Chemokine and cyclooxygenase-2 expression in human endometrium coincides with leukocyte accumulation

The endometrium contains a resident population of leukocytes, the number and subtype of which vary throughout the menstrual cycle and in early pregnancy. Factors controlling these fluctuations are unknown, but a combination of proliferation in situ and migration from the vasculature has been proposed. Locally acting inflammatory mediators, including specific chemokines and prostaglandins, have been implicated in these processes. Interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) are potent chemoattractants and activators for neutrophils and monocytes respectively. Locally acting prostaglandins modulate vascular permeability, and a synergistic action of prostaglandin E (PGE) with IL-8 has been described. In the present study IL-8, MCP-1 and cyclooxygenase-2 (COX-2), the inducible isoform of prostaglandin synthase, were all localized in the endometrium by immunohistochemistry throughout the menstrual cycle and in early pregnancy. All three inflammatory mediators were localized to the perivascular cells of blood vessels in endometrium and decidua, and additional immunoreactivity for COX-2 was identified in the glandular epithelium. The intensity of immunostaining was reduced in the periovulatory, early and mid-secretory phases and significantly increased premenstrually. These results further support the hypothesis that there is a premenstrual migration of leukocytes into the endometrium mediated by chemokines.      

A new spontaneous mouse mutation of Hoxd13 with a polyalanine expansion and phenotype similar to human synpolydactyly

Human synpolydactyly (SPD) is an inherited congenital limb malformation caused by mutations in the HOXD13 gene. Heterozygotes are typically characterized by 3/4 finger and 4/5 toe syndactyly with associated duplicated digits; hands and feet of homozygotes are very small because of a shortening of the phalanges, metacarpal and metatarsal bones. Here we describe the phenotype and molecular basis of a spontaneous mutation of Hoxd13 in mice that provides a phenotypically and molecularly accurate model for human SPD. The new mutation, named synpolydactyly homolog (spdh), is a 21 bp in-frame duplication within a polyalanine- encoding region at the 5'-end of the Hoxd13 coding sequence. The duplication expands the stretch of alanines from 15 to 22; the same type of expansion occurs in human SPD mutations. spdh/spdh homozygotes exhibit severe malformations of all four feet, including polydactyly, syndactyly and brachydactylia. The phenotype of spdh is much more severe than that exhibited by mice with a genetically engineered, presumably null, disruption of Hoxd13. Thus spdh probably acts in a dominant-negative manner and will be valuable for examining interactions with other Hox genes and their protein products during limb development. Homozygous mice of both sexes also lack preputial glands and males do not breed; therefore, spdh/spdh mice may also be valuable in studies of reproductive physiology and behavior.      

The immunolocalization of bcl-2 at the maternal-fetal interface in healthy and failing pregnancies

Programmed cell death by apoptosis occurs in both fetal and maternal tissues during early pregnancy. To investigate a role for apoptosis at the maternal-fetal interface, we have immunolocalized the bcl-2 protein in formalin-fixed decidual and placental tissue collected from women undergoing surgical termination of pregnancy (n = 22), from women undergoing a sporadic miscarriage (n = 16) and from women with a history of recurrent pregnancy loss (more than three consecutive pregnancy losses; n = 22) undergoing a further miscarriage. In all three groups, bcl-2+ cells were found in aggregates and dispersed in the stroma, and immunoreactivity was observed in glandular epithelium. Double immunostaining revealed that a majority of stromal bcl-2+ cells were CD56+ large granular lymphocytes. A computerized image analysis revealed no significant differences in percentage area of bcl-2 or CD56+ immunostaining. Significantly more biopsies from the surgical termination group (4/10) had > 20% positive immunostaining for CD56 compared with 0% in the other two groups combined (0/20; P < 0.05). Bcl- 2 immunoreactivity was observed in the villi syncytiotrophoblast, and staining intensity was consistently greater in the surgical termination group. The possible roles of bcl-2 at the maternal-fetal interface are discussed.      

迷走神经电刺激治疗癫痫的现状与展望

Electrical vagus nerve stimulation （VNS） has been approved by FDA and is widely used in recent years for the treatment of epilepsy and possibly other medical conditions such as depression. The current success rate of VNS for epilepsy is about 50%, but there are complications, potential risks and cost concerns. One of the major limitations for this new therapy is that its antiseizure mechanisms are by no means clear. In particular, it is not known whether the therapeutic effect is vagal specific, what types of nerve fibers in the vagus nerve are contributing to the therapeutic effects, or what individual patients would benefit from the use of the expensive and invasive VNS implantation. There are controversies regarding how and where the VNS takes effect on epilepsy in the central nervous system. The poor understanding of VNS has inevitably limited the application and success of the therapy. The current review analyses the pros and cons of VNS for epilepsy in vis-à- vis other available therapies including Chinese medical methods, and explores the possible mechanisms in order to stimulate further improvement of this new technology.     

Comparison of the ISAAC video questionnaire (AVQ 3.0) with the ISAAC written questionnaire for estimating asthma associated with bronchial hyperreactivity

Background A standardized protocol is essential for international comparisons of asthma prevalence and severity. The International Study of Asthma and Allergies in Childhood (ISAAC) used a standardized written questionnaire (WQ) and a video questionnaire (AVQ3.0) to survey the prevalence and severity of asthma in 13–14-year-old schoolchildren in different countries. Objective To compare the effectiveness of WQ and AVQ3.0 in predicting bronchial hyperresponsiveness (BHR), defined as having a provocation dose of inhaled methacholine causing a 20% fall in baseline FEV₁ of 7.8μmol. Methods One hundred and eighty-nine Chinese schoolchildren completed a written questionnaire followed by a video questionnaire on asthma symptoms. They then underwent bronchial challenge to methacholine. Results Fair correlations were seen between the first two corresponding questions (moderate wheezing at rest and exercise wheeze) in the two questionnaires with Kapper indices of 0.44 and 0.43, respectively. The ability to predict BHR, as indicated by the Youden's index, was similar between the corresponding questions of the two questionnaires, except for ‘severe wheeze’ which had a significantly higher Youden's index in AVQ3.0 (0.44) than the corresponding question in WQ (0.11, P<0.05). Conclusion The ISAAC International video questionnaire is at least as effective as the ISAAC written questionnaire in predicting BHR. It therefore provides a simple and valid tool for international comparisons of asthma prevalence and severity.     

Predictive Factors in Recurrent Spontaneous Aborters—A Multicenter Study

PROBLEM : Compare data from several centers relating to success rates in recurrent spontaneous miscarriage and assess the significance of indicators of subsequent pregnancy loss. METHOD : Data from 777 couples with unexplained recurrent spontaneous abortion from independent studies at seven centers were analyzed using logistic regression analysis. The following covariates were considered: age of patient, number of previous spontaneous abortions, length of previous abortions history, sub-fertility index (defined as the product of the number of spontaneous abortions and the abortion history), whether a patient was a primary or secondary aborter, and whether a patient had received leukocyte immunotherapy. RESULTS : There was a highly significant difference between the seven centers in success rates in the subsequent pregnancy and a highly significant association between success rate and each of the following covariates: the number of previous abortions, the length of the previous abortion history and the sub-fertility index. In particular, for each increase of 10 units in the value of the sub-fertility index, up to a value of 30, the odds in favor of a successful pregnancy decreased by a factor of 0.6, i.e., 40%. There was, however, little evidence of an association between the success rate in the subsequent pregnancy and age, parity, or immunization with cells from the husband. CONCLUSIONS : The sub-fertility index may be a useful measure of likelihood of success in a subsequent pregnancy.     

Efficacy of Intracytoplasmic Sperm Injection (ICSI) Treatment in the Immunological Infertile Patients

PROBLEM: To evaluate the efficacy of intracytoplasmic sperm injection (ICSI) treatment in the immunological infertile patients. METHODS: The subjects were 60 cycles of 44 immunological infertile patients and these clinical data were analysed, retrospectively. They were classified into female and male immunological infertility group and were treated with conventional IVF, ICSI, and half-ICSI. RESULTS: The fertilization rate of ICSI (60.3%) and half-ICSI (60.7%) cycles were significantly (P<0.01) higher than conventional IVF (42.6%) cycles. In the male immunological infertility group, fertilization rate was significantly (P<0.01) higher in ICSI (60.7%) and half-ICSI (66.7%) cycles than in conventional IVF (27.4%) cycles and clinical pregnancy rate was higher in ICSI (54.5%) and half ICSI (33.3%) than in conventional IVF (25.0%) cycles. CONCLUSIONS: We suggest that ICSI treatment is highly effective method to improve fertilization and pregnancy rate in IVF-ET program of male immunological infertility.     

Deficient syncytiotrophoblast tumour necrosis factor-alpha characterizes failing first trimester pregnancies in a subgroup of recurrent miscarriage patients

Pregnancy failure in mice has been associated with increased placental concentrations of the pro-inflammatory cytokine tumour necrosis factor- alpha (TNF-alpha). To investigate the role of uterine TNF-alpha in human first trimester miscarriage, we have collected human decidual and trophoblast tissue from women (i) undergoing surgical termination of pregnancy (n = 27), (ii) undergoing a sporadic miscarriage (n = 20) and (iii) with a history of recurrent pregnancy loss [>3 consecutive pregnancy losses (n = 26)] undergoing a further miscarriage. Formalin fixed tissues were examined for TNF-alpha mRNA (in-situ hybridization) and protein (immunohistochemistry). In decidua from all three groups, TNF-alpha protein and mRNA were co-localized to the decidual stroma, the luminal surface of some maternal vessels and to the glandular epithelium. Chorionic villi from the normal pregnancy and the sporadic miscarriage group exhibited co-localized TNF-alpha protein and mRNA in the syncytiotrophoblast and cytotrophoblast. In the recurrent miscarriage group, however, 63.6% of the biopsies showed positive immunostaining in only the cytotrophoblast, compared with 4.0% of women undergoing surgical termination of pregnancy and 0.0% of women with a sporadic failed pregnancy (P < 0.001). TNF-alpha mRNA was also localized exclusively to this layer. This may be a secondary effect caused by a different mechanism of pregnancy loss unique to this subgroup.      

Isolation and Characterization of Rat Trophoblast Cells

ABSTRACT: Previous immunohistochemical studies of the rat placenta using specific alloantisera and/or monoclonal antibodies showed that the basal zone trophoblasts stained for Pa and A^a class I major histocompatibility complex (MHC) antigens and for the human SP1-related antigen. In an effort to isolate the basal zone trophoblast cells from the rat placenta, we used these markers to assess the degree of purification of the cells separated by density gradient centrifugation using either Ficoll-Hypaque or Percoll as the gradient medium. The cells were put either on the top or at the bottom of discontinuous density gradients in the range of 1.005-1.10 or/ml. The cell separation profiles for the two media were different. With Percoll, most of the trophoblast cells (80–95%) were collected at the density gradients 1.04/1.06 and 1.06/1.08, whereas with Ficoll-Hypaque, these gradients separated only a small fraction (4–23%) of the trophoblast cells, and most of them pelleted at the bottom of the tube. The trophoblast cells separated by Ficoll-Hypaque, however, showed fewer contaminant cells than those separated by the Percoll gradients.     

Ontogeny of Expression of Pa and RT1.Aa Antigens on Rat Placenta and on Fetal Tissues

ABSTRACT: The unique pregnancy-associated (Pa) antigen, which is a class I antigen encoded by the major histocompatibility complex (MHC), elicits a nondestructive maternal antibody response. By contrast, the class I transplantation antigen RTI.A^a elicits a destructive antibody response in tissue transplantation but not during pregnancy. With the use of the avidin-biotin complex (ABC) immunohistochemical method, the Pa and RTl.A^a antigens were localized on the basophilic and giant cells of the basal zone trophoblast, the endovascular trophoblast and decidual interstitial trophoblast, and the chorioallantoic membrane but not on the labyrinthine zone trophoblast as early as the 12th day of gestation. These two antigens were also expressed on the epidermis, hair follicles, spleen, thymic medulla, bronchial epithelium, intestinal epithelium, the hepatic Kupffer cells, endocardium, endothelium of blood vessels, renal tubular cells and glomeruli, and renal pelvis and ureter of fetal and adult rat tissues. Absorption studies with placental tissue confirmed the presence of these two antigens in the rat placenta, and antibody-blocking studies confirmed their unique specificities.