Biomedical subjects

Joseph Genebriera

Publications and source records attributed to Joseph Genebriera.

4 recordsLinked to original sources

PubMed2006

CD4 T cell-induced, bid-dependent apoptosis of cutaneous dendritic cells regulates T cell expansion and immune responses.

The fate of dendritic cells (DCs) after Ag presentation may be DC subset-specific and controlled by many factors. The role of activation-induced apoptosis in regulating DC function is not clear. We investigated the fate of cutaneous DCs (cDCs), specifically Langerhans cells (LCs), and observed that they undergo apoptosis after successful Ag presentation to CD4 T cells. Caspase-specific inhibitors revealed that LC lines use a type II apoptosis pathway in response to CD4 T cells. In support of this, BH3-interacting domain (Bid) protein was present at high levels and specifically cleaved in the presence of Ag-specific T cells. Significant resistance to apoptosis by OT-2 CD4 cells was also observed for Bid knockout (KO) LCs in vitro. To test whether Bid was required to regulate LC function in vivo, we measured contact sensitization and topical immunization responses in Bid KO mice and observed markedly enhanced ear swelling and proliferation responses compared with wild-type mice. Furthermore, when Ag-pulsed Bid KO migratory cDCs were inoculated into wild-type recipients, an increase in both the rate and percentage of expanded OT-2 T cells expressing IFN-gamma was observed. Thus, enhanced Ag presentation function was intrinsic to Bid KO cDCs. Therefore, Bid is an important regulator of LC viability and Ag presentation function.

Animals↗

PubMed2006

Thermoregulatory sweat testing in patients with erythromelalgia.

OBJECTIVES: To examine the results of thermoregulatory sweat testing in patients with erythromelalgia and to compare them with the results of other neurophysiologic tests of small-fiber nerve function. DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: Thirty-two consecutive patients with erythromelalgia who had thermoregulatory sweat testing in addition to vascular and nerve testing. INTERVENTION: The following information was abstracted for each patient: demographics, clinical presentation, and results of thermoregulatory sweat testing, vascular (noninvasive) testing, and nerve testing (electromyography and autonomic reflex screen, including quantitative sudomotor axon reflex test). MAIN OUTCOME MEASURES: Results of thermoregulatory sweat testing to evaluate small-fiber neuropathy, compared with other tools used to estimate small-fiber neuropathy. RESULTS: Thermoregulatory sweat testing results were abnormal in 28 (88%) of 32 patients, and quantitative sudomotor axon reflex test results were abnormal in 22 patients (69%). Abnormalities noted on thermoregulatory sweat testing varied from local hypohidrosis or anhidrosis to global anhidrosis. Global or almost-global anhidrosis was present in 8 patients (25%); in 19 patients (59%) the anhidrosis was distal, and 1 other patient (3%) had a less specific pattern of anhidrosis (multifocal or regional). The area of anhidrosis generally corresponded to the area that was symptomatic of the erythromelalgia. CONCLUSIONS: Small-fiber neuropathy is prevalent in most patients with erythromelalgia. Thermoregulatory sweat testing is a sensitive and useful marker of small-fiber neuropathy in these patients.

Adolescent↗

PubMed2006

Histopathologic findings in primary erythromelalgia are nonspecific: special studies show a decrease in small nerve fiber density.

The histopathology of primary erythromelalgia has been poorly characterized. A total of 33 skin biopsy specimens from 29 patients with a diagnosis of primary erythromelalgia were re-examined. Histopathologic findings were nonspecific. Vascular thrombi were not identified. A relative decrease in small nerve fiber density was noted in specimens from 13 of 16 patients.

Adult↗

PubMed2005

Evaluation of the cytotoxic effect of the monoterpene indole alkaloid echitamine in-vitro and in tumour-bearing mice.

The cytotoxic effect of various concentrations of echitamine chloride was studied in HeLa, HepG2, HL60, KB and MCF-7 cell lines in-vitro and in mice bearing Ehrlich ascites carcinoma (EAC). Exposure of various cells to different concentrations of echitamine chloride resulted in a concentration-dependent cell killing, and KB cells were found to be most sensitive amongst all the cells evaluated. EAC mice treated with 1, 2, 4, 6, 8, 12 or 16 mg kg-1 echitamine chloride showed a dose-dependent elevation in the anti-tumour activity, as evident by increased number of survivors in comparison with the non-drug treated controls. The highest dose of echitamine chloride (16 mg kg-1) caused toxicity in the recipient mice, therefore 12 mg kg-1 was considered the best cytotoxic dose for its anti-tumour effect. Administration of 12 mg kg-1 echitamine chloride resulted in an increase in the median survival time (MST) up to 30.5 days, which was 11.5 days higher than the non-drug treated control (19 days). Administration of 16 mg kg-1 echitamine chloride to EAC mice resulted in a time dependent elevation in lipid peroxidation that reached a peak at 6 h post-treatment, whereas glutathione concentration declined in a time dependent manner and a maximum decline was reported at 3 h post-treatment. Our study demonstrated that echitamine chloride possessed anti-tumour activity in-vitro and in-vivo.

Alkaloids↗