To demonstrate the cellular and subcellular localization of mouse vasa homologue protein during germ cell development, specific antibody was raised against the full-length MVH protein. The immunohistochemical analyses demonstrated that MVH protein was exclusively expressed in primordial germ cells just after their colonization of embryonic gonads and in germ cells undergoing gametogenic processes until the post-meiotic stage in both males and females. The co-culture of EG cells with gonadal somatic cells indicated inductive MVH expression caused by an intercellular interaction with gonadal somatic cells. In adult testis, MVH protein was localized in the cytoplasm of spermatogenic cells, including chromatoid bodies in spermatids, known to be a perinuclear nuage structure which includes polar granules that contain VASA protein in Drosophila.

Purpose: LATS1 and LATS2 are tumor suppressor genes implicated in the regulation of cell cycle. Methylation status of the promoter regions of these genes as well as its correlation with their mRNA levels were studied in human breast cancers. Correlation of LATS1 and LATS2 mRNA levels with clinicopathologic characteristics of breast tumors were also studied.Experimental Design: Methylation status of promoter regions of LATS1 and LATS2 was studied by a methylationspecific PCR and mRNA expression levels of LATS1 and LATS2 were determined by a real-time PCR assay in 30 breast cancers. In addition, correlation of LATS1 and LATS2 mRNA levels with clinicopathologic characteristics was studied in 117 breast cancers.Results: Methylation-specific PCR showed that of 30 tumors, LATS1 promoter region was hypermethylated in 17 tumors (56.7%) and LATS2 promoter region was hypermethylated in 15 (50.0%) tumors. LATS1 mRNA levels in breast tumors with hypermethylation (2.15 F F 0.37, mean F F SE) were significantly (P < 0.01) lower than those without hypermethylation (6.09 F F 1.38), and LATS2 mRNA levels in breast tumors with hypermethylation (1.42 F F 0.66) were also significantly (P < 0.01) lower than those without hypermethylation (3.10 F F 1.00). The decreased expression of LATS1 or LATS2 mRNA was significantly associated with a large tumor size, high lymph node metastasis, and estrogen receptor and progesterone receptor negativity. Furthermore, the decreased expression of LATS1 mRNA, but not LATS2 mRNA, was significantly (P < 0.05) associated with a poor prognosis.Conclusions: Hypermethylation of the promoter regions of LATS1 and LATS2 likely plays an important role in the down-regulation of their mRNA levels in breast cancers, and breast cancers with a decreased expression of LATS1 or LATS2 mRNA levels have a biologically aggressive phenotype.

Elevated intake of white rice is associated with an increased risk of type 2 diabetes in Japanese women. The finding that is suggestive of a positive association of rice intake in physically inactive men deserves further investigation.

The entire nucleotide sequence of an infectious clone of human T-cell leukemia virus type II provirus was determined. This provirus consists of 8952 nucleotides. In addition to long terminal repeats and gag, pol, env, and X, a protease gene that is responsible for processing the gag precursor protein was found. The protease gene is encoded in a different frame from gag and poi and was located between the gag and pol open reading frames. Human T-cell leukemia virus type I (HTLV-I) and human Tcell leukemia virus type II (HTLV-II) are typical exogenous human retroviruses and have some characteristics in common with other retroviruses (1-3). These two viruses are related. The gag proteins of these virions show immunological cross-reactivity (4). The nucleotide sequences of the env regions of the two viruses show about 65% homology (5), although their envelope proteins show low cross-reactivity (6). In addition, HTLV-II and HTLV-I have a sequence of about 1.6 kilobase pairs (kbp), called X or pX, between env and the 3' long terminal repeat (LTR) (3,7,8). From comparison of this sequence in the two viruses, we and others previously predicted that this sequence might be translated (7,8), and, in fact, proteins of 41 and 38 kDa were found to be encoded from this region in HTLV-I-and HTLV-Il-infected cells, respectively (9)(10)(11)(12).To elucidate the functions of other regions of the HTLV-TI genome, we have determined the entire nucleotide sequence of the provirus. The provirus examined was molecularly cloned from a patient (Mo) with hairy cell leukemia and was found to be replication competent (8, 13). Analysis of the nucleotide sequence indicated that the HTLV-II provirus has the structure LTR-gag-protease-pol-env-X-LTR in this order from the 5' end of the genome (Fig. 1).MATERIALS AND METHODS DNAs and Sequencing. An infectious clone of HTLV-II provirus, XH6.0, was subcloned in pBR322 at the BamHI site (13). The corresponding subclones, pH6-B5.0 and pH6-B3.5, which covered the 5' and 3' halves of the original provirus, respectively, were used for sequencing. The method of Maxam and Gilbert was mainly used for sequencing (14), and the M13 phage method (15) was used for sequencing part of the region of the pol gene. RESULTS AND DISCUSSIONThe nucleotide sequence of HTLV-II provirus consists of 8952 bases, as shown in Fig. 2. In addition to three major open reading frames, corresponding to gag, poi, and env, there are four large open reading frames. Three are located in the X region as reported previously (8) and the other is between the 3' end of gag and the 5' end of poi. This open reading frame was identified as the gene that codes for a protease that processes the precursor Gag protein to mature forms. The provirus has a genome structure (as shown in Fig. 4) different from that of any other retrovirus but similar to that of HTLV-I (3) and bovine leukemia virus (BLV) (16).LTR and 5' Noncoding Region. As we reported previously (17), the LTR has 763 bases, in which several functional domains, such as a promotor,...

Established risk factors for diabetes in western populations were also identified as predictors of the disease among Japanese. Moderate to high alcohol consumption was positively associated with the incidence of diabetes in Japanese lean (BMI < or = 22 kg/m2) men.