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.      

Coronary heart disease, chronic inflammation, and pathogenic social hierarchy: a biological limit to possible reductions in morbidity and mortality

We suggest that a particular form of social hierarchy, which we characterize as "pathogenic", can, from the earliest stages of life, exert a formal analog to evolutionary selection pressure, literally writing a permanent developmental image of itself upon immune function as chronic vascular inflammation and its consequences. The staged nature of resulting disease emerges "naturally" as a rough analog to punctuated equilibrium in evolutionary theory, although selection pressure is a passive filter rather than an active agent, like structured psychosocial stress. Exposure differs according to the social constructs of race, class, and ethnicity, accounting in large measure for observed population-level differences in rates of coronary heart disease across industrialized societies. American Apartheid, which enmeshes both majority and minority communities in a social construct of pathogenic hierarchy, appears to present a severe biological limit to continuing declines in coronary heart disease for powerful as well as subordinate subgroups: "Culture"--to use the words of the evolutionary anthropologist Robert Boyd--"is as much a part of human biology as the enamel on our teeth".     

Inflammatory Bowel Disorders

Infiltration of leucocytes into the mucosa is a hallmark feature of a number of inflammatory bowel disorders, most notably Crohn's disease and ulcerative colitis. The interactions between circulating leucocytes and the vascular endothelium that permit leucocyte migration to a site of injury or infection are mediated via a variety of adhesion molecules. There is now ample evidence for alterations in adhesion molecule expression and function in inflammatory bowel disorders. This raises the possibility that adhesion molecules could be targets for novel therapies. Indeed, many existing anti-inflammatory drugs are capable of modulating adhesion molecule expression or function. Moreover, intensive research is under way to develop more selective and effective modulators of adhesion molecules, in the hope that they will be useful for treating various inflammatory disorders.     

Effects of intracerebral implants of steroid hormones on scent marking in the ovariectomized female gerbil (Meriones unguiculatus)

The effects of intracerebral implants of steroid hormones on scent marking in the female gerbil (Meriones unguiculatus) were studied in two experiments. In Experiment 1 various steroids were implanted alone or in combination into the preoptic and anterior hypothalamic area of ovariectomized females. Unilateral implants of testosterone + estrogen, estrogen, estrogen + progesterone, testosterone and testosterone + progesterone stimulated a significant level of marking when compared to controls. Experiment 2 utilized bilateral implants of estrogen dissolved in paraffin in order to explore the distribution hormone sensitive areas in the brain which might be important in the regulation of scent marking in the female gerbil. Pellets of estrogen-paraffin were implanted stereotaxically into either the anterior hypothalamus, preoptic area, septum, hippocampus, thalamus, amygdala or anterior olfactory nucleus of ovariectomized females. Total dosage of hormone implanted was 8.2–8.4 μg. A significant level of marking resulted in animals receiving implants into the anterior hypothalamus, preoptic area and septum when compared to controls. Marking appeared at about the same rate in each of these groups; however, the level of marking attained differed. By the last trial, anterior hypothalamic implanted animals were marking significantly more often than animals in either the preoptic or septum groups. Although there was no evidence of ieakage from the brain, the data suggested that some rapid diffusion of hormone, largely restricted to the brain, was taking place or that the three areas were differentially responsive to the hormone. The data do indicate that some localization of function does exist with respect to regulation of scent marking in the female.     

Distinct expression and localization of serine protease HtrA1 in human endometrium and first-trimester placenta.

Mammalian embryos cannot survive without the placenta. Development of the human placenta requires trophoblast proliferation, differentiation, and invasion as well as highly coordinated modulation of the maternal uterus. HtrA1 is a member of the recently identified mammalian HtrA (high temperature requirement factor A) serine protease family with a high level of expression in the placenta. In this study, we examined whether HtrA1 expression (mRNA and protein) is associated with placental development in the human. HtrA1 is up-regulated in both endometrial glands and decidual cells during endometrial preparation for embryo implantation and during first-trimester pregnancy at placentation. HtrA1 expression was also detected in certain trophoblast subtypes during early pregnancy. The villous syncytiotrophoblast and cytotrophoblast showed the strongest expression while the interstitial extravillous trophoblast showed the lowest or no expression of HtrA1. The distinct distribution of HtrA1 at the maternal-trophoblast interface suggests that HtrA1 may play a role in placental development.