On the causal association between exposure to leather dust and nasal cancer: further evidence from a case-control study

A case-control study was performed on the incident cases of nasal cavity tumours which occurred between 1968 and 1982 among the residents of Vigevano (Lombardy region, northern Italy). This area is characterised by a high prevalence of shoemakers (especially in leather); the activity has predominated in Vigevano since the beginning of this century. Twenty one cases were identified (16 men and five women); 20 were histologically confirmed as nasal epithelial tumours; 17 had already died at the time of interview and the occupational history was obtained from the next of kin. Two controls per case were selected from the general population and matched by vital status, age, sex, and residence. The overall odds ratio for the subjects exposed to leather dust was 47.1 for men and 3.5 for women. The odds ratio was higher for adenocarcinoma and among the workers exposed to the worst working conditions. A significant trend for the level of exposure to leather dust was found. Nevertheless, even the jobs characterised by a relatively low exposure were found to have a significantly higher risk (OR = 7.5). Smoking habits and exposure to solvents are unlikely to confound the relation between exposure to leather and nasal tumours.     

Motor functions of the striatum in the rat: critical role of the lateral region in tongue and forelimb reaching

The findings of this study indicate a critical and selective role of the rat's lateral striatum in performance of tongue and forelimb reaching. To test the hypothesis of regional specificity of motor control in the striatum, the effects of bilateral, ibotenate-induced lesions of either the lateral or the medial regions of the striatum on reaching movements of the tongue and the forelimbs were examined. Lesions of the lateral striatum caused severe and chronic impairments of movement initiation, postural synergisms and amplitude of both tongue and forelimb reaches. In contrast, lesions of the medial striatum produced mild or no chronic alterations of these motor parameters. These findings support the hypothesis of a selective role of the lateral striatum in the initiation and execution of reaching movements.     

Expression of leukocyte adhesion molecules in the liver of patients with chronic hepatitis B virus infection.

Virus-specific T-cell responses are believed to be involved in the pathogenesis of liver cell injury secondary to hepatitis B virus infection. In this study, liver biopsy specimens from patients with chronic hepatitis B virus infection were analyzed for expression of two major pathways of adhesion used by cytotoxic T cells to interact with target cells. The lymphocyte function-associated antigen 3 was found preferentially expressed on hepatocytes of patients with active hepatitis B virus replication, whereas the expression of the intercellular adhesion molecule 1 on hepatocytes seemed more closely related with inflammatory activity. Adhesion molecules were also highly expressed on T lymphocytes found in areas of piecemeal and spotty necrosis, indicating the presence of antigen-specific "memory" T cells at the site of hepatocellular injury. This study suggests that the expression of the lymphocyte function-associated antigen 3 on hepatocytes may be important for viral elimination. The coordinate expression of the intercellular adhesion molecule 1 may regulate inflammatory response and enhance viral antigen presentation to T cells. Conversely, the absence of hepatocyte adhesion molecules might be a favorable factor for viral persistence.     

Epstein-Barr virus induced lymphoproliferative tumors in severe combined immunodeficient mice are oligoclonal.

Severe combined immunodeficient (SCID) mice reconstituted with lymphocytes from Epstein-Barr virus (EBV) negative human donors develop aggressive tumors after the chimeric mice are infected with EBV. The tumors were composed of human B cells that expressed EBV encoded antigens (latent membrane protein and EBV nuclear antigen2). Southern blot analysis of DNA from 16 SCID/hu tumors with human Ig gene probes showed that each tumor contained multiple heavy and light chain gene rearrangements. Ig kappa gene rearrangements were frequent, while clonal lambda gene rearrangements were infrequent. Analysis of EBV terminal repeat sequences indicated two or more fused termini in each tumor, consistent with a multiclonal origin. Linear terminal repeat segments and viral antigens (EA-D and EA-R) associated with EBV replication were not detected in the tumors. High levels of human Igs in the SCID/hu serum were oligoclonal and primarily contained kappa light chains. Before the appearance of overt tumors, circulating cells with human and EBV DNA could be detected in the SCID/hu mice by the polymerase chain reaction. We conclude that EBV infection in SCID/hu chimeric mice produces a limited number of transformation events, which give rise to oligoclonal tumors resembling EBV-associated lymphoproliferative disorders in some immune-deficient patients.     

Histamine‐N‐methyl transferase polymorphism and risk for multiple sclerosis

Background: Histamine N‐methyltransferase (HNMT) is the main metabolizing enzyme of histamine (a mediator of inflammation implicated in the pathogenesis of multiple sclerosis‐MS) in the CNS. We have investigated the possible association between a single nucleotide polymorphism of the HNMT (chromosome 2q22.1), that causes the amino acid substitution Thr105Ile (decreasing enzyme activity) and the risk for MS. Methods: We studied the frequency of the HNMT genotypes and allelic variants in 228 MS patients and 295 healthy controls using a PCR‐RLFP method. Results: The frequencies of the HNMT genotypes and allelic variants did not differ significantly between MS patients and controls, and were unrelated with the age of onset of MS, gender, and course of MS. Conclusion: The HNMT polymorphism is not related with the risk for MS.     

A modified epitope identified for generation and monitoring of PSA-specific T cells in patients on early phases of PSA-based immunotherapeutic protocols

Efficacy of vaccination in cancer patients on immunotherapeutic protocols can be difficult to evaluate. The aim of this study was therefore to identify a single natural or modified epitope in prostate-specific antigen (PSA) with the ability to generate high levels of PSA-specific T cells to facilitate monitoring in patients after vaccination against prostate cancer. To the best of our knowledge, this study describes for the first time the peptide specificity of T cells stimulated by endogenously processed PSA antigen. The peptide specificity of HLA-A*0201-restricted CD8⁺ T cells against human and rhesus PSA was investigated both in vivo after DNA vaccination in HLA-A*0201-transgenic mice and in vitro after repetitive stimulation of human T cells with DNA-transfected human dendritic cells (DCs). One of seven native PSA peptides, psa53–61, was able to activate high levels of PSA-specific CD8⁺ T cells in HLA-A*0201-transgenic mice after PSA DNA vaccination. Psa53–61 was also the only peptide that induced human T cells to produce IFNγ after stimulation with PSA transfected DCs, however not in all donors. Therefore, plasmids encoding modified epitopes in predicted HLA-A*0201 sequences were constructed. One of these modified PSA plasmids consistently induced IFNγ producing CD8⁺ T cells to the corresponding modified peptide as well as to the corresponding native peptide, in all murine and human T cell cultures. This study demonstrates a novel concept of introducing a modified epitope within a self-tumor antigen, with the purpose of eliciting a reliable T cell response from the non-tolerized immune repertoire, to facilitate monitoring of vaccine efficacy in cancer patients on immunotherapeutic protocols. The purpose of such a modified epitope is thus not to induce therapeutically relevant T cells but rather to, in case of weak or divergent T cell responses to self antigens/peptides, help answer questions about efficacy of vaccine delivery and about the possibility to induce immune responses in the selected and often immunosuppressed cancer patients.     

Social class, family history and type of schizophrenia

To date, there are numerous studies supporting a genetic model of schizophrenia. There is a paucity of studies, however, screening for a connection between family history of serious mental illness and deficit vs. nondeficit schizophrenia. The aim of the present study was to explore the association between family history, deficit vs. nondeficit schizophrenia and socioeconomic status (SES) of family of origin. Patients (N = 437) from a United States psychiatric hospital were separated into deficit vs. nondeficit presentation and bifurcated into poor vs. nonpoor SES. Family history data were utilized to classify patients into subgroups characterized by serious mental illness within immediate family, within extended family, or no evidence of mental illness. Statistical testing was conducted using logistic regression analysis. SES of family of origin was significantly associated with schizophrenic subtype independently of family history, sex and race; specifically, poverty raised the risk of deficit schizophrenia. Family history of mental illness showed no net association, and no statistical interaction with poverty, in predicting risk of deficit schizophrenia.     

Switching from HPLC/UV to MEIA for whole blood sirolimus quantitation: comparison of methods

Sirolimus is a immunosuppressive agent for renal transplant recipients. Monitoring of whole blood sirolimus concentration is necessary in order to improve clinical outcomes. An increasing number of clinical laboratories (4-14% during 2005) are using microparticle enzyme immunoassay (MEIA) for sirolimus quantitation but previous reports indicated a high variability, with a mean difference of 17% for MEIA method vs. high-performance liquid chromatography/ultraviolet (HPLC/UV). This study was aimed at comparing the reliability of MEIA with the HPLC/UV method. Blood samples from transplant patients were processed using both HPLC/UV and MEIA assays. Comparison and Bland-Altman plots, as well as regression analysis and paired t-test were used to compare results of the assays. Concentrations were stratified into three groups and used to investigate whether any observed difference between methods could be influenced by sirolimus concentration. Regression analysis yielded a coefficient of correlation R of 0.9756, the line of best fit being y=0.9832x+0.1976. The statistical analysis showed no difference between the two sets of experimental data. The average percentage difference between the two methods was found to be -0.2+/-19.2%. On the basis of our present results, the tested MEIA assay is able to quantify sirolimus concentration with a clinically acceptable imprecision, similar to that of HPLC/UV method.