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Hajime Nawata

Publications and source records attributed to Hajime Nawata.

At least 19 recordsLinked to original sources
PubMed2003

Saturated free fatty acids, palmitic acid and stearic acid, induce apoptosis by stimulation of ceramide generation in rat testicular Leydig cell.

In men, obesity has generally been associated with reduced plasma testosterone levels and with elevation of the plasma free fatty acids (FFAs). In this study, we investigated the effects of saturated FFAs including palmitic acid (PA) and stearic acid (SA), and polyunsaturated FFA arachidonic acid (AA) on the survival of rat testicular Leydig cell cultured in vitro. PA and SA markedly suppressed Leydig cell survival in a time- and dose-dependent manner. In contrast, AA stimulated the cell proliferation at 5-10 times of physiological concentration. The suppressive effect of PA and SA on cell survival was caused by apoptosis evidenced by DNA ladder formation and Annexin V-EGFP/propidium iodide staining of the cells. The apoptotic effect of PA was possibly mediated by ceramide generation because it could be completely blocked by ceramide synthase inhibitor fumonisin B1 and exogenous ceramide itself could directly induce apoptosis in vitro. Surprisingly, the apoptosis induced by PA could be partly prevented by AA. These results indicate that PA and SA induce apoptosis in testicular Leydig cells by ceramide production and these apoptotic effects may be a possible mechanism for reproductive abnormalities in obese men, and AA can partly prevent the apoptotic effect induced by saturated FFA.

Animals↗
PubMed2003

[Cofactor diseases].

Explore the source record for details and available documents.

Androgen-Insensitivity Syndrome↗
PubMed2003

Expression of apoptosis-associated protein RCAS1 in macrophages of histiocytic necrotizing lymphadenitis.

Receptor-binding cancer antigen expressed on SiSo cells (RCAS1), which is recognized by the 22-1-1 monoclonal antibody (MoAb) against human uterine adenocarcinoma cell line SiSo, has been identified on various kinds of cancer cells. RCAS1 appears to be an apoptosis-associated protein that induces apoptosis in activated T-cells and erythroid progenitor cells. We previously demonstrated that monocytes/macrophages express RCAS1. In the present study, we investigated RCAS1 expression by 22-1-1 MoAb in histiocytic necrotizing lymphadenitis (HNL), which is characterized by necrotic lesions consisting of T-cells undergoing apoptosis and macrophages in proliferation. Expression of RCAS1 was analyzed by immunohistochemical staining in 9 cases of HNL and in 9 cases of reactive lymphadenitis used as a control. The ratio of RCAS1+ cells to CD68+ cells (monocytes/macrophages) was significantly higher in the patients with HNL than in the patients with reactive lymphadenitis (P = .0002; paired t test). Our findings suggest that RCAS1 expressed on macrophages may play an important role in the induction of activated T-cell apoptosis in cases of HNL.

Adolescent↗
PubMed2003

Novel germline mutation of the PTEN gene in a Japanese family with Cowden disease.

We report a novel germline mutation of the PTEN gene in a Japanese family with Cowden disease. A 46-year-old Japanese man and his mother were diagnosed as having Cowden disease. Their physical examinations revealed multiple facial trichilemmoma, oral mucosal papillomatosis, palmoplantar keratosis, and gastrointestinal polyposis. The single-strand conformation polymorphism (SSCP) analysis showed an abnormal band on exon 7 of their PTEN gene. Direct sequence analysis of exon 7 detected a TAAA insertion to codon 221, producing a stop codon (c.663ins TAAA).

Adult↗
PubMed2003

Interleukin-8 gene and protein expression are up-regulated by interleukin-1beta in normal human ovarian cells and a granulosa tumor cell line.

OBJECTIVE: To evaluate the expression, regulation, and role of interleukin (IL)-8 in human ovary. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Sixteen premenopausal women. INTERVENTION: Follicular fluid and granulosa lutein cells (GLCs) were collected during IVF cycles. Ovarian stromal and theca cells were obtained from women underwent surgery. KGN cells, the human granulosa cell tumor cell line, were also used. MAIN OUTCOME MEASURES: The levels of IL-8 and IL-1beta in follicular fluid and IL-8 protein production were determined using ELISA. Interleukin-8 and IL-8 receptor gene expression in ovarian cells and the effect of IL-8 on the proliferation of stromal cells were determined. The expression of pIkappaB was evaluated by Western blot, and the effect of NF-kappaB inhibitor APDC was examined by Northern blot analysis and ELISA in KGN cells. The levels of IL-8 and IL-1beta in follicular fluid; each concentration and the volume showed a positive correlation. Reverse transcription polymerase chain reaction showed the presence of IL-8 mRNA in all ovarian cells. In contrast, IL-8 receptor mRNA was only detected in stromal cells. The expression of IL-8 in GLCs and KGN cells was increased by addition of IL-1beta and TNFalpha. Interleukin-8 increased the proliferation of ovarian stromal cells. The expression of pIkappaB in KGN cells was induced by IL-1beta, and the effects were reduced by APDC. CONCLUSION(S): Interleukin 8 induced by IL-1beta via activation of NF-kappaB in granulosa cells may have a role in the periovulatory period of follicular maturation.

Blotting, Northern↗
PubMed2003

Clinical significance of serum RCAS1 levels detected by monoclonal antibody 22-1-1 in patients with cholangiocellular carcinoma.

BACKGROUND/AIMS: The tumor-associated antigen, RCAS1, has been reported to be expressed in various types of cancer, including cholangiocarcinoma. We measured serum RCAS1 levels in patients with intrahepatic cholangiocellular carcinoma (CCC) and other hepatobiliary diseases, and examined the clinical significance of serum RCAS1 as a tumor marker. METHODS: Sera collected from the patients and healthy volunteers were used for ELISA for RCAS1. The values of RCAS1 for CCC patients were compared to those of other tumor marker proteins. RESULTS: Serum RCAS1 levels exceeded the normal limit in a high percentage (73.9%) of CCC patients. The positivity rate was higher than those of CA19-9 and CEA. No correlation was found between the RCAS1 and CA19-9 concentrations. Serum RCAS1 was positive in many cases that were negative for CA19-9. Surgical resection of CCC reduced the RCAS1 level to within the normal range. On the other hand, serum RCAS1 levels were elevated in very few cases of benign hepatobiliary disease. CONCLUSIONS: As a tumor marker in CCC, RCAS1 is, at least, of complementary value to CA19-9 and CEA. Measuring serum RCAS1 contributes to the diagnostic accuracy, and is useful for estimating tumor progression or therapeutic effect.

Adult↗
PubMed2003

p16(INK4a) induces differentiation and apoptosis in erythroid lineage cells.

OBJECTIVE: Hematopoiesis is regulated by proliferation, differentiation, and death. p16(INK4a) has been reported to regulate apoptosis and differentiation of diverse cells, as well as arresting the cell cycle at G1 phase. The aim of this study is to explore the properties of p16 in apoptosis and differentiation of erythroid cells. METHODS: We transfected the INK4a gene to K562 cells, which defect the INK4a gene, and compared the effect of enforced expression of p16(INK4a) with that of various additives, topoisomerase I inhibitor (SN 38), interferon-alpha, phosphatidyl-inositol-3 kinase inhibitor (LY294002), and serum deprivation, which arrest cell cycle at different phases. We also investigated the role of p16(INK4a) in normal day-6 human erythroid colony-forming cells by transfecting the INK4a gene. RESULTS: p16(INK4a) induced cell cycle arrest at the G0/G1 phase, and promoted erythroid differentiation in viable K562 cells, but induced apoptosis in K562 cells with incomplete differentiation. The apoptosis induced by p16 was accompanied with downregulation of bcl-x and nuclear NF-kappaB. These findings were not observed in K562 cells treated with various additives. p16(INK4a) decreased the cell viability and promoted apoptosis in day-9 ECFC. CONCLUSION: We propose that p16(INK4a) plays a role in maintaining homeostasis during erythroid differentiation, and that the mechanisms for this effect are not confined to those inducing cell cycle arrest.

Apoptosis↗
PubMed2003

Activation function-1 domain of androgen receptor contributes to the interaction between two distinct subnuclear compartments.

The nucleus contains different sets of functional compartments often called "speckles". The splicing factor compartment (SFC) has been speculated to consist of SFs and transcription factors, which thus make transcription-splicing coupling possible at the periphery of SFC. Androgen receptor (AR), as well as glucocorticoid receptor (GR), is unique since most, if not all, of its activities are mediated via the constitutive activity of the activation function-1 (AF-1) function. Transcriptionally active AR produces 250-400 subnuclear fine speckles11 shared with GR or estrogen receptor (ER), which colocalize with chiefly activation function-2 (AF-2)-interacting p160 family- or CBP-related speckles. We herein report the isolation of ANT-1 (AR N-terminal domain (NTD) transactivating protein-1) enhancing autonomous AF-1 transactivation function of AR or GR, but not of estrogen receptor alpha (ERalpha). The ANT-1 was identical to a binding protein of human splicing factor U5 snRNP (U5 snRNP-associated protein). ANT-1 was compartmentalized into 15-20 coarse SFC speckles which were spatially distinct from but surrounded by the AR compartments. Our results suggest that ANT-1 may play a key role in the molecular interaction between two spatially distinct subnuclear compartments in a receptor-specific fashion, and thereby induce the strong autonomous transactivation functions either of AR- or GR-AF-1.

Binding Sites↗
PubMed2003

Sarcomatous hepatocellular carcinoma: a special reference to ordinary hepatocellular carcinoma.

BACKGROUND: Sarcomatous hepatocellular carcinoma (HCC) has a worse prognosis than ordinary HCC. The relationship between the malignant potential of sarcomatous HCC and cell proliferation or cell adhesion is unknown. This study was undertaken to clarify this relationship. METHODS: In 21 cases of sarcomatous HCC, including 16 surgically resected and five autopsy cases, immunohistochemistry was used to compare the sarcomatous component (s-comp) and the ordinary component (o-comp) within each sarcomatous HCC. RESULTS: We found 15 epithelial-cadherin (E-cadherin)-positive cases in o-comp (79%) and nine positive cases in s-comp (43%). The difference between sarcomatous HCC and ordinary HCC in E-cadherin-positive tumor prevalence was significant (P < 0.05). The Ki-67 (MIB1) labeling index ratio was 127 +/- 40 in s-comp and 80 +/- 33 in o-comp, and there was a greater tendency to have an ability to multiply in s-comp than in o-comp (P = 0.096). CONCLUSION: This study indicated that the loss of E-cadherin related to a morphological alteration in sarcomatous HCC; however, no relationship in respect to the malignant potential was found.

Adult↗
PubMed2003

Confirmation of superoxide generation via xanthine oxidase in streptozotocin-induced diabetic mice.

Reactive oxygen species (ROS) may play key roles in vascular inflammation and atherogenesis in patients with diabetes. In this study, xanthine oxidase (XO) system was examined as a potential source of superoxide in mice with streptozotocin (STZ)-induced experimental diabetes. Plasma XO activity increased 3-fold in diabetic mice (50 +/- 33 microU/ml) 2 weeks after the onset of diabetes, as compared with non-diabetic control mice (15 +/- 6 microU/ml). In vivo superoxide generation in diabetic mice was evaluated by an in vivo electron spin resonance (ESR)/spin probe method. Superoxide generation was significantly enhanced in diabetic mice, and the enhancement was restored by the administration of superoxide dismutase (SOD) and 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron), which was reported to scavenge superoxide. Pretreatment of diabetic mice with XO inhibitors, allopurinol and its active metabolite oxipurinol, normalized the increased superoxide generation. In addition, there was a correlation (r = 0.78) between the level of plasma XO activity and the relative degree of superoxide generation in diabetic and non-diabetic mice. Hence, the results of this study strongly suggest that superoxide should be generated through the increased XO seen in the diabetic model mice, which may be involved in the pathogenesis of diabetic vascular complications.

1,2-Dihydroxybenzene-3,5-Disulfonic Acid Disodium ↗
PubMed2003

Expression and diagnostic evaluation of the human tumor-associated antigen RCAS1 in pancreatic cancer.

INTRODUCTION: Receptor-binding cancer antigen expressed on SiSo cells (RCAS1) is one of the membrane molecules expressed on human cancer cells and is presumed to play a protective role for tumor cells against immune surveillance by inhibition of clonal expansion and induction of cell death in immunocytes. AIMS: To address whether RCAS1 is expressed in pancreatic cancer and whether serologic diagnostic evaluation is useful compared with that of carbohydrate antigen 19-9 (CA19-9) and soluble Fas ligand. METHODOLOGY: Immunohistochemical expression of RCAS1 was examined by staining with a 22-1-1 monoclonal antibody, and serum RCAS1 concentrations were determined by an enzyme-linked immunosorbent assay in 20 cases of ductal adenocarcinoma of the pancreas and other pancreatic diseases. RESULTS: Immunohistochemically, RCAS1 detection occurred in 100% (20/20) of ductal adenocarcinoma of the pancreas cases, 100% (6/6) of intraductal papillary-mucinous adenoma of the pancreas cases, and 40% (2/5) of chronic pancreatitis cases. RCAS1 was found in the cytoplasm of cancer cells and ductal cells. Serum RCAS1 concentrations in patients with ductal adenocarcinoma of the pancreas were significantly higher than those in patients with chronic pancreatitis (p < 0.0001), acute pancreatitis (p < 0.005), and autoimmune pancreatitis (p < 0.001). RCAS1 concentrations in patients with intraductal papillary-mucinous adenoma of the pancreas were also significantly higher than those in patients with chronic pancreatitis (p < 0.05) and autoimmune pancreatitis (p < 0.05). Positive serum RCAS1 samples (concentration, > or = 10 U/mL) were found most often in cases of pancreatic neoplasm (80% [16/20], ductal adenocarcinoma of the pancreas; and 60% [3/5], intraductal papillary-mucinous adenoma of the pancreas). By contrast, in cases of pancreatic inflammatory diseases, raised concentrations occurred in 9.4% (3/32) of chronic pancreatitis cases, none (0/6) of acute pancreatitis cases, and none (0/8) of autoimmune pancreatitis cases. The sensitivity of CA19-9 for ductal adenocarcinoma of the pancreas was 75% and the specificity was 73.1% compared with chronic pancreatitis. On the other hand, the sensitivity of RCAS1 for ductal adenocarcinoma of the pancreas was 80% and the specificity was 96.2% compared with chronic pancreatitis. The specificity of RCAS1 for chronic pancreatitis was higher than that of CA19-9. Serum soluble Fas ligand concentrations were not considerably different among these patients. CONCLUSIONS: RCAS1 was highly expressed in ductal adenocarcinoma of the pancreas, and serum RCAS1 concentrations in patients with ductal adenocarcinoma of the pancreas were significantly higher than those in patients with other inflammatory pancreatic diseases. Our results indicate that serum RCAS1 concentrations could be a new marker in screening procedures for pancreatic cancer.

Aged↗
PubMed2003

Protein kinase C-dependent increase in reactive oxygen species (ROS) production in vascular tissues of diabetes: role of vascular NAD(P)H oxidase.

Hyperglycemia seems to be an important causative factor in the development of micro- and macrovascular complications in patients with diabetes. Several hypotheses have been proposed to explain the adverse effects of hyperglycemia on vascular cells. Both protein kinase C (PKC) activation and oxidative stress theories have increasingly received attention in recent years. This article shows a PKC-dependent increase in oxidative stress in diabetic vascular tissues. High glucose level stimulated reactive oxygen species (ROS) production via a PKC-dependent activation of NAD(P)H oxidase in cultured aortic endothelial cells, smooth muscle cells, and renal mesangial cells. In addition, expression of NAD(P)H oxidase components were shown to be upregulated in vascular tissues and kidney from animal models of diabetes. Furthermore, several agents that were expected to block the mechanism of a PKC-dependent activation of NAD(P)H oxidase clearly inhibited the increased oxidative stress in diabetic animals, as assessed by in vivo electron spin resonance method. Taken together, these findings strongly suggest that the PKC-dependent activation of NAD(P)H oxidase may be an essential mechanism responsible for increased oxidative stress in diabetes.

Animals↗
PubMed2003

Gastric mucosa-associated lymphoid tissue lymphoma with adult T cell leukemia/lymphoma cell infiltration. case report.

This is the first case report of gastric mucosal-associated lymphoid tissue lymphoma with adult T cell leukemia/lymphoma (ATLL) cell infiltration. A 43-yr-old Japanese woman who was seropositive for antihuman T cell leukemia virus-I antibody complained of epigastric pain in April, 1996. Endoscopy showed gastric ulcers in the antrum. Biopsy specimens showed Helicobacter pylori infection. Her symptoms were relieved by treatment with ranitidine. In March, 1998, she complained of epigastric pain and abdominal fullness. Smears of peripheral blood revealed atypical lymphocytes with nuclear irregularity, consistent with ATLL cells. She was diagnosed to have ATLL. Endoscopy revealed multiple gastric ulcers in the antrum and the angle. Biopsy specimens demonstrated small centrocyte-like cells forming lymphoepithelial lesions, with infiltrations of large atypical lymphoid cells of ATLL. On immunohistochemical staining, the small centrocyte-like cells were positive for B cell markers (L26, CD20), whereas the large atypical lymphoid cells were positive for T cell marker (UCHL-1, CD45RO). Her findings were attributed to gastric mucosal-associated lymphoid tissue lymphoma with gastric involvement with ATLL.

Adult↗
PubMed2003

Activin signaling through type IB activin receptor stimulates aromatase activity in the ovarian granulosa cell-like human granulosa (KGN) cells.

In addition to a stimulatory effect on FSH production by the pituitary gland, activin is thought to have a paracrine or autocrine role in follicular development in the ovary, where it is produced. Recently, we established a human ovarian granulosa tumor cell line, KGN, which possesses in vivo characteristics of granulosa cells, namely the expression of functional FSH receptors and cytochrome P-450 aromatase. Here, we have demonstrated the activin signaling pathway and its role in KGN cells. A series of transient transfection experiments revealed that activin type IB receptor (ActRIB) is an essential component of the activin signaling pathway in KGN cells. Smad2 was found to act downstream of ActRIB as an intracellular signal transmitter. Smad7, but not Smad6, was an inhibitory Smad in the pathway. Finally, we show that FSH receptor expression and cytochrome P-450 (P-450) aromatase activity was up-regulated by activin stimulation through ActRIB in KGN cells. These results show that we have clarified the signaling mechanisms and the roles of activin in the human granulosa cell line, KGN. Activin signaling mediated by ActRIB-Smad2 system in the ovary may thus be essential for the regulation of follicular differentiation.

Activin Receptors, Type I↗
PubMed2003

[Trials of regeneration and gene therapies in endocrine organs, especially in adrenal glands].

Recent progress in trials of regeneration and gene therapy in endocrine organs, especially in adrenal glands has been reviewed. Gene therapies using adenovirus have been most frequently tested in vivo and in vitro, aiming at improvement of steroidogenesis and suppression of adrenal tumor growth. Although the effects were temporal, promising results have been obtained. Interestingly, adrenocortical tissue was shown to be formed by transplantation of adrenocortical cells and to replace the adrenal functions of adrenalectomized animals. Engineered ES cells stably expressing Ad4BP/SF-1 were shown to be directed toward steroidogenic lineage, suggesting a future possibility of regeneration of adrenal cells.

Adenoviridae↗