Engineered secreted T-cell receptor alpha beta heterodimers.

We have produced a soluble form of a mouse alpha beta T-cell antigen receptor (TCR) by shuffling its variable (V) and constant (C) domains to the C region of an immunoglobulin kappa light chain. These chimeric molecules composed of V alpha C alpha C kappa and V beta C beta C kappa chains were efficiently secreted (up to 1 micrograms/ml) by transfected myeloma cells as noncovalent heterodimers of about 95-kDa molecular mass. In the absence of direct binding measurement, we have refined the epitopic analysis of the soluble V alpha C alpha C kappa-V beta C beta C kappa dimers and shown that they react with an anti-clonotypic antibody and two antibodies directed to the C domain of the TCR alpha and beta chains. Conversely, we have raised three distinct monoclonal antibodies against the soluble TCR heterodimers and shown that they recognize surface-expressed TCRs. Two of these antibodies were found to react specifically with the products of the V alpha 2 (V delta 8) and V beta 2 gene segments, respectively. When considered together, these data suggest that these soluble TCR molecules are folded in a conformation indistinguishable from that which they assume at the cell surface.     

The 24-hour rhythm of blood pressure differs from that of leg hemodynamics in orthotopic heart transplant recipients

BACKGROUND: This study was aimed at investigating whether a circadian rhythm of peripheral resistance exists in patients with orthotopic cardiac transplantation (OCT) and whether it parallels that of blood pressure (BP). METHODS: BP and leg flow and resistance (plethysmography) were monitored for 24 hours in 13 denervated OCT recipients and 13 control patients with native heart, matched for casual blood pressure. RESULTS: On the basis of BP trend, control patients showed a BP reduction during sleep, whereas OCT recipients did not. Leg resistance was significantly lower and leg flow significantly higher during sleep than during waking in all patients, and the extent of the nocturnal decrease was similar in the two categories. CONCLUSIONS: The decrease in leg resistance in patients confined to bed for 24 hours is caused by peripheral mechanisms and does not depend on the autonomic control of the heart. The nocturnal decline in BP depends, on the contrary, on cardiac control and is lost in patients with denervated heart.     

The Effects of Oil Well Drill Cuttings on Soil and Rice Plant Development (Oryza sativa) Under Two Redox Conditions

Few studies have focused on the release of toxic elements from oil well drill cuttings and their effect on soil. The present study evaluated these effects using rice growth as the endpoint. Drill cuttings were collected from a Brazilian well and added in doses of 300, 3,000 and 6,000 mg kg^?1 soil, which was maintained at oxidized or reduced conditions. When the redox potential reached approximately ?250 mV, barium concentrations were determined by geochemical fractionation. Overall, doses of 300 and 3,000 mg kg^?1 promoted plant development, while a dose of 6,000 mg kg^?1 inhibited it due to the associated increase in electrical conductivity and exchangeable sodium concentration. In addition, the lower redox potential promoted solubilization of barite from the drill cuttings, which increased barium absorption by plants and translocation to grain, posing a risk to human health.     

Angiogenesis inhibition and depression in older men

Background

Cardiovascular diseases have been associated with depression in later life, and a potential mechanism is inhibition of angiogenesis. We designed this study to determine if depression is associated with higher serum concentration of endostatin, an endogenous angiogenesis inhibitor.

Methods

We performed a cross-sectional examination of a random sample of men aged 69–86 years. Those who scored 7 or higher on the 15-item Geriatric Depression Scale were deemed depressed. We determined the concentration of serum endostatin using a reproducible assay. Other measures included age, education, body mass index, smoking, history of depression, use of antidepressants, hypertension, diabetes, coronary heart disease and stroke, high sensitivity C-reactive protein, plasma homocysteine, triglycerides and cholesterol. We used logistic regression to investigate the association between endostatin and depression, and adjusted the analyses for confounding factors.

Results

Our sample included 1109 men. Sixty-three (5.7%) men were depressed. Their serum endostatin was higher than that of nondepressed participants (p = 0.021). Men in the highest decile of endostatin had greater adjusted odds of depression (odds ratio [OR] 1.78, 95% confidence interval [CI] 1.03–3.06). A doubling of endostatin doubled the odds of depression (OR 1.93, 95% CI 1.31–2.84). The probability of depression increased with the concentration of endostatin in a log-linear fashion up to a maximum of about 20%–25%.

Limitations

The cross-sectional design limits the study’s ability to ascribe causality to the association between high endostatin and depression.

Conclusion

Serum endostatin is associated with depression in older men. It remains to be established whether correction of this imbalance is feasible and could decrease the prevalence of depression in later life.     

Postpartum urinary stress incontinence: analysis of the associated risk factors and neurophysiological tests

AIM: The aim of this paper is to estimate the prevalence of postpartum urinary stress incontinence (USI) three months after vaginal delivery and to analyze the risk factors more frequently correlated with USI. Pelvic floor neurophysiology was performed to assess pudendal nerve damage in symptomatic women. METHODS: A total of 562 women were interviewed and underwent urogynecological evaluation three days after vaginal delivery. They were contacted by telephone 12 weeks later. Chart abstraction was conducted to obtain obstetrical data. Three months after delivery women presenting persistent USI were invited to return for electrophysiological tests. Univariate and logistic regression analyses were performed to reveal any significant association between USI and risk factors. RESULTS: Prevalence of postpartum USI three days after delivery was 15%, decreasing to 10.6% at follow-up three months later. Multivariate analysis of risk factors revealed that persistent USI was significantly associated with: preconception USI (P<0.05), USI developed de novo after delivery (P<0.05), family history of incontinence (P<0.05), chronic cough (P<0.05) and smoking (P<0.05). No obstetric variables were independently connected with incontinence. Neurophysiological tests revealed nerve damage in 36% of the symptomatic puerperae. CONCLUSION: Persistent postpartum incontinence is associated with several maternal and urogynecological risk factors that can help to detect women at risk for early intervention.