Congenital nephrotic syndrome of the Finnish type (NPHS1) is an autosomal-recessive disorder, characterized by massive proteinuria in utero and nephrosis at birth. In this study, the 150 kb critical region of NPHS1 was sequenced, revealing the presence of at least 11 genes, the structures of 5 of which were determined. Four different mutations segregating with the disease were found in one of the genes in NPHS1 patients. The NPHS1 gene product, termed nephrin, is a 1241-residue putative transmembrane protein of the immunoglobulin family of cell adhesion molecules, which by Northern and in situ hybridization was shown to be specifically expressed in renal glomeruli. The results demonstrate a crucial role for this protein in the development or function of the kidney filtration barrier.

Objective: The incidence of breast cancer has progressively increased, making it the leading cause of cancer deaths in Japan. Breast cancer accounts for 20.4% of all new cancers with a reported agestandardized rate of 63.6 per 100 000 women. Methods: The Japanese Guidelines for Breast Cancer Screening were developed based on a previously established method. The efficacies of mammography with and without clinical breast examination, clinical breast examination and ultrasonography with and without mammography were evaluated. Based on the balance of the benefits and harms, recommendations for populationbased and opportunistic screenings were formulated. Results: Five randomized controlled trials of mammographic screening without clinical breast examination were identified for mortality reduction from breast cancer. The overall relative risk for women aged 40-74 years was 0.75 (95% CI: 0.67-0.83). Three randomized controlled trials of mammographic screening with clinical breast examination served as eligible evidence for mortality reduction from breast cancer. The overall relative risk for women aged 40-64 years was 0.87 (95% confidence interval: 0.77-0.98). The major harms of mammographic screening were radiation exposure, false-positive cases and overdiagnosis. Although two case-control studies evaluating mortality reduction from breast cancer were found for clinical breast examination, there was no study assessing the effectiveness of ultrasonography for breast cancer screening. Conclusions: Mammographic screening without clinical breast examination for women aged 40-74 years and with clinical breast examination for women aged 40-64 years is recommended for population-based and opportunistic screenings. Clinical breast examination and ultrasonography are not recommended for population-based screening because of insufficient evidence regarding their effectiveness.

Japanese smokers attempt to quit at a lower rate than smokers in the United Kingdom and United States, but factors that predict attempts (primarily markers of motivation) and success of attempts (primarily dependence) are similar to those found in western samples.

The complete primary structure of the mouse laminin ␣4 chain was derived from cDNA clones. The translation product contains a 24-residue signal peptide preceding the mature ␣4 chain of 1,792 residues. Northern analysis on whole mouse embryos revealed that the expression was weak at day 7, but it later increased and peaked at day 15. In adult tissues the strongest expression was observed in lung and cardiac and skeletal muscles. Weak expression was also seen in other adult tissues such as brain, spleen, liver, kidney, and testis. By in situ hybridization of fetal and newborn tissues, expression of the laminin ␣4 chain was mainly localized to mesenchymal cells. Strong expression was seen in the villi and submucosa of the developing intestine, the mesenchymal stroma surrounding the branching lung epithelia, and the external root sheath of vibrissae follicles, as well as in cardiac and skeletal muscle fibers. In the developing kidney, intense but transient expression was associated with the differentiation of epithelial kidney tubules from the nephrogenic mesenchyme. Immunohistologic staining with affinity-purified IgG localized the laminin ␣4 chain primarily to lung septa, heart, and skeletal muscle, capillaries, and perineurium.

Ultrasonography has been used for breast cancer screening in Japan. Screening using a conventional hand-held probe is operator dependent and thus it is possible that some areas of the breast may not be scanned. To overcome such problems, a mechanical whole breast ultrasound (US) scanner has been proposed and developed for screening purposes. However, another issue is that radiologists might tire while interpreting all images in a large-volume screening; this increases the likelihood that masses may remain undetected. Therefore, the aim of this study is to develop a fully automatic scheme for the detection of masses in whole breast US images in order to assist the interpretations of radiologists and potentially improve the screening accuracy. The authors database comprised 109 whole breast US imagoes, which include 36 masses (16 malignant masses, 5 fibroadenomas, and 15 cysts). A whole breast US image with 84 slice images (interval between two slice images: 2 mm) was obtained by the ASU-1004 US scanner (ALOKA Co., Ltd., Japan). The feature based on the edge directions in each slice and a method for subtracting between the slice images were used for the detection of masses in the authors proposed scheme. The Canny edge detector was applied to detect edges in US images; these edges were classified as near-vertical edges or near-horizontal edges using a morphological method. The positions of mass candidates were located using the near-vertical edges as a cue. Then, the located positions were segmented by the watershed algorithm and mass candidate regions were detected using the segmented regions and the low-density regions extracted by the slice subtraction method. For the removal of false positives (FPs), rule-based schemes and a quadratic discriminant analysis were applied for the distribution between masses and FPs. As a result, the sensitivity of the authors scheme for the detection of masses was 80.6% (29/36) with 3.8 FPs per whole breast image. The authors scheme for a computer-aided detection may be useful in improving the screening performance and efficiency.