Novel BEST1 mutation in autosomal recessive bestrophinopathy in Japanese siblings.

PURPOSE: Autosomal recessive bestrophinopathy (ARB) is a disease that results from the mutations in the BEST1 gene. It is characterized by multifocal yellowish lipofuscin deposits, cystoid macular edema, and subretinal fluid. Among approximately 270 BEST1 mutations, only 40 that include both heterozygous and homozygous mutations are associated with ARB. However, very few ARB-related mutations have been reported in the Japanese population. Therefore, in this study, we aimed to identify BEST1 mutations and describe the genotype-phenotype relationship in Japanese dizygotic twins presenting with ARB. MATERIALS AND METHODS: We performed clinical examinations in Japanese dizygotic twin patients (male: 29 years) with ARB as well as whole-exome sequencing in seven family members of these twins. RESULTS: In this study, we have reported on a novel BEST1 mutation, the p. Phe151Cys mutation, associated with ARB in Japanese dizygotic twins who had bi-allelic p. Ala160Pro mutations in BEST1. The clinical features observed were binocular abnormalities of the fundus, such as multifocal yellowish subretinal deposits, cystoid macular edema, and subretinal fluid. The full-field electroretinography results were subnormal. CONCLUSION: It was indicated that the novel BEST1 mutations identified may be strongly correlated with binocular ARB. This study provides significant information of the genotype-phenotype association in Japanese ARB patients. Further, the genetic analysis that we performed was very useful for the differential diagnosis and might have implications in the development of future treatment modalities.

Predictive factors for ocular complications caused by anticancer drug S-1.

PURPOSE: To identify predictive factors for ocular complications caused by the anticancer drug S-1. METHODS: A questionnaire was administered to 39 patients who underwent S-1 chemotherapy at Kobe City Medical Center General Hospital, with the aim to determine whether these patients were aware of the ocular complications caused by S-1. Cognition rate was determined. The 26 patients who requested opthalmological examination for further evaluation studied further and classified into two groups-those who had developed corneal epithelial complications, conjunctival injection or chemosis, or lacrimal duct blockages (referred to as the positive group) and those without these findings (referred to as the negative group). Predictive factors, such as age, sex, total administration days, total dose, presence or absence of anticancer drug pretreatment, and single-drug or combination-drug therapy, were investigated and compared between groups. RESULTS: Of the 39 patients who completed the questionnaire, ten were aware of the potential for ocular complications due to S-1 chemotherapy (cognition rate 25.6 %). Of the 26 patients who had requested opthalmological examination and entered into the study, 13 (26 eyes) were classified into the positive group, with corneal complications observed in 15 eyes (57.7 %), conjunctivitis in 26 eyes (100 %), and lacrimal duct blockage in 14 eyes (53.8 %). Cognition rate in the 13 patients in the positive group and the 13 patients in the negative group was 38.5 % (5 patients) and 7.7 % (1 patient), respectively. Patient age was significantly different between the two groups, with the patients in the positive group being significantly older than those in the negative group (mean age ± standard deviation: 71.6 ± 6.8 vs. 63.5 ± 7.3 years, respectively; P = 0.0077, Student's t test). No other significant predictive factors were detected. CONCLUSION: Older patients were at greater risk of S-1-related ocular complications, but these complications were not associated with total administration days or total dose.

Predictive factors for recurrence of macular edema after successful intravitreal bevacizumab therapy in branch retinal vein occlusion.

PURPOSE: Our aim was to investigate predictive factors associated with efficacy and recurrence after intravitreal bevacizumab (IVB) therapy for macular edema (ME) in patients with branch retinal vein occlusion (BRVO). METHODS: Fifty-two eyes of 52 patients who underwent IVB as a primary treatment against ME associated with BRVO were included retrospectively. Based on the postoperative central retinal thickness (CRT), the patients were classified into two groups: an effective group in which the CRT decreased to ≤250 µm within postoperative 3 months and an ineffective group in which the CRT remained >250 µm throughout the first 3 months. The effective group was then divided into two subgroups: a recurrent group in which ME had once resolved but recurred afterward, and a nonrecurrent group in which the resolution of ME was maintained throughout the follow-up period without additional injections. Preoperative factors such as age, gender, estimated elapsed time from disease onset to IVB, visual acuity, and CRT were compared between groups. RESULTS: There was no significant difference between effective (n = 37) and ineffective (n = 15) groups in all preoperative factors. Between recurrent (n = 26) and nonrecurrent (n = 11) groups, elapsed time was significantly different (29.7 ± 29.5 vs. 15.7 ± 8.9 weeks, respectively; P = 0.036), and there were no significant differences in the remaining factors. CONCLUSIONS: Early IVB treatment against BRVO may suppress ME recurrence.

Synthesis of OSW-1 derivatives by site-selective acylation and their biological evaluation.

A strategy to site-selectively monoacylate an antitumor saponin OSW-1 was developed using an organotin reagent to rapidly access its derivatives that are useful as chemical probes. 4″-O-Acylated OSW-1 derivatives bearing a fluorophore, an alkyne tag, or biotin were prepared in good yields and were shown to maintain highly cytotoxic activity.

Fluorescent analog of OSW-1 and its cellular localization.

OSW-1 is a steroidal saponin, which has emerged as an attractive anticancer agent with highly cancer cell selective activity. A fluorescent analog was prepared from the natural product to analyze its cellular uptake and localization. We found that the fluorescent analog is rapidly internalized into cells and is primarily distributed in endoplasmic reticulum and Golgi apparatus.

High prevalence of intermediate-risk human papillomavirus infection in uterine cervices of Kenyan women infected with human immunodeficiency virus.

The aim of this study was to investigate an association between certain human papillomavirus (HPV) types and human immunodeficiency virus (HIV) infections. Sexually active females (n = 487; 19-61 years old) were enrolled in the study. Subjects underwent Pap testing and evaluations of HIV and HPV infection status on uterine cervical cell samples. HPV genotyping was performed using a Kurabo GeneSQUARE DNA microarray test. Overall, 23 HPV genotypes were detected, and the most prevalent HPV genotype was HPV-52, followed by HPV-39, -54, -45, -56, -53, -31, -42, -16, -68, and -51. HPV-30, -53, -54, -61, and -66, which are associated with abnormal cytology, are categorized as intermediate-risk in this study. Detection of both high- and intermediate-risk HPV types was significantly associated with cervical abnormality and HIV infection. Multivariate analysis revealed that some high-risk HPV types (HPV-31, -45, -51, -56, and -59) and most intermediate-risk HPV types were associated with HIV infection, while the high-risk types (HPV-16, -18, -33, -35, -39, -52, -58, and -68) were not. The oncogenic effect of the most malignant HPV types (e.g., HPV-16 and -18) appear to be lower, while that of intermediate-risk types are greater, in areas with a high prevalence of HIV infection.

A human immunodeficiency virus screening algorithm to address the high rate of false-positive results in pregnant women in Japan.

BACKGROUND: Prenatal human immunodeficiency virus (HIV) testing is essential for the prevention of mother-to-child transmission. However, false-positive results of screening testing are a concern as they may cause unnecessary emotional stress to pregnant women waiting for confirmatory test results. In regions with an extremely low prevalence, the positive predictive values of screening are unacceptably low rate. Here, we propose a HIV screening algorithm consisting of serial two fourth-generation enzyme immunoassays to reduce the number of false-positive screening results. METHODOLOGY/PRINCIPAL FINDINGS: When 6461 pregnant women presenting to two maternity hospitals located in the Tokyo metropolitan area of Japan from September, 2004 to January, 2006 were tested using Enzygnost HIV Integral as a first screening test, 27 showed positive reactions. When these positive reaction samples were tested using VIDAS HIV DUO Quick as a second screening test, only one of them had a positive reaction, and the remaining 26 were nonreactive. Confirmatory Western blots and nucleic acid amplification test also showed that one was positive and the remaining 26 were negative; the subject who was positive with the confirmatory tests was identical to the subject who was positive with the second screening test. Thus, by adding the second screening test, the false-positive rate was improved from 0.4% to 0%, and the positive predictive value from 3.7% to 100%, compared with the single screening test. CONCLUSION: By applying our serial screening algorithm to HIV testing in maternity hospitals, many uninfected pregnant women would not need to receive confirmatory tests and be subjected to emotional turmoil while waiting for their confirmatory test results. This algorithm would be suitable for HIV testing of pregnant women living in low prevalence regions such as Japan.

Human papillomavirus infection and cervical abnormalities in Nairobi, Kenya, an area with a high prevalence of human immunodeficiency virus infection.

Human papillomavirus (HPV) infection and cervical abnormalities, and their association with human immunodeficiency virus (HIV) infection were studied in 488 women who visited a health center in Nairobi. PCR-based HPV and cervical cytology tests were carried out on all participants, and peripheral CD4+ T cells and plasma HIV RNA were quantitated in HIV positive women. HIV were positive in 32% (155/488) of the women; 77% of these were untreated, and the others had been treated with anti-retroviral drugs within 6 months. Cervical HPV infection was detected in 17% of HIV negative and 49% of HIV positive women. Low-grade squamous intraepithelial lesions were observed in 6.9% of HIV negative and 21% of HIV positive women, while high-grade squamous intraepithelial lesions and cancer were seen in 0.6% and 5.8%, respectively. Multivariate analysis revealed that HIV and HPV infections were associated with each other. Cervical lesions were significantly associated with high-risk HPVs and with HIV infection, depending on HPV infection. HPV infection increased in accordance with lower CD4+ T cell counts and higher HIV RNA levels, and high-grade lesions were strongly associated with high-risk HPV infection and low CD4+ T cell counts. Immunosuppression as a result of HIV infection appears to be important for malignant progression in the cervix. Nationwide prevention of HIV infection and cervical cancer screening are necessary for the health of women in this area. High-risk HPV infection and low CD4+ T cell counts are the risk factors for cervical cancer.

Prevalência de enteroparasitoses no Jardim Uniäo da Vitória, Londrina-PR / Enteroparasitosis prevalence in the Jardim Uniäo da Vitória, Londrina-PR

O Jardim Uniäo da Vitória, localizado na Regiäo Sul da cidade de Londrina, abrange uma populaçäo de 12.000habitantes segundo informaçöes extra-oficiais e apresenta condiçöes de vida precária. Näo possui esgoto e parte dele näo é atendido pelo sistema de abastecimento de água tratada. Levando-se em conta que a presença ou ausência de água tratada e esgoto nas moradias podem ser traduzidas como indicadores de saúde de uma populaçäo, os autores tiveram como objetivo estabelecer a prevalência de enteroparasitose na populaçäo do Jardim Uniäo da Vitória e relacionar os resultados obtidos com o saneamento básico observado. Através dos resultados obtidos em 62 amostras do sexo masculino e56 amostras do sexo feminino constatou-se que, 56,8 por cento apresentaram positividade, sendo este resultado compatível com as condiçöes de saneamento básico observados