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Biomedical subjects

H Takizawa

Publications and source records attributed to H Takizawa.

At least 19 recordsLinked to original sources
PubMed2006

The balance of VEGF-C and VEGFR-3 mRNA is a predictor of lymph node metastasis in non-small cell lung cancer.

A positive association between vascular endothelial growth factor-C (VEGF-C) expression and lymph node metastasis has been reported in several cancers. However, the relationship of VEGF-C and lymph node metastasis in some cancers, including non-small cell lung cancer (NSCLC), is controversial. We evaluated the VEGF-C and vascular endothelial growth factor receptor-3 (VEGFR-3) expression in NSCLC samples from patients who had undergone surgery between 1998 and 2002 using real-time quantitative RT-PCR and immunohistochemical staining. We failed to find a positive association between VEGF-C and VEGFR-3 mRNA expression and lymph node metastasis in NSCLC. An immunohistological study demonstrated that VEGF-C was expressed not only in cancer cells, but also in macrophages in NSCLC, and that VEGFR-3 was expressed in cancer cells, macrophages, type II pneumocytes and lymph vessels. The VEGF-C/VEGFR-3 ratio of the node-positive group was significantly higher than that of the node-negative group. Immunohistochemical staining showed that VEGFR-3 was mainly expressed in cancer cells. The immunoreactivity of VEGF-C and VEGFR-3 was roughly correlated to the mRNA levels of VEGF-C and VEGFR-3 in real-time PCR. VEGF-C mRNA alone has no positive association with lymph node metastasis in NSCLC. The VEGF-C/VEGFR-3 ratio was positively associated with lymph node metastasis in NSCLC. This suggests that VEGF-C promotes lymph node metastasis while being influenced by the strength of the VEGF-C autocrine loop, and the VEGF-C/VEGFR-3 ratio can be a useful predictor of lymph node metastasis in NSCLC.

Adult↗
PubMed2006

Estimation of the remaining periodontal ligament from attachment-level measurements.

AIM: Accurate assessment of the remaining area of periodontal attachment assists in determining the prognosis of a tooth. The aim of this study was to determine formulae to estimate the remaining area of periodontal attachment from attachment-level measures. MATERIALS AND METHODS: Roots of 30 extracted teeth of each tooth type were coated with vinyl acetate solution and alpha-cyanoacrylate monomer to produce a membrane. The membrane was removed after guidelines were drawn to simulate various attachment levels. The root surface area on the apical side of each simulated attachment level was measured using image analysis software. The net or percent root surface area and corresponding attachment level data were fitted to a linear, quadratic, cubic, and exponential functions and a growth curve. RESULTS: The linear function provided the most appropriate fit for the data. For net root surface area, a steeper slope was evident for tooth types with a larger mean total root surface area. For percent root surface area, a steeper slope was evident for tooth types with a shorter root length. CONCLUSIONS: A linear function provides the most appropriate formula for estimation of the remaining area of periodontal attachment based on the attachment-level measurement.

Bucrylate↗
PubMed2006

[Clinical analysis of operative and hospital deaths in primary lung cancer].

In our department, there were 313 thoracic surgeries for primary lung cancer from January 1994 to December 2003. We clinically reviewed for the operative and hospital death (n=18, 5.8%). The patients were 16 males and 2 females (70.6 +/- 5.6 years old). The surgical procedures were 4 pneumonectomies, 13 lobectomies (3 bronchoplasties) and 1 partial resection. The mean interval until postoperative death was 122.5 +/- 156.1 days. There were 5 direct operative deaths within 30 days (1.6%). There were 4 cancer deaths, 2 hemoptyses, 2 operative bleeding, 2 thromboses, 2 cerebral hemorrhages, 1 pyothorax, 1 pneumonia, 1 respiratory failure, 1 multiple organ failure after chemotherapy and 2 unexplained deaths. The patients with pneumonectomy or aged significantly had high mortality. For postoperative complications such as hemoptysis or bleeding, perioperative management that takes these issues into consideration is needed. Furthermore, we must carefully review the preoperative evaluation and combined treatment, because there were many cancer deaths among cases showing early recurrence and metastasis.

Adenocarcinoma↗
PubMed2005

Interferon-gamma is produced by CD8 T cells in response to HLA-A24-restricted hepatitis C virus epitopes after sustained virus loss.

Differences in cytotoxic T lymphocyte activity in hepatitis C virus infection may account for the outcome of interferon monotherapy. To investigate this hypothesis, we analysed the response of peripheral CD8(+) T cells that recognized epitopes presented by HLA-A*2402. We synthesized HLA/beta2-microglobulin/peptide complexes using two epitopes. Production of interferon-gamma by CD8(+) T cells in response to plastic-bound monomeric HLA/peptide complex was observed frequently in sustained virus responders (SVR) (n = 13) against all the peptides, NS31296-1304 (the percentage of responding patients, 61.5%) and core 129-137 (53.8%), while no interferon-gamma production was observed in non-responders (NR) (n = 13) for any of the peptides. Tetramer-staining showed the presence of CD8(+) T cells specific for all the peptides except NS31296-1304 in two SVR at the end of interferon monotherapy, although hardly any such cells were found in four NR. Specific killing was observed against peptides NS31296-1304 (3/4) and core 129-137 (1/4) in sustained responders but none in non-responders. These results suggest that the responses of cytotoxic T lymphocytes (CTLs) were induced during interferon therapy in these patients and that interferon-gamma production by CD8(+) T lymphocytes against HCV NS31296-1304 and core 129-137 are well maintained in patients with SVR compared with those with NR. These findings emphasize the importance of the CD8(+) T cell response in controlling HCV infection.

Adult↗
PubMed2004

Evidence from mucin core protein expression that some Paget's disease on areola can be of extramammary-like histogenesis and part of multisite disease.

Triple extramammary Paget's disease, which consists ordinarily of bilateral axillary and genital lesions, is uncommon. Triple extramammary Paget's disease involving other sites has never been reported, although solitary extramammary Paget's disease can occur at various sites around the body. Erythematous plaques on the areola, axilla and genitalia of a 91-year-old man were surgically removed under the clinical diagnosis of multiple extramammary Paget's disease. Histology revealed that all three lesions consisted of intraepidermal nests of Paget cells and other isolated Paget cells scattered in the epidermis. Although adnexal invasion was observed in the genital lesion, neither intraductal invasion nor underlying breast carcinoma was detected in the areolar lesion. Immunohistochemically, the Paget cells in all lesions expressed simple epithelial cytokeratins (CK8, 18 and 19), mucin (MUC)1 and MUC5AC, but neither CK20 nor MUC2. From the histological findings, the present case was interpreted as triple extramammary Paget's disease rather than synchronous mammary and extramammary Paget's disease. Furthermore, the mucin core protein expression pattern, which was identical to that observed in extramammary Paget's disease, supported the above interpretation.

Aged↗
PubMed2002

Characterization of the human ABO gene promoter in erythroid cell lineage.

BACKGROUND: The human ABO blood group system is important in transfusion and organ transplantation. Although the molecular basis of the ABO gene has been established, recent studies have begun to characterize the mechanism of the ABO gene expression. MATERIALS AND METHODS: Transient transfection assays were carried out in human erythroleukaemia HEL cells and human gastric cancer KATOIII cells. Electrophoretic mobility shift assays were performed using nuclear extracts derived from both cells. RESULTS: Our characterization of the 5'-upstream sequence of the ABO genes indicated that the region between -117 and +31 is essential to direct expression of a reporter gene in erythroid cells. We show that a sequence located between positions -22 and -14 of the ABO promoter binds a ubiquitous transcription factor Sp1 or Sp1-like protein(s). Mutation of this site abrogates binding of those factors and reduces the ability of the ABO promoter to function in erythroleukaemia cells and gastric cancer cells. CONCLUSION: The expression of the ABO promoter appears to be influenced by the binding of Sp1 or Sp1-like protein(s) in both erythroid and epithelial cell lineages.

ABO Blood-Group System↗
PubMed2002

Potentiation of human lung fibroblast chemotaxis by the thromboxane A(2) analog U-46619.

Fibroblast production of extracellular matrix is crucial not only for normal tissue development and maintenance of tissue structure but also for the repair and remodeling processes after injury. Thromboxane A(2) (TXA(2)) is a potent mediator in inflammatory processes. The aim of this study was to investigate the effect of TXA(2) on chemotaxis of human fetal lung (HFL-1) fibroblasts induced by human plasma fibronectin or platelet-derived growth factor BB (PDGF-BB). By using the blindwell chamber technique, the TXA(2) agonist U-46619 alone had no chemotactic activity. However, U-46619 (200 nmol/L) stimulated HFL-1 fibroblast chemotaxis to human plasma fibronectin (20 microg/mL; 161.8% +/- 13.4%; P <.005) and to PDGF-BB (10 ng/mL; 188.5% +/- 7.0%; P <.005). Checkerboard analysis of human plasma fibronectin-directed migration confirmed that the TXA(2) agonist increased both chemotaxis and chemokinesis. The stimulatory effect of the TXA(2) agonist was concentration dependent and increased with time. Another agent known for stimulating the protein kinase C pathway, phorbol 12-myristate 13-acetate (10(-8) mol/L), had a similar effect, stimulating chemotaxis to fibronectin (146.2% +/- 8.6%). The stimulatory effect of the TXA(2) agonist on HFL-1 fibroblast chemotaxis was inhibited by the synthetic thromboxane receptor antagonist SQ29,548 (10(-5) mol/L) and the protein kinase C inhibitor calphostin (10(-7) mol/L). In summary, TXA(2) appears to stimulate fibroblast chemotaxis to fibronectin and PDGF, perhaps by modulating the rate of fibroblast migration. Such an effect may contribute to regulation of wound healing and the development of fibrotic disorders.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed2002

Prostaglandin D2 inhibits fibroblast migration.

Fibroblasts play an important role in the repair and remodelling processes following injury. Prostaglandin D2 (PGD2) is a potent mediator in inflammatory processes. In this study, the effect of the PGD2 on human foetal lung fibroblasts (HFL-1) chemotaxis induced by human plasma fibronectin (HFn) was investigated using the blindwell chamber technique. PGD2 inhibited HFL-1 chemotaxis to HFn (20 microg x mL(-1)) by 20.8 +/- 3.8% (p<0.05). Checkerboard analysis of HFn-directed migration confirmed that PGD2 inhibited both chemotaxis and chemokinesis. The effect of PGD2 was concentration-dependent and the inhibitory effect diminished with time. The PGD2 receptor (DP) agonist BW245C (500 nM) had a similar effect, inhibiting chemotaxis to 39.4 +/- 6.3%. The inhibitory effects of both PGD2 and BW245C on HFL-1 chemotaxis were blocked by the DP receptor antagonist AH6809 (2 microM). The inhibitory effect of PGD2 on fibroblast chemotaxis was also blocked by the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) inhibitor, KT5720, suggesting a DP receptor-initiated, cAMP-dependent effect mediated by PKA. Prostaglandin D2 appears to inhibit fibroblast chemotaxis, perhaps by modulating the rate of fibroblast migration. Such an effect may contribute to regulation of the wound healing response following injury in asthma patients.

Cell Movement↗
PubMed2001

Expression of natural killer receptor alleles at different Ly49 loci occurs independently and is regulated by major histocompatibility complex class I molecules.

Ly49 receptor genes are expressed by subsets of natural killer (NK) cells in an overlapping fashion, accounting for the capacity of NK subsets to attack host cells that have selectively downregulated self-major histocompatibility complex (MHC) class I molecules. It was shown previously that most NK cells express only one or the other allele of a given Ly49 gene, while a smaller population expresses both alleles. However, the methods used to detect monoallelic and biallelic cells were nonquantitative. Here, new allele-specific antibodies were used to provide the first quantitative examination of biallelic and monoallelic expression of Ly49A and Ly49G2. The results demonstrate conclusively that most Ly49A(+) and Ly49G2(+) NK cells express the corresponding gene in a monoallelic fashion, with a smaller subset expressing both alleles. Unexpectedly, biallelic Ly49A(+) NK cells were more numerous than predicted by completely independent allelic expression, suggesting some heterogeneity among NK progenitors in the potential to express a given Ly49 gene. The data also show that cells expressing one allele of Ly49G2 may express Ly49A from the same or opposite chromosome with equal likelihood, indicating that the expressed allele is chosen independently for different Ly49 genes. Finally, the data demonstrate that biallelic expression of Ly49A or Ly49G2 occurs least frequently in mice that express ligands for these receptors (H-2(d) mice), and most frequently in class I-deficient mice. Thus, biallelic expression of Ly49 genes is regulated by interactions of NK cell progenitors with MHC class I molecules.

Alleles↗
PubMed2001

Intervention of thymus and activation-regulated chemokine attenuates the development of allergic airway inflammation and hyperresponsiveness in mice.

Thymus- and activation-regulated chemokine (TARC; CCL17) is a lymphocyte-directed CC chemokine that specifically chemoattracts CC chemokine receptor 4-positive (CCR4(+)) Th2 cells. To establish the pathophysiological roles of TARC in vivo, we investigated here whether an mAb against TARC could inhibit the induction of asthmatic reaction in mice elicited by OVA. TARC was constitutively expressed in the lung and was up-regulated in allergic inflammation. The specific Ab against TARC attenuated OVA-induced airway eosinophilia and diminished the degree of airway hyperresponsiveness with a concomitant decrease in Th2 cytokine levels. Our results for the first time indicate that TARC is a pivotal chemokine for the development of Th2-dominated experimental allergen-induced asthma with eosinophilia and AHR. This study also represents the first success in controlling Th2 cytokine production in vivo by targeting a chemokine.

Animals↗
PubMed2001

MHC-dependent shaping of the inhibitory Ly49 receptor repertoire on NK cells: evidence for a regulated sequential model.

Engagement of MHC class I-specific inhibitory receptors regulates natural killer (NK) cell development and function. Using both new and previously characterized anti-Ly49 monoclonal antibodies, we comprehensively determined expression and co-expression frequencies of four Ly49 receptors by NK cells from MHC-congenic, MHC class I-deficient, and Ly49A-transgenic mice to study mechanisms that shape the inhibitory Ly49 repertoire. All Ly49 receptors were expressed on partially overlapping subsets. Significantly, in the absence of class I MHC, several receptor pairs were co-expressed more frequently than predicted from a purely random expression model, indicating that biases independent of MHC class I underlie receptor co-expression in some cases. MHC interactions were found to inhibit Ly49 co-expression variably depending on the MHC allele and the receptor pair examined. These data extend previous evidence that interactions with MHC shape the repertoire. It was previously proposed that developing NK cells express Ly49 receptors sequentially and cumulatively, until self-MHC specific receptors are expressed and inhibit new receptor expression. Fulfilling a major prediction of this model, we found that class I recognition by a Ly49A transgene expressed by all developing NK cells equivalently inhibited expression of endogenous self-specific and nonself-specific Ly49 receptors.

Animals↗
PubMed2001

Regional differences in homicide patterns in five areas of Japan.

This article describes regional differences in the homicide patterns which occurred in Sapporo City and the surrounding area, and in Akita, Ibaraki, Chiba and Toyama prefectures in Japan. Information collected from each case of homicide included factors such as age, sex of the victim and assailant, causes of death, disposition of the offender, relationship between assailant and victim, reasons for criminal action, et al. The statistical features of homicidal episodes among the five different regions showed considerable variation, as follows. The mean death rates for homicide (number of victims per 100,000 of population) during the period 1986-1995 were 0.44 (Sapporo), 0.8 (Akita), 0.58 (Toyama), 0.7 (Ibaraki) and 0.75 (Chiba), respectively. Close family relationship between the victim and assailant was observed in the homicidal acts which occurred in Sapporo, Akita and Toyama. Assailant's relationship to victim was commonly extra-familial in Ibaraki and Chiba-neighboring megalopolis Tokyo, where some events of murder by a foreigner occurred. Homicide by female assailant, murder by mentally abnormal killers and homicide-suicide events were closely associated with family members. And these factors contributed to the considerable number of victims in Sapporo, Akita and Toyama. But, this close family relationship of the victim to the assailant did not correspond with the elevation in the number of deaths, and it was rather inversely related to the higher death rates recognized in Ibaraki and Chiba. This comparative study suggested that rapid urbanization considerably affects regional differences in homicide patterns.

Journal Article↗
PubMed2001

Gender difference in the relationships among hyperleptinemia, hyperinsulinemia, and hypertension.

Studies reveals that plasma leptin levels (LEP) in females are higher than those in males, and that LEP in hypertensive subjects are higher than those in BMI-matched normotensive subjects. To investigate the relationships among LEP, blood pressure (BP) and insulin sensitivity, we studied these relationships in 133 Japanese males and 263 females. LEP were positively correlated with BP, body mass index, body fat mass (FM) and homeostasis model assessment (HOMA). Regression analysis in which age and FM were adjusted showed LEP were associated with BP and HOMA. Even with adjustment by age, FM and HOMA, LEP were still positively correlated BP in males. LEP in insulin-resistant hypertensives was significantly higher than those in insulin-sensitive hypertensives, in insulin-sensitive normotensives and in insulin-resistant normotensives in males. However, in females, a significantly higher LEP was observed in insulin-resistant subjects than in insulin-sensitive subjects regardless of hypertension. These data suggest that it would be sexual difference in the relationships among hyperleptinemia, hyperinsulinemia and hypertension.

Adult↗
PubMed2001

A family with liddle's syndrome caused by a mutation in the beta subunit of the epithelial sodium channel.

Liddle's syndrome is a rare form of autosomal-dominant salt-sensitive hypertension. Constitutive activation of the amiloride-sensitive distal renal epithelial sodium channel (ENaC) is essential for salt-sensitive hypertension. Recently, several DNA analysis studies have indicated that there is a mutation of C-terminus of either the beta or y subunit. We sequenced the C-termini of the beta and -gamma subunits of the ENaC in a Japanese family with hypertension and hypopotassemia without excess minerarocorticoids, clinically diagnosed as Liddle's syndrome. The mutation of the ENaC of this family was beta R564X. Since such case seem to be rare in the literature, detailed data are shown in this report.

Aldosterone↗
PubMed2001

Increased expression of transforming growth factor-beta1 in small airway epithelium from tobacco smokers and patients with chronic obstructive pulmonary disease (COPD).

Tobacco smoke is believed to cause small airway disease and then chronic obstructive pulmonary disease (COPD), but the molecular mechanisms by which small airway obstruction occurs remain unknown. To study the gene expression levels of transforming growth factor (TGF)-beta1, a potent fibrogenic factor, in small airway epithelium from smokers and patients with COPD, we harvested highly pure samples of epithelial cells from small airways under direct vision by using an ultrathin bronchofiberscope BF-2.7T (outer diameter 2.7 mm with a biopsy channel of 0.8 mm in diameter). The expression levels of TGF-beta1 were evaluated by reverse transcription-polymerase chain reaction (RT-PCR). The mRNA levels of TGF-beta1 corrected by beta-actin transcripts were significantly higher in the smoking group and patients with COPD than those in nonsmokers (p < 0.01). Furthermore, among smokers and patients with COPD, TGF-beta1 mRNA levels correlated positively with the extent of smoking history (pack-years) and the degree of small airway obstruction as assessed by measurements of flow-volume curves. Immunocytochemistry of the cells demonstrated more intense stainings for TGF-beta1 in samples from smokers and patients with COPD than from nonsmokers. Spontaneously released immunoreactive TGF-beta1 levels from cultured epithelial cells were more elevated in subjects with a history of smoking and patients with COPD than in nonsmokers. Our study showed a close link between smoking and expression of TGF-beta1 in small airways. Our results also suggested that small airway epithelial cells might be involved in obstructive changes found in smokers and patients with COPD.

Analysis of Variance↗
PubMed2001

Benzene-extracted components are important for the major activity of diesel exhaust particles: effect on interleukin-8 gene expression in human bronchial epithelial cells.

Epidemiologic and experimental studies suggest that diesel exhaust particles (DEPs) may be related to increasing respiratory mortality and morbidity. We have shown that DEPs augmented the production of inflammatory cytokines by human airway epithelial cells in vitro. To better understand the mechanisms of their proinflammatory activities, we studied the effects of several components extracted from DEPs on interleukin (IL)-8 expression in human bronchial epithelial cell line BEAS-2B and normal human airway epithelial cells obtained from very peripheral airways by an ultrathin bronchoscope. We used several agents active on signal transduction pathways in cytokine expression, such as the protein kinase C inhibitor staurosporin, antioxidant agents including N-acetyl cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC), and p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580. Benzene-extracted components showed effects mimicking DEPs on IL-8 gene expression, release of several cytokines (IL-8; granulocyte macrophage colony-stimulating factor; and regulated on activation, normal T cells expressed and secreted) and nuclear factor (NF)-kappa B activation. We also found that NAC, PDTC, and SB203580 suppressed the activities of DEPs and their benzene extracts, suggesting the roles of oxidants-mediated NF-kappa B activation and p38MAPK pathways. Finally, benzo[a]pyrene, one of the important compounds included in the benzene component, replicated the activities shown by DEPs.

Acetylcysteine↗