No abstract

No abstract

Renal ultrasonography was performed in 45,905 adults, including 41,364 without any signs suggesting urinary tract malignancies, 1,667 with microscopic hematuria only and 2,874 with some signs of malignancy. Renal lesions were found in 355 adults (0.858%) in the asymptomatic, 39 (2.3%) in the microscopic hematuria and 75 (2.6%) in the symptomatic groups, respectively. Renal cell carcinoma was found in 35 (7.5%) lesions: 19 (5.4%) in the asymptomatic, none in the microscopic hematuria and 16 (21.3%) in the symptomatic groups. A total of 47 patients, including 12 other renal cell carcinoma patients transferred from related hospitals, was grouped into 28 without and 19 with symptoms. Primary tumor size and clinical stages were significantly smaller and lower, respectively, in the asymptomatic group than in the symptomatic group. Radical nephrectomy was performed in all but 2 asymptomatic patients. The 5-year survival rates after nephrectomy were 94.7 and 60.9% for the asymptomatic and symptomatic groups, respectively (p less than 0.01). The results indicate that ultrasonography is a useful tool to detect low stage asymptomatic renal cell carcinoma at low cost.

Tec is the prototype of a recently emerging subfamily among nonreceptor type protein-tyrosine kinases and is known to become tyrosine-phosphorylated and activated by a wide range of cytokine stimulations in hematopoietic cells. Although Tec was recently shown to be involved in the cytokine-driven activation mechanism of c-fos transcription, it is yet obscure how Tec relays the signals from cell surface receptors to the nucleus. To identify signaling molecules acting downstream of Tec, we have looked for Tec-interacting proteins (TIPs) by using the yeast two-hybrid system. Here we report the identification and characterization of a novel protein, TIP3, which has been simultaneously identified by other groups as SOCS-1, JAB, or SSI-1. TIP3 carries one Src homology 2 domain with a sequence similarity to that of CIS. In 293 cells, TIP3 associates with Tec and suppresses its kinase activity. Interestingly, TIP3 can also down-regulate the activity of Jak2 but not that of Lyn. We propose that SOCS-1/JAB/SSI-1/TIP3 is a novel type of negative regulator to a subset of protein-tyrosine kinases.Tec is the prototype of a recently emerging subfamily among cytoplasmic protein-tyrosine kinases (PTKs), 1 the Tec family comprised of Tec (1), Btk (2, 3), Itk/Tsk/Emt (4 -6), Txk (7), and Bmx (8). Many members of this family are abundantly expressed in hematopoietic tissues, and Tec has been shown to be involved in the intracellular signaling systems of a wide range of cytokines including interleukin (IL)-3, IL-6, stem cell factor, granulocyte colony-stimulating factor, erythropoietin, and thrombopoietin (9 -14). In addition to cytokine receptors, recent studies have indicated that other cell surface receptors on lymphocytes, such as CD28 (15) We have recently revealed that transient introduction of Tec into an IL-3-dependent cell line, BA/F3 (17), resulted in marked elevation of the promoter activity of the c-fos protooncogene and that introduction of kinase-dead Tec suppressed the IL-3-driven activation of the c-fos promoter, suggesting that Tec is directly involved in the cytokine-driven activation mechanism of c-fos proto-oncogene.2 To investigate how Tec regulates c-fos transcription, we have searched for Tec-interacting proteins (TIPs) by using yeast two-hybrid screening and have identified seven TIPs. Here we report the molecular cloning and characterization of a novel protein, TIP3. The predicted TIP3 protein contains one Src homology (SH) 2 domain with the highest similarity to that of mouse CIS (18). In the reconstitution system in 293 cells, TIP3 was shown to bind to Tec and suppress its activity. We could further reveal that TIP3 is a negative regulator of Jak2. EXPERIMENTAL PROCEDURESIsolation of TIP3 cDNA-By using the MATCHMAKER two-hybrid system (CLONTECH, Palo Alto, CA), we conducted a yeast two-hybrid screen in which human Tec kinase domain (amino acids 357-630) fused to the DNA-binding domain of GAL4 was used as a "bait" to identify cDNA clones from a variety of cDNA libraries. From more than three million transf...