As a base for human transcriptome and functional genomics, we created the "full-length long Japan" (FLJ) collection of sequenced human cDNAs. We determined the entire sequence of 21,243 selected clones and found that 14,490 cDNAs (10,897 clusters) were unique to the FLJ collection. About half of them (5,416) seemed to be protein-coding. Of those, 1,999 clusters had not been predicted by computational methods. The distribution of GC content of nonpredicted cDNAs had a peak at ∼58% compared with a peak at ∼42%for predicted cDNAs. Thus, there seems to be a slight bias against GC-rich transcripts in current gene prediction procedures. The rest of the cDNAs unique to the FLJ collection (5,481) contained no obvious open reading frames (ORFs) and thus are candidate noncoding RNAs. About one-fourth of them (1,378) showed a clear pattern of splicing. The distribution of GC content of noncoding cDNAs was narrow and had a peak at ∼42%, relatively low compared with that of protein-coding cDNAs.

The age-adjusted incidence of prostate cancer is low in Japan, and it has been suggested that the traditional Japanese diet, which includes many soy products, plays a preventive role against prostate cancer. We performed a case-control study on dietary factors and prostate cancer in order to assess the hypothesis that the traditional Japanese diet reduces the risk of prostate cancer. Four geographical areas (Ibaraki, Fukuoka, Nara, and Hokkaido) of Japan were selected for the survey. Average daily intake of food from 5 years before the diagnosis was measured by means of a semi-quantitative food frequency questionnaire. We studied 140 cases and 140 individually age ( ± ± ± ±5 years)-matched hospital controls for analysis. Estimates of age-adjusted odds ratios (ORs) and linear trends were calculated by conditional logistic regression models with adjustment for cigarette smoking and total energy intake as confounding factors. Consumption of fish, all soybean products, tofu (bean curds), and natto (fermented soybeans) was associated with decreased risk. ORs of the fourth vs. first quartile and 95% confidence intervals (95%CIs) were 0.45 (0.20-1.02) for fish, 0.53 (0.24-1.14) for all soybean products, 0.47 (0.20-1.08) for tofu, and 0.25 (0.05-1.24) for natto. Consumption of fish and natto showed significantly decreasing linear trends for risk (P < < < <0.05). Consumption of meat was significantly associated with increased risk (the OR of the second vs. first quartile was 2.19, 95%CI 1.00-4.81). Consumption of milk, fruits, all vegetables, green-yellow vegetables, and tomatoes showed no association. Our results provide support to the hypothesis that the traditional Japanese diet, which is rich in soybean products and fish, might be protective against prostate cancer. (Cancer Sci 2004; 95: 238-242) he age-standardized incidence of prostate cancer is low in Japan (10.0 per 100,000), being approximately one-tenth of that in the United States.1) Among Japanese immigrant in Hawaii, age-standardized incidence of prostate cancer is approximately ten times that in Japan.2) It is suggested that environmental factors such as dietary habits play a major role in causation of prostate cancer. A number of case-control studies have indicated that high intake of fat, especially saturated fat, increases the risk of prostate cancer.3) In contrast, high intake of isoflavone, which is mainly found in soybeans and soy products, may reduce the risk of prostate cancer. 4,5) The traditional Japanese diet which includes many soy products is richer in isoflavone, 6,7) and contains less fat than the Western diet. However, an epidemiological study of prostate cancer in Kyoto in 1988 8) yielded no evidence that fat or soybeans were associated with the risk of prostate cancer.Recently in Japan, the incidence rate of prostate cancer has been increasing cocomitantly with the westernization of dietary habits. We carried out a case-control study on dietary factors and prostate cancer to assess the hypothesis that the traditional Japanese diet reduc...

The genes Tlx1 (Hox11), Enx (Hox11L2, Tlx-2) and Rnx (Hox11L2, Tlx-3) constitute a family of orphan homeobox genes. In situ hybridization has revealed considerable overlap in their expression within the nervous system, but Rnx is singularly expressed in the developing dorsal and ventral region of the medulla oblongata. Tlx1-deficient and Enx-deficient mice display phenotypes in tissues where the mutated gene is singularly expressed, resulting in asplenogenesis and hyperganglionic megacolon, respectively. To determine the developmental role of Rnx, we disrupted the locus in mouse embryonic stem (ES) cells. Rnx deficient mice developed to term, but all died within 24 hours after birth from a central respiratory failure. The electromyographic activity of intercostal muscles coupled with the C4 ventral root activity assessed in a medulla-spinal cord preparation revealed a high respiratory rate with short inspiratory duration and frequent apnea. Furthermore, a coordinate pattern existed between the abnormal activity of inspiratory neurons in the ventrolateral medulla and C4 motorneuron output, indicating a central respiratory defect in Rnx mice. Thus, Rnx is critical for the development of the ventral medullary respiratory centre and its deficiency results in a syndrome resembling congenital central hypoventilation.

As an extension of our human cDNA project for accumulating sequence information on the coding sequences of unidentified genes, we here present the entire sequences of 100 cDNA clones of unidentified genes, named KIAA1673-KIAA1772, from three sets of size-fractionated cDNA libraries derived from human adult whole brain, hippocampus, and fetal whole brain. The average sizes of the inserts and corresponding open reading frames of cDNA clones analyzed here were 4.9 kb and 2.7 kb (corresponding to 895 amino acid residues), respectively. By computer-assisted analysis of the deduced amino acid sequences, 44 predicted gene products were classified into five functional categories of proteins relating to cell signaling/communication, nucleic acid management, cell structure/motility, protein management, and metabolism. Furthermore, the expression profiles of the genes were also studied in 10 human tissues, 8 brain regions, spinal cord, fetal brain and fetal liver by reverse-transcription-coupled polymerase chain reaction, the products of which were quantified by enzyme-linked immunosorbent assay.

We examined associations between nutritional and other lifestyle factors and the prevalence of prostate cancer in a casecontrol study of Japanese men. Two hundred patients and 200 age-matched controls (65 y) were selected from 3 geographic areas of Japan. BMI, physical activity, occupation, family history of prostate cancer, and medical history were not associated with prostate cancer risk. Isoflavones and their aglycones (genistein and daidzein) were significantly associated with decreased risk. The odds ratio for the highest category ($89.9 mg/d) compared with the lowest category (,30.5 mg/d) of isoflavone intake was 0.42 (95% CI ¼ 0.24-0.72) and the linear trend was significant (P , 0.01). PUFA, (n-6) fatty acids, and magnesium were significantly associated with decreased risk but not after adjustment for isoflavone intake. Isoflavone intake was correlated with the intake of PUFA (r ¼ 0.68, P , 0.001), (n-6) fatty acids (r ¼ 0.69, P , 0.001), and magnesium (r ¼ 0.56, P , 0.001), because soy products contain high levels of these nutrients. On the other hand, isoflavone significantly decreased the risk of prostate cancer regardless of adjustment by PUFA, (n-6) fatty acids or magnesium. In conclusion, our findings indicate that isoflavones might be an effective dietary protective factor against prostate cancer in Japanese men.

To investigate the molecules that regulate the acquisition of cis-diamminedichloroplatinum (II) (cisplatin) resistance, we performed cDNA microarrays using two pairs of parental and cisplatin-resistant bladder cancer cell lines. We found a markedly reduced expression of inositol 1,4,5-trisphosphate (IP 3 ) receptor type1 (IP 3 R1), endoplasmic reticulum membrane protein, in cisplatin-resistant cells. The suppression of IP 3 R1 expression using small interfering RNA in parental cells prevented apoptosis and resulted in decreased sensitivity to cisplatin. Contrarily, overexpression of IP 3 R1 in resistant cells induced apoptosis and increased sensitivity to cisplatin. These results suggest that cisplatin-induced downregulation of IP 3 R1 expression was closely associated with the acquisition of cisplatin resistance in bladder cancer cells.

A case of multicentric papillary renal cell carcinoma (RCC) associated with renal adenomatosis in the bilateral kidneys is reported. Bilateral multiple renal cysts in a 46-year-old man were pointed out incidentally by ultrasonography. Some of the left renal lesions were considered to be RCC, and left radical nephrectomy was performed accordingly. The left kidney was occupied by numerous solid nodules, which ranged from yellow to tan in color, and some of the large ones had foci of hemorrhage and necrosis. Microscopically, most of the tumors showed papillary RCC associated with renal adenoma, while others consisted only of adenomas. Ten months later, multiple lesions of the right kidney, which were initially considered to be multiple cysts, were found to have become enlarged and some of them were diagnosed as RCC. Thus, right radical nephrectomy was also performed, and these tumors showed the same features as the left renal tumors. The patient's familial history was not remarkable. The kidneys revealed various histological features, ranging from dysplastic to adenoma or carcinoma, including transitional or overlapping features between them. The findings suggest an adenoma-carcinoma sequence in papillary RCC. It is worth considering such entities.

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