High-resolution HLA-DRB1 and DQB1 genotyping in Japanese patients with testicular germ cell carcinoma.

We report for the first time the frequency distributions of HLA-DRB1 and -DQB1 genes in 55 patients with testicular germ cell carcinoma (TGC) using the modified PCR-RFLP method and compare the results with those for 1216 healthy Japanese control subjects. The modified PCR-RFLP method produced accurate, reproducible cleavage patterns that are easily discriminated. HLA-DRB1*0410 was the susceptibility allele (RR = 3.26, P = 0.006) and DQB1*0602 appears to be a candidate protective allele (RR = 0.26, P = 0.02) for TGC in the Japanese. None of the HLA-DRB1 and -DQB1 alleles showed a specific tendency for histological type or clinical stage of the tumours. Previous studies based on serotyping methods failed to show these allelic associations. High-resolution genotyping is essential because the peptide-binding domain of MHC class II molecules is determined more precisely by their genotypes than by their serotypes. In addition, inherent technical difficulties and typing errors of up to 25% make serotyping inefficient. Our results suggest that high-resolution genotyping is a useful genetic marker to determine risk for TGC.     

The Arg753GLn polymorphism of the human toll-like receptor 2 gene in tuberculosis disease.

Toll-like receptor 2 (TLR2), a member of the Toll-like receptor family, plays an important role in recognition of, and subsequent immune response activation against, mycobacteria. The genetic polymorphism of TLR2 (arginine to glutamine substitution at residue 753 (Arg753Gln)) has been associated with a negative influence on TLR2 function, which may, in turn, determine the innate host response to mycobacteria. The aim of the present study was to investigate the Arg753Gln single nucleotide polymorphism of the TLR2 gene in tuberculosis (TB) patients compared to healthy controls. A retrospective case/control study was carried out. The Arg753Gln polymorphism of the TLR2 gene was studied in 151 TB patients compared to 116 ethnically and age-matched healthy control subjects. The TLR2 polymorphism (adenine (A) allele) was observed in 17.9 and 7.7% of TB patients and controls, respectively. When the ratios of the three genotypes were compared between the two groups, the AA genotype was found to be more significantly associated with TB. Allele frequencies for guanine (G) and A were found to be 0.95 and 0.05 in the control group and 0.86 and 0.14 in the TB patient group, respectively. The risk of developing TB disease was increased 6.04- and 1.60-fold for carriers of the AA and GA genotypes, respectively. In conclusion, the present data suggest that the arginine to glutamine substitution at residue 753 polymorphism of the Toll-like receptor 2 gene influences the risk of developing tuberculosis.     

Synthesis of 3-[2-(2,3-dihydro-5-phenyl-4-substituted-3H-1,2,4- triazole-3-thione-2-yl)-acetylamino]-2-methyl-4(3H)-quinazolinones and their pharmacological activities

Some 2-methyl-3-triazole-substituted-4(3H)-quinazolinones 3a-f were prepared and tested for their H1- and H2-antihistaminic activities. In addition these compounds are central nervous system depressants and anticonvulsants. 3e shows highly significant decrease of locomotor activity.     

Effects of simplifying choice tasks on estimates of taste heterogeneity in stated-choice surveys

Researchers usually employ orthogonal arrays or D-optimal designs with little or no attribute overlap in stated-choice surveys. The challenge is to balance statistical efficiency and respondent burden to minimize the overall error in the survey responses. This study examined whether simplifying the choice task, by using a design with more overlap, provides advantages over standard minimum-overlap methods. We administered two designs for eliciting HIV test preferences to split samples. Surveys were undertaken at four HIV testing locations in San Francisco, California. Personal characteristics had different effects on willingness to pay for the two treatments, and gains in statistical efficiency in the minimal-overlap version more than compensated for possible imprecision from increased measurement error.     

Sympathetic skin responses from postauricular region in Meniere's disease.

OBJECTIVE: To investigate the sympathetic nervous system activity in Meniere's disease (MD) by recording sympathetic skin responses (SSRs) from the postauricular region (PA). METHODS: Twenty-one patients with definite unilateral MD diagnosis and 12 healthy volunteers were studied by evoking right and left PA-SSRs with electrical stimulation of the left median nerve at the wrist in attack and interval periods of MD. Mean latencies and maximum amplitudes were used in statistical analyses. RESULTS: In unilateral definite MD patients, the mean latencies were longer and the maximum amplitudes were smaller on the involved ear side than those on the normal ear side (p<0.01 for both amplitude and latency) and than those from the controls (p<0.01 and p<0.05). In three patients, there was no detectable PA-SSR on the involved ear side while there were SSRs on the healthy side. In four patients, the responses were absent bilaterally during the attack period. CONCLUSIONS: There is a marked asymmetric sympathetic hypofunction in the area of the PA region of the involved ear in MD patients. SIGNIFICANCE: The PA region is a new site for recording sympathetic skin responses. PA-SSR is a useful tool to investigate sympathetic nervous system function in MD patients.     

A clinico-pathological study of laryngeal and hypopharyngeal carcinoma: correlation of cord-arytenoid mobility with histopathologic involvement.

OBJECTIVE: This study evaluates the vocal cord and arytenoid mobility in relation to the tumoral involvement of the cricoarytenoid joint (CAJ), thyroarytenoid (TA) muscle, and posterior cricoarytenoid (PCA) muscle in whole-organ sections of total laryngectomy specimens. STUDY DESIGN AND SETTING: The study was prospectively carried out between 1998 and 2003 and involved 133 primary squamous cell carcinoma cases of larynx or pyriform sinus that were treated with total laryngectomy. Preoperative mobility of vocal cords and arytenoids were evaluated separately and correlated with histopathologic findings. RESULTS: In cases with fixed vocal cord CAJ, TA muscle, and PCA muscle were involved in 42.4%, 72.9%, and 27.1% of the cases, respectively, while in cases with fixed arytenoid these structures were affected in 40%, 66.3%, and 25.3% of the cases. Weight effect seemed to play a role in 60% and 50% of the cases of supraglottic and pyriform sinus carcinoma, respectively. CONCLUSION: Careful evaluation of the mobility of the cord arytenoid unit separately helps the surgeon to better understand the patterns of tumoral extension guiding for the appropriate surgery which should be undertaken.     

Combinational IL-2/IL-15 induction does not further enhance IL-15-induced lymphokine-activated killer cell cytotoxicity against human leukemia/lymphoma cells

In vitro comparisons of induction of perforin (PFP), granzyme B (GRB), production of cytokines, and cell-mediated cytotoxicity by interleukin-2 (IL-2), interleukin-15 (IL-15), or combinational IL-2/IL-15-induced lymphokine-activated killer cells were studied in this study. Whereas IL-2-induction was associated with a decrease in cultured cell population over a 7-day period, IL-15 alone or in combination with IL-2 resulted in significant increase including cytotoxic T lymphocytes and subsets of CD56+ lymphocytes, particularly cytokine-induced killer and cytolytic natural killer-T lymphocytes. The overall PFP, GRB, and tumor necrosis factor-alpha expression in different subtypes were also significantly higher with IL-15 alone or in combination with IL-2 induction with resultant superior cytotoxicity compared to IL-2 treatment. There was no significant advantage of addition of IL-2 over IL-15 induction. These results offer further information on the cytotoxic potency of these cytokines and their mechanisms of action implicating potential use of IL-15 as part of cytokine adoptive immunotherapy.