Glucocorticoid effects on phenylethanolamine N-methyltransferase (PNMT) in explants of embryonic rat medulla oblongata

Although glucocorticoid hormones have important roles in the development of neurotransmitter systems in cells derived from the neural crest, it is not known whether they have parallel effects on neuronal development in the brain. To address this issue, we have established an in vitro system of fetal medulla oblongata (MO) to follow development of the epinephrine-synthesizing enzyme, phenylethanolamine N-methyltransferase (PNMT). Embryonic MO was explanted from E13 or E18 embryos and maintained for up to 3 weeks. Successful culture of adrenergic neurons was possible only in explants taken from young embryos, since E18 explants failed to develop. In E13 explants, immunoreactivity to both PNMT and tyrosine hydroxylase, the rate limiting enzyme in catecholamine synthesis, was observed. PNMT catalytic activity which was barely detectable at the time of explanation increased markedly during the first week in vitro. To study the effects of glucocorticoids on PNMT development in central neurons, MO explants were grown in glucocorticoid deficient medium in which rat serum from adrenalectomized rats was substituted for human placental serum. Addition of natural glucocorticoids, cortisol or corticosterone, or the mineralcorticoid, deoxycorticosterone, during the third culture week had no effect on PNMT activity. Dexamethasone (DEX), a synthetic glucocorticoid, also had no effect on PNMT during the first or second weeks in culture. However, addition of DEX during the third culture week resulted in a doubling of PNMT activity. However, attempts to block the DEX effect during the third week or to block the increase in PNMT activity during the first week in control cultures with the glucocorticoid receptor antagonist, dexamethasone 21-mesylate, were unsuccessful. These results suggest that PNMT in central neurons does not require glucocorticoids for ontogeny during the embryonic period. This is in contrast to PNMT in adrenal medulla which requires glucocorticoids for normal development during both the embryonic and postnatal periods. More generally, these studies suggest that development of the same neurotransmitter phenotype in brain and periphery may be differentially regulated.     

血管细胞粘附分子调控造血的研究进展

本文简述了血管细胞粘附分子 (Vascularcelladhesionmolecule 1,VCAM 1)的结构和生物学功能 ,总结了VCAM 1在恶性血液病骨髓基质中的表达和意义 ,探讨了VCAM 1在造血干细胞动员和归巢中的作用 ,指出VCAM 1作用机制的深入研究将对恶性血液病的治疗提供更为有效的方法。     

Cell sizing in chronic lymphoproliferative disorders: an aid to differential diagnosis.

AIMS: To determine if leucocyte volume distribution analysis (LVDA), obtained using a Coulter Counter Model S Plus IV, can be used to aid differentiation of chronic lymphoproliferative disorder (CLPD) subtypes. METHODS: Mean lymphocyte volume and lymphocyte distribution width were measured on each patient (n = 90) using a hard copy of an amplified LVDA histogram. The mean lymphocyte volume was taken as the mean of the values on either side of the peak at half maximum height. The lymphocyte distribution width was taken as the range of cell values between the two values used to calibrate the mean lymphocyte volume. A template showing typical histograms from commonly occurring CLPD was also produced on an acetate sheet. This was used to examine the histogram from each new patient to evaluate its usefulness as an alternative to the calculation of mean lymphocyte volume and lymphocyte distribution width. RESULTS: Mean lymphocyte volume and lymphocyte distribution width were significantly higher in B cell lymphocytic leukaemia of mixed cell type (B CLL/PL), B cell non-Hodgkin's lymphoma with peripheral blood spill, hairy cell leukaemia and T cell prolymphocytic leukaemia than in B cell chronic lymphocytic leukaemia (B CLL). The mean lymphocyte volume, but not the lymphocyte distribution width, was also significantly higher in T cell chronic lymphocytic leukaemia than in B CLL. The template gave an immediate preliminary indication of possible subtype(s) of disorder and could be used as an alternative to measurement of mean lymphocyte volume and lymphocyte distribution width. CONCLUSIONS: Electronic haematology analysers producing an LVDA provide a useful, cost effective cell sizing analysis which can aid the differentiation of subtypes of CLPD.     

Glycoproteins present in human follicular fluid that inhibit the zona- binding capacity of spermatozoa

Previous studies have suggested that human follicular fluid contains factors that reduce the zona-binding capacity of spermatozoa. The present study provides further evidence of the existence of such factors. Using the hemizona binding assay (HZA), we have shown that the inhibitory effect of human follicular fluid on the zona-binding capacity of spermatozoa is concentration-dependent, an inhibitory effect being detected when the concentration of human follicular fluid was > or = 10%. A 1% concentration of human follicular fluid did not possess this inhibitory activity. Heating human follicular fluid at 56 degrees C for 30 min did not affect its inhibitory properties; treatment with proteinase-K abolished such inhibition. Human follicular fluid was fractionated sequentially by concanavalin-A affinity chromatography, Mono Q ion-exchange chromatography and Superose-12 gel filtration. The zona binding inhibitory activity resided in the fraction which bound to the lectin and Mono Q column and contained molecules with native molecular weights of 32 and 192 kDa. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis suggested that the 192 kDa glycoprotein was a tetramer, while the 32 kDa glycoprotein remained as a single molecular species under denaturing conditions. We conclude that two glycoproteins were responsible for the zona binding inhibitory activity of human follicular fluid. The physiological role of these factors remains unclear.      

Moral reasoning as a catalyst for cultural competence and culturally responsive care

The importance of developing cultural competence among healthcare professionals is well recognized. However, the widespread reports of insensitivity and deficiencies in care for culturally diverse patients illuminate the need to review how cultural competence development is taught, learnt and applied in practice. Unless we can alter the ‘hearts and minds’ of practising nurses to provide the care that they know they should, culturally insensitive care will continue operating in subtle ways. This paper explores the ideas behind nurses’ actions and omissions when caring for culturally diverse patients and proposes the need to examine cultural competence development through a moral reasoning lens. Examining cultural competence development through a moral reasoning lens can help empower nurses, whilst nurturing commitment and courage to providing quality care that meets the needs of culturally diverse patients. The model of morality provides a framework that explores how moral motivation and behaviour occur and can provide a vehicle for critically examining the knowledge, skills and attitudes required to provide culturally responsive care.     

Response from lieberman and colleagues

Respond on comments on Lieberman's article: Cyclosiloxanes Produce Fatal Liver and Lung Damage in Mice. Environ Health Perspect 107:161-165     

Seasonal Variation in Internet Keyword Searches: A Proxy Assessment of Sex Mating Behaviors

The current study investigated seasonal variation in internet searches regarding sex and mating behaviors. Harmonic analyses were used to examine the seasonal trends of Google keyword searches during the past 5 years for topics related to pornography, prostitution, and mate-seeking. Results indicated a consistent 6-month harmonic cycle with the peaks of keyword searches related to sex and mating behaviors occurring most frequently during winter and early summer. Such results compliment past research that has found similar seasonal trends of births, sexually transmitted infections, condom sales, and abortions.