Biomedical subjects

N Iwata

Publications and source records attributed to N Iwata.

At least 55 records · Page 3Linked to original sources

PubMed2001

[Usefulness of CT-guided RFA for hepatocellular carcinoma].

US-guided puncture is the simplest and most popular method in the RFA treatment for HCC. However, depending on the location of tumors, it is often difficult to detect them by US. We report here the utility of CT-guided RFA for the treatment of HCC. We performed CT-guided RFA for 27 nodules in 21 patients with HCC from July 1999 to June, 2001. We used the LeVeen Needle Electrode made by Boston Company and the Cool-tip type electrode made by Radionics Company. We judged the effects of the treatment by dynamic CT within 7 days after RFA. We were able to accomplish the treatment for all patients with the exception of one case who developed severe pain during RFA. We experienced transient increases of AST/ALT in a few cases, subcutaneous emphysema in one case, pleural effusion and ascites in two cases, but conservative treatments were effective for all cases. US-guided puncture was especially useful for the treatment of the tumors localized below the diaphragm that were hardly detectable by US.

Aged↗

PubMed2000

Characterization of the CIN85 adaptor protein and identification of components involved in CIN85 complexes.

CIN85 is an 85-kDa adaptor protein whose functions in signaling pathways are presently unknown. Using the yeast two-hybrid screen, the B cell linker protein (BLNK) was identified as a binding partner of CIN85. Coimmunoprecipitation experiments using mammalian cells revealed that CIN85 directly bound to BLNK through its SH3 domains. Immunostaining analysis showed that CIN85 and BLNK were colocalized in the cytoplasm. These results indicate a potential role of CIN85 in the B cell receptor-mediated signaling pathway. It was also found that Crk-I, Crk-II, p130(Cas), p85-PI3K, Grb2, and Sos1 were components of CIN85 complexes. CIN85 interacted with itself through its coiled-coil region, resulting in formation of a tetramer. Both the coiled-coil region and SH3 domains of CIN85 were responsible for its subcellular localization. Our data suggest that CIN85 may serve for regulation of various signaling events through formation of its diverse complexes.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Frequent hypermethylation of CpG islands and loss of expression of the 14-3-3 sigma gene in human hepatocellular carcinoma.

The 14-3-3 sigma gene has been implicated in G2/M cell cycle arrest by p53. Frequent inactivation of the 14-3-3 sigma gene by hypermethylation of CpG islands has recently been reported in human breast carcinoma. The aim of this study was to examine the methylation status of CpG islands of the 14-3-3 sigma gene in hepatocellular carcinoma (HCC). The methylation status of the 14-3-3 sigma gene was evaluated in four normal liver tissues and 19 paired specimens of carcinoma and adjacent non-tumorous liver tissues using bisulfite-single strand conformation polymorphism (bisulfite-SSCP), a combination of sodium bisulfite modification and fluorescence-based polymerase chain reaction (PCR)-SSCP. The 14-3-3 sigma protein expression was examined by immunohistochemical staining. Hypermethylation of CpG islands of the 14-3-3 sigma gene was detected in 89% (17/19) of the HCC tissues but not in any of the four normal liver tissues. All of the 14 methylation-positive HCC samples analysed by immunohistochemistry showed loss of 14-3-3 sigma expression, while both of the methylation-negative HCC samples retained the expression, and a significant correlation was found between methylation and loss of expression. Lower levels of methylation were detected in adjacent non-tumorous liver tissues (6/16 in cirrhotic tissues and 1/3 in chronic hepatitis tissues), but the 14-3-3 sigma expression was retained in all of these tissues. In a methylation-positive HCC cell line, HLE, 5-aza-2'-deoxycytidine (5-aza-dC)-induced demethylation of CpG islands led to reactivation of gene expression, indicating that hypermethylation plays a causal role in inactivation of the 14-3-3 sigma gene in HCC. Hypermethylation and the resulting loss of expression of the 14-3-3 sigma gene corresponds to one of the most common abnormalities reported to date in HCC, suggesting their crucial role in the development and/or progression of HCC.

14-3-3 Proteins↗

PubMed2000

Cloning and characterization of a novel adaptor protein, CIN85, that interacts with c-Cbl.

The c-Cbl protooncogene product is a prominent substrate of protein tyrosine kinases and is rapidly tyrosine-phosphorylated upon stimulation of a wide variety of cell-surface receptors. We have identified a novel c-Cbl-interacting protein termed CIN85 with a molecular mass of 85 kDa which shows similarity to adaptor proteins, CMS and CD2AP. CIN85 mRNA is expressed ubiquitously in normal human tissues and cancer cell lines analyzed. CIN85 was basally associated with c-Cbl. For interaction of CIN85 with c-Cbl, the second SH3 domain of CIN85 was shown to serve as a central player. The CIN85-c-Cbl association was enhanced shortly after stimulation of 293 cells with epidermal growth factor (EGF) and gradually diminished to a basal level, which correlated with a tyrosine phosphorylation level of c-Cbl. Our results suggest that CIN85 may play a specific role in the EGF receptor-mediated signaling cascade via its interaction with c-Cbl.

Adaptor Proteins, Signal Transducing↗

PubMed2000

Psychometric properties of the State-Trait Anxiety Inventory among Japanese clinical outpatients.

The factor structure and internal consistency of the Japanese adaptation of the State-Trait Anxiety Inventory Form Y (STAI-JY) were examined for 218 Japanese clinical outpatients (86 males, 132 females) with psychiatric and/or psychosomatic complaints. An initial principal-component analysis revealed that the first three components were considered to reflect the "overall anxiety" component, the "presence-absence of anxiety (positive-negative)" component, and the "state-trait anxiety" component. The component related to presence or absence of anxiety was larger than the state-trait anxiety component. Factors followed by an oblique (promax) rotation were labeled "Anxiety-absent" and "Anxiety-present" factors for a two-factor structure, and "Anxiety-present," "Anxiety-absent/state," and "Anxiety-absent/trait" factors for a three-factor structure that was suggested by the scree test. The internal consistencies for both the state and trait anxiety subscales of the STAI-JY were at a satisfactory level, whereas slightly higher Cronbach's as were obtained from separate calculation for anxiety-present and anxiety-absent items. Similarities and differences in the factor structure of the STAI-JY were discussed in comparison with those reported earlier for the general population in Japan and for individuals in Western countries.

Adolescent↗

PubMed2000

Low novelty-seeking differentiates obsessive-compulsive disorder from major depression.

OBJECTIVE: To make a direct comparison of patients with obsessive-compulsive disorder (OCD) and major depression (MD) and a normal control group in terms of the Temperament and Character Inventory (TCI) personality dimensions. METHOD: Additionally to 43 patients with primary OCD, 43 MD patients and 43 normal subjects who were matched against the OCD patients for sex and age filled out the TCI. RESULTS: Compared to the controls, the OCD and MD patients scored significantly higher on harm avoidance and significantly lower on self-directedness and co-operativeness. The OCD patients scored significantly lower on novelty-seeking than the MD patients and the controls. CONCLUSION: Whereas OCD and MD share similar personality deviations on harm avoidance, self-directedness and co-operativeness, OCD is distinguishable from MD in terms of low novelty-seeking. Low novelty-seeking may have a profound relationship to the specific aetiology of OCD.

Adolescent↗

PubMed2000

Identification of the major Abeta1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition.

Alzheimer amyloid beta-peptide (Abeta) is a physiological peptide constantly anabolized and catabolized under normal conditions. We investigated the mechanism of catabolism by tracing multiple-radiolabeled synthetic peptide injected into rat hippocampus. The Abeta1-42 peptide underwent full degradation through limited proteolysis conducted by neutral endopeptidase (NEP) similar or identical to neprilysin as biochemically analyzed. Consistently, NEP inhibitor infusion resulted in both biochemical and pathological deposition of endogenous Abeta42 in brain. This NEP-catalyzed proteolysis therefore limits the rate of Abeta42 catabolism, up-regulation of which could reduce the risk of developing Alzheimer's disease by preventing Abeta accumulation.

Amino Acid Sequence↗

PubMed2000

Predicting the severity of intestinal graft-versus-host disease from leukotriene B4 levels after bone marrow transplantation.

Intestinal graft-versus-host disease (GVHD) produces clinical manifestations and histological changes resembling those of ulcerative colitis and has been treated with drugs which are used for ulcerative colitis. These two conditions also resemble each other with respect to changes of cytokines. Accordingly, we investigated whether the level of leukotriene B4, a risk factor for ulcerative colitis, was also a risk factor or prognostic indicator for intestinal GVHD. The pre-conditioning leukotriene B4 level was significantly related to the grade of intestinal GVHD in 42 patients (P < 0.01). Compared with patients who did not develop severe intestinal GVHD after bone marrow transplantation, those who did had significantly higher interleukin-2 and interferon-gamma levels during the aplastic phase (P <0.01), followed by higher tumor necrosis factor-alpha levels during the recovery phase (P < 0.0001), with significant elevation of tumor necrosis factor-alpha and interferon-gamma occurring in association with exacerbations of intestinal GVHD (P < 0.001). These findings suggest a similarity between the pathogenesis of ulcerative colitis and intestinal GVHD and raise the possibility that leukotriene B4 may be a useful prognostic indicator for intestinal GVHD.

Adolescent↗

PubMed2000

Identification of a naturally occurring Pro385-Ser385 substitution in the GABA(A) receptor alpha6 subunit gene in alcoholics and healthy volunteers.

In the rat, variation in alcohol and benzodiazepine sensitivity has been correlated with an inherited variant of the GABA(A)alpha6 receptor. Our goal was to identify polymorphisms in the human GABA(A)alpha6 receptor gene and determine whether a variant of the receptor is associated with alcoholism. The GABA(A)alpha6 receptor gene coding region was screened in 80 unrelated patients with alcoholism using single strand conformational polymorphism analysis. For rapid genotyping, a Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) assay was developed. A relatively abundant amino acid substitution and three synonymous DNA substitutions were detected. The synonymous variants, 35A>G, 665A>G, and 1031G>C had rare-allele frequencies of 0.25, 0.02, and 0.47, respectively. The Pro385Ser substitution is located in the second intracellular domain of the receptor adjacent to a putative phosphorylation site. Pro385Ser has rarer allele frequencies of 3.3% and 4.8% in 196 Finnish alcoholic patients and 189 controls, respectively (P = NS). A naturally occurring non-conservative Pro385Ser was detected in the GABA(A)alpha6 receptor. The variant is not associated with alcoholism.

Alcoholism↗

PubMed2000

Habitual snoring in an outpatient population in Japan.

In order to investigate the occurrence and history of sleep problems in Japan, the 11-Centre Collaborative Study on Sleep Problems (COSP) project was carried out. Complaints of snoring are examined, and its prevalence, risk factors and screening reliability are discussed. The subjects who participated in the study were 6445 new outpatients from a general hospital. They were asked to answer a sleep questionnaire that consisted of 34 items with seven demographic items; each item was composed of four grades of frequency. In order to offset possible seasonal variations in sleep habits, data were collected across four seasons. Sleep patterns, insomnia, hypersomnia, parasomnia and circadian rhythm sleep disorders were covered. Habitual snoring was seen in 16.0% of males and 6.5% of females. Male predominance was noted. From these data, the relationship between habitual snoring and sleep complaints was statistically analyzed. Habitual snorers (HS) were observed to wake up more frequently during sleep (17.8% of males, 21.5% of females) than were non-habitual snorers (NHS; 6.6% of males, 9.7% of females). Mid-sleep awakening of HS was also more frequent than it was for NHS; however, there were no differences in difficulty in falling asleep and early morning awakening. Body mass index, cigarette smoking and alcohol consumption were also correlated with habitual snoring.

Adult↗

PubMed2000

Canine extracutaneous mast-cell tumours consisting of connective tissue mast cells.

Two cases of canine extracutaneous mast-cell tumours were encountered, originating from the mucosa of either the oral cavity or the small intestine. The dogs had no neoplasms in the skin. Immunohistochemical and ultrastructural studies demonstrated that the neoplastic cells had the features of connective tissue mast cells. It would seem, therefore, that at least some extracutaneous forms of the neoplasm originate from connective tissue mast cells. Heparin was a useful cytological marker to diagnose this type of mast-cell tumour.

Animals↗

PubMed2000

Biochemical identification of the neutral endopeptidase family member responsible for the catabolism of amyloid beta peptide in the brain.

Amyloid beta peptide (Abeta) is a physiological peptide that is constantly catabolized in the brain. We previously demonstrated that an endopeptidase sensitive to phosphoramidon and thiorphan conducts the initial rate-limiting proteolysis of Abeta in vivo, but the exact molecular identity of the peptidase(s) has remained unknown because of the molecular redundancy of such activity. We analyzed the brain-derived enzyme by means of immuno-depletion and gene disruption, and demonstrate here that neprilysin accounts for the majority of the Abeta-degrading activity. Furthermore, kinetic analysis, giving a K(m) value of 2.8 +/- 0.76 microM, indicated that Abeta(1-42) is a relevant substrate for neprilysin.

Amino Acid Sequence↗

PubMed2000

Responses of Japanese and American university students to the STAI items that assess the presence or absence of anxiety.

Symptom endorsements and item response patterns on the anxiety-present and anxiety-absent items of the State-Trait Anxiety Inventory Form Y (Spielberger, 1983) for 149 Japanese (99 living in Japan and 50 studying in the United States) and 76 American university students were compared. Although mean scores for the state and trait anxiety-absent items were comparable for Japanese students living in Japan and Japanese international students studying in the United States, the scores of both Japanese groups were significantly higher than those of American students. These differences were attributable to much higher scores of Japanese students on anxiety-absent items that corresponded to a lack of positive feelings. Japanese students had a tendency to inhibit positive (anxiety-absent) feelings, resulting in higher anxiety scores. Responses to anxiety-present and anxiety-absent items should be considered independently in scoring anxiety scales.

Adolescent↗

PubMed2000

Activation of cerebral function by CS-932, a functionally selective M1 partial agonist: neurochemical characterization and pharmacological studies.

A newly synthesized agonist for muscarinic acetylcholine (ACh) receptors CS-932, (R)-3-(3-iso-xazoloxy)-1-azabicyclo-[2.2.2]octane hydrochloride, showed a relatively higher affinity for M1 than M2 receptors expressed in Chinese hamster ovary (CHO)-cells in comparison with ACh. CS-932 elevated the intracellular Ca2+ level only in M1-CHO cells, although ACh increased the level in both M1- and M3-CHO cells. CS-932 and ACh reduced forskolin-stimulated accumulation of cAMP in M2-CHO cells by 20% and 80%, respectively. This neurochemical profile of CS-932 indicates that the compound can activate M1-receptor-mediated functions selectively. CS-932 increased firing of cholinoceptive neurons in rat hippocampal slices, and this excitation was antagonized by pirenzepine, but not by AF-DX 116. CS-932 increased awake and decreased slow wave sleep episodes of daytime EEG in free-moving rats. It counteracted scopolamine-induced slow waves in rat cortical EEG. CS-932 also increased the power of alpha- and beta-waves, but decreased delta-wave of the cortical EEG in anesthetized monkeys. It ameliorated scopolamine-induced impairment of working memory in rats. Orally administered CS-932 had the best penetration into the brain among the muscarinic agonists tested and caused the least salivary secretion among the cholinomimetics examined. These results indicate that CS-932 has potential as a cognitive enhancer with fewer side effects in therapy for Alzheimer disease.

Animals↗

PubMed2000

Creating notifications tailored for individual workers by using a database: a conceptual framework and its application.

Although prevention strategies to assure good mental health in the workplace have become important, worker notification in studies using psychometric tests has rarely been discussed. Until now it has been difficult to prepare a large number of notifications that are tailored well for individual workers. We have developed a system to create notifications that explain the results for individual workers in plain language using a relational database (RDB). First, scores for each test were divided into categories and the workers' data was classified. Then, explanations were written for each category. RDB software read component files into a database file, integrated all data, and printed out notifications. After the system was developed, we realized its high potential for use in occupational health care, as well as in many other fields. We also report an example of its application.

Databases, Factual↗

PubMed2000

T-cell-specific expression of kinase-defective Eph-family receptor protein, EphB6 in normal as well as transformed hematopoietic cells.

Although most kinase-defective growth factor receptor proteins are associated with pathogenic conditions, a kinase-defective Eph-family receptor protein, EphB6, is expressed in normal human tissues. We generated monoclonal antibodies specific for human EphB6 to characterize its expression on human hematopoietic cells. A very small population of normal human peripheral white blood cells (0.57 +/- 0.07%, n = 12) expressed EphB6. The EphB6-positive cells were CD2+, CD7+, CD3+ and CD4+ or CD8+ lymphocytes, but they did not express CD19 or CD11b. In human bone marrow, only 1.5 +/- 0.19% of lymphocytes expressed EphB6. Compared with the expression in peripheral lymphocytes, prominent expression of EphB6 protein was demonstrated in CD4+CD8+ double-positive mouse thymocytes. The T-cell lineage-specific expression was strictly conserved in human leukemia/lymphoma cells. Among T-cell-derived leukemia cells, the expression level of EphB6 seemed to decrease with maturation of the cells. These results suggest that EphB6 expression is regulated in T-cell development.

Animals↗

PubMed2000

Feasibility of high-dose chemotherapy without stem cell support as a first-line treatment for non-Hodgkin's aggressive lymphoma: a pilot study.

A regimen which incorporates cyclophosphamide, doxorubicin, vincristine and prednisolone (CHOP) is the standard treatment for patients with non-Hodgkin's lymphoma (NHL), but it has not been effective in patients with aggressive NHL who are at high risk. The aim of the present trial was to investigate the feasibility of high-dose chemotherapy (HDC) without stem cell support as a first-line treatment. The primary endpoint was a complete remission rate. The second endpoint was survival. Fourteen patients with aggressive NHL entered the study and were treated according to the K93 protocol (3 cycles of CHOP, high-dose etoposide and ifosfamide, and high-dose methotrexate) Eleven patients (79%) achieved complete remission (CR) and two (14%) achieved partial remission (PR). Overall survival (OS) after five years was 79%. The actuarial five year disease free survival (DFS) for the eleven cases of CR was 75%. During chemotherapy, grade IV hematologic toxicity was observed in all patients and grade IV non-hematologic toxicity in only one patient, who experienced oral ulcers. Peripheral blood stem cell (PBSC) apheresis was performed in eight cases. One harvesting was enough to provide an adequate number of CD34+ cells for the subsequent PBSC transplantation (PBSCT). In conclusion our study confirmed the efficacy of the K93 protocol in obtaining a good response (CR + PR) rate and a very good DFS rate in most cases of aggressive NHL, with acceptable toxicity. This regimen may improve the outcome in cases of aggressive NHL without stem cell support. It seems worthwhile to conduct a randomized controlled study comparing the K93 protocol with the standard CHOP regimen.

Adult↗

PubMed2000

Low serum cholesterol levels and depressive state in human dock visitors.

OBJECTIVE: The purpose of the present study was to investigate an association between serum cholesterol levels and depressive state. METHOD: Physical examinations and mental assessments were performed for 13702 human dock visitors. We obtained 13571 sets of complete data for serum total cholesterol, the scores for depressive state and possible confounders such as sex, age, body weight, body mass index (BMI), recent weight loss, total protein and concomitant medical diagnoses. RESULTS: Their depressive state varied significantly across the serum cholesterol levels after adjusting age and gender. After controlling all the above confounding variables the significance still remained, not only in the categorical analysis but also in the continuous analysis. CONCLUSION: The present findings suggest that there is an association between cholesterol and depressive state.

Adult↗