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Biomedical subjects

K Nasu

Publications and source records attributed to K Nasu.

At least 37 records · Page 2Linked to original sources
PubMed2001

[Complete cytogenetic response to interferon-alpha in a patient with chronic myelogenous leukemia undergoing hemodialysis].

We describe a complete cytogenetic response to interferon-alpha in a patient with chronic myelogenous leukemia undergoing chronic hemodialysis. Although IFN-alpha therapy has been applied to patients with chronic hepatitis C receiving hemodialysis, the pharmacokinetics of IFN-alpha in patients with poor renal function still remain unclear. In the present patient, the serum IFN-alpha concentration remained high even 48 hours after injection (42.9 IU/ml), and IFN-alpha was almost completely removed by hemodialysis (< 6 UI/ml). The patient was treated with IFN-alpha (3 x 10(6) IU, three times a week), and cytogenetic disappearance (0%) of the Ph-positive clone was confirmed 31 months after the start of therapy. Recombinant human erythropoietin (Epo) was used to treat anemia due to renal failure and IFN-alpha therapy. The anemia was controllable with Epo, and no adverse effect was observed.

Anemia↗
PubMed2001

Expression pattern of hybrid phenotype in adult acute lymphoblastic leukemia.

We examined the expression of hybrid phenotype in 236 adults with acute lymphoblastic leukemia (ALL; 188 B-lineage ALL and 48 T-lineage ALL). In B-lineage ALL, myeloid antigen (mAg) CD15 was concentrated in CD10-CD20- cases (49%); CD13 (42%); and CD33 (43%) in CD10+CD20- cases. This trend had no correlation with the presence of Ph1 or t(4;11) chromosomal abnormality. T-cell antigen CD2, CD4, and CD7 was seen in four, four, and two cases, respectively, and CD4+ and CD7+ cases commonly expressed CD13 and/or CD33 (CD13/CD33). In T-lineage ALL, expression of mAg, CD11b (47%), CD13 (38%), CD15 (28%), and CD33 (51%) was restricted to CD3- cases. B-cell antigen CD19 was found in two cases with CD7 solely as T-cell antigen, and these cases possessed CD13/CD33. CD21 was detected in three cases with CD3. In whole ALL, CD13/CD33 was associated closely with the presence of stem-cell antigen CD34, and in T-lineage ALL, CD13/CD33 had a significant correlation with additional stem-cell features, such as HLA-DR, multidrug resistance 1 (MDR1) and c-kit gene expression. Our results suggest that immature ALL cells frequently express B+M+, T+M+, and occasionally B+T+M+ phenotype; that B+T+M- phenotype is extremely rare; and that mAg expression in B-lineage ALL is complicated as compared to T-lineage ALL.

Adolescent↗
PubMed2001

Effect of the extracellular matrix on pancreatic endocrine cell function and its biocompatibility in dogs.

The effect of the synthetic extracellular matrix (ECM) in a diffusion chamber for a bioartificial endocrine pancreas (Bio-AEP) on pancreatic endocrine cells in vitro and its biocompatibility in dogs were investigated. Two different types of ECM were used: type I collagen treated with low antigen (type I LA), and reconstituted basement membrane matrix (Matrigel) derived from Englbreth-Holm-Swarm (EHS) mouse sarcoma. Matrigel contains growth and differentiation factors and cell adhesion molecules such as laminin, heparan sulfate proteoglycan, and entactin. Purified porcine pancreatic endocrine (PE) cells were suspended in type I LA or Matrigel and then placed into a 12-well culture plate (4 x 10(7) cells/ml gel/well). The insulin accumulation from PE cells in Matrigel was significantly greater than that in type I LA (9.3 +/- 3.6 mU/well vs. 2.3 +/- 1.3 mU/well). When Bio-AEP with Matrigel and PE cells was implanted into the abdominal cavity of a pancreatectomized diabetic dog, the exogenous insulin requirement for maintaining normoglycemia was reduced for the first 4 weeks. However, after 6 weeks of implantation, fasting blood glucose levels suddenly increased. Laparotomy revealed encapsulated Bio-AEP with thick fibrous tissue. Following removal of the Bio-AEP from the abdominal cavity, another Bio-AEP containing type I LA and PE cells was implanted into the same dog. The exogenous insulin requirement was gradually decreased to almost half that of preimplantation levels. Bio-AEPs containing type I LA or Matrigel, but not PE cells, were implanted into the abdominal cavities of four healthy dogs. After 4 weeks of implantation, the Bio-AEP with Matrigel was encapsulated with fibrous tissue similar to that in the diabetic dog, but the Bio-AEP with type I LA was not. These results indicate that Matrigel may be incompatible with dogs and that the type I LA is more suitable for Bio-AEP.

Animals↗
PubMed2001

[Multislice CT of the thorax: effects of contrast material pushed with saline solution using a dual power injector on contrast material dose and perivenous artifacts].

A new method of power injection of contrast material flushed with saline solution for thoracic multislice CT using a dual power injector was evaluated in 105 patients. The patients were categorized into 3 groups of 35 patients each, according to the protocol of contrast material administration: (1) 100 mL of non-ionic contrast material(300 mgI/mL), (2) 75 mL of the same contrast material, and (3) 75 mL of the same contrast material flushed with 30 mL of saline solution. Scanning was performed in a caudal-to-cranial direction. Mean attenuation for the three protocols was measured in the superior vena cava, pulmonary trunk, ascending aorta, and descending aorta. Vascular opacification and perivenous artifacts were graded using four-point scoring by a consensus panel of three blinded radiologists. Intravenous injection of 75 mL of contrast material flushed with saline solution provided significantly better vascular opacification in the superior vena cava(p < 0.001) and pulmonary trunk(p < 0.02) than that provided by a 75 mL or 100 mL injection of contrast material alone. A similar degree of enhancement was observed in the ascending and descending aorta. Further, perivenous artifacts in the subclavian vein were significantly reduced (p < 0.05).

Adult↗
PubMed2000

Adenoviral transfer of cyclin-dependent kinase inhibitor genes suppresses collagen-induced arthritis in mice.

In rheumatoid synovial tissues, synovial fibroblasts are activated by proinflammatory cytokines and proliferate to develop hyperplastic pannus tissues, which irreversibly damage the affected joints. We recently reported that the cyclin-dependent kinase inhibitors p16(INK4a) and p21(Cip1) are not expressed in vivo in rheumatoid synovial fibroblasts, but are readily inducible in vitro. This observation was followed by the successful treatment of rat adjuvant arthritis by local p16(INK4a) gene transfer, showing that the inhibition of the cell cycle of the synovial cells ameliorates the arthritis. In this study, we show that another animal model of rheumatoid arthritis, murine collagen-induced arthritis, can be effectively treated by local gene transfer of p21(Cip1) as well as that of p16(INK4a). The anti-arthritic effects were observed even when the treatment was conducted after the arthritis had developed. Furthermore, the effects included suppression of the expression of proinflammatory cytokines such as IL-1ss, IL-6, and TNF-alpha. Our results demonstrate that the ectopic expression of cyclin-dependent kinase inhibitors not only prevents synovial overgrowth but also ameliorates the proinflammatory milieu in the affected joints. The induction of p21(Cip1) in rheumatoid synovial tissues by pharmacological agents may also be an effective strategy to treat rheumatoid arthritis.

Adenoviridae↗
PubMed2000

Expression of c-Ets1 is associated with malignant potential in endometrial carcinoma.

BACKGROUND: The protooncogene c-ets1 is a transcriptional factor that controls the expression of a number of genes involved in extracellular matrix remodeling. It might play a role in the regulation of physiologic processes such as cell proliferation and differentiation and also is associated with angiogenesis, cell migration, and tumor invasion. METHODS: To elucidate the involvement of c-Ets1 in endometrial carcinogenesis, the authors analyzed serial frozen sections for c-Ets1 protein expression in 20 cases of endometrial carcinoma and 20 cases of normal endometria by fluorescent immunohistochemistry. The authors analyzed the relation between the percentages of c-Ets1 stained cells and patient characteristics including histologic grade, surgical stage, presence of invasion to greater than one-half myometrium, presence of vascular involvement, presence of lymph node metastasis, and clinical outcome. RESULTS: In the normal endometria, c-Ets1 was weakly detected at the luminal surface of endometrial glands in both the proliferative and secretory phases. Most of the c-Ets1 proteins were found in the cytoplasm and partly in the nucleus of endometrial carcinoma glands, and also in fluid secreted from endometrial carcinoma glands. Moreover, c-Ets1 was strongly expressed in the head portion of papillary carcinoma tissues that invaded the stroma. c-Ets1 expression was associated significantly with histologic grade (P < 0.005), the presence of invasion to greater than one-half myometrium (P < 0.001), surgical stage (P < 0.005), and vascular involvement (P = 0.009). CONCLUSIONS: The authors' results show that c-Ets1 expression in endometrial carcinoma correlates with the malignant potential of this tumor.

Endometrial Neoplasms↗
PubMed2000

Genotype analysis of the CYP2C19 gene in HCV-seropositive patients with cirrhosis and hepatocellular carcinoma.

This study was conducted to assess whether the genotypic frequency of Smephenytoin 4'-hydroxylase CYP2C19 gene differs in Japanese cirrhotic patients who developed hepatocellular carcinoma. Thirty-eight patients with cirrhosis were studied. The wild-type allele CYP2C19*1 and the two mutated alleles, CYP2C19*2 and CYP2C19*3, were identified by PCR-RFLP method. Individuals with homozygous CYP2C19*2 or CYP2C19*3 mutation and those with CYP2C19*2 and CYP2C19*3 heterozygous mutation were predicted to be the poor metabolizer (PM) phenotype. The overall frequency of PM predicted from the genotyping analysis was 29% (11 of the 38 patients), consisting of 5 patients homozygous for CYP2C19*2, two homozygous for CYP2C19*3 and four heterozygous for the two defects. Among 24 HCV-seropositive patients with cirrhosis and hepatocellular carcinoma, the frequency of PM was 41.7% and significantly higher than that observed in 186 healthy controls. We postulate that the PM phenotype caused by the mutation of CYP2C19 gene in cirrhotic patients with HCV infection is associated with a high risk for developing hepatocellular carcinoma.

Alleles↗
PubMed2000

Photoinduced polarization inversion in a polymeric molecule

The polymeric molecule can exhibit a new photoinduced phenomenon where the electric dipole of the molecule with a bipolaron is reversed by absorbing one photon. This photoinduced polarization inversion occurred in a single molecule is an ultrafast process with a relaxation time of 200 fs.

Journal Article↗
PubMed2000

[Healing in the intestinal anastomosis--comparison of the Albert-Lembert and Gambee methods].

An experimental comparative histomorphological study was made on intestinal healing processes following an Albert-Lembert suture with approximation of the serosal surface and Gambee's layer to layer anastomosis of a dog. There was no obvious complications such as postoperative hemorrhage, anastomotic stenosis or anastomotic leakage. Although both anastomoses resulted in a good healing process, Gambee's layer to layer suture, which caused the submucosal layers to face each other, showed better wound healing at the anastomosis in terms of layer to layer attachment. As a conclusion, Gambee's layer to layer anastomosis seemed to be a better anastomotic technique in terms of wound healing for the intestinal anastomosis.

Anastomosis, Surgical↗
PubMed2000

Distribution of alpha1-adrenoceptor subtype mRNA and identification of subtype responsible for renovascular contraction in human renal artery.

This study was intended to quantify the amounts of the alpha1-adrenoceptor subtype mRNAs in human renal artery and to demonstrate the distribution of receptor subtypes responsible for the contraction of the renal artery. RNase protection assay showed that the mean amount of alpha1a mRNA was much greater than that of alpha1b or alpha1d mRNAs in both the main and branch renal arteries. However, the abundance of alpha1a mRNA in human renal artery was much less than in our previous data in the prostate. In situ hybridization showed that all alpha1 subtype mRNAs were localized in the smooth muscle cells of the tunica media of the artery, and the distribution pattern of these three mRNAs in the main artery was the same as in the branch artery. However, the intensity of signals for alpha1d and alpha1b antisense RNAs probes was lower than that for the alpha1a antisense RNA probe. In the functional study, concentration-response curves to noradrenaline pretreated with KMD-3213, an alpha1A/L-adrenoceptor selective antagonist, seemed to be biphasic in nature. Chloroethyclonidine (CEC) failed to inactivate the noradrenaline-induced contraction, and prazosin showed relatively low affinity with a pA2 value of 8.8. These data suggest that the alpha1A/L-adrenoceptor mediates primarily those responses to noradrenaline in this artery. The other alpha1-adrenoceptor subtypes could also mediate the secondary contractile response to noradrenaline in this artery.

Adrenergic alpha-Antagonists↗
PubMed2000

Stereochemical fate of C-26 and C-27 during the conversion of isofucosterol to sitosterol and of 24-methylenecholesterol to campesterol and dihydrobrassicasterol in Oryza sativa cell cultures.

Administration of pro-R-methyl-13C-labeled isofucosterol to cultured cells of Oryza sativa revealed that the pro-R and pro-S methyls at C-25 become the pro-R and pro-S methyls at C-25 of sitosterol, respectively. Similar administration experiments using pro-S-methyl-13C-labeled 24-methylenecholesterol established that the pro-R and pro-S methyls at C-25 of 24-methylenecholesterol become the pro-R and pro-S methyls of campesterol, and the pro-S and pro-R methyls of dihydrobrassicasterol, respectively. These results are compatible with our recently proposed 'syn-SE2' mechanism' for double bond isomerization of delta 24(28) into delta 24(25).

Cells, Cultured↗
PubMed2000

Production of interleukin (IL)-6 and IL-8 by a choriocarcinoma cell line, BeWo.

To clarify the biological and pathological features of choriocarcinoma, we evaluated the in vitro production of cytokines by a choriocarcinoma cell line, BeWo. We measured the concentration of interleukin (IL)-6 and IL-8 in the culture media of BeWo cells after stimulation with various modulatory agents of cytokine expression by enzyme-linked immunosorbent assays. Northern blot analysis was used to examine the expression of IL-6 and IL-8 mRNA in these cells. A weak expression of IL-6 and IL-8 was detected in unstimulated BeWo cells by both methods. IL-6 transcription and secretion were dose-dependently enhanced by stimulation with IL-1beta, tumour necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta1 and 12-O-tetradecanoyl phorbol-13-acetate (TPA). Forskolin, lipopolysaccharide and interferon-gamma had no effect on these cytokines production. The TNF-alpha-induced secretion of IL-6 was inhibited by dexamethasone. The TPA-induced production of IL-6 was inhibited by 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine and sphyngosine, suggesting the involvement of a protein kinase C-dependent pathway. Levels of IL-8 mRNA and protein were also dose-dependently increased by stimulation with IL-1beta, TNF-alpha and TPA. In contrast to IL-6, the expression of IL-8 was not affected by TGF-beta1. It is suggested that, in addition to the production of steroidal and non-steroidal hormones, these cytokines may serve as part of a cytokine network that modulates the proliferation and angiogenesis of choriocarcinomas.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed2000

Alternating combination chemotherapy C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, bleomycin, vinblastine, dacarbazine) in clinical stage II-IV Hodgkin's disease: a multicenter phase II study (JCOG 8905). The Lymphoma Study Group of the Japan Clinical Oncology Group.

BACKGROUND: The main form of cytotoxic treatment for advanced Hodgkin's disease (HD) is conventional dose multiagents chemotherapy. As HD is not common in Japan, we conducted a phase II study of the commonly used combination chemotherapy (CCT) regimen established in the West for Japanese patients with advanced HD to confirm the efficacy and safety. METHOD: Between October 1989 and February 1993, a multicenter phase II study of alternating CCT C-MOPP (cyclophosphamide, vincristine, procarbazine, prednisone) and ABVd (adriamycin, vinblastine, bleomycin, dacarbazine) to evaluate its clinical usefulness for clinical stage (cS) II-IV HD was conducted by the Lymphoma Study Group of the Japan Clinical Oncology Group. RESULTS: Seventy-nine previously untreated patients were enrolled in the study. For 67 eligible patients, the response rate was 92.5% with 83.6% complete response (CR). For 40 cS II and 27 cS III/IV patients the response rate was 95.0% with 90.0% CR and 88.9% with 74.1% CR, respectively. The overall 5-year survival rate was 84.8%. Those of cS II and cS III/IV were 92.5 and 73.1%, respectively. There was no significant difference between cS II and cS III/IV (p = 0.1025). The progression-free 4-year survival rate was 72.8%. Those of cS II and cS III/IV were 77.5 and 65.7%, respectively. There was no significant difference between cS II and cS III/IV (p = 0.2483). Grade 4 toxicity by the criteria of the World Health Organization consisted of leukocytopenia in 28.4% of patients. There was GPT elevation in 4.5%, nausea/vomiting in 11.9% and CNS in 1.5% of patients, but there was no treatment-related death. CONCLUSION: The C-MOPP/ABVd regimen for Japanese patients with advanced HD is considered to be one of the effective CCTs according to the results of the present phase II study.

Adolescent↗
PubMed2000

Effects of lipopolysaccharide and cytokines on production of RANTES by cultured human endometrial stromal cells.

RANTES (regulated upon activation, normal T cell expressed and secreted), which is a potent chemoattractant for eosinophils, lymphocytes, and monocytes, was recently detected in the human endometrium. The effects of modulators of endometrial function, including lipopolysaccharide (LPS), tumour necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-4 and interferon-gamma (IFN-gamma), on the production of RANTES by endometrial stromal cells (ESC) were examined by an enzyme-linked immunosorbent assay and Northern blot analysis. The concentration of RANTES in the culture media of non-stimulated ESC was below the level of detection. The concentration of RANTES was increased by the addition of TNF-alpha, IL-1beta and LPS. IFN-gamma synergistically enhanced the TNF-alpha- and LPS-induced RANTES expression, but had no effect on the IL-1beta-induced RANTES expression. The TNF-alpha-induced production of RANTES by ESC was inhibited by IL-4. The transcription of RANTES in ESC was also stimulated by TNF-alpha, IL-1beta and LPS in a dose-dependent manner. It is suggested that the LPS and cytokines secreted by the maternal decidual tissue and the developing embryo may regulate the production of RANTES by ESC. The modulation of RANTES concentration in the local environment may contribute to the pathophysiological processes of human reproduction by regulating the immunological reaction at the fetal-maternal interface.

Adult↗
PubMed2000

Platelet-activating factor induces an imbalance between matrix metalloproteinase-1 and tissue inhibitor of metalloproteinases-1 expression in human uterine cervical fibroblasts.

Platelet-activating factor (PAF) is involved in such reproductive processes as parturition. We investigated the effect of PAF on the expression of matrix metalloproteinase-1 (MMP-1) and that of tissue inhibitor of metalloproteinases-1 (TIMP-1) in human uterine cervical fibroblasts. Uterine cervical tissue was obtained from patients who underwent cesarean section at term. Collagenase-dispersed fibroblasts were cultured and used in the experiments. PAF receptor was identified in the uterine cervical fibroblasts by use of reverse transcription-polymerase chain reaction and Southern blot analysis. Northern blot analysis showed that PAF increased the expression of MMP-1 mRNA in a time-dependent manner, whereas expression of TIMP-1 mRNA was not affected by PAF. Concentration of MMP-1 protein in the PAF-treated culture media significantly exceeded that in control cultures. The PAF-induced production of MMP-1 protein was abolished by treatment with WEB 2170, a specific PAF receptor antagonist. Results suggest that PAF may accelerate collagenolysis in the human uterine cervix by inducing an imbalance in the activity between MMP-1 and TIMP-1, thus contributing to the cervical ripening during parturition.

Adult↗
PubMed2000

Upregulation of human cytotrophoblast invasion by hepatocyte growth factor.

Mesenchymal-epithelial interactions exert powerful influences on tissue architecture. At the molecular level, hepatocyte growth factor (HGF; produced by mesenchyme) and its c-met tyrosine kinase receptor (expressed on epithelial cells) participate in this paracrine dialogue. In the present study, anti-HGF immunoreactivity was usually detected in association with the mesenchymal cores of chorionic villi in situ, whereas cytotrophoblasts (CTBs) stained for c-met. In pre-eclampsia, mesenchymal HGF staining was either very low or was not observed, whereas CTB c-met expression was unchanged compared with control samples. These findings suggest that faulty signals emanating from the villus mesenchyme may contribute to the failure of CTB invasion that is associated with pre-eclampsia. In the present study, this hypothesis was tested and it was found that HGF treatment stimulates CTB invasion in vitro by four times. These immunolocalization and functional data indicate that HGF-c-met interactions play a key role in regulating the depth of CTB invasion in normal pregnancy and pre-eclampsia.

Case-Control Studies↗