Unusual mixed gonadal dysgenesis associated with Müllerian duct persistence, polygonadia, and a 45,X/46,X,idic(Y)(p) karyotype

Mixed gonadal dysgenesis (MGD) is a developmental anomaly in which most of the patients have a dysgenetic testis, a contralateral streak and a 45,X/46,XY karyotype. This entity involves an heterogeneous group of gonadal and phenotypic abnormalities with a wide clinical spectrum. The phenotype depends on the ratio of testicular tissue which induces virilization. Although the karyotype in these patients is 45,X/46,XY, no genotype-phenotype correlation has been found to date. Müllerian ducts persistence (MDP) in MGD is rare; however, four patients with both entities and different karyotypes have been described. Here we present the data on a newborn patient with an atypical MGD associated with MDP, two left testes, a gonadal streak on the right, and absence of Wolffian derivatives. PCR analysis identified all the Y-derived sequence tested in the father, while the patient had them all except the AZF b,c regions which were lost. FISH analysis of the paternal Y chromosome documented Yq paracentric inversion while the patient's karyotype was 45,X/46,X,idic(Yp). No mutations were observed in MIS/MISRII genes.     

Bordetella bronchiseptica flagellin is a proinflammatory determinant for airway epithelial cells

Motility is an important virulence phenotype for many bacteria, and flagellin, the monomeric component of flagella, is a potent proinflammatory factor. Of the three Bordetella species, Bordetella pertussis and Bordetella parapertussis are nonmotile human pathogens, while Bordetella bronchiseptica expresses flagellin and causes disease in animals and immunocompromised human hosts. The BvgAS two-component signal transduction system regulates phenotypic-phase transition (Bvg+, Bvg-, and Bvg(i)) in bordetellae. The Bvg- phase of B. bronchiseptica is characterized by the expression of flagellin and the repression of adhesins and toxins necessary for the colonization of the respiratory tract. B. bronchiseptica naturally infects a variety of animal hosts and constitutes an excellent model to study Bordetella pathogenesis. Using in vitro coculture models of bacteria and human lung epithelial cells, we studied the effects of B. bronchiseptica flagellin on host defense responses. Our results show that B. bronchiseptica flagellin is a potent proinflammatory factor that induces chemokine, cytokine, and host defense gene expression. Furthermore, we investigated receptor specificity in the response to B. bronchiseptica flagellin. Our results show that B. bronchiseptica flagellin is able to signal effectively through both human and mouse Toll-like receptor 5.     

Cyclooxygenase-2 protein reduces tamoxifen and N-(4-hydroxyphenyl)retinamide inhibitory effects in breast cancer cells

Approximately 30-40% of estrogen receptor alpha (ERalpha)-positive breast tumors express high levels of the cyclooxygenase-2 (COX-2) protein, and these high levels have been associated with a poorer prognosis in breast cancer patients. We speculate that high levels of COX-2 induce drug resistance in ERalpha-positive breast tumors, thus reducing the survival rate of patients with such tumors. Human breast cancer cell lines that express high levels of COX-2 are generally ERalpha negative. To determine whether COX-2 induces drug resistance, plasmids encoding the COX-2 gene were stably transfected into ERalpha-positive MCF-7 human breast cancer cells (MCF-7/COX-2). MCF-7/COX-2 cells were resistant to the selective estrogen receptor modulator tamoxifen but not to its analog, raloxifene. MCF-7/COX-2 cells were also resistant to the retinoid N-(4-hydroxyphenyl)retinamide (4-HPR) but not to its analog, all-trans retinoic acid. In contrast, the sensitivities of MCF-7/COX-2 cells to doxorubicin and paclitaxel were similar to those of the parental MCF-7 cells. We then determined which COX-2 product, prostaglandin E2 (PGE2) or prostaglandin F2alpha is involved in the COX-2-mediated drug resistance. PGE2, but not PGF2alpha, blocked the antiproliferative effects of tamoxifen and 4-HPR. Agonists that activate PGE2 receptors and their downstream kinase effectors, protein kinases A and C, also blocked the growth inhibitory effects of these drugs. Increased levels of Bcl-2 and Bcl-XL proteins have been reported in mammary tumors of COX-2 transgenic mice and in human colon cancer cell lines that have high levels of COX-2. However, we did not observe any changes in Bcl-2, Bcl-XL, or Bax expression induced by COX-2 or PGE2. Here we report the novel findings that COX-2 uses PGE2 to stimulate the activities of protein kinases A and C to induce selectively tamoxifen and 4-HPR resistance in ERalpha-positive breast cancer cells.     

Complementary tasks to measure working memory in distinct prefrontal cortex subregions in rats

Acquisition of odor-guided or visually-guided delayed win-shift behavior was evaluated in rats after lidocaine-induced inactivation within the agranular insular area of the prefrontal cortex (PFC) or the prelimbic area of the PFC. Additional sites and tasks were used to control for neuroanatomical and behavioral specificity of lidocaine inactivation of the agranular insular and prelimbic areas. Results showed that acquisition of the odor-guided delayed win-shift task was dependent on the agranular insular area, whereas acquisition of the visually-guided version was dependent on the prelimbic area. This dissociation suggests that the stimulus modality used is critical for revealing working memory functions of different PFC subregions. The described methods provide a complementary means to study working memory in PFC subregions using a radial-arm maze.     

Student perspectives on diversity and the cultural climate at a U.S. medical school.

PURPOSE: To obtain the perspectives of medical students at one school on racial/ethnic campus diversity and cultural competence and to gain their perceptions of the institutional climate around diversity at their university and of reasons for minority underrepresentation at their medical school. METHOD: A student-driven survey of all medical students (N = 398) at a single medical school in the spring of 2003, supplemented by four focus groups from all racial and ethnic groups on the campus. RESULTS: A large majority of the responding students (n = 216; 54%) endorsed the value of campus diversity and the importance of cultural competence to the process of becoming a clinician. Most students felt their university had achieved a positive cultural climate, characterized by openness to diverse perspectives and attention to equity. Most students also felt that the university's programs and policies reflected a commitment to diversity, but fewer students--those from underrepresented minorities (URMs) in particular--felt that the university truly valued having a diverse student body and faculty. Most students felt that the lack of diversity on campus was a barrier to recruiting and retaining minority candidates. Some minority students also blamed the medical school's limited social, academic, and financial support, as well as inadequate efforts to recruit minority students. CONCLUSIONS: Medical students generally place a high value on campus diversity and cultural competence. URM students in particular felt that their university could do more to implement its commitment to diversity, including making greater efforts to recruit and retain URM students. These views constitute a barometer for medical schools to gauge and track their efforts to enhance campus diversity, incorporate cultural competence education, and create an inclusive and welcoming climate for students of all backgrounds.     

Using common sense model in eating disorders

The aim of this study was to explore the relationships proposed in the Common Sense Model (CSM) in eating disorder (ED) patients. Method: 98 female (ED) patients completed measures of illness representation and psychosocial adjustment. Results: The confirmatory structural equation analysis revealed that illness representation dimensions were predictors of psychosocial adjustment. The hypothesis that coping mediates the relationship between illness representation and adjustment could not be confirmed. Conclusions: It may be helpful to consider the relationships between illness representation and adjustment when carrying out therapeutic work with these patients.     

Complex distal 10q rearrangement in a girl with mild intellectual disability: follow up of the patient and review of the literature of non-acrocentric satellited chromosomes

We report on an intellectually disabled girl with a de novo satellited chromosome 10 (10qs) and performed a review of the literature of the non-acrocentric satellited chromosomes (NASC). Satellites and stalks normally occur on the short arms of acrocentric chromosomes; however, the literature cites several reports of satellited non-acrocentric chromosomes, which presumably result from a translocation with an acrocentric chromosome. This is, to our knowledge, the third report of a 10qs chromosome. The phenotype observed in the proband prompted a search for a structural rearrangement of chromosome 10q. By microsatellite analysis we observed a 4 Mb deletion on the long arm of chromosome 10, approximately 145 kb from the telomere. FISH and array CGH analyses revealed a complex rearrangement involving in range from the centromere to the telomere: A 9.64 Mb 10q26.11-q26.2 duplication, a 1.3 Mb region with no copy number change, followed by a 5.62 Mb 10q26.2-q26.3 deletion and a translocation of satellite material. The homology between the repeat sequences at 10q subtelomere region and the sequences on the acrocentric short arms may explain the origin of the rearrangement and it is likely that the submicroscopic microdeletion and microduplication are responsible for the abnormal phenotype in our patient. The patient presented here, with a 15-year follow-up, manifests a distinct phenotype different from the 10q26 pure distal monosomy and trisomy syndromes.