security of the conversion from CsA to FK 506 to treat those two complications. From August 1996 to May 1997, 15 patients (9 males, 6 females) aged from 23 to 63 years old (38 +/- 14, mean +/- SD) were switched from CsA to FK 506, 12 for GH, 2 for HT and one for combined presentation. FK 506 was first initiated at a dose of 0.15 mg/kg/day and then adjusted to a level target of 8 ng/ml. The conversion was done on an out patient basis at average 35 (5-83) months after transplantation. Patients were followed prospectively for 12 months. There was a significant reduction in GH in all patients within 3 months. Five out 13 patients had a complete resolution of GH within three months of conversion, 9/12 within 6 months and all by 12 months. HT resolved completely within 6 months. No rejection episode occurred and the serum creatinin remain stable over one year post conversion. Conversion from CsA to FK 506 is thus a safe and valid option to treat CsA induced GH and HT.

Adult↗

Biophysical characterization of cationic lipid: DNA complexes.

To better understand the structures formed by the interaction of cationic lipids with DNA, we undertook a systematic analysis to determine the biophysical characteristics of cationic lipid:DNA complexes. Four model cationic lipids with different net cationic charge were found to interact in similar ways with DNA when that interaction was compared in terms of the apparent molar charge ratio of lipid to DNA. When DNA was present in charge excess over the cationic lipid, the complex carried a net negative charge as determined by zeta potential measurements. Under these conditions, some DNA was accessible to ethidium bromide, and free DNA was observed in agarose gels and in dextran density gradients. Between a lipid:DNA charge ratio of 1.25 and 1.5:1, all the DNA became complexed to cationic lipid, as evidenced by its inaccessibility to EtBr and its complete association with lipid upon agarose gel electrophoresis and density gradient separations. These complexes carried a net positive charge. The transition between negatively and positively charged complexes a occurred over a very small range of lipid to DNA ratios. Employing a fluorescent lipid probe, the addition of DNA was shown to induce lipid mixing between cationic lipid-containing vesicles. The extent of DNA-induced lipid mixing reached a maximum at a charge ratio of about 1.5:1, the point at which all the DNA was involved in a complex and the complex became positively charged. Together with freeze-fracture electron micrographs of the complexes, these biophysical data have been interpreted in light of the existing models of cationic lipid:DNA complexes.

Cations↗

Detection of a transforming fragment of herpes simplex virus type 2 in clinical specimens by PCR. The Canadian Women's HIV Study Group.

A PCR assay for the sensitive detection of a transforming fragment of herpes simplex virus type 2 (HSV-2) was developed. Oligonucleotide primers were selected in Xho-2, a transforming region of the BglII N fragment of HSV-2. The assay reached a sensitivity endpoint of 10 copies of the Xho-2 subfragment and did not show cross-reactivity with other herpesviruses, including HSV-1. All 42 HSV-2 isolates scored positive in the assay. The Xho-2 PCR assay was evaluated with 216 clinical specimens and the results were compared with those of cell culture. The best protocol for processing specimens contained in viral transport medium included a centrifugation step followed by cell lysis. Of the 107 specimens positive for HSV-2 by culture, 105 were PCR positive (sensitivity, 98.1%). For one of the two falsely negative samples, beta-globin as well as sequences from the HSV-2 DNA polymerase gene could not be amplified. The other sample scored positive in both of these reactions but was indeterminate in duplicate tests by Xho-2 PCR. Two of 109 HSV-2 culture-negative specimens tested positive in the PCR assay (specificity, 98.2%). The latter two samples tested positive in a PCR test for the HSV-2 DNA polymerase gene. This novel tool was shown to be sensitive and specific for HSV-2 sequences and should allow for the investigation of the role of HSV-2 in genital cancers.

Adult↗

[Colonic adenocarcinoma and scleroderma].

The association of cancer and connective tissue disease is well known, the most frequent being certainly with dermatomyositis. The association cancer and PSS is more controversial. The incidence of neoplasia in that group seems to be comparable with the general population but the proportion of certain types of cancer is different, and the temporal relationship with the apparition of symptoms of PSS is stunning. The hypothesis actually in favor is an imbalance of the immune system, which cause the diminution of the immune surveillance and the apparition of cancer and a concomitant dysregulation of the system, causing the fibrosis of the PSS. We describe a 75 year-old white female who developed a colic adenocarcinoma; she also had, concomitantly, a systemic scleroderma, with sclerodactyly and pulmonary fibrosis. The patient corresponded to the criteria of the American Rheumatism Association for progressive systemic scleroderma (PSS). The prognosis of patients with PSS depends on their systemic involvement but also, we believe, in the more aged group, on the apparition of a neoplasia.

Adenocarcinoma↗

[Urticaria and antihistamines].

Urticaria is often incapacitating, yet it is not always easy to know whether a patient should undergo testing and what treatment should be prescribed. This article provides a systematic approach to urticaria and its treatment.

Family Practice↗