The effects of estrogen on cortisol metabolism in female baboons

We examined Cortisol (F) dynamics in female baboons $\text{(Papio anubis)}$ treated with diethylstilbestrol (DES) or estradiol (E₂) and compared values with those previously measured in nonpregnant and pregnant animals. Five regularly menstruating baboons (12–18 kg, BW) were administered 5 mg DES daily via fruit or 0.5 mg E₂/0.1ml oil sc for 30 days. Blood samples, obtained before and after treatment, were assayed for serum F concentrations and serum Cortisol binding capacity (CBC). The metabolic clearance (MCR) and production rate (PR) of F and the catabolism of i.v. administered [³H] F were examined 25 and 30 days after initiation of estrogen treatment. Compared with values in nonpregnant baboons, F metabolism in estrogen treated animals is significantly altered and is characterized by increased formation of unconjugated metabolites, decreased glucuronylation, increased excretion of unconjugated F, cortisone, and highly polar metabolites, and increased CBC. These changes induced by estrogen are similar to those observed in intact pregnant baboons and permit the suggestion that the pattern of F metabolism and the level of CBC in baboon pregnancy are the result of elevated estrogen production.However, estrogen also caused a significant decrease in the MCR and PR of F, parameters which, by contrast, are similar in intact pregnant and nonpregnant baboons. These findings indicate that while estrogen also influences the rate of F clearance and F production, these effects of estrogen are not apparent during pregnancy. Collectively, these findings allow the suggestion that estrogen is a major factor which alters F metabolism and increases serum CBC in baboon gestation. However, additional factors are operative in primate pregnancy which maintain PR and MCR of F at levels similar to those of nonpregnant baboons.     

Unexpected metabolites produced from clomethiazole

The heterocyclic drug clomethiazole is metabolized by body passage partly to small aliphatic molecules. The occurrence of such unexpected metabolites is usually overlooked. An appropriate method for their detection is the comparison of urine profiles during drug intake and after withdrawal of the drug.     

High Amplitude Phase Resetting in Rev-Erbα/Per1 Double Mutant Mice

Over time, organisms developed various strategies to adapt to their environment. Circadian clocks are thought to have evolved to adjust to the predictable rhythms of the light-dark cycle caused by the rotation of the Earth around its own axis. The rhythms these clocks generate persist even in the absence of environmental cues with a period of about 24 hours. To tick in time, they continuously synchronize themselves to the prevailing photoperiod by appropriate phase shifts. In this study, we disrupted two molecular components of the mammalian circadian oscillator, Rev-Erbα and Period1 (Per1). We found that mice lacking these genes displayed robust circadian rhythms with significantly shorter periods under constant darkness conditions. Strikingly, they showed high amplitude resetting in response to a brief light pulse at the end of their subjective night phase, which is rare in mammals. Surprisingly, Cry1, a clock component not inducible by light in mammals, became slightly inducible in these mice. Taken together, Rev-Erbα and Per1 may be part of a mechanism preventing drastic phase shifts in mammals.     

Tissue distribution and ultrastructure of B lymphocytes reacting with the monoclonal antibody anti-Y29/55

The reactivity of normal tonsilar cells with the monoclonal antibody anti-Y29/55 is characterized at the tissue and ultrastructural cytological level. Using an indirect immuno-alkaline phosphatase method on frozen sections the antibody labels mantle zone and germinal center lymphocytes. This staining reaction is more generalized in B-lymphocyte areas than that obtained with antibodies to IgM and IgD. By indirect immunoperoxidase staining, as well as by an indirect rosetting procedure in cell suspensions, the reactive cell population were either small resting lymphocytes or activated lymphocytes corresponding to centrocytes, centroblasts, immunoblasts and plasmoblasts; some plasma cells were also labeled. These results characterize the monoclonal antibody anti-Y29/55 as a pan-B-marker antibody, useful for labeling resting and activated peripheral B-lymphocytes in frozen tissue sections and cell suspensions.     

Various effects of angiotensin II on amygdaloid neuronal activity in normotensive control and hypertensive transgenic [TGR(mREN-2)27] rats.

The effects of iontophoretically ejected angiotensin II (Ang II) on the firing rate of neurons in the basolateral complex and the central and cortical amygdala were investigated in two strains of urethane anesthetized rats. In normotensive Sprague-Dawley rats, Ang II induced a significant increase in the discharge rate of responsive amygdaloid neurons. In contrast, in the hypertensive transgenic [TGR(mREN-2)27] rats with higher brain Ang II level, Ang II more often caused inhibitory effects on the amygdaloid firing rate in comparison with controls. The distribution of nonresponsive, excited, and inhibited neurons differed significantly in the two rat strains. Moreover, the responsiveness of amygdaloid neurons was significantly higher in transgenic rats in comparison with controls. Both the increase and the decrease in the firing rate caused by Ang II could be blocked either by angiotensin AT(1) or by AT(2) receptor-specific antagonists. In many cases, the Ang II-induced decrease in the firing rate was antagonized by bicuculline, a gamma-aminobutyric acid (GABA(A)) antagonist. The higher responsiveness of amygdaloid neurons in transgenic rats as well as the predominance of inhibitory effects, presumedly mediated by GABAergic interneurons, could change the output of the amygdala and its influence on thirst, kidney, and cardiovascular function or on processes of learning and anxiety.     

Race,Ethnicity and Ancestry in Unrelated Transplant Matching for the National Marrow Donor Program: A Comparison of Multiple Forms of Self-Identification with Genetics

We conducted a nationwide study comparing self-identification to genetic ancestry classifications in a large cohort (n = 1752) from the National Marrow Donor Program. We sought to determine how various measures of self-identification intersect with genetic ancestry, with the aim of improving matching algorithms for unrelated bone marrow transplant. Multiple dimensions of self-identification, including race/ethnicity and geographic ancestry were compared to classifications based on ancestry informative markers (AIMs), and the human leukocyte antigen (HLA) genes, which are required for transplant matching. Nearly 20% of responses were inconsistent between reporting race/ethnicity versus geographic ancestry. Despite strong concordance between AIMs and HLA, no measure of self-identification shows complete correspondence with genetic ancestry. In certain cases geographic ancestry reporting matches genetic ancestry not reflected in race/ethnicity identification, but in other cases geographic ancestries show little correspondence to genetic measures, with important differences by gender. However, when respondents assign ancestry to grandparents, we observe sub-groups of individuals with well- defined genetic ancestries, including important differences in HLA frequencies, with implications for transplant matching. While we advocate for tailored questioning to improve accuracy of ancestry ascertainment, collection of donor grandparents’ information will improve the chances of finding matches for many patients, particularly for mixed-ancestry individuals.