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Abstract:In the present study, we first examined the expression of T-cadherin in human CNS by northern blot analysis, immunohistochemical staining, and in situ hybridization. Northern blot analysis demonstrated expression of T-cadherin in human adult cerebral cortex, medulla, thalamus, and midbrain. Immunohistochemical staining with a newly generated monoclonal antibody, designated MA-511, revealed strong expression of Tcadherin in neural cell surface membrane and neurites in adult cerebral cortex, medulla oblongata, and nucleus olivaris. Little or no expression of T-cadherin was found in spinal cord. We further examined T-cadherin expression in various developing nervous systems, and found that T-cadherin expression was lower in developing brain than in adult brain. In situ hybridization revealed that neural cells in medulla oblongata and nucleus olivaris, but not in spinal cord, possessed T-cadherin molecules. We transfected T-cadherin-negative TGW and NH-12 neuroblastoma cells with a T-cadherin cDNA-containing expression vector. T-cadherin-expressing neuroblastoma cells lost mitogenic proliferative response to epidermal growth factor. Epidermal growth factor is known to be required for proliferation of neural stem cells. This finding, together with those of the present study, suggests that T-cadherin functions as a negative regulator of neural cell growth. Key Words: T-cadherinBrain-Monoclonal antibody-MA-511-Epidermal growth factor-Neuroblastoma.

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A global transcriptional co-activator, the SNF/SWI complex, has been characterized as a chromatin remodeling factor that enhances accessibility of the transcriptional machinery to DNA within a repressive chromatin structure. On the other hand, mutations in some human SNF/SWI complex components have been linked to tumor formation. We show here that SYT, a partner protein generating the synovial sarcoma fusion protein SYT-SSX, associates with native human SNF/SWI complexes. The SYT protein has a unique QPGY domain, which is also present in the largest subunits, p250 and the newly identified homolog p250R, of the corresponding SNF/SWI complexes. The C-terminal region (amino acids 310 -387) of SSX1, comprising the SSX1 portion of the SYT-SSX1 fusion protein, binds strongly to core histones and oligonucleosomes in vitro and directs nuclear localization of a green fluorescence protein fusion protein. Experiments with serial C-terminal deletion mutants of SSX1 indicate that these properties map to a common region and also correlate with the previously demonstrated anchorage-independent colony formation activity of SYT-SSX in Rat 3Y1 cells. These data suggest that SYT-SSX interferes with the function of either the SNF/SWI complexes or another SYT-interacting co-activator, p300, by changing their targeted localization or by directly inhibiting their chromatin remodeling activities.The chromatin structure of active eukaryotic genes is subject to dynamic change by chromatin modifiers such as ATP-dependent chromatin remodeling factors (reviewed in Refs. 1-5). Homologs of a yeast prototype ATP-dependent remodeling complex, SNF/SWI, appear to be widely present in eukaryotes from yeast to humans (6 -8). Functions of the subunits of the SNF/ SWI complexes (9, 10) were first demonstrated by genetic studies in Saccharomyces cerevisiae, which showed that SWI1/ ADR6, SWI2/SNF2, SWI3, and SNF5 are required for the expression of a set of genes that include the HO, GAL1, SUC2, and ADH2 genes (11-13). In Drosophila melanogaster, the SWI2/SNF2 homolog brm was originally identified as a suppressor of Polycomb mutations (14). The Drosophila complex has been isolated, and some of the subunits have been characterized (15, 16), revealing that the SNF/SWI complexes are highly conserved in subunit composition and in primary structure among yeast, fruit fly, and human. A number of studies have described various biochemical properties of the human and yeast SNF/SWI complexes, as well as other ATP-dependent chromatin remodeling complexes (reviewed in Refs. 1-3, 17). For instance the SNF/SWI complexes are recruited by transcriptional activators to nucleosomal templates (18 -23), perturb nucleosome positioning, and facilitate binding of activator proteins to nucleosomes (24 -26). Mechanisms for this perturbation have been proposed to involve interconversion between two different nucleosomal states (27), sliding of histone octamers (28) or a change of DNA topology (29, 30).The human complexes are composed of at least nine subunits that include appar...

The present study was designed to evaluate the pathological and immunohistochemical findings of Mycobacterium avium intracellulare complex (MAC) lung infection.A retrospective study was performed in five cases with positive cultures for MAC in whom lung resections were performed between January 1989 and December 1996. A determination of whether or not MAC caused pulmonary disease was made using the 1997 criteria defined by the American Thoracic Society. In addition, MAC was cultured from all of the five lung specimens. Pathological and immunohistochemical findings as well as chest computed tomography (CT) findings were evaluated in these five patients.Pathological findings of bronchiectasis, bronchiolitis, centrilobular lesion, consolidation, cavity wall and nodules were demonstrated, respectively, in relation to chest CT findings. Extensive granuloma formation throughout the airways was clearly demonstrated. Immunohistochemical staining demonstrated: 1) epithelioid cells and giant cells; 2) myofibroblasts extensively infiltrating the cavity wall; and 3) B-cells detected in aggregates in the vicinity of the epithelioid granulomas.This study identified pathological and immunohistochemical characteristics of Mycobacterium avium complex infection relative to chest computed tomography findings and allowed the conclusion that bronchiectasis and bronchiolitis were definitely caused by Mycobacterium avium complex infection. Eur Respir J 1999; 13: 535±540.

A ndrogens play an important role in the development and maintenance of the normal prostate as well as the initiation and progression of prostate cancer.(1,2) Androgen deprivation therapy remains the mainstay of treatment for prostate cancer once it has progressed outside the prostate capsule.(2) The androgen receptor (AR) belongs to the steroid hormone subfamily of nuclear hormone receptors and mediates the signal of androgens. AR is complexed in the cytoplasm to chaperone proteins that keep the receptor in a transcriptionally inactive form. Upon binding to the ligands, AR dissociates from the chaperone and translocates to the nucleus, where it binds to androgen response elements (ARE), recruits coregulators, and activates target genes such as prostate specific antigen (PSA).(1,2) PSA belongs to the kallikrein-like serine protease family; it is produced almost exclusively by the prostate epithelial cells, and is used as a serum marker for the diagnosis and progression of prostate cancer.(3) The 5′ upstream promoter and enhancer region of the PSA gene contains several ARE to which ligandactivated AR binds and induces expression of PSA. (4)(5)(6) The JAK/STAT (Janus family tyrosine kinase [JAK]/signal transducer and activator of transcription [STAT]) signal pathway is involved in the control of gene expression in response to extracellular stimuli including cytokines and hormones, as well as growth factors, and regulate a variety of biological responses, such as development, differentiation, and proliferation. (7,8) Once STAT proteins are activated by tyrosine-phosphorylation, they form homo-or heterodimers and translocate to the nucleus, where they bind to specific sequences of target genes, thereby stimulating gene transcription. STAT3 is one of the seven STAT family members. Recent studies have shown that STAT3 is constitutively activated in a wide variety of cancer cells, including those from cancers of the head and neck, breast and prostate, and multiple myeloma, as well as malignant lymphoma. (7)(8)(9)(10)(11) Thus, STAT3 might be a promising molecular target in a variety of cancer cells.AKT/protein kinase B (PKB) is a serine (Ser)/threonine (Thr) protein kinase and plays an important role in controlling cell growth and apoptosis.(12) Upstream of AKT is phosphatidylinositol 3-kinase (PI3-K), which activates AKT by phosphorylation at Ser 473 and Thr 308 of AKT.(12) The activated AKT phosphorylates target molecules including Bad, forkhead transcriptional factor (FKHR), and glycogen synthase kinase-3 (GSK-3β), which induce antiapoptotic effects.(13-15) Phosphatase and rensin homologue (PTEN) phosphatase is a major negative regulator of the PI3-K/AKT signal pathway. (16,17) In many cancer types, including prostate cancer, phosphatase and tensin homologue (PTEN) is inactivated by several mechanisms, including homozygous deletions, hemizygous deletions and mutations on the second allele, or methylation of its promoter region. Loss of expression of this phosphatase results in constitutive activation of AKT signalin...

There is increasing acknowledgment of the public health burden of metabolic syndrome. The metabolic syndrome is defined as emerging cardiovascular risk factors, or atherosclerosis, that are related to underlying insulin resistance. One of the adipokines, adiponectin, has antiatherogenic effects and augments the metabolic effects of insulin. To reduce mortality from cardiovascular disease, it is important to understand the pathophysiological properties of adiponectin and receptors in atherosclerotic regions. Recently, T-cadherin, which has been recognized as a unique cadherin molecule, has been characterized as a novel adiponectin receptor on vascular endothelial cells and smooth muscle. Notably, T-cadherin (also known as CDH13, cadherin 13, and H-cadherin) is abundantly expressed in injured vascular endothelial and smooth muscle cells in atherosclerotic regions. In the present review, we describe recent progress in research on adiponectin receptors, with emphasis on the unique vascular adiponectin receptor, T-cadherin, and its role in vascular disease.