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T Suwa

Publications and source records attributed to T Suwa.

At least 19 recordsLinked to original sources
PubMed2005

Molecular cloning of a class IV chitinase allergen from Japanese cedar (Cryptomeria japonica) pollen and competitive inhibition of its immunoglobulin E-binding capacity by latex C-serum.

BACKGROUND: Japanese cedar (Cryptomeria japonica) pollinosis is one of the most prevalent allergic diseases in Japan. Only three C. japonica allergens, Cry j 1, Cry j 2, and CJP-6, have been characterized. The full IgE-binding spectrum of C. japonica pollen allergens demonstrates that many allergens remain to be identified. OBJECTIVE: The aim of this study was to characterize a novel allergen with a high frequency of IgE binding. METHODS: The cDNA coding for a high-frequency IgE-binding protein, designated CJP-4, was cloned from the total mRNA of C. japonica pollen. The corresponding native allergen was purified by affinity precipitation with colloidal chitin and gel chromatography. The IgE-binding ability of purified native CJP-4 was characterized by ELISA and ELISA inhibition. RESULTS: The CJP-4 cDNA encoded 281 amino acids with significant sequence homology to class IV chitinases. Purified native CJP-4, migrated as a homogeneous 34-kDa protein on SDS-PAGE, revealed endochitinase activity on native PAGE. The purified protein displayed the ability to bind IgE from all patients tested (31/31) in ELISA, whereas Cry j 1 bound to IgE at a 71% frequency (22/31). Pre-incubation with latex C-serum completely inhibited the reaction of pooled sera IgE from patients with C. japonica pollinosis and/or latex allergy to purified CJP-4. CONCLUSION: We identified CJP-4 as a novel and fourth C. japonica chitinase allergen with high IgE-binding frequency. The competitive IgE-binding profile between C. japonica chitinase and latex C-serum indicated that C. japonica chitinase should be an important pan-allergen in C. japonica pollen.

Allergens↗
PubMed2005

Age-related changes in haematology and serum chemistry of Weiser-Maples guineapigs (Cavia porcellus).

Age-related changes in haematology and serum chemistry values were examined in male and female Weiser-Maples guineapigs (Cavia porcellus). Haematological changes that significantly (P<0.01) correlated with ageing were increased white blood cell and neutrophil counts in both sexes, decreased lymphocyte counts in both sexes, decreased reticulocyte and platelet counts in males, and decreased basophil counts in females. For serum chemistry, increases in total protein, triglycerides, blood urea nitrogen and creatinine were seen in both sexes, along with increases in total cholesterol in males and sodium in females. Decreased alkaline phosphatase in both sexes and decreased chloride in males were significantly (P<0.01) associated with age. These age-related changes are compared with the published literature.

Age Factors↗
PubMed2003

Double-blind randomised trial comparing the non-steroidal aromatase inhibitors letrozole and fadrozole in postmenopausal women with advanced breast cancer.

BACKGROUND: To compare the efficacy, safety and tolerability of letrozole, an advanced non-steroidal aromatase inhibitor, and fadrozole hydrochloride, an older-generation drug in this class, we conducted a randomised double-blind trial in postmenopausal women with advanced breast cancer. PATIENTS AND METHODS: One hundred and fifty-seven postmenopausal women with advanced breast cancer were enrolled and randomly assigned to receive letrozole or fadrozole in a multicentre, randomised double-blind trial in Japan. One hundred and fifty-four eligible patients were treated with either letrozole 1.0 mg once daily (n = 77) or fadrozole 1.0 mg twice daily (n = 77), for a minimum of 8 weeks. RESULTS: Letrozole showed a significantly higher overall objective response rate [complete response (CR) + partial response (PR)] than fadrozole (31.2% and 13.0%, respectively; P = 0.011, Fisher's exact test). Clinical benefits defined as CR, PR and stable disease (no change in status for more than 24 weeks) were also higher in patients treated with letrozole (50.6%) than fadrozole (35.1%). Letrozole was significantly superior to fadrozole in terms of the dominant lesion in soft tissue, bone and viscera (P = 0.011, stratified Mantel-Haenszel test). Median time to progression was 211 days in the letrozole group and 113 days in the fadrozole group with no significant difference (P = 0.175, log-rank test). Letrozole markedly reduced the estradiol, estrone and estrone sulfate levels in peripheral blood within 4 weeks. The suppressive effect of fadrozole on these hormone levels was insufficient. Adverse drug reactions were observed in 35.9% of the patients treated with letrozole and in 39.5% of those treated with fadrozole with no significant difference between the two groups (P = 0.74, Fisher's exact test). Most of the adverse drug reactions were rated as grade 1 or 2. CONCLUSIONS: The results show letrozole at a dose of 1.0 mg once daily to be more effective in treating postmenopausal women with advanced breast cancer than fadrozole at 1.0 mg twice daily, with similar safety and tolerability profiles.

Administration, Oral↗
PubMed2003

Auricular chondritis in young ear-tagged Crj:CD(SD)IGS rats.

Gross and histopathological features of auricular chondritis in young Crj:CD(SD)IGS rats were examined. Although the rats were identified with metallic ear tags on the right pinnae, auricular chondritis was also observed on the contralateral (left) ear in some animals. Histopathologically, the lesions were characterized by granulomatous inflammation with destruction of the normal cartilaginous plate, formation of new cartilaginous nodules and osseous metaplasia. Proliferative cell nuclear antigen (PCNA) positive cells were present predominantly in chondrocytes found in the centre of the newly-formed cartilaginous nodules. The results suggest that the newly-formed cartilaginous nodules were due to interstitial proliferation of chondrocytes.

Animals↗
PubMed2003

Zonal expression of dickkopf-3 and components of the Wnt signalling pathways in the human adrenal cortex.

The mechanisms underlying the differentiation of the adrenal cortex into zones are unclear. Microarray studies on RNA from microdissected zona reticularis (ZR) and zona fasciculata/zona glomerulosa (ZF/ZG) derived from adult human adrenal glands showed that a gene of the dickkopf family (DKK), DKK3, is differentially expressed in the zones. The Dickkopf proteins are morphogens involved in Wnt signalling. Northern blotting showed higher DKK3 transcript levels in ZF/ZG than ZR samples. In situ hybridization on adult human adrenal gland sections showed that DKK3 expression was much higher in the ZG than in the ZF or ZR. DKK3 expression was also higher in the medulla. We screened for expression of other members of the DKK family and the related Wingless-type mouse mammary tumor virus integration site gene family (WNT), frizzled (FZD), and dishevelled (DVL) gene families. Among dickkopf family members, only DKK3 was expressed at a detectable level in both human and mouse adrenocortical RNA samples. Consistent with previously published data on the effects of Wnt4 gene disruption in the mouse, we found only WNT4 expression within the WNT family in both human and mouse RNA. Northern blotting showed that WNT4 was expressed at a higher level in ZF/ZG cells than in ZR. The higher level of DKK3 and WNT4 expression in ZF/ZG cells was confirmed by real-time PCR. In the frizzled and dishevelled families we found FZD1, FZD2 and DVL3 transcripts in human adrenocortical RNA, and FZD2 and DVL3 in mouse adrenocortical RNA. These data show that a variety of genes of the Wnt signalling pathways are expressed in the adrenal cortex. The zonal distribution of DKK3 expression suggests that it could be involved in zonal differentiation or growth.

Adaptor Proteins, Signal Transducing↗
PubMed2002

Pharmacokinetic and pharmacodynamic analysis of TS-943, a selective non-peptide platelet glycoprotein-IIb/IIIa (GPIIb/IIIa) receptor antagonist, using a nonlinear mixed effect model in dogs.

A simultaneous analysis of the pharmacokinetics and pharmacodynamics of TS-943, a selective nonpeptide platelet glycoprotein-IIb/IIIa (GPIIb/IIIa) receptor antagonist, was made in dogs using a nonlinear mixed effect model. Plasma concentrations of TS-943 were determined after bolus intravenous injection, constant infusion and bolus plus constant infusion. Pharmacokinetic/pharmacodynamic data were fitted using NONMEM software. The pharmacokinetics of TS-943 fitted a two-compartment open model with first-order elimination. The pharmacodynamic model that best fitted platelet aggregation was an inhibitory sigmoid Emax model. The final estimates for E0 (baseline effect), Emax (maximum effect), IC50 (50% inhibitory concentration) and gamma (Hill coefficient) were 66.3%, 64.3%, 104 ng mL(-1) and 1.37, respectively. Correlations between TS-943 plasma concentration and extension of template bleeding time were examined by fitting with an exponential model. The TS-943 plasma concentration necessary to double bleeding time (C2-BTE) was approximately 209 ng mL(-1). The model estimated that the C2-BTE/IC50 (inhibition of platelet aggregation) ratio was approximately 2.0-fold in dogs. Our results suggest that the ratio values for dogs and man are comparable. A nonlinear mixed effect model was a useful tool for exploring the concentration-effect relationship for both efficacy and safety of TS-943 in dogs and man. In this study, the dog was found to be a useful model for screening of efficacy and safety of TS-943 in man.

Amidines↗
PubMed2001

Cytokines involved in the systemic inflammatory response induced by exposure to particulate matter air pollutants (PM(10)).

Elevated levels of ambient particulate matter (PM(10)) have been associated with increased cardiopulmonary morbidity and mortality. We previously showed that the deposition of particles in the lung induces a systemic inflammatory response that includes stimulation of the bone marrow. This marrow response is related to mediators released by alveolar macrophages (AM) and in this study we measured cytokines produced by human AM exposed to ambient particles of different composition and size. Identified cytokines were also measured in the circulation of healthy young subjects exposed to air pollutants during the 1997 Southeast Asian forest fires. Human AM were incubated with particle suspensions of residual oil fly ash (ROFA), ambient urban particles (EHC 93), inert carbon particles, and latex particles of different sizes (0.1, 1, and 10 microm) and concentrations for 24 h. Tumor necrosis factor-alpha (TNF-alpha) increases in a dose-dependent manner when AM were exposed to EHC 93 particles (p < 0.02). The TNF response of AM exposed to different sizes of latex particles was similar. The latex (158 +/- 31%), inert carbon (179 +/- 32%), and ROFA (216 +/- 34%) particles all show a similar maximum TNF response (percent change from baseline) whereas EHC 93 (1,020 +/- 212%, p < 0.05) showed a greater maximum response that was similar to lipopolysaccharide (LPS) 1 microg/ml (812 +/- 320%). Macrophages incubated with an optimal dose of EHC 93 particles (0.1 mg/ml) also produce a broad spectrum of other proinflammatory cytokines, particularly interleukin (IL)-6 (p < 0.01), IL-1 beta (p < 0.05), macrophage inflammatory protein-1 alpha (MIP-1 alpha) (p < 0.05), and granulocyte macrophage colony-stimulating factor (GM-CSF) (p < 0.01) with no difference in concentrations of the anti-inflammatory cytokine IL-10 (p = NS). Circulating levels of IL-1 beta, IL-6, and GM-CSF were elevated in subjects exposed to high levels of PM(10) during an episode of acute air pollution. These results show that a range of different particles stimulate AM to produce proinflammatory cytokines and these cytokines are also present in the blood of subjects during an episode of acute atmospheric air pollution. We postulate that these cytokines induced a systemic response that has an important role in the pathogenesis of the cardiopulmonary adverse health effects associated with atmospheric pollution.

Aged↗
PubMed2001

Differentially expressed genes in zona reticularis cells of the human adrenal cortex.

The zona reticularis (ZR) cell in the human adrenal cortex is responsible for the secretion of dehydroepiandrosterone, but its biology, origin, and putative decrease in number during aging are poorly understood. In the present experiments, we investigated to what extent ZR and zona fasciculata (ZF) cells differ in patterns of gene expression. Both cell types were purified by microdissection from adult adrenal cortex specimens. After a brief period in culture, RNA was harvested from the cells and used to prepare radioactively labeled probes following amplification by PCR. Probes were used in hybridizations of arrays of cDNAs on nylon membranes (PCR products or plasmids obtained from an adrenal cDNA library). Analysis of hybridization intensities showed that 17 of the 750 genes studied differed in expression by more than 2-fold. Several genes expressed at higher levels in ZR cells encode components of the major histocompatibility complex or enzymes involved in peroxide metabolism. Members of the tubulin gene family were expressed at higher levels in ZF cells. Differential expression of four of the genes was confirmed by Northern blotting. These differences show that although ZR and ZF cells are similar in gene expression, ZR cells have a gene expression pattern related to the unique biology of this cell type.

Adult↗
PubMed2001

Gastrointestinal stromal tumor of the lesser omentum: report of a case.

We describe herein an extremely unusual case of a gastrointestinal stromal tumor (GIST) of the lesser omentum. A 45-year-old man was admitted to our hospital with an intra-abdominal mass that was subsequently misdiagnosed as a submucosal tumor of the stomach. The tumor arose from the lesser omentum and was removed without difficulty. Histologically, the tumor was composed of spindle-shaped cells with an interlacing bundle pattern, and immunohistochemical examination showed that it was positive for myeloid stem cell antigen (CD34), but negative for HHF35 and S-100 protein. These findings were consistent with a GIST lacking myogenic features and neural attributes. The patient had an uneventful postoperative course, and was free of recurrence when last seen 11 months after his operation.

Gastrointestinal Neoplasms↗
PubMed2001

Telomere shortening and decline in replicative potential as a function of donor age in human adrenocortical cells.

Telomere shortening is the cause of replicative senescence of mammalian cells in culture and may be a cause of cellular aging in vivo. Some tissues clearly show telomere shortening during aging in humans, but the relationship between replication history and telomere length is obscured by complex relationships between stem cells and more differentiated cell types. Previous experiments on the adrenal cortex and human adrenocortical cells in culture indicate that the proliferative biology of this tissue is relatively simple; cell division occurs continuously throughout life, without evidence for a distinct stem cell compartment. In this tissue we investigated the relationship between telomere biology and replicative senescence by measuring replicative capacity and telomere length as a function of donor age. Cells cultured from adrenal tissue from donors of different ages showed a strong age-related decline in total replicative capacity, falling from about 50 population doublings for fetal cells to an almost total lack of division in culture for cells from older donors. Telomere restriction fragment (TRF) length was analyzed in the same sets of cells and decreased from a value of about 12 kb in fetal cells to approximately 7 kb in cells from older donors. The latter value is consistent with that in fibroblasts which have reached replicative senescence. Furthermore, there was a good correlation in individual donor samples between TRF length and replicative capacity in culture. To confirm the relationship between telomere length, telomerase, and replicative capacity, we measured telomere length in cells before and after infection with a retrovirus encoding hTERT, the catalytic component of human telomerase. The adult adrenal cortex does not have telomerase activity; cells after transduction with the hTERT retrovirus had high telomerase activity. Whereas control cells underwent a replication-dependent shortening in telomeres during long-term growth in culture, hTERT-modified cells maintained telomere length and are probably immortalized. Symmetric cell division in human adrenocortical cells, occurring slowly over the life span, is associated with progressive telomere shortening and may result in proliferative defects in vivo in old age, which could partly account for the age-related changes in the structure and function of the human adrenal cortex.

Adolescent↗
PubMed2001

The human melanocyte: a model system to study the complexity of cellular aging and transformation in non-fibroblastic cells.

The melanocyte is a neural crest-derived cell that localizes in humans to several organs including the epidermis, eye, inner ear and leptomeninges. In the skin, melanocytes synthesize and transfer melanin pigments to surrounding keratinocytes, leading to skin pigmentation and protection against solar exposure. We have investigated the process of replicative senescence and accompanying irreversible cell cycle arrest, in melanocytes in culture. As was found in other cell types, progressive telomere shortening appears to trigger replicative senescence in normal melanocytes. In addition, senescence is associated with increased binding of the cyclin-dependent kinase inhibitor (CDK-I) p16(INK4a) to CDK4, down-regulation of cyclin E protein levels (and consequent loss of cyclin E/CDK2 activity), underphosphorylation of the retinoblastoma protein RB and subsequent increased levels of E2F4-RB repressive complexes. In contrast to fibroblasts, however, the CDK-Is p21(Waf-1) and p27(Kip-1) are also down-regulated. These changes appear to be important for replicative senescence because they do not occur in melanocytes that overexpress the catalytic subunit of the enzyme telomerase (hTERT), or in melanomas, which are tumors that originate from melanocytes or melanoblasts. In contrast to unmodified melanocytes, hTERT overexpressing (telomerized) melanocytes displayed telomerase activity, stable telomere lengths and an extended replicative life span. However, telomerized melanocytes show changes in cell cycle regulatory proteins, including increased levels of cyclin E, p21(Waf-1) and p27(Kip-1). Cyclin E, p21(Waf-1) and p27(Kip-1) are also elevated in many primary melanomas, whereas p16(INK4a) is mutated or deleted in many invasive and metastatic melanomas. Thus, the molecular mechanisms leading to melanocyte senescence and transformation differ significantly from fibroblasts. This suggests that different cell types may use different strategies to halt the cell cycle in response to telomere attrition and thus prevent replicative immortality.

Cell Cycle Proteins↗
PubMed2001

Anti-inflammatory response in patients with obstructive jaundice caused by biliary malignancy.

BACKGROUND: Obstructive jaundice potentially modulates the host defense mechanism resulting in perioperative infection. It has been reported that a systemic inflammatory response occurs in patients with obstructive jaundice. An anti-inflammatory response was studied in 29 jaundiced patients undergoing biliary drainage. RESULTS: Plasma concentrations of interleukin (IL)-10, soluble tumor necrosis factor receptor (STNFR) p55, STNFR p75, IL-1 receptor antagonist (IL-1ra), IL-6 and soluble CD14 (sCD14) were measured by using immunoassay. Plasma concentrations of IL-10, STNFR p55, STNFR p75, IL-1ra, IL-6 and sCD14 were significantly higher in jaundiced patients than in the controls (P < 0.01). After biliary drainage, the concentrations of IL-10, the three cytokine antagonists, and IL-6 decreased significantly (P < 0.05). The sCD14 concentration did not decrease. At the time of drainage, the concentrations of STNFR p55 and STNFR p75 were significantly higher in 10 patients with positive bile cultures than in 19 patients with negative bile cultures (P < 0.05). Bile cultures became positive 14 days after drainage in 10 patients, and remained negative in nine. The concentration of STNFR p55 before drainage was significantly higher in the former group (P = 0.05). The plasma concentrations of IL-10 and STNFRs were significantly correlated with the IL-6 concentration, body temperature and the white blood cell count (P < 0.05). Serum total bilirubin levels did not affect plasma levels of anti-inflammatory mediators, and sCD14. CONCLUSION: Jaundiced patients exhibited an anti-inflammatory immune response that potentially modulates the host defense mechanism and results in anergy and increased susceptibility to infection. Biliary infection may be one of the major stimuli of the immune response.

Aged↗
PubMed2001

Interleukin-6 changes deformability of neutrophils and induces their sequestration in the lung.

Interleukin-6 (IL-6) is an important mediator of both the hepatic and the bone marrow components of the acute-phase response. Previous studies from our laboratory have shown that cells released into the circulation from the marrow preferentially sequester in the lung. The present study was designed to examine the mechanism of this sequestration using a single dose of recombinant human IL-6 to stimulate the marrow in rabbits. Marrow release was monitored by labeling polymorphonuclear leukocyte (PMN) precursors in the marrow with the thymidine analogue, 5'-bromo-2-deoxyuridine (BrdU), 24 h before IL-6 treatment. This treatment caused a neutrophilia that was associated with the increase of circulating BrdU- labeled PMN (PMN(BrdU)) and morphometric studies confirmed that PMN(BrdU) released from the marrow preferentially sequestered in the lung microvessels compared to unlabeled PMN. IL-6 treatment increases PMN F-actin content (p < 0.05) that was not due to cell activation by IL-6. In vitro studies show that IL-6 treatment decreased the deformability of circulating PMN (p < 0.05). These studies confirm that IL-6 treatment causes an accelerated release of PMN from the bone marrow and shows that these newly released PMN have high levels of F-actin, are less deformable, and preferentially sequester in lung microvessels.

Actins↗
PubMed2001

Participatory assessment of the environment from children's viewpoints: development of a method and its trial.

To understand the actual viewpoints of children about daily life and the environment, the authors, adopting a participatory strategy, visited 21 classes of Japanese school children, improved in a stepwise process their ways of question-asking, and developed "WIFY"(what is important for you); a set of interactive questions composed of a basic question and three accompanying instructions. In applying WIFY, 59 fourth graders, 22 in Nagasaki, Japan and 37 in Beijing, China, reported their viewpoints in each of classroom settings. In both settings, when children were allowed to communicate with each other by the use of WIFY answering sheet, spontaneous exchanges arose and continued. WIFY itself is supposed to bring out and enhance mutual collaboration and spontaneous networking. In this instance, WIFY functioned as a communication tool. When answering sheets were collected and obtained responses were analyzed as cases, a rather materialistic view was suggested among Japanese children and a more disciplined view, which put much value on school and home, was suggested among Chinese children. Further studies are needed to confirm the changing environmental views of children from the collaborative research framework.

Attitude↗
PubMed2001

Telomerase activity in primary cultures of normal adrenocortical cells.

Telomerase activity was measured in isolated cells from bovine and human adrenal cortex, in cells in primary culture, in cells in later passages in culture, and in cells genetically modified by expression of hTERT (human telomerase reverse transcriptase). Telomerase activity in freshly isolated bovine adrenocortical cells and in human adrenal cells from donors of various ages (6-79 years) was very low or undetected. However, primary bovine adrenocortical cell cultures were strongly positive for telomerase activity, and primary human adrenocortical cell cultures were weakly positive. Both cell types proliferate in primary culture but proliferation of bovine cells is much more vigorous. When primary bovine cells were subcultured to make successively secondary and tertiary cultures, telomerase activity declined strongly, and was undetected by the third passage. There was only a slight decrease in growth rate over this period. Levels of the telomerase RNA component did not change with passage number when assessed by semi-quantitative competitive RT-PCR. When both bovine and human cells were infected with a retrovirus encoding hTERT, telomerase activity in the cells was very high. We conclude that in the adrenal cortex, as in some other tissues, TERT expression is regulated and upregulation of telomerase activity is associated with rapid proliferation in primary culture. Telomerase activity is not maintained, and introduction of TERT is required for stable telomerase activity and for immortalization.

Adolescent↗
PubMed2000

Long-term survival achieved by resection of metastases in the liver and lung in a patient with recurrent colonic cancer: report of a case.

A 58-year-old man who underwent a potentially curative resection of cancer of the sigmoid colon at another hospital was subsequently followed up at our hospital. A lateral segmentectomy was performed for a solitary hepatic metastasis, and partial resection of right S1 was later carried out for a pulmonary metastasis. Another pulmonary metastasis was found 6 years after his third operation and to minimize the area to be resected, bronchial arterial infusion chemotherapy was performed twice. A 51% reduction in the size of the tumor was achieved, so a right upper lobectomy and wedge resection of the bronchus were performed. The patient remains alive 14 years after the initial resection of colonic cancer. This case is considered noteworthy because it demonstrates the potential effectiveness of local adjuvant chemotherapy and the possibility of extended survival in a patient who has undergone resection of both hepatic and pulmonary metastases from colonic cancer.

Adenocarcinoma↗