Age-related deficits in brain androgen binding and metabolism, testosterone, and sexual behavior of male rats

Brain androgen binding and metabolism, serum testosterone (T), and sexual behavior were measured in old and young male Fischer 344 rats. After completion of sexual behavior tests, blood was collected for T assay and brains were removed for simultaneous measurements of cytosolic (ARc) and nuclear (ARn) androgen receptors and aromatase activity (AA) in the preoptic area (POA), hypothalamus (HYP) and amygdala (AMG). In Experiment 1, old and young intact males were examined. None of the old males ejaculated in any of the tests of sexual behavior whereas all of the young males ejaculated. The old males had lower levels of serum T, lower levels of ARn in the POA and HYP and lower levels of AA in the POA. The ARc levels of the old and young males did not differ. Experiment 2 was designed to determine if the deficits in brain androgen binding and metabolism were due to low levels of T. Old and young T-treated gonadectomized (GX-T) males and young intact (I) males were examined. T levels were comparable in the young and old GX-T males and were higher in each of these groups than in the young I males. In sexual behavior tests, all of the young but only 25% of the old GX-T males ejaculated. Although ARn levels in the old GX-T males were lower than in the young GX-T males, they were comparable to the young I male levels. No age-related differences in T induction of AA were observed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of ultrasonographic findings in spontaneous abortions with normal and abnormal karyotypes

To determine whether ultrasonographic findings can predict the karyotype of spontaneous abortions, 137 pregnancies (54 spontaneous, 83 assisted ovulatory cycles) that subsequently aborted and had chromosome analysis performed on the products of conception were studied ultrasonographically. Transvaginal ultrasound was performed using an Acuson 128XP/10 with 7.5 MHz probe. The numbers of empty gestational sacs, small and normal for gestational size, embryonic poles and embryos with documented cardiac activity were calculated. The frequency of each of these findings in pregnancies with normal and abnormal karyotypes was compared. Of the 137 spontaneous abortions, 51 had normal chromosome analyses and 86 had abnormal karyotypes (68 aneuploidies and 18 polyploidies). Ultrasonographic findings in the 51 karyotypically normal pregnancies included 16 (31%) with empty gestational sacs, and 35 (69%) with embryonic poles, of which 24 (69%) were at least 1 week smaller than expected for gestational age and 11 (31%) were the expected size. Embryonic cardiac activity was documented in 22 (63%) of the 35 embryonic poles. Amongst 86 pregnancies with abnormal karyotypes, similar frequencies of ultrasound findings were found: 23 (27%) with empty gestational sacs, 42 (67%) with embryonic poles smaller than expected for gestational age, and 50 (79%) embryos lost after documentation of embryonic cardiac activity. No differences in the frequency of ultrasonographic findings of empty gestational sacs, small embryonic pole and embryonic cardiac activity were observed between karyotypically normal and abnormal spontaneous abortions. Ultrasonographic findings cannot predict the karyotype of spontaneous abortions.      

Constitutive macropinocytosis allows TAP-dependent major histocompatibility compex class I presentation of exogenous soluble antigen by bone marrow-derived dendritic cells

Dendritic cells expanded from mouse bone marrow (BMDC) with granulocyte/macrophage-colony-stimulating factor have potent T cell-stimulatory properties both in vitro and in vivo. This has been well documented for major histocompatibility complex (MHC) class II-restricted responses, and more recently using peptide-loaded and protein-pulsed DC for CD8 responses following adoptive transfer in mice. An unresolved question concerns the capacity of BMDC to present exogenous antigen on MHC class I molecules, an unconventional mode of MHC class I loading for which there is now considerable evidence, particularly in macrophages. Here, we show that BMDC exhibit high levels of macropinocytosis driven by constitutive membrane ruffling activity. Up to one-third of actively ruffling and macropinocytosing BMDC transferred pinocytosed horseradish peroxidase into the cytosol following a 15-min pulse, suggesting that they might be capable of presenting exogenous soluble antigen on MHC class I molecules. We show that BMDC presented exogenous ovalbumin to a T cell hybridoma more effectively, more rapidly, and at lower exogenous antigen concentrations than BM macrophages on a cell-for-cell basis. Presentation was TAP dependent, brefeldin A sensitive, and blocked by inhibitors of proteasomal processing, demonstrating use of the classical MHC class I pathway. Although effective presentation of exogenous antigen by BMDC occurred in the absence of agents which stimulate macropinocytosis, treatment with phorbol myristate acetate (PMA) enhanced both pinocytosis and MHC class I presentation by BMDC. Finally, PMA-stimulated BMDC exposed to exogenous ovalbumin in vitro were able to prime an antigen-specific cytotoxic T lymphocyte response following adoptive transfer in vivo.     

Gonadotrophin-releasing hormone agonist dose-dependency of pituitary desensitization during controlled ovarian hyperstimulation in IVF

The aim of this study was to find the minimal effective daily s.c. dose of the gonadotrophin-releasing hormone (GnRH) agonist, triptorelin acetate, that suppresses the GnRH-induced release of luteinizing hormone (LH) at time of human chorionic gonadotrophin (HCG) injection and thereby prevents spontaneous LH surges during in-vitro fertilization (IVF) stimulation cycles. Therefore, a double-blind, prospective and randomized titration study was performed. A total of 48 IVF patients were divided into four groups of 12 patients. Each group received a different dose of triptorelin acetate, namely 5, 15, 50 or 100 microg s.c. daily. Standard ovarian stimulation was carried out using urinary follicle stimulating hormone (FSH) preparations. A 500 microg GnRH test was performed 90 min before the HCG injection in order to measure the degree of pituitary desensitization. Spontaneous LH surges were not detected in any of the groups, although three patients in the 5 microg group had ovulated at the time of ovum retrieval. The pituitary LH response to the GnRH test at time of HCG, expressed as area under the curve (AUC), appeared to be dose-dependent. Thus, a daily s.c. dose of 100 microg triptorelin acetate appears to be too high, since adequate desensitization of the pituitary (i.e. no spontaneous LH surge) can be achieved with doses as low as 15 and 50 microg.      

Signaling mechanisms regulating self-renewal and differentiation of pluripotent embryonic stem cells

An ability to propagate pluripotent embryonic cells in culture is the foundation both for defined germline modification in experimental rodents and for future possibilities for broad-based cellular transplantation therapies in humans. Yet, the molecular basis of the self-renewing pluripotent phenotype remains ill-defined. The relationship between factors that influence embryonic stem cell propagation in vitro and mechanisms of stem cell regulation operative in the embryo is also uncertain. In this article we discuss the role of intracellular signalling pathways in the maintenance of pluripotency and induction of differentiation in embryonic stem cell cultures and the mammalian embryo.     

The occupation of fishing as a risk factor in cancer of the lip.

To study the role of commercial fishing and related factors in the development of lip cancer, a project that included a case-control study and a cohort analysis was undertaken in Newfoundland. Household survey data were linked with cancer-registry and census data. In comparison with other males, fishermen had a probability of development of lip cancer that was 1.5 times higher (by the case-control method, P less than 0.05) or 4.4 times higher (by cohort analysis, P less than 0.001). Despite the effect of pipe smoking, "outdoorness" and age on the development of lip cancer in general, the occupation of fishing was an additional, independent contribution to the risk. Unexpectedly, using the mouth as a third hand to handle tar-coated nets seemed to protect fishermen from the disease. It was not possible to attribute the higher risk to a particular work activity, nor was a specific responsible carcinogen identified.     

2B4 co-stimulation: NK cells and their control of adaptive immune responses

NK cells have primarily been defined by their ability to kill infected cells, tumor cells and some normal cells expressing low levels of MHC class I molecules. NK cells have also been shown to affect adaptive immune responses by their production of both pro- and anti-inflammatory cytokines. Recently it has been shown that adaptive immune responses can be enhanced or maintained also through direct lymphocyte-lymphocyte interactions. One of these interactions was identified to occur between 2B4 and CD48, where 2B4 acted as a co-stimulatory ligand for both NK cells and T cells. In the current article, we discuss the role of 2B4 in the development of adaptive immune responses and the role of NK-T cell interactions in these responses.     

Acculturation and psychosocial stress show differential relationships to insulin resistance (HOMA) and body fat distribution in two groups of blacks living in the US Virgin Islands

The objective of this study was to determine whether acculturation and psychosocial stress exert differential effects on body fat distribution and insulin resistance among native-born African Americans and African-Caribbean immigrants living in the US Virgin Islands (USVI). Data collected from a non-diabetic sample of 183 USVI-born African Americans and 296 African-Caribbean immigrants age > 20 on the island of St. Croix, USVI were studied. Information on demographic characteristics, acculturation and psychosocial stress was collected by questionnaire. Anthropometric measurements were taken, and serum glucose and insulin were measured from fasting blood samples. Insulin resistance was estimated by the homeostasis model assessment (HOMA) method. The results showed that in multivariate regression analyses, controlling for age, education, gender, BMI, waist circumference, family history of diabetes, smoking and alcohol consumption, acculturation was independently related to logarithm of HOMA (InHOMA) scores among USVI-born African Americans, but not among African-Caribbean immigrants. In contrast, among USVI-born African Americans psychosocial stress was not significantly related to InHOMA, while among African-Caribbean immigrants psychosocial stress was independently related to InHOMA in models that included BMI, but not in those which included waist circumference. This study suggests that acculturation and psychosocial stress may have a differential effect on body fat distribution and insulin resistance among native-born and immigrant blacks living in the US Virgin Islands.