Significance of lateral biopsy specimens during transrectal ultrasound-guided prostate biopsies in Japanese men

OBJECTIVES: Lateral biopsies are thought to have a better cancer detection rate compared with standard sextant biopsies. This study aimed to determine whether lateral peripheral zone biopsies in Japanese men who underwent transrectal ultrasound-guided prostate biopsies provided a significantly higher cancer detection rate than sextant biopsies. METHODS: Between 1999 and 2004, data were collected from 461 men who underwent prostate biopsy and had enough data regarding the performance of lateral biopsies for statistical analysis. There were two categories in this study: (i) patients who underwent sextant prostate biopsies; and (ii) patients who underwent sextant biopsies plus lateral biopsies. RESULTS: Prostate cancer was detected in 141 (30.6%) of 461 patients. It was detected in 24 (22.2%) of 108 patients who underwent sextant biopsies and 117 (33.1%) of 353 patients who underwent sextant plus lateral biopsies. Lateral biopsies were not associated with a statistically higher rate of positive biopsy findings; however, we found a significantly higher ratio of patients with positive findings in those with prostate specific antigen (PSA) levels 10 ng/mL (one of 71, 1.4%) among those who had positive cores only in lateral biopsy samples (P < 0.0001). CONCLUSIONS: Lateral biopsies did not show a significantly higher detection ratio of prostate cancer compared to sextant biopsies. However, lateral biopsies were more effective than sextant biopsies in patients with lower PSA levels. Our findings might be useful for the establishment of biopsy strategies to detect prostate cancer, especially in patients with lower PSA levels.     

Independent association of antibodies against human papillomavirus type 16 and E7 proteins with cervical cancer

The E4 open reading frame (ORF) of human papillomaviruses (HPVs) is transcribed in abundant mRNAs encoding an fusion gene during the productive infection, and the HPV 16 E7 ORF encodes an oncoprotein detectable in the cell lines derived from cervical carcinoma. We examined 421 human sera, which included 108 samples from the patients with cervical carcinoma, for the presence of IgG antibodies against the HPV 16 E4 and E7 proteins by enzyme-linked immunosorbent assay. Bacterially expressed fusion protein lac- and nonfusion protein E7 were purified and used as antigens. All of the 22 serum samples positive for anti-E7 antibody and the 11 out of 15 samples positive for anti- antibody were from the patients with cervical carcinoma, but only one sample was found to contain both anti- and anti-E7 antibodies. These findings show specific and independent association of these antibodies with cervical carcinoma.     

Survival benefit from non-highly active antiretroviral therapy in a resource-constrained setting

Mortality rates among HIV-1-infected patients attending a government hospital in northern Thailand were investigated to evaluate the effect of antiretroviral (ARV) drug therapy on mortality. Demographic, clinical, and laboratory data and history of ARV drug therapy were collected from all HIV-1-infected adult patients who attended the Day Care Center clinic from October 2, 1995 through October 31, 1999. The survival status of patients until October 31, 1999 was ascertained from the hospital records, mailing letters, and death certificates at the Provincial Health Office. Of 1110 patients who attended the clinic, we had data on duration of follow-up for 1081 (97%) with a total of 1175 person-years of observation; 607 (54.7%) patients died. Clinical status, CD4 group, ARV drug group, and registered year were independently associated with death. The adjusted hazard ratio of monotherapy to no therapy was 0.65 (95% CI: 0.48, 0.87; p = .001) and that of dual therapy was 0.43 (95% CI: 0.29, 0.62; p < .001). The mortality rate of patients attending a government hospital in northern Thailand is high. Suboptimum ARV drug regimens like dual therapy had a substantial survival benefit. Further cost reduction for multiple ARV drug regimens is impatiently awaited.     

Occurrence of free, defective viral DNA in a hamster tumor induced by human papovavirus BK

We characterized viral DNA present in an osteosarcoma cell line (Os-513), which had been originally induced in a hamster with human papovavirus BK (BKV), by hybridization of ³²P-labeled BKV DNA to DNA extracted from cells, undigested or digested with various restriction endonucleases, fractionated by electrophoresis, and transferred to a nitrocellulose filter. Os-513 was found to contain free viral DNA and high molecular weight DNA with viral sequences. The free viral DNA seemed to be defective, for its size was about two-thirds of the wild type. The deletion, one-third of the entire BKV DNA, extended over a segment between map positions 0.72 and 0 which includes the leader and intervening sequences and part of the body sequences for late mRNAs. The high molecular weight DNA with viral sequences appeared to be composed of tandem, head-to-tail repeats of the same defective BKV DNA as the free DNA.     

Purification and characterization of an extracellular proteinase from Hendersonula toruloidea.

An extracellular proteinase from a fast-growing strain of Hendersonula toruloidea was demonstrated when it was cultivated in liquid medium containing bovine serum albumin as the sole nitrogen source. Purification to homogeneity of the proteinase was performed by carboxymethyl cellulose, CM Sephadex G-50, and Sephacryl S-200 column chromatographies. The purified enzyme was a chymotrypsinlike serine proteinase, as indicated by the strong inhibitory activities of diisopropyl fluorophosphate, phenylmethylsulfonyl fluoride, L-1-tosylamido-2-phenylethylchloromethyl ketone, and chymostatin and good kinetic constants for a synthetic substrate, Suc-Ala-Ala-Pro-Phe-MCA. The enzyme had a pI of 8.4, a pH optimum of 9.0, and a molecular weight of 34,000. Skin constituents such as stratum corneum and nail, but not hair, were easily digested by this enzyme. Thus, this extracellular proteinase may play a role in the invasion of thickly keratinized skin and nail by this organism.     

Leisure-time physical activity and related lifestyle characteristics among middle-aged Japanese. Japan Lifestyle Monitoring Study Group

The present study describes leisure-time physical activity status and related lifestyle factors in middle-aged Japanese. Data were obtained from 1,893 (905 men, 988 women) participants aged 40-69 years who had either been selected from a public registry or who had visited a healthcare facility. Subjects responded to a self-administered questionnaire and were interviewed using an assessment method for leisure-time and on-the-job physical activity within the last 12 months by trained interviewers. According to the leisure-time physical activity score, men and urban residents tended to engage in more leisure-time physical activity than did women and rural residents, respectively. Leisure-time physical activity tended to be inversely associated with on-the-job physical activity in all cases aside from women in urban regions, and also to be associated with higher levels of education in rural regions. Subjects engaging in more leisure-time physical activity had higher odds ratios of certain lifestyle factors, indicating a healthy lifestyle that included a variety of foods in their diet and a subjective sense of wellness in both men and women, in addition to non-smoking and drinking milk in men. These results suggested that leisure-time physical activity is influenced by socio-environmental factors, and that it is accompanied by other healthy behavior.     

Are the associations between life-style related factors and plasma total homocysteine concentration different according to polymorphism of 5,10-methylenetetrahydrofolate reductase gene (C677T MTHFR)? A cross-sectional study in a Japanese rural population

Mild hyperhomocysteinemia is one of the known strong risk factors for atherosclerotic diseases, and therefore it is important to clarify factors that could determine plasma total homocysteine (tHcy) level. A cross-sectional study with a random sample of 455 Japanese rural residents aged 40-69 years was conducted in 2000 to investigate the associations of plasma tHcy concentration with 5,10-methylenetetrahydrofolate reductase (MTHFR) gene and selected life-style related factors. The frequency of the mutant allele, Valine (V) allele, was 0.40 and the prevalence of VV genotype was 14.3%. Plasma tHcy concentration in VV was significantly higher than those in two other genotypes. There were significant inverse associations of plasma tHcy with serum folate and serum vitamin B12 (P<0.001 for trend, respectively); both being stronger in VV than in other genotypes. The number of cigarettes smoked per day was positively associated with plasma tHcy concentration. A multivariate regression analysis revealed that serum folate, serum vitamin B12, and MTHFR genotype were independently associated with plasma tHcy. The inter-individual variance of plasma tHcy was more explained by serum folate and vitamin B12 than by MTHFR genotype. Higher intakes of folate, vitamin B12, and non-smoking may be important to prevent mild hyperhomocysteinemia and the eventual atherosclerotic diseases in this Japanese rural population.     

Detergent-induced epidermal barrier dysfunction and its prevention

Various detergents are used as skin cleansing products. In some cases, skin cleanser removes not only dirt but also valuable skin lipids. Therefore, detergents may disrupt epidermal barrier function despite that using of detergents are required for good skin hygiene. Lipid supplements can reverse detergent-induced dysfunction of the skin barrier. Elevated transepidermal water loss (TEWL) and riboflavin penetration in 5% SLS-treated rat and human skin were reversed by supplementation of monoglyceride (MG), squalene (SQ), cholesterol ester (CE) and pseudo-ceramide (Cer2). MG and Cer2 achieved the best results. MG appears to inhibit elution of intercellular ceramides, since more ceramides remained when the detergent was supplemented with MG. Topical application of Cer2 is not effective for recovery from artificially induced barrier disruption, but supplemented Cer2 into skin cleanser has a beneficial effect for prevention of detergent-induced barrier disruption. In conclusion, the prevention of barrier disruption is most important matter for maintaining skin health and barrier function. Therefore, we think that Cer2-supplemented skin cleanser is useful for conservation of skin barrier function.     

Nasal immunization of mice with peptide having a cross-neutralization epitope on minor capsid protein L2 of human papillomavirus type 16 elicit systemic and mucosal antibodies

A common cross-neutralization epitope for human papillomavirus types 6 and 16 (HPV 6 and 16) is present in the region of amino acids (aa) 108-120 of HPV-16 minor capsid protein, L2. We nasally immunized Balb/c mice with a synthetic peptide with the 13 aa HPV 16 L2 sequence, and examined the antibodies elicited. ELISA showed that the immunization induced predominantly IgG and IgA antibodies cross-binding to L1/L2-capsids of HPVs 6, 16, and 18 in sera and in vaginal secretions, respectively. The serum containing the IgG antibody and the vaginal wash containing the IgA antibody neutralized HPV 16 pseudovirions and HPV 11 authentic virions, as shown by surrogate infectivity assays. From their cross-binding activity for HPV 16 and 18, the peptide-induced antibodies can probably cross-neutralize most of the genital HPVs. The peptide-induced neutralizing activity in vaginal wash was comparable to that induced by nasally immunization with HPV 16 L1-capsids. Unlike Balb/c, C57BL/10, which has different MHC class II, did not respond to the peptide immunization, but aa substitutions in the peptide to fulfill the requirement for the C57BL/10 agretope rendered the modified peptides immunogenic. The results provide a basis for development of a peptide vaccine against broad-spectrum of genital HPVs for humans.