A comparative study of flow cytometric T cell receptor Vß repertoire and T cell receptor gene rearrangement in the diagnosis of large granular lymphocytic lymphoproliferation.

INTRODUCTION: Large granular lymphocytes (LGLs) are medium- to large-sized lymphocytes with azurophilic cytoplasmic granules. Reactive vs. neoplastic LGLs are usually morphologically indistinguishable. METHODS: We investigated 25 consecutive cases of LGL lymphoproliferation using flow cytometric T cell receptor Vß (FC-Vß) repertoire and T cell receptor gene rearrangement (TCR-GR) in detecting clonality. RESULTS: Seventeen patients (68%) were T-LGL leukemia (T-LGLL) with a male predominance, a median age of 67, and a median absolute LGL count of 2.592 × 10(9) /L. All cases were clonal using the FC-Vß analysis, and all but one (94%) was clonal by TCR-GR. Eight patients (32%) had reactive LGL lymphoproliferation. Two had EBV-associated infectious mononucleosis; one was clonal by both FC-Vß and TCR-GR; and the other was clonal only by TCR-GR. The remaining six cases were polyclonal by both assays. Patients with reactive LGL lymphoproliferation were more frequently associated with an underlying/concurrent malignancy than those with T-LGLL (4/8 cases vs. 1/17; P = 0.023, Fisher's exact test). We compared the demographic, hemogram, and clonality data between these two groups and found that the only significant difference was the lower median platelet count in the LGL lymphocytosis group (201 × 10(9) /L vs. 223 × 10(9) /L; P = 0.031; Student's t-test). A literature review including the current study showed a high sensitivity of FC-Vß analysis for T-LGLL (97.2%; 107/110 cases). CONCLUSIONS: FC-Vß analysis was slightly more sensitive than TCR-GR for the detection of clonal T cell lymphoproliferation. However, we must interpret the laboratory findings with clinical context as clonal T cell lymphoproliferation may occur in patients with viral infection.

Cancer aggregation and complex segregation analysis of families with female non-smoking lung cancer probands in Taiwan.

Previous studies have found that having a first-degree blood relative with lung cancer was a possible predictor of lung cancer risk, but some studies have indicated that the association is non-significant or only significant for a subset of the studied population. To determine the familial aggregation and whether there is any evidence for a gene controlling the susceptibility to developing lung cancer in female non-smokers, multiple logistic regression methods for estimating covariate effects and maximum likelihood segregation analyses were performed using data from 216 female non-smoking lung cancer probands (2328 individuals) in a population-based case-control study. Having a family history of lung cancer was found to be a significant predictor of lung cancer for non-smoking females (Adjusted Odds Ratio (OR)=5.7, 95% Confidence Interval (CI)=1.9-16.9). Having a female relative with lung cancer (adjusted OR=14.4, 95% CI=2.7-75.5) was more strongly associated with the lung cancer risk than was having a male relative with lung cancer. This association was stronger for probands aged less than 60 years at onset (adjusted OR=11.2, 95% CI=2.2-56.9). All of the Mendelian models fitted the data significantly better than the sporadic (no major type) model or the environmental model (P<0.00l). The Mendelian codominant models provided the best fit of the data for the early onset probands and showed a stronger effect for a major susceptibility locus for non-smoking lung cancer probands. The results of this study provide evidence that a rare autosomal codominant gene may influence the risk lung cancer in non-smoker and is responsible for the familial aggregation observed in non-smoking lung cancer patients.

Identification of carcinogens in cooking oil fumes.

According to earlier studies, fumes from cooking oils were found to be genotoxic in several short-term tests such as the Ames test, sister chromatid exchange, and SOS chromotest. Fume samples from six different commercial cooking oils (safflower, olive, coconut, mustard, vegetable, and corn) frequently used in Taiwan were collected. Polycyclic aromatic hydrocarbons (PAHs) were extracted from the air samples and identified by high-performance liquid chromatography and confirmed by gas chromatography/mass spectrometry. Extracts of fumes from safflower oil, vegetable oil, and corn oil contained benzo[a]pyrene (BaP), dibenz[a,h]anthracene (DBahA), benzo[b]fluoranthene (BbFA), and benzo[a]anthracene (BaA). Concentrations of BaP, DbahA, BbFA, and BaA were 2.1, 2.8, 1.8, and 2.5 microg/m3 in fumes from safflower oil; 2.7, 3.2, 2.6, and 2.1 microg/m3 in vegetable oil; and 2.6, 2.4, 2.0, and 1.9 microg/m3 in corn oil, respectively. The authors constructed models to study the efficacy of table-edged fume extractors used commonly by Taiwanese restaurants. Concentrations of BaP were significantly decreased when the fume extractor was working (P<0.05) and the average reduction in percentage was 75%. The other identified PAHs were undetected. These results indicated that exposure to cooking oil fumes could possibly increase exposure to PAHs, which may be linked to an increased risk of lung cancer. The potential carcinogenic exposure could be reduced by placing table-edged fume extractors near cooking pots.

Mutagenicity and aromatic amine content of fumes from heated cooking oils produced in Taiwan.

According to toxicological studies, there are several unidentified mutagens derived from cooking oil fumes appearing in kitchens of Chinese homes where women daily prepare food. Data are limited to an analysis of aromatic amines from cooking oil fumes, which are known to be carcinogenic for bladder cancer. Fume samples from three different commercial cooking oils frequently used in Taiwan were collected and analysed for mutagenicity in the Salmonella/microsome assay. Aromatic amines were extracted from the samples and identified by HPLC and confirmed by gas chromatography/mass spectrometry (GC/MS). Extracts from three cooking oil fumes were found to be mutagenic in the presence of S-9 mix. All samples contained 2-naphthylamine (2-NA) and 4-aminobiphenyl (4-ABP). Concentrations of 2-NA and 4-ABP were 31.5 and 35.7 microg/m3 in fumes from sunflower oil, 31.9 and 26.4 mg/m3 in vegetable oil, and 48.3 and 23.3 microg/m3 in refined-lard oil, respectively. Mutagenicities of the three cooking oil condensates were significantly reduced (P<0.05) by adding the antioxidant catechin (CAT) into the oils before heating. Significant difference existed between the amounts of aromatic amines with and without adding CAT (P<0.05). These results indicate that exposure to cooking oil fumes in Taiwan might be an important but controllable risk factor in the aetiology of bladder cancer.

Genotoxicity of fumes from heated cooking oils produced in Taiwan.

Epidemiologic investigations of lung cancer among Taiwanese nonsmoking women have found that exposure to fumes from cooking oils may be an important risk factor. Fume samples from three different commercial cooking oils (lard, soybean, and peanut oils) often used in Taiwan for preparing Chinese meals were collected for genotoxicity analysis in SOS chromotest and sister chromatid exchange (SCE) assays. The induction factors of the SOS chromotest in Escherichia coli PQ 37 were dependent on the concentrations of lard and soybean cooking oil extracts without S9 mix. In addition, when CHO-K1 cells were exposed to condensates of cooking oil fumes for 12 h, SCEs showed a dose-related increase in extracts of lard and soybean oil fumes. This result provides experimental evidence and is in accordance with the findings of epidemiologic studies that women exposed to the emitted fumes of cooking oils are at an increase risk of contracting lung cancer.

SARA, a FYVE domain protein that recruits Smad2 to the TGFbeta receptor.

Smads transmit signals from transmembrane ser/thr kinase receptors to the nucleus. We now identify SARA (for Smad anchor for receptor activation), a FYVE domain protein that interacts directly with Smad2 and Smad3. SARA functions to recruit Smad2 to the TGFbeta receptor by controlling the subcellular localization of Smad2 and by interacting with the TGFbeta receptor complex. Phosphorylation of Smad2 induces dissociation from SARA with concomitant formation of Smad2/Smad4 complexes and nuclear translocation. Furthermore, mutations in SARA that cause mislocalization of Smad2 inhibit TGFbeta-dependent transcriptional responses, indicating that the regulation of Smad localization is important for TGFbeta signaling. These results thus define SARA as a component of the TGFbeta pathway that brings the Smad substrate to the receptor.

Nitro-polycyclic aromatic hydrocarbon contents of fumes from heated cooking oils and prevention of mutagenicity by catechin.

According to earlier studies, fumes from cooking oils were found to be mutagenic and several polycyclic aromatic hydrocarbons (PAHs), (benzo(a)pyrene (B(a)P), benz(a)antracene (B(a)A), and dibenz(a,h)anthracene (DB(ah)A)) were identified. Fume samples from three different commercial cooking oils frequently used in Taiwan were collected and nitro-polycyclic aromatic hydrocarbons (NPAHs) were extracted from the samples and identified by HPLC chromatography. Extracts from three cooking oil fumes contained 1-nitropyrene (1-NP) and 1,3-dinitropyrene (1,3-DNP). Concentrations of 1-NP and 1,3-DNP were 1.1 +/- 0.1 and 0.9 +/- 0.1 micrograms/m3 in fumes from lard oil, 2.9 +/- 0.3 and 3.4 +/- 0.2 micrograms/m3 in soybean oil, 1.5 +/- 0.1 and 0.4 +/- 0.1 micrograms/m3 in peanut oil, respectively. The preventive effect of three natural antioxidants (gamma-tocopherol (TOC), lecithin (LEC), and catechin (CAT)) for the reduction of mutagenicity and amounts of PAHs and NPAHs of fumes from cooking oils were evaluated. Mutagenicity of cooking oil fumes occurred, and the concentration of B(a)P were significantly reduced (p < 0.05), by adding CAT into cooking oils before heating. B(a)A, DB(ah)A, and two NPAHs were not detected when the concentration of CAT was 500 ppm in all three cooking oil fumes. These results indicate that fumes of cooking oils contained PAHs and NPAHs that may be a risk factor for lung cancer among cooks and the carcinogens could be reduced by adding the natural antioxidant, catechin.

Prevention of exposure to mutagenic fumes produced by hot cooking oil in Taiwanese kitchens.

We evaluated the mutagens in fumes produced by heating three different cooking oils used in Taiwan to temperatures of 100 degrees C, 200 degrees C, and 300 degrees C, and constructed models to study the efficacy of fume extractors used commonly by Taiwanese women. Particulates of volatile emissions from lard (at 200 degrees C and 300 degrees C) and soybean oil (at 300 degrees C) were found to be mutagenic in the Salmonella/microsomal test with S9 mix, indicating that exposure of Taiwanese women to cooking oil fumes may be an important risk factor in the etiology of their lung cancer. Mutagenicity of lard and soybean oil fumes collected at 300 degrees C was obtained when a commonly used fume extractor was located at a usual distance of 70 cm above the oil surface, whereas the fume samples were not, or weakly, mutagenic in the Salmonella/ microsomal assay when the distance between fume extractor and oil surface was 60 cm or less. Reduction in mutagenicity was on average 1.2 +/- 0.5 revertants/cm (the percent reduction in mutagenicity was 46%), pointing to a possible cooking practice involving significant reductions in exposure to harmful oil fumes and, consequently, a decreased risk of lung cancer in Taiwanese housewives.

Mutagenicity and polycyclic aromatic hydrocarbon content of fumes from heated cooking oils produced in Taiwan.

According to epidemiologic studies, exposure of women to fumes from cooking oils appears to be an important risk factor for lung cancer. Fume samples from three different commercial cooking oils frequently used in Taiwan were collected and analyzed for mutagenicity in the Salmonella/microsome assay. Polycyclic aromatic hydrocarbons were extracted from the samples and identified by HPLC chromatography. Extracts from three cooking oil fumes were found to be mutagenic in the presence of S9 mix. All samples contained dibenz[a,h]anthracene (DB[a,h]A) and benz[a]anthracene (B[a]A). Concentration of DB[a,h]A and B[a]A were 1.9 and 2.2 micrograms/m3 in fumes from lard oil, 2.1 and 2.3 micrograms/m3 in soybean oil, 1.8 and 1.3 micrograms/m3 in peanut oil, respectively. Benzo[a]pyrene (B[a]P) was identified in fume samples of soybean and peanut oil, in concentrations of 19.6 and 18.3 micrograms/m3, in this order. These results provide experimental evidence and support the findings of epidemiologic observations, in which women exposed to the emitted fumes of cooking oils are at increased risk of contracting lung cancer.

Tattooing as a risk of hepatitis C virus infection.

The association of hepatitis C virus (HCV) infection and tattooing was studied in 87 tattooed and 126 tattoo free healthy young men who did not engage in intravenous drug use or multiple sexual activity. Antibody against HCV (anti-HCV) was tested in serum specimens by enzyme immunoassay with C100-3, NS3, and core antigens; 11 of the 87 (12.6%) tattooed and 3 of the 126 (2.4%) tattoo free subjects were positive for anti-HCV (odds ratio = 5.9, 95% CI = 1.6-22.0). A relationship was demonstrated by an increased risk for HCV infection with an increasing number of tattooed site (P(trend) = 0.002). All but one of the 87 tattooed subjects had been infected by hepatitis B virus (HBV) and 25 were carriers of hepatitis B surface antigen (HBsAg). None of the 25 HBsAg carriers was positive for anti-HCV whereas 11 of the 62 HBsAg non-carriers had anti-HCV, suggesting a negative association between the HBsAg carriage and the long lasting anti-HCV (P = 0.02, Fisher's exact). The status of the tattooer was also an important determinant for HCV infection; the risk was higher if tattooing was done by a non-professional friend than by a professional tattooist. Tattooing, probably with improperly sterilized needles, can clearly pose an increased risk for HCV infection in Taiwan. This study indicates the need for legal standards for hygienic tattooing as part of preventive measures for the control of parenterally transmitted infections.

Prevalence of betel quid chewing habit in Taiwan and related sociodemographic factors.

The prevalence of betel quid chewing habit in Taiwan was surveyed in a group of Chinese people from Kaohsiung city and in a second group from the aboriginal inhabitants of South Taiwan. In all 1299 participants constituted Group 1 (85.2% response rate) and 827 Group 2 (70.1% response rate). People were interviewed in their homes in house-to-house survey, according to a structured questionnaire developed and evaluated by the authors. Of the Kaohsiung inhabitants covering all ages and both sexes, 6% was a current betel chewer and 4% was an ex-chewer, whereas 42% of the aborigines aged over 15 yr was a current chewer and 1% an ex-chewer. Lifetime prevalence was 10%. Betel chewing enjoys islandwide popularity among the 20 million inhabitants of Taiwan; the number of current and ex-users was estimated at 2.0 million (95% CI 1.6-2.4 million). The betel quid was prepared in two different ways. In one, used mainly by aborigines, fresh areca nut was simply wrapped with betel leaf and in another, popular mainly among Chinese, a lengthwise piece of betel fruit and lime paste was sandwiched between two halves of an areca nut. A high proportion of chewers was also a smoker and drinker, but tobacco was not found to be chewed together with betel quid. Consumption varied between 14 to 23 portions per day, with individual frequencies ranging widely from 1 to over 200 portions a day. A statistical analysis of sociodemographic factors showed that lesser educated older men, blue collar workers, smokers and drinkers were the likeliest betel chewers.

Successful use of pooled sera to estimate HIV antibody seroprevalence and eliminate all positive cases.

Pooling specimens when testing them in large numbers can save scarce resources and several earlier reports have indicated this to be a feasible strategy. In an HIV antibody mass screening test carried out in our laboratory, we used Dorfman's two-stage model. We sought to establish the optimal number of specimens in a pool, and to achieve maximum efficiency while maintaining both sensitivity and specificity. Before testing for HIV antibody, five positive samples were placed in a set of 1012 sera in a double blind manner, one positive sample into a second set of 1012 sera and none in a third set. The positive rate was assumed to be 0.2% for each set of 1012 sera. As indicated by our model, 22 individual serum samples were placed into each of 46 pools which, when tested by particle agglutination assays, lead to the identification of all positive samples. We concluded that the prevalence rate can be estimated in the first stage, 95% confidence intervals were given, and the efficiency rate could be calculated for the identification of all infected specimens in a large number of samples showing low prevalence rates.