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Chlamydiaspecies cause a broad spectrum of diseases in humans including severe chronic sequelae related to persistent forms. Despite the lack of detectable amounts of peptidoglycan, several studies suggest the presence of small quantities of peptidoglycan or its derivative at least in some stages of the growth cycle. Based on recent discovery in Chlamydiaeof the aminotransferase pathway for biosynthesis of meso-diaminopimelic acid, we demonstrated the up-regulation of the gene (cp0259) encoding L,L-diaminopimelate aminotransferase in chlamydial persistent forms. This finding may be important in the search for target molecules to diagnose and treat Chlamydia-associated chronic diseases.

Two histidine residues in glutamate decarboxylase from Escherichia coli, potential participants in catalysis because they are conserved among amino acid decarboxylases and because they are at the active site in the homologous enzyme ornithine decarboxylase, were mutated. His-275 is shown to bind the cofactor pyridoxal 5'-phosphate but not to contribute directly to catalysis. The H275N enzyme was unable to bind the cofactor whereas the H275Q mutant contained 50% of the normal complement of cofactor and its specific activity (expressed per mole of cofactor) was 70% of that of the wild-type enzyme. The H167N mutant bound the cofactor tightly, its specific activity was approximately half that of the wild-type enzyme and experiments in D2O showed that it catalyzed replacement of the carboxyl group with retention of configuration as does the wild-type enzyme. Comparison of reaction profiles by observing changes in the absorbance of the cofactor after stopped-flow mixing, revealed that a slow reaction, in which approximately one-third of the wild-type enzyme is converted to an unreactive complex during catalysis, does not occur with the H167N mutant enzyme. This reaction is attributed to a substrate-induced conformational change, a proposal that is supported by differential scanning calorimetry.

Background As yet, no population-based prospective studies have been conducted to investigate the incidence and clinical outcome of glioblastoma (GBM) or the diffusion and impact of the current standard therapeutic approach in newly diagnosed patients younger than aged 70 years. Methods Data on all new cases of primary brain tumors observed from January 1, 2009, to December 31, 2010, in adults residing within the Emilia-Romagna region were recorded in a prospective registry in the Project of Emilia Romagna on Neuro-Oncology (PERNO). Based on the data from this registry, a prospective evaluation was made of the treatment efficacy and outcome in GBM patients. Results Two hundred sixty-seven GBM patients (median age, 64 y; range, 29–84 y) were enrolled. The median overall survival (OS) was 10.7 months (95% CI, 9.2–12.4). The 139 patients ≤aged 70 years who were given standard temozolomide treatment concomitant with and adjuvant to radiotherapy had a median OS of 16.4 months (95% CI, 14.0–18.5). With multivariate analysis, OS correlated significantly with KPS (HR = 0.458; 95% CI, 0.248–0.847; P = .0127), MGMT methylation status (HR = 0.612; 95% CI, 0.388–0.966; P = .0350), and treatment received in a high versus low-volume center (HR = 0.56; 95% CI, 0.328–0.986; P = .0446). Conclusions The median OS following standard temozolomide treatment concurrent with and adjuvant to radiotherapy given to (72.8% of) patients aged ≤70 years is consistent with findings reported from randomized phase III trials. The volume and expertise of the treatment center should be further investigated as a prognostic factor.