Sertoli cells (SCs) are testis-derived cells that secrete trophic factors important for the development of germ cells. Both porcine and rat SCs have been used as graft facilitators — neonatal porcine ...SCs to support islets in diabetes and 15-day-old rat SCs to enhance dopaminergic neuron transplants in Parkinson's disease models. However, there has never been a study examining the optimal SCs preparation to enhance tyrosine hydroxylase expression in the ventral mesencephalon (VM) neuron. The aim of this study was to compare the ability of both rat and porcine SCs to enhance tyrosine hydroxylase expression (TH) and neuronal survival at the same postnatal developmental ages. The SCs were isolated from 1-, 9-, or 15-day-old rat, or neonate (2–5 days), 2-month, or 4-month-old pig, and co-cultured with VM tissue from 13.5-day-old embryos. Our results showed that VM neurons co-cultured with SCs dispersed over the culture plate and had extensive neuritic outgrowth, while VM neurons cultured alone tended to cluster together forming a mass of cells with limited neurite outgrowth. TH expression was significantly increased when VM neurons were co-cultured with 15-day rat SCs or 2-month pig SCs but not when the cells were co-cultured with other ages of SCs. This suggests that secretion of trophic factors by SCs varies according to the developmental age, and it is critical for the success of graft facilitation that SCs from the appropriate age and species be used.
Studies examined the phenotypic characteristics of glutamate-induced cell death and their relationship to calpain and caspase-3 activation. Cell viability was assessed by fluorescein diacetate and ...propidium iodide staining and lactate dehydrogenase release. Calpain and caspase-3 activity was inferred from signature proteolytic fragmentation of α-spectrin. Characterization of cell death phenotypes was assessed by Hoechst 33258 and DNA fragmentation assays. Exposure of septohippocampal cultures to 1.0, 2.0, and 4.0 mmol/L glutamate induced a dose-dependent cell death with an LD50 of 2.0 mmol/L glutamate after 24 hours of incubation. Glutamate treatment induced cell death in neurons and astroglia and produced morphological alterations that differed from necrotic or apoptotic changes observed after maitotoxin or staurosporine exposure, respectively. After glutamate treatment, cell nuclei were enlarged and eccentrically shaped, and aggregated chromatin appeared in a diffusely speckled pattern. Furthermore, no dose of glutamate produced evidence of internucleosomal DNA fragmentation. Incubation with varying doses of glutamate produced calpain and caspase-3 activation. Calpain inhibitor II (N-acetyl-Leu-Leu-methionyl) provided protection only with a narrow dose range, whereas carbobenzoxy-Asp-CH2-OC(O)-2, 6-dichlorobenzene (Z-D-DCB; pan-caspase inhibitor) and MK-801 (N-methyl-d-aspartate receptor antagonist) were potently effective across a wider dose range. Cycloheximide did not reduce cell death or protease activation.
Context Whether immunosuppressive treatment adversely affects survival is unclear.Objective To assess whether immunosuppressive drugs increase mortality.Design Retrospective cohort study evaluating ...overall and cancer mortality in relation to immunosuppressive drug exposure among patients with ocular inflammatory diseases. Demographic, clinical, and treatment data derived from medical records, and mortality results from United States National Death Index linkage. The cohort’s mortality risk was compared with US vital statistics using standardised mortality ratios. Overall and cancer mortality in relation to use or non-use of immunosuppressive drugs within the cohort was studied with survival analysis.Setting Five tertiary ocular inflammation clinics.Patients 7957 US residents with non-infectious ocular inflammation, 2340 of whom received immunosuppressive drugs during follow up.Exposures Use of antimetabolites, T cell inhibitors, alkylating agents, and tumour necrosis factor inhibitors.Main outcome measures Overall mortality, cancer mortality.Results Over 66 802 person years (17 316 after exposure to immunosuppressive drugs), 936 patients died (1.4/100 person years), 230 (24.6%) from cancer. For patients unexposed to immunosuppressive treatment, risks of death overall (standardised mortality ratio 1.02, 95% confidence interval CI 0.94 to 1.11) and from cancer (1.10, 0.93 to 1.29) were similar to those of the US population. Patients who used azathioprine, methotrexate, mycophenolate mofetil, ciclosporin, systemic corticosteroids, or dapsone had overall and cancer mortality similar to that of patients who never took immunosuppressive drugs. In patients who used cyclophosphamide, overall mortality was not increased and cancer mortality was non-significantly increased. Tumour necrosis factor inhibitors were associated with increased overall (adjusted hazard ratio HR 1.99, 95% CI 1.00 to 3.98) and cancer mortality (adjusted HR 3.83, 1.13 to 13.01).Conclusions Most commonly used immunosuppressive drugs do not seem to increase overall or cancer mortality. Our results suggesting that tumour necrosis factor inhibitors might increase mortality are less robust than the other findings; additional evidence is needed.
Herron et al examine whether gender affects career advancement in the field of arts management and, if so, what factors contribute to the inequity. In middle management, while some differences do ...exist, the majority of salary discrepencies are found in the upper management positions.
This study examines factors predicting the context of HIV related sexual behaviors in a random, community sample of 227 African American single and married women, ages 18 to 50. Structural equation ...models tested associations between women's past sexual histories, relationship factors, and risks for unintended pregnancies, sexually transmitted diseases (STDs), including HIV, as well as risk reduction efforts since Magic Johnson's HIV disclosure. Sexual communication and past sexual experiences, most notably histories of STDs, physical, and sexual abuse, were significantly associated with increased HIV related sexual risk taking. Magic Johnson's HIV disclosure increased protective behaviors. Results suggest that a more comprehensive assessment of past victimization and cultural factors influencing women's behavior to reduce risks is needed in HIV prevention programs for African American women. The need for specific knowledge about women's sexuality and relationship risks beyond what currently is being offered in prevention programs is discussed.
Examined factors predicting the context of HIV-related sexual behaviors in African American women. Surveys investigated demographics; sexual history, behavior, attitudes, risk, and communication; ...drug use; contraception; and risk reduction efforts since Magic Johnson's HIV disclosure. Demographics, sexual communication, and past sexual experiences related to increased HIV-related sexual risk-taking. Johnson's disclosure increased protective behaviors. (SM)
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