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.     

Fine-needle aspiration of thyroid lesions in 57 pregnant and postpartum women

Palpable thyroid nodules are common in women. The thyroid gland may enlarge in response to hyperemia, relative iodine depletion, and slight stimulation by β Human Chorionic Gonadotrophin (HCG) during pregnancy. The presence of goiter or a discrete nodule requires investigation. Fine-needle aspiration (FNA), a reliable diagnostic tool, can be safely used during pregnancy. The tenet that a “histologic hyperplasia” accompanies the physiologic hyperplasia of pregnancy may hamper FNA interpretation. We reviewed 97 (10 previous, 46 pregnant, 13 postpartum, 1 spontaneous abortion, and 27 follow-up) aspirates of thyroid nodules from 57 patients. Cytologic diagnoses were divided into five categories: 31 benign, 7 cellular adenomatoid nodules, 5 suspicious for papillary carcinoma, 12 papillary carcinomas, and 2 follicular neoplasms. There were an unanticipated number of carcinomas. Lesions present before pregnancy did not show “progression” or significant change. No characteristic features ascribable to pregnancy were identified. Standard diagnostic criteria may be used in the evaluation of FNA of thyroid nodules from pregnant patients. Diagn. Cytopathol. 16:122–125, 1997. © 1997 Wiley-Liss, Inc.     

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.     

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.     

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.     

Comparison of Short-Duration and Chronic Premenarchal Vulvar Complaints

Study ObjectiveTo compare clinical characteristics, treatment histories, and microbiology of premenarchal girls who presented to a pediatric gynecology specialty clinic with short-duration and chronic vulvar symptoms.DesignRetrospective cohort study.SettingPediatric and adolescent gynecology clinic at a tertiary care children's hospital.ParticipantsOne hundred eighty-two premenarchal patients ages 2-14 years who presented to a pediatric gynecology specialty clinic with vulvar complaints and who were evaluated with a yeast and/or bacterial culture.InterventionsNone.Main Outcome MeasuresChronic and short-duration vulvar symptoms, microbiology, and diagnosis.ResultsPatients with chronic symptoms were more likely to present with itching (59/102 (57.8%) vs 34/80 (42.5%); P = .04), redness or rash (53/102 (52.0%) vs 22/80 (27.5%); P = .0009), and discomfort (59/102 (57.8%) vs 30/80 (37.5%); P = .006), compared with patients with short-duration symptoms. Overall, 44.5% of patients had a history of antifungal treatment, with a greater proportion of patients with chronic symptoms having received antifungal treatment compared with those with short-duration symptoms (53/102 (52.0%) vs 28/80 (35.0%); P = .02). Despite a history of antifungal treatment in nearly half of the patients, Candida albicans was isolated in only 3/144 (2.1%) yeast cultures. Bacterial vulvar cultures were positive in 75/159 (47.2%), and there was no difference among the symptom duration groups (38/71 (53.5%) vs 37/88 (42.1%); P = .15).ConclusionVulvovaginitis is a common gynecological diagnosis among premenarchal girls with short-duration and chronic vulvar symptoms. Regardless of symptom duration, yeast cultures are rarely positive. Antifungal treatment should be avoided in toilet-trained prepubertal girls.     

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.     

Composition of the HLA‐DR‐associated human thymus peptidome

Major histocompatibility complex class II (MHC‐II) molecules bind to and display antigenic peptides on the surface of antigen‐presenting cells (APCs). In the absence of infection, MHC‐II molecules on APCs present self‐peptides and interact with CD4⁺ T cells to maintain tolerance and homeostasis. In the thymus, self‐peptides bind to MHC‐II molecules expressed by defined populations of APCs specialised for the different steps of T‐cell selection. Cortical epithelial cells present peptides for positive selection, whereas medullary epithelial cells and dendritic cells are responsible for peptide presentation for negative selection. However, few data are available on the peptides presented by MHC molecules in the thymus. Here, we apply mass spectrometry to analyse and identify MHC‐II‐associated peptides from five fresh human thymus samples. The data show a diverse self‐peptide repertoire, mostly consisting of predicted MHC‐II high binders. Despite technical limitations preventing single cell population analyses of peptides, these data constitute the first direct assessment of the HLA‐II‐bound peptidome and provide insight into how this peptidome is generated and how it drives T‐cell repertoire formation.     

Molecular epidemiology,resistance profiles and clinical features in clinical plasmid-mediated AmpC-producing Enterobacteriaceae

During the 30 months of surveillance period, 85 pAmpC-producing isolates were detected (prevalence 0.56% overall): bla_CMY-2 gene in 70 E. coli, 2 K. pneumoniae and 6 P. mirabilis isolates; and the bla_DHA-1 gene in 4 E. coli and 3 K. pneumoniae. In 8.23% of them, other β-lactamases (predominantly OXA-1) were identified. All pAmpC-producing isolates were susceptible to carbapenems, whereas high resistance to nalidixic acid, ciprofloxacin and trimethoprim-sulfamethoxazole was observed among pAmpC-producing isolates (80%, 60%, and 44.7%, respectively). In hospital patients, predisposing factors such as prior antibiotic use, previous hospitalization, presence of an indwelling device, invasive urinary tract procedures and mechanical ventilation were observed. In the community setting, urinary tract infection was the most common type of infection related to pAmpC-producing isolates. A wide heterogeneity of clones was found among our E. coli isolates by PFGE, suggesting that this mechanism of resistance is not due to the dissemination of a clonal strain. Surveillance of these resistance mechanisms in the community is thus needed. Awareness of pAmpC dynamic is required to prevent introduction into hospitals and to control the spread of this emerging resistance within the community.