Cigarette tar yield and risk of upper digestive tract cancers: case-control studies from Italy and Switzerland.

BACKGROUND: Tobacco smoking is one of the main risk factors for oral, pharyngeal and oesophageal cancers in developed countries. Information on the role of the tar yield of cigarettes in upper digestive tract carcinogenesis is sparse and needs to be updated because the tar yield of cigarettes has steadily decreased over the last few decades. PATIENTS AND METHODS: We analysed two case-control studies, from Italy and Switzerland, conducted between 1992 and 1999, involving 749 cases of oral and pharyngeal cancer and 1770 controls, and 395 cases of squamous-cell oesophageal carcinoma and 1066 matched controls. Odds ratios (ORs) were estimated by unconditional multiple logistic regression models, including terms for age, sex, study centre, education and alcohol consumption. RESULTS: Based on the brand of cigarettes smoked for the longest time, the multivariate ORs for current smokers compared with never smokers were 6.1 for <20 mg and 9.8 for >or=20 mg tar for oral and pharyngeal neoplasms, and 4.8 and 5.4 for oesophageal cancer, respectively. For the cigarette brand smoked in the previous six months, the ORs for >or=10 mg compared with <10 mg were 1.9 for cancer of the oral cavity and pharynx and 1.8 for oesophageal cancer, after allowance for number of cigarettes and duration of smoking. CONCLUSIONS: The present study confirms the direct relationship between the tar yield of cigarettes and upper digestive tract neoplasms, and provides innovative information on lower tar cigarettes, which imply reduced risks compared with higher tar ones. However, significant excess risks were observed even in the lower tar category, thus giving unequivocal indications for stopping smoking as a priority for prevention of upper digestive tract neoplasms.     

Risk of cancer other than Kaposi's sarcoma and non-Hodgkin's lymphoma in persons with AIDS in Italy. Cancer and AIDS Registry Linkage Study.

Record linkage was carried out between the national Registry of AIDS and 13 Cancer Registries (CRs) covering, in 1991, about 15% of the Italian population. Observed and expected numbers of cancers and standardized incidence ratios (SIRs) were assessed in 6067 persons with AIDS, for a total of 25,759 person-years. Significantly increased SIRs were found for Hodgkin''s disease [8.9, 95% confidence interval (CI) 4.4-16.0], in which seven of 11 cases were of mixed cellularity type; invasive carcinoma of the cervix uteri (15.5; 95% CI 4.0-40.1); and non-melanomatous skin cancer (3.0, 95% CI 1.3-5.9), in which five of eight cases were basal cell carcinoma. An excess was also seen for brain tumours, but this may be partly due to misdiagnosis of brain non-Hodgkin''s lymphoma or other brain diseases occurring near the time of the AIDS diagnosis. The risk for all cancer types, after exclusion of Kaposi''s sarcoma (KS) and non-Hodgkin''s lymphoma (NHL), was approximately twice the general population risk. An increased SIR for Hodgkin''s disease in persons with AIDS is thus confirmed, though it is many times smaller than that for NHL. An association with invasive carcinoma of the cervix is also shown at a population level. The excess of non-melanomatous skin cancer seems to be lower than in transplant recipients.     

Importance of cell-matrix interactions in rat islet beta-cell secretion in vitro: role of alpha6beta1 integrin

It has long been recognized that islet cell function is rapidly altered in vitro, but can be maintained, at least in part, when cells are layered on defined extracellular matrices. The present work addresses the influence of short-term cell-matrix interactions on islet beta-cell function and provides first insight into the molecular basis of these interactions. When primary rat beta-cells were allowed to attach to a matrix produced by a rat carcinoma cell line (804G), there was an increased insulin secretory response to secretagogues. This change was the result of an increase in the proportion of actively secreting beta-cells and in the amount of insulin secreted per active cell, as shown using the reverse hemolytic plaque assay. In turn, the spreading or flattening of beta-cells on this matrix was enhanced by secretagogues, and flattened cells secreted more insulin than rounded cells. Using indirect immunofluorescence, it was found that 1)alpha6beta1 integrins are present at the surface of islet cells in situ, 2) alpha6beta1 expression is heterogeneous among purified beta-cells and is upregulated by insulin secretagogues, 3) alpha6beta1 expression is higher in spreading cells, and 4) anti-alpha6beta1-specific antibodies decrease spreading. These observations demonstrate that islet cell-matrix interactions can improve the sensitivity of insulin cells to glucose and are mediated, at least in part, by alpha6beta1 integrins, suggesting that outside-in signaling through alpha6beta1 integrin plays a major role in the regulation of beta-cell function.     

Information processing in the spinocerebellar system

The purpose of this study was to determine whether sensory information about limb kinematics relayed to the cerebellum over spinocerebellar pathways may be modified at the cerebellar level. We tested this by recording from dorsal spinocerebellar tract (DSCT) and Purkinje cells under the same experimental conditions in which the hindlimbs of anesthetized cats were passively moved through a series of step-like movement cycles. A population analysis of the response behavior showed that DSCT neurons encode a combination of limb axis position and movement velocity, whereas the Purkinje cells located in the DSCT cerebellar target areas encode limb axis velocity and position independently. We conclude from this that the cerebellum may somehow extract a velocity component from the afferent input signal.     

Cooperative cytotoxicity of proteasome inhibitors and tumor necrosis factor-related apoptosis-inducing ligand in chemoresistant Bcl-2-overexpressing cells.

PURPOSE: Bcl-2 overexpression is frequently detected in lymphoid malignancies, being associated with poor prognosis and reduced response to therapy. Here, we evaluated whether Bcl-2 overexpression affects the cytotoxic activity of proteasome inhibitors taken alone or in association with conventional anticancer drugs or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). EXPERIMENTAL DESIGN: Jurkat cells engineered to overexpress Bcl-2 were treated with proteasome inhibitors (MG132, epoxomicin, and bortezomib), anticancer drugs (etoposide and doxorubicin), TRAIL, or combinations of these compounds. Cell death and loss of mitochondrial transmembrane potential were detected by flow cytometry. Cytosolic relocalization of cytochrome c and SMAC/Diablo, caspase cleavage, and Bcl-2 and Mcl-1 levels were determined by immunoblotting. Nuclear factor-kappaB inhibition was done by retroviral transduction with a dominant-negative mutant of IkappaBalpha. RESULTS: Bcl-2 overexpression results in significant inhibition of apoptosis in response to proteasome inhibitors, antiblastics, and TRAIL. Addition of TRAIL to proteasome inhibitors results in a synergistic cytotoxic effect in Bcl-2-overexpressing cells, whereas this result is not reproduced by the combination of proteasome inhibitors with antiblastic drugs. Importantly, proteasome inhibitors plus TRAIL induce mitochondrial dysfunction irrespective of up-regulated Bcl-2. Bcl-2 cleavage to a fragment with putative proapoptotic activity and elimination of antiapoptotic Mcl-1 may both play a role in proteasome inhibitors-TRAIL cooperation. Conversely, nuclear factor-kappaB inhibition by proteasome inhibitors is per se insufficient to explain the observed synergy. CONCLUSIONS: Combined proteasome inhibitors and TRAIL overcome the apoptotic threshold raised by Bcl-2 and may prove useful in the treatment of chemoresistant malignancies with up-regulated Bcl-2.     

Indexing of Fatty Acids in Poultry Meat for Its Characterization in Healthy Human Nutrition: A Comprehensive Application of the Scientific Literature and New Proposals

Chicken meat is becoming the most consumed in the world for both economic and nutritional reasons; regarding the latter, the lipid profile may play positive or negative roles in the prevention and treatment of diseases. In this study, we define the state of the art of lipid-based nutritional indexes and used the lipid content and fatty acid profile (both qualitative and quantitative) of breast meat of two poultry genotypes with different growth rates and meat traits. Further, we summarize and review the definitions, implications, and applications of nutritional indexes used in recent years and others of our own design to provide a useful tool to researchers working in the field of meat quality (not only in poultry) to select the most appropriate index for their own scientific purposes. All indexes show advantages and disadvantages; hence, a rational choice should be applied to consider the nutritional effect of meat on human health and for a possible assessment of the most suitable rearing systems (genotype, feeding, farming system or postmortem handling).     

Antiproliferative oleanane saponins from Meryta denhamii

Eight new oleanane saponins (1- 8) together with four know saponins (9-12) were isolated from the aerial parts of Meryta denhamii. Their structures were elucidated by 1D and 2D NMR experiments including 1D TOCSY, DQF-COSY, ROESY, HSQC, and HMBC spectroscopy, as well as ESIMS analysis. The antiproliferative activity of all compounds was evaluated using three murine and human cancer cell lines: J774.A1, HEK-293, and WEHI-164.     

Searching for bridges between psychopathology and real-world functioning in first-episode psychosis: A network analysis from the OPTiMiSE trial

BackgroundNetwork analysis has been used to explore the interplay between psychopathology and functioning in psychosis, but no study has used dedicated statistical techniques to focus on the bridge symptoms connecting these domains. The current study aims to estimate the network of depressive, negative, and positive symptoms, general psychopathology, and real-world functioning in people with first-episode schizophrenia or schizophreniform disorder, focusing on bridge nodes.MethodsBaseline data from the OPTiMiSE trial were analyzed. The sample included 446 participants (age 40.0 ± 10.9 years, 70% males). The network was estimated with a Gaussian graphical model, using scores on individual items of the positive and negative syndrome scale (PANSS), the Calgary depression scale for schizophrenia, and the personal and social performance scale. Stability, strength centrality, expected influence (EI), predictability, and bridge centrality statistics were computed. The top 20% scoring nodes on bridge strength were selected as bridge nodes.ResultsNodes from different rating scales assessing similar psychopathological and functioning constructs tended to cluster together in the estimated network. The most central nodes (EI) were Delusions, Emotional Withdrawal, Depression, and Depressed Mood. Bridge nodes included Depression, Conceptual Disorganization, Active Social Avoidance, Delusions, Stereotyped Thinking, Poor Impulse Control, Guilty Feelings, Unusual Thought Content, and Hostility. Most of the bridge nodes belonged to the general psychopathology subscale of the PANSS. Depression (G6) was the bridge node with the highest value.ConclusionsThe current study provides novel insights for understanding the complex phenotype of psychotic disorders and the mechanisms underlying the development and maintenance of comorbidity and functional impairment after psychosis onset.