High levels of functional endopeptidase 24.11 (CD10) activity on human thymocytes: preferential expression on immature subsets.

Although it is now well established that cells of the immune system express most of the exopeptidases described so far, little information is available concerning the identification and the characterization of the peptidases associated with the surface of human thymocytes. In the present study we have focused on CD10 expression on thymocytes using both FACS and enzymatic analysis. Unfractionated intact human thymocytes were shown to express significant levels of CD10-specific enzymatic activity, as assessed by the hydrolysis of the neutral endopeptidase (NEP) substrate Suc-Ala-Ala-Phe-pNA and of D-Ala2-Leu-enkephalin, a typical NEP substrate. CD10 activity was abolished by specific NEP inhibitors, including thiorphan, retrothiorphan and phosphoramidon. Moreover, high performance liquid chromatography (HPLC) analysis showed that intact thymocytes and purified NEP hydrolysed thymopentin, a thymic factor known to induce the maturation of prothymocytes into thymocytes. Finally, CD 10/NEP was preferentially associated with CD3- CD3low and immature CD4- CD8- thymocytes. The data demonstrate for the first time that human thymocytes express functional NEP and suggest a role for this enzyme in the maturation of human thymocytes.     

Regional cerebral flow velocity waveforms in the human fetus.

The purpose of this study was to determine regional cerebral flow velocity waveforms in the human fetus. Flow velocity waveforms were determined at the level of the middle cerebral artery, vertebral artery, and intracerebellar arteries in 25 fetuses between 23 and 39 weeks' gestation. The pulsatility index was used to quantify the waveforms. Technically acceptable waveforms were obtained at all three vessels in 20 fetuses. The pulsatility index was lowest for the intracerebellar artery in all the fetuses studied. The pulsatility indices of the vertebral artery and middle cerebral artery were not significantly different. These data suggest that significant fetal regional cerebral blood flow differences occur in utero, with intracerebellar arterial resistance being lower than resistance in other regions of the brain.     

Reduction in the middle cerebral artery pulsatility index after decompression of polyhydramnios in twin gestation.

Amniotic fluid decompression was performed for symptomatic polyhydramnios complicating four sets of discordant twin gestations. Doppler ultrasound waveforms of the middle cerebral artery were determined before and after the procedure in seven of the eight fetuses. After amniocentesis, the pulsatility index of the middle cerebral artery (PIMCA) was reduced in all fetuses (p < 0.01). When one considers only the larger twin in each set, the magnitude of the change in PIMCA was relatively consistent among the different sets (-0.60 +/- 0.14; p < 0.01; range, -0.45 to -0.79). The smaller twins showed a much more variable response (-0.82 +/- 0.70; range, -0.05 to -1.75). The pulsatility index of the umbilical artery (PIUA) showed no consistent trend in the five subjects in which it was determined. In principle, the cerebrovascular dilation indicated by the PIMCA measurements may in part be due to acute increases in maternal and fetal carbon dioxide tensions following relief of maternal restrictive lung dysfunction. More importantly, the acute fall in amniotic fluid pressure--the external pressure to which the fetoplacental unit is exposed--leads to pooling of blood in fetal and placental veins, and thereby reduces the effective blood volume of the fetoplacental unit. This effective hypovolemia, functionally analogous to that produced by fetal hemorrhage, elicits changes in regional vascular resistances that favor cerebrovascular perfusion. The impact of acute amniotic fluid decompression on the fetal circulation reflected in the marked changes in PIMCA suggests a role for monitoring to avoid large acute changes in pressure during therapeutic amniocentesis.     

Safety assessment of high fructose corn syrup (HFCS) as an ingredient added to cigarette tobacco

A tiered testing strategy has been developed to evaluate the potential for new ingredients, tobacco processes, and technological developments to alter the biological activity that results from burning tobacco. A series of studies was initially conducted with cigarettes containing 3% high fructose corn syrup (HFCS) as an alternate tobacco casing material to corn syrup/invert sugar, including determination of selected mainstream cigarette smoke (MS) constituent yields, Ames assay, sister chromatid exchange (SCE) assay in Chinese hamster ovary (CHO) cells, a 30-week dermal tumor-promotion evaluation of cigarette smoke condensate (CSC) in SENCAR mice, and a 13-week subchronic inhalation study of MS in Sprague-Dawley rats. A second series of studies was conducted with cigarettes containing 3%, 4% and 5% HFCS including MS chemistry, Ames assay, SCE assay in CHO cells, and a neutral red cytotoxicity assays. Collectively, mainstream smoke chemistry, genotoxicity, dermal tumor-promotion, and inhalation toxicity studies demonstrated no differences between cigarettes with 3% HFCS and cigarettes with 3% corn syrup/invert sugar. Also, mainstream smoke chemistry and genotoxicity of cigarettes with 4% and 5% HFCS were not different from cigarettes with 3% HFCS. In conclusion, the addition of up to 5% HFCS to cigarette does not alter the mainstream smoke chemistry or biological activity of mainstream smoke or mainstream smoke condensate as compared to cigarettes with 3% corn syrup/invert sugar with regard to the parameters investigated and presented.     

Validity of a Brazilian version of the Older Americans Resources and Services (OARS) mental health screening questionnaire

A validity study of the Brazilian version of the 15-item Short Psychiatric Evaluation Schedule (SPES), included in the mental health assessment of Older Americans Resources and Services (OARS), designed to detect psychiatric disorders in the elderly, against the "caseness" criterion suggested by Cooper and Schwarz was carried out with a community sample, as part of a survey to study health and living conditions of the elderly in a large urban center of a developing country, S?o Paulo, Brazil. The screening questionnaire was completed by 292 subjects, and 91 were selected for the psychiatric interview. The validity coefficients were as follows: sensitivity 61%, specificity 89%, positive predictive value 66%, negative predictive value 87% and misclassification rate 18%. A discriminant analysis using a stepwise procedure was then applied to select the best item discriminators of the screening questionnaire. The best set of discrimination comprised six items leading to the following validity coefficients: sensitivity 82%, specificity 77%, positive predictive value 58%, negative predictive value 92% and misclassification rate 21%. The possible factors related to false positive and false negative responses on the screening are discussed.