Genomic screen for loci associated with tobacco usage in Mission Indians

Background  

The prevalence of tobacco usage in Native American adults and adolescents is higher than any other racial or ethnic group, yet biological risk and protective factors underlying tobacco use in this ethnic group remain unknown. A genome scan for loci associated with tobacco use phenotypes was performed with data collected from a community sample of Mission Indians residing in Southwest California.     

Experimental isovolemic haemodilution-induced augmentation of carotid blood flow and oxygen transport through graded carotid stenoses.

The effect of haemodilution without volume expansion (isovolemic haemodilution) was assessed with respect to blood flow and oxygen transport across stenotic lesions of progressive severity in the dog carotid artery. As the mean haematocrit (Hct) was reduced from 40 +/- 1% (+/- SEM) to 32 +/- 0% (p less than 0.001), reductions in vascular resistance were significant across the 90% (p less than 0.001) and 95% (p less than 0.0003) relative carotid stenoses. Isovolemic haemodilution reduced fresh blood viscosity significantly by 27 +/- 3% (p less than 0.001) and 42 +/- 4% (p less than 0.001) at the low shear rates of 10 sec-1 and 1 sec-1 which are typical of low-flow states. Following a 20% reduction in Hct 30 to 35% increase (p less 0.001) in carotid blood flow occurred at non-critical degrees of stenosis while a mean 83% increase (p less than 0.001) occurred at the highly critical 95% relative stenosis. Oxygen transport after a 22% decrease in blood haemoglobin was significantly increased by 28% (p less than 0.01) at the 95% relative stenosis level. These data provide a physiologic rationale for the beneficial effects of haemodilution in acute cerebral ischaemia, cerebral vasospasm and cerebral revascularization or carotid endarterectomy.     

IDEC-131 (Anti-CD154), Sirolimus and Donor-Specific Transfusion Facilitate Operational Tolerance in Non-Human Primates

CD154-specific antibody therapy prevents allograft rejection in many experimental transplant models. However, initial clinical transplant trials with anti-CD154 have been disappointing suggesting the need for as of yet undetermined adjuvant therapy. In rodents, donor antigen (e.g., a donor blood transfusion), or mTOR inhibition (e.g., sirolimus), enhances anti-CD154's efficacy. We performed renal transplants in major histocompatibility complex-(MHC) mismatched rhesus monkeys and treated recipients with combinations of the CD154-specific antibody IDEC-131, and/or sirolimus, and/or a pre-transplant donor-specific transfusion (DST). Therapy was withdrawn after 3 months. Triple therapy prevented rejection during therapy in all animals and led to operational tolerance in three of five animals including donor-specific skin graft acceptance in the two animals tested. IDEC-131, sirolimus and DST are highly effective in preventing renal allograft rejection in primates. This apparently clinically applicable regimen is promising for human renal transplant trials.     

Obstetrician-gynecologists as primary care physicians: The Oregon experience—Early perceptions regarding the effects of legislative action

OBJECTIVE: Our purpose was to assess whether legislative action influenced the role of obstetrician-gynecologists as primary care physicians. STUDY DESIGN: An observational study was performed on the basis of a questionnaire sent to 410 obstetrician-gynecologists and 27 medical directors of managed-care organizations. RESULTS: Of 67% of obstetrician-gynecologists and 96% of medical directors who responded, there was agreement as to the content of primary care, but a minority (38%) of obstetrician-gynecologists identified themselves as primary care providers. A minority of medical directors (35%) felt that obstetrician-gynecologists should serve in that role. Both obstetrician-gynecologists and medical directors felt that legislation had little impact. CONCLUSION: The reticence of obstetrician-gynecologists to assume a major role in primary care appears to be the result of an uneasiness with accepting a more comprehensive role in patient management and gatekeeping. They appear comfortable with the more traditional roles but feel that training and experience has not prepared them well for the management of more complex medical problems. (Am J Obstet Gynecol 1998;178:1222-8.)     

Transforming Growth Factor-β1 Induces Apoptosis through Down-Regulation of c-mycGene and Overexpression of p27Protein in Cervical Carcinoma

Transforming growth factor-β1 (TGF-β1) is known to be a potent growth inhibitor for many cell types, including most epithelial cells. In skin keratinocytes, TGF-β1 has been shown to inhibit growth and to rapidly reduce c-mycexpression. However, the molecular mechanism of TGF-β1 action on cell growth of cervical carcinoma has not yet been elucidated. We thus assessed the effect of TGF-β1 on the growth of cervical carcinoma cell lines. Two cervical squamous carcinoma cell lines, CUMC-3 and CUMC-6, were incubated with varying concentrations of TGF-β1, and growth inhibition was evaluated with tetrazolium-based colorimetric assay. After culture in TGF-β1 for 24 h, inhibition of growth was detected in a dose-dependent manner at concentrations of 0.1–10 ng/ml in both cell lines. This effect of TGF-β1 on cultured carcinoma cells was associated with apoptotic process including oligonucleosomal ladder DNA and apoptotic body formations. Northern blot analysis revealed c-mycmRNA expression was suppressed by 10 ng/ml of TGF-β1 following 3 h of treatment in both cell lines. Western blot analysis showed that the level of p27^Kip1protein was increased after TGF-β1 treatment in both cell lines. These results suggest that the mechanisms by which TGF-β1 inhibits the growth of cervical carcinoma are complex and may include effects on down-regulation of c-mycgene, and overexpression of p27^Kip1protein.