Coexistence of salivary gland cysticercosis with squamous cell carcinoma of the mandible.

Cysticercosis is a parasitic infestation caused by the pork tapeworm larval stage, Cysticercus cellulosae. The majority of the cases present in ocular, cerebral, and subcutaneous locations. We report the presence of cysticercosis inside the submandibular gland in association with squamous cell carcinoma of the inferior alveolar ramus of the mandible. To the best of our knowledge, this is the first case report documenting cysticercosis inside a salivary gland. A 65-year-old male presented with complaints of an ulcerative lesion on the inferior alveolar ramus present for 2 months. Histological examination revealed a keratinizing well-differentiated squamous cell carcinoma involving the alveolar margin and mandible. The histopathological examination of the submandibular gland revealed cysticercosis. This case emphasizes the importance of adequate sampling of all the tissues obtained for associated infectious disorders, more so in immunosuppressed patients, which will help the clinician to manage the case appropriately.     

Characterization of HLA DR3/DQ2 transgenic mice: a potential humanized animal model for autoimmune disease studies

Linkage studies indicate close associations of certain HLA alleles with autoimmune diseases. To better understand how specific HLA alleles are related to disease pathogenesis, we have generated an HLA DR3/DQ2 transgenic mouse utilizing a 550-kb yeast artificial chromosome (YAC) construct containing the complete DRalpha, DRbeta1, DRbeta3, DQalpha, and DQbeta regions. The transgenic mouse (4D1/C2D) in an I-Abeta(o) background appears healthy with no signs of autoimmune diseases. Lymphoid tissues as well as CD4(+) T cells develop normally. Characterization of the transgene expression demonstrates that approximately 90% of B cells express high levels of DR3 and 50-70% of B cells express DQ2. CD11c(+) dendritic cells express high levels of DR and DQ. Approximately 12-18% of resting T cells are positive for DR expression, and further up-regulation to 40-50% expression is seen upon activation with anti-CD3/anti-CD28 mAb. These results suggest that the transgenic construct confers a high fidelity to the normal human temporal and spatial expression profile. Analysis of T cell receptor repertoire in transgenic mice confirms that DR3/DQ2 are able to mediate thymic selection. Furthermore, transgenic mice respond to a DR3-restricted antigen, demonstrating antigen processing and presentation by antigen-presenting cells (APC). Purified T cells from ovalbumin (OVA)-immunized 4D1 mice respond to human APC co-cultured with OVA, suggesting appropriate antigen/DR3 or DQ2 recognition by murine T cells. Immunoglobulin isotype switching is also observed, indicating functional T-B cognate interactions. Thus, the DR3/DQ2 transgenic mouse has normal lymphoid development and functionality that are mediated by HLA transgenes and can be used to investigate HLA-associated immunological questions.     

Diagnostic role of fibreoptic bronchoscopy in pulmonary tuberculosis

Fibreoptic bronchoscopy with bronchial aspiration* washings and biopsy was performed in 104 patients suspected clinically and radio logically of having pulmonary tuberculosis diagnostic yield in 9230% (96/104) cases. Diagnostic yield for tuberculosis was in 69.22% (72/ 104) cases, it includes positive aspiration and washings smear in 38.46%(40/l04) patients,positive mycobacteriai culture alone in 26.92% (28/104) cases and positive biopsy in 3*84% (4/ 104) patients, Non-tuberculous conditions like pneumonia and bronchogenic carcinoma were diagnosed in 19.23% (20/104) cases and 3.84% (4/104) cases respectively. These results suggest that in areas with high prevalence of tuberculosis, bronchoscopy should be performed for early diagnosis and initiation of therapy in sputum smear-negative cases of pulmonary tuberculosis.     

CD4 cell counts in adults with newly diagnosed HIV infection in Barbados.

OBJECTIVE: To evaluate the absolute CD4 cell counts of all the newly diagnosed HIV-infected persons who presented at the Ladymeade Reference Unit (LRU), which serves as the national HIV/AIDS referral and treatment center for the country of Barbados. DESIGN AND METHODS: The study group was comprised of HIV-infected adults who had been diagnosed with HIV infection and referred to the LRU between January and December 2002. All the patients referred to the LRU had a CD4 cell count done at their first visit to the unit, as part of the routine workup to assess their disease status and need for antiretroviral therapy. RESULTS: Of the 106 newly diagnosed adults, 62 of them (58.5%) were males, who had a median age at presentation of 40 years; the other 44 of them (41.5%) were females, and their median age at presentation was 36 years. Nearly one-fifth (18.2%) of the females were aged 16-25 years, whereas only 8.1% of the males were in this age group. The majority (57.6%) of the study group were diagnosed because they presented with an HIV/AIDS-related illness. Overall, the median CD4 cell count at the time of diagnosis was 183/microL; 52 of 103 adults (50.5%) with a newly diagnosed HIV infection had a CD4 cell count that was < 200. Among males, the median CD4 cell count was 161/microL, and 32 (53.3%) of 60 males had CD4 cell counts < 200. In contrast, among females, the median CD4 cell count was 223, and 20 (46.5%) of 43 females had a CD4 cell count that was < 200/microL. However, this difference in the proportion of males and females with a CD4 cell count less than 200/microL was not statistically significant (P = 0.63). CONCLUSIONS: At the time of HIV diagnosis, over one-half of the adults had an initial CD4 cell count that was consistent with relatively advanced disease. Proportionally more women than men presented at a younger age, and proportionally more women than men presented in the early stages of the disease. These patterns indicate a clear need for enhanced educational efforts regarding the importance of HIV testing for at-risk individuals across Barbados. This testing could improve efforts to reduce transmission as well as the prognosis for patients who receive antiretroviral therapy.     

Structural basis for substrate discrimination by E. coli repair enzyme,AlkB

E. coli AlkB, a repair enzyme of the dioxygenase family, catalyses the removal of mutagenic methylated nucleotides from the genome. Known for substrate promiscuity, AlkB''s catalytic mechanism and conformational changes accompanying substrate binding have been extensively dissected. However, the structural parameters of various substrates governing their recognition by AlkB still remain elusive. In this work, through solution-state vibrational spectra of methylated substrates bound to AlkB in combination with computational analysis, we show that the recognition specificity is dictated by the protonation states of the substrates. Specificity is conferred predominantly through hydrogen bonding and cation–π interactions. Furthermore, we report on the interaction of AlkB with normal, unmodified nucleotides, wherein the presence of an exocyclic amino group serves as an essential criterion for the initial process of substrate recognition. Taken together, these results provide a rationale for structural determinants of substrate specificity as well as mode of lesion discrimination employed by AlkB.

Positive charge on methylated nucleotides is a prime criterion for substrate recognition by E. coli AlkB.     

The Diagnosis of Concussion in Pediatric Emergency Departments: A Prospective Multicenter Study

Background

The accurate identification of children with a concussion by emergency physicians is important to initiate appropriate anticipatory guidance and management.

A genome-wide association study of antidepressant response in Koreans

We conducted a three-stage genome-wide association study (GWAS) of response to antidepressant drugs in an ethnically homogeneous sample of Korean patients in untreated episodes of nonpsychotic unipolar depression, mostly of mature onset. Strict quality control was maintained in case selection, diagnosis, verification of adherence and outcome assessments. Analyzed cases completed 6 weeks of treatment with adequate plasma drug concentrations. The overall successful completion rate was 85.5%. Four candidate single-nucleotide polymorphisms (SNPs) on three chromosomes were identified by genome-wide search in the discovery sample of 481 patients who received one of four allowed selective serotonin reuptake inhibitor (SSRI) antidepressant drugs (Stage 1). In a focused replication study of 230 SSRI-treated patients, two of these four SNP candidates were confirmed (Stage 2). Analysis of the Stage 1 and Stage 2 samples combined (n=711) revealed GWAS significance (P=1.60 × 10^-8) for these two SNP candidates, which were in perfect linkage disequilibrium. These two significant SNPs were confirmed also in a focused cross-replication study of 159 patients treated with the non-SSRI antidepressant drug mirtazapine (Stage 3). Analysis of the Stage 1, Stage 2 and Stage 3 samples combined (n=870) also revealed GWAS significance for these two SNPs, which was sustained after controlling for gender, age, number of previous episodes, age at onset and baseline severity (P=3.57 × 10^-8). For each SNP, the response rate decreased (odds ratio=0.31, 95% confidence interval: 0.20–0.47) as a function of the number of minor alleles (non-response alleles). The two SNPs significantly associated with antidepressant response are rs7785360 and rs12698828 of the AUTS2 gene, located on chromosome 7 in 7q11.22. This gene has multiple known linkages to human psychological functions and neurobehavioral disorders. Rigorous replication efforts in other ethnic populations are recommended.