Interferon-gamma differentially regulates antigen-processing functions in distinct endocytic compartments of macrophages with constitutive expression of class II major histocompatibility complex molecules

Treatment of pregnant female Sprague-Dawley rats on Gestational Day 15 with a single oral dose of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (0.5, 1.0, or 2.0 micrograms/kg) or indole-3-carbinol (I3C, 1.0 or 100 mg/kg), an aryl hydrocarbon (Ah) receptor agonist which is found in cruciferous vegetables, resulted in reproductive abnormalities in the male offspring (three to five litters in each treatment group). Anogenital distance and crown to rump length were altered by both compounds; however, the timing of the effects (Day 1 or 5) was variable and the responses were not necessarily dose-dependent. In 62-day-old offspring, seminal vesicle (24 to 26%), prostate (32 to 44%), testicular parenchymal (14%), and epididymal weight (19%) were decreased by one or more doses of TCDD. In contrast, I3C at one or more doses decreased daily sperm production/g testicular parenchyma (13 to 20%) and daily sperm production/testis (22%). Total number of sperum in the epididymis was significantly decreased (30 to 33%) in rats perinatally exposed to TCDD and this was due to a decreased (49 to 51%) number of sperm in the tail of the epididymis. Perinatal exposure to I3C did not affect any of these parameters. TCDD did not affect epididymal transit time of sperm through the complete epididymis at any of the doses (0.5 to 2.0 micrograms/kg). However, at the two highest doses (1.0 and 2.0 micrograms/kg), TCDD increased epididymal transit rate of sperm through the tail of the epididymis by 33 and 37%, respectively. In contrast, primarily due to decreased transit rate (39%) of sperm through the head plus body of the epididymis. I3C (1 mg/kg) significantly increased total epididymal transit time by 31%. In conclusion, perinatal exposure of pregnant rats to I3C, an Ah receptor agonist similar to TCDD, causes reproductive abnormalities in male rat offspring; however, I3C and TCDD elicited both common and different responses.     

Margatoxin increases dopamine release in rat striatum via voltage-gated K+ channels

The distribution of iodinated margatoxin ([125I]margatoxin) binding sites in rat was investigated by autoradiography. Rat striatum expresses a high density of margatoxin binding sites and, therefore, the effects of margatoxin, charybdotoxin and iberiotoxin have been studied on [3H]dopamine release from rat striatal slices in vitro. Margatoxin (0.1-100 nM) and charybdotoxin (10-1000 nM), but not iberiotoxin increased the spontaneous and the electrically evoked [3H]dopamine release. [3H]dopamine release by margatoxin was inhibited by tetrodotoxin and omega-conotoxin GVIA, but not by atropine, naloxone, N(omega)-nitro-L-arginine and neurokinin or neurotensin receptor antagonists. In the buffer solution used for release experiments, [125I]margatoxin labels a maximum of 0.12 pmol of sites/mg protein in rat striatal membranes with a Kd of 5 pM. [125I]margatoxin binding was inhibited by margatoxin (Ki of 4 pM), charybdotoxin (Ki of 162 pM) but not by iberiotoxin. We conclude that inhibition of margatoxin-sensitive voltage-gated K+ channels increases [3H]dopamine release demonstrating their role in repolarization of nigrostriatal projections. In contrast, iberiotoxin-sensitive, high-conductance Ca2+-activated K+ channels are not involved in release of [3H]dopamine.     

Continuing medical education via questionnaire studies. Three pilot projects for anesthesiology, cardiology and neurology

The Danish Medical Association and the scientific societies have initiated three studies to evaluate the use of questionnaires for continuous medical education. One study was a questionnaire in anaesthesiology with 30 questions with answers yes/no/no answer, which was sent to 600 specialists in anaesthesiology. One study was in cardiology with a multiple choice questionnaire, sent to 300 general practitioners and 75 specialists in internal medicine outside cardiology. One study concerned the educational value of State-of-the-Art articles about neurology in Ugeskrift for Laeger (Journal of the Danish Medical Association) sent to 500 doctors outside neurology. All questionnaires were sent anonymously, with one general reminder. For the anaesthesiology study 234 questionnaires were returned (40.5%). In the cardiology study 195 questionnaires were returned (52%). For the study on neurology 278 answered (56%). Only about half of the questionnaires were returned for the three studies, and a lot of effort and resources were put into the studies. An extension from these small pilot studies to a general systematic continuous methodology with updated questionnaires in the postgraduate medical education seems troublesome. An optional self-registration for medical education such as The Canadian "Mocomp concept" might be a more realistic suggestion.     

What are the symptoms of varicose veins? Edinburgh vein study cross sectional population survey

OBJECTIVE: To define the relations between age, sex, lower limb symptoms, and the presence of trunk varicose veins on clinical examination. DESIGN: Cross sectional population study. SETTING: 12 general practices with catchment areas geographically and socioeconomically distributed throughout Edinburgh. PARTICIPANTS: An age stratified random sample of 1566 people (699 men and 867 women) aged 18-64 selected from the computerised age-sex registers of participating practices. MAIN OUTCOME MEASURES: Self administered questionnaire on the presence of lower limb symptoms and physical examination to determine the presence and severity of varicose veins. RESULTS: Women were significantly more likely than men to report lower limb symptoms such as heaviness or tension, swelling, aching, restless legs, cramps, and itching. The prevalence of symptoms tended to increase with age in both sexes. In men, only itching was significantly related to the presence and severity of trunk varices (linear test for trend, P=0.011). In women there was a significant relation between trunk varices and the symptoms of heaviness or tension (P相似文献   

Two aspects of the therapeutic alliance: Differential relations with depressive symptom change.

Objective: The therapeutic alliance has been linked to symptom change in numerous investigations. Although the alliance is commonly conceptualized as a multidimensional construct, few studies have examined its components separately. The current study explored which components of the alliance are most highly associated with depressive symptom change in cognitive therapy (CT). Method: Data were drawn from 2 published randomized, controlled clinical trials of CT for major depressive disorder (n = 105, mean age = 40 years, female = 62%, White = 82%). We examined the relations of 2 factor-analytically derived components of the Working Alliance Inventory (WAI; Horvath & Greenberg, 1986, 1989) with symptom change on the Beck Depression Inventory—II (BDI–II; Beck, Steer, & Brown, 1996) that occurred either prior to or subsequent to the examined sessions. WAI ratings were obtained at an early and a late session for each therapist–patient dyad. Results: Variation in symptom change subsequent to the early session was significantly related to the WAI factor that assesses therapist–patient agreement on the goals and tasks of therapy but not to a factor assessing the affective bond between therapist and patient. In contrast, both factors, when assessed in a late session, were significantly predicted by prior symptom change. Conclusions: These findings may reflect the importance, in CT, of therapist–patient agreement on the goals and tasks of therapy. In contrast, the bond between therapist and patient may be more of a consequence than a cause of symptom change in CT. The implications of these results and directions for future research are discussed. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Development of monoclonal gammopathy precedes the development of Epstein-Barr virus-induced posttransplant lymphoproliferative disorder

Epstein-Barr virus (EBV)-induced posttransplant lymphoproliferative disorder (PTLD) develops in 3% to 10% of solid organ transplant recipients with a resultant mortality of up to 70%. Unfortunately, there is no current marker which identifies patients who will develop this disease. We therefore conducted a risk factor analysis of variables that might predict the development of PTLD. Specifically, since EBV may cause both PTLD and the development of monoclonal proteins (M protein), we sought to determine if the development of an M protein preceded and therefore might serve as a predictive marker of subsequent PTLD. Before and after liver transplantation, 201 patients were evaluated for the presence of urine and serum M proteins. Patients were followed to monitor the development of PTLD for a mean of 1,733 days. PTLD developed in seven patients (3.5%), three (43%) of whom died from disseminated PTLD. PTLD was classified as polymorphous in six patients and monomorphous in one patient. Fifty-seven patients (28%) developed an M protein after transplantation: five of seven patients (71%) with PTLD and 52/194 (27%) of patients without PTLD. Multivariate risk factor analysis for the development of an M protein after transplantation identified cytomegalovirus (CMV) donor seropositivity (P = 0.0002) and postoperative symptomatic CMV infection (P = 0.019) as risk factors. Whereas EBV serostatus of either the donor or recipient was not found to be a risk factor for the occurrence of either an M protein or PTLD, the development of a serum immunoglobulin M (IgM) M protein (P = 0.04) and of any urine M protein (P = 0.01) was identified by univariate analysis as being associated with the development of PTLD. Further studies are needed to determine the predictive value of M proteins as a marker for PTLD. Until such time, the development of serum or urine M protein should heighten the suspicion of developing PTLD.     

The evolving health care system: the role of the Health Resources and Services Administration

The toxicity of Atrazine and that of its Desethylatrazine metabolite has been defined employing two organisms already tested in our labs the Dugesia gonocephala, belonging to a scissiparous strain coming from the island of Tavolara (Sardinia) and the Thamnocephalus platyurus, crustacean anostracan produced under form of quiescent cysts from Creasel Ltd. (Deinze, Belgium). It has been defined the lethal concentrations at 50% of Atrazine and of Desethylatrazine, of which it has been studied also the report dose-effect in the comparisons of the rectilinear motility. The results highlight that in the comparisons of the T. platyurus Atrazine expounds a toxicity of around three times that of its metabolite; this is not seen with the Planarians that are equally sensitive to both the compounds. The use of these two experimental models for the evaluation of the contamination of bodies of water is shown to be particularly useful given their great sensitivity to pollutants.     

The activity of ENU, iPMS and MMS in male mouse germ cells using the Muta Mouse positive selection transgenic mutation assay

The alkylating agents ethyl nitrosourea (ENU), isopropyl methanesulphonate (iPMS) and methyl methanesulphonate (MMS) are potent male rodent germ cell mutagens. The mutagenic activity of these compounds in male mouse germ cells has been evaluated using the Muta Mouse positive selection transgenic mutation assay. Both ENU (150 mg/kg) and iPMS (100 mg/kg) gave increased mutant frequencies in testicular DNA recovered 50 days after dosing. During the course of the mutation assays on iPMS its activity as a dominant lethal mutagen was confirmed by mating the treated animals with virgin (non-transgenic) females on day 10 post-dosing. Ova analysis on animals exposed to iPMS confirmed earlier reports that the dose level used caused sterility in mice 40 days after dosing. This sterility was shown to be due to aspermia in the treated mice at day 50 post-dosing. These collected findings indicate that at day 50 post-dosing with iPMS, mutations in testicular DNA can be observed in sterile animals. MMS (100 mg/kg) was not mutagenic to either testicular DNA or epididymal sperm DNA, 10 or 50 days, respectively, after dosing.     

Association of a redefined proximal mouse chromosome 11 imprinting region and U2afbp-rs/U2af1-rs1 expression

Mice with maternal and paternal disomy for chromosome 11 (Chr 11) show growth retarded and overgrowth phenotypes, respectively, which can be attributed to genomic imprinting. Previous studies have defined the region of Chr 11 responsible (the Chr 11 imprinting region) as lying proximal to the T30H translocation breakpoint at the borders of G-bands 11B1.2 and 11B1.3. Evidence is presented here with two new translocations, T57H and T41Ad, which sequentially reduce the size of the imprinting region and locate it proximal to the T41Ad breakpoint in G-band 11A3.2. It therefore lies close to the centromere. The imprinted gene, U2af1-rs1, is known to be located within the original region and has been regarded as a candidate for the imprinting effects. Meiotic and mitotic chromosome FISH analysis, together with U2af1-rs1 expression studies are now described which show that the gene lies within the newly defined imprinting region and that its expression levels relate to the presence/absence and number of functional paternal alleles. U2af1-rs1 therefore remains a candidate gene for the Chr 11 imprinting effects. However, another recently reported imprinted gene, Meg1/Grb10, that lies within the region is also a good candidate, as it encodes a growth factor receptor. Meg1/Grb10 maps about 15 cM from U2af1-rs1 and is separated by conserved regions showing homology with two different human chromosomes. For these reasons, and because the two human homologues of U2af1-rs1 and Meg1/Grb10 also lie on different chromosomes, it would seem likely that the two genes identify two distinct imprinting domains within the small proximal region of mouse Chr 11.