PJA-BP expression and TCR delta deletion during human T cell differentiation

Recombination of deltaRec to psiJalpha will delete the TCR delta gene, which is thought to play an important role in the bifurcation of the TCR alphabeta versus TCR gammadelta differentiation lineages. We recently detected a DNA-binding protein in human thymocytes, the so- called PJA-BP, which recognizes the psiJalpha gene segment and might be one of the factors involved in the regulation of preferential deltaRec- psiJalpha rearrangements. We now investigate PJA-BP expression and its correlation with TCR delta gene deletion in thymocytes. Our electrophoretic mobility shift assay experiments showed that the PJA-BP is evolutionary conserved in human, murine and simian thymocytes. Using a large series of human hematopoietic malignancies (n = 30), we conclude that PJA-BP expression is thymocyte specific and seems to be restricted to thymocytes committed to the TCR alphabeta lineage. Analysis of seven well-defined human thymocyte subpopulations showed that preferential deltaRec-psiJalpha rearrangements as well as PJA-BP expression can be detected from the immature CD34-/CD1+/CD3- /CD4+/CD8alpha+beta- thymocyte differentiation stage onwards. These experiments indicate that expression of PJA-BP in human thymocytes starts simultaneously with preferential deltaRec-psiJalpha rearrangements, which supports our hypothesis that PJA-BP is one of the factors involved in the preferential recombination of deltaRec to psiJalpha.      

Chlamydia trachomatis stimulates human peripheral blood B lymphocytes to proliferate and secrete polyclonal immunoglobulins in vitro

Infectious Chlamydia trachomatis (LGV strain), obligate intracellular bacteria, stimulated human peripheral blood lymphocytes to proliferate and secrete immunoglobulins in vitro. In contrast, mock-infected preparations were unable to induce similar responses in peripheral blood lymphocytes. Although levels of immunoglobulin secreted into the media of LGV-stimulated cultures were greater than 10 micrograms/ml, we estimated that less than 1% of these molecules were directed against the bacteria itself, suggesting polyclonal antibody production. Since stimulation with Formalin-killed bacteria resulted in comparable numbers of plaque-forming cells (PFC) as infectious particles, we concluded that the polyclonal immunoglobulin response was not dependent on the in vitro chlamydial infectious process. The polyclonal PFC response induced by LGV was highly sensitive to monocyte inhibition. Although LGV induced proliferation of predominantly B cells, the numbers of generated PFC was increased by the addition of autologous T cells. Neither lymphocyte proliferation nor PFC responses of normal human volunteers correlated significantly with the presence or titer of antichlamydial antibodies in their sera.     

Battered women presenting in general practice

The problems of battered women have recently been highlighted. They consult doctors, who can be an important source of help. We examined their initial presenting complaint to general practitioners. Questionnaires were sent to 27 London refuges for battered women and to 100 randomly selected general practitioners. Seventy-two women and 49 doctors replied. The results indicated that these women are more likely to present with psychological symptoms. Many cases are not detected because the battering is concealed. The attitude of doctors may prevent these patients discussing their real problems. Further studies are needed.     

Expression of superoxide dismutase and xanthine oxidase in myometrium, fetal membranes and placenta during normal human pregnancy and parturition

Superoxide, an agent which attenuates the half-life of nitric oxide, is metabolized and synthesized by superoxide dismutase (SOD) and xanthine oxidase, respectively. Over the last few years much work has focused on the role of nitric oxide in human parturition. The aim of this study was to determine whether the onset of human parturition is associated with a change in the expression of copper/zinc superoxide dismutase (Cu/Zn SOD), manganese superoxide dismutase (Mn SOD) or xanthine oxidase within the uterus. Samples of myometrium, placenta, decidua and fetal membranes were obtained from women before and after the onset of labour at term. Immunocytochemistry was used to localize Cu/Zn SOD, Mn SOD and xanthine oxidase and measure SOD enzyme activity. Cu/Zn and Mn SOD-like immunoreactivity was detected in syncytiotrophoblast cells, villous stromal cells and endothelial cells of blood vessels in the placenta. In the myometrium Cu/Zn and Mn SOD were localized to myocytes and endothelial cells and to some vascular smooth muscle cells. In the fetal membranes we observed staining for Cu/Zn SOD and Mn SOD in the amnion, chorion, extravillous trophoblast and decidua. There was no difference in SOD enzyme activity or staining intensity for SOD between different cell types before and during labour. Xanthine oxidase immunoreactivity was identified in each of the tissues examined and again there was no difference in immunostaining in tissues obtained from women delivered before or after the onset of labour. These results show that the pregnant uterus is capable of both synthesizing and degrading superoxide and suggest that superoxide dismutase and xanthine oxidase may play a role in the maintenance of uterine quiescence during pregnancy, but not in the initiation of parturition.      

Hydrosalpinges adversely affect markers of endometrial receptivity

While in-vitro fertilization (IVF) was initially developed in women with tubal factor infertility, recent clinical studies have suggested that the presence of hydrosalpinges lowers implantation and pregnancy rates. We postulated that these hydrosalpinges cause impaired endometrial receptivity. A total of 103 women with hydrosalpinges were prospectively evaluated, and compared with 55 infertile and 44 fertile controls. All women had endometrial biopsies during the window of implantation, analysed by conventional histological criteria, and also stained for three integrin markers of endometrial receptivity (alpha1beta1, alpha4beta1 and alpha vbeta3). Women with hydrosalpinges (cases) expressed significantly less of the alpha vbeta3 integrin compared with controls. There was no difference in expression of alpha1beta1 or alpha4beta1 among groups. A significantly greater number of cases had out of phase histology and missing alpha vbeta3 (type I defects) and absent integrin expression despite normal histological maturation (type II) defects, compared with controls. Of 20 women with impaired endometrial receptivity who were also biopsied after hydrosalpinx surgery, 70% demonstrated increased alpha vbeta3 expression. Seventy-seven percent of type I and 57% of type II defects were corrected postoperatively. Using markers of endometrial receptivity, this study demonstrates that inflammatory hydrosalpinges have an adverse effect on endometrial receptivity, which in some cases may be overcome by surgical treatment of the hydrosalpinx.      

大鼠视皮质胼胝体轴突的生后发育和形态──生物素结合的葡聚糖胺顺行示踪法研究

采用生物素结合的葡聚糖胺顺行示踪法研究了大鼠视皮质主要胼胝体投射区即１７／１８ａ交界区胼胝体轴突的生后发育和形态。在生后５天时，此交界区胼胝体轴突从白质向灰质Ⅰ层垂直生长，在灰质内仅有极少量的侧支抽芽。至生后１３天时，皮质Ⅰ层最先出现致密的由胼胝体轴突终支组成的终末丛。到生后１７天时，类似的终末丛也见于皮质Ⅱ／Ⅲ，Ⅴ和Ⅵ层，这种分布型式与成年大鼠者相似。以上结果表明，绝大部分胼胝体轴突首先生长到达Ⅰ层并先在Ⅰ层发出终支，然后再在其它皮质层发出侧支及终支，因而提示皮质Ⅰ层在胼胝体联系的生后发育中可能发挥重要作用。     

Repeated i.v. cocaine exposure produces long-lasting behavioral sensitization in pregnant adults, but behavioral tolerance in their offspring

Repeated exposure to cocaine during sensitive periods of forebrain development produces specific, long-lasting changes in the structure and function of maturing neural circuits. Similar regimens of drug exposure in adult animals with mature, homeostatically regulated nervous systems produce neuroadaptations that appear to be quite different in nature and magnitude. We studied the ability of cocaine to induce behavioral sensitization and/or tolerance following repeated administration of i.v. cocaine (3 mg/kg, twice daily) to pregnant rabbits during the period of peak differentiation within the rabbit cerebral cortex (embryonic day [E] 16-E25). Offspring and the adult mothers were behaviorally tested following acute administration of amphetamine 2 months after the litters were born. The offspring, having received cocaine during the prenatal sensitive period, showed profound behavioral tolerance to the amphetamine challenge. In contrast, the mothers of these offspring, who received cocaine at the same dose and duration, and experienced the same period of withdrawal, exhibited robust behavioral sensitization. These data indicate that specific adaptive changes in neural signaling and/or circuitry that occur in response to repeated exposure to psychostimulants are highly dependent upon the maturational state of the brain during which the exposure occurs.