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Biomedical subjects

T Fujisawa

Publications and source records attributed to T Fujisawa.

At least 19 recordsLinked to original sources
PubMed1996

Identification of a Hydra homologue of the beta-catenin/plakoglobin/armadillo gene family.

The beta-catenin/plakoglobin/armadillo gene family encodes a group of highly conserved proteins which play important roles in cadherin-mediated cell adhesion and in signal transduction mechanisms involved in regulating development. This gene family previously had been isolated only from higher metazoans. Here, we describe the isolation and characterization of a beta-catenin (beta Ctn) homologue from Hydra magnipapillata, a diploblastic lower metazoan. Comparison of the putative amino acid (aa) sequence of Hydra beta Ctn, with its homologues in higher metazoans, shows that a repeating 42-aa motif present in its central domain is highly conserved throughout the metazoa. This suggests that beta Ctn appeared very early in metazoan evolution, possibly when primitive multicellular animals started to form epithelial cell layers.

Amino Acid Sequence↗
PubMed1996

Efficacy of interferon in treating chronic hepatitis C in children with a history of acute leukemia.

Interferon (IFN) is effective in treating adults as well as children with chronic hepatitis C. We investigated the efficacy of IFN therapy in 13 children with underlying acute leukemia who had chronic hepatitis C (age range, 5 to 17 years; mean age, 9.9 years). Natural IFN- alpha was administered at a dose of 0.1 mega unit (MU)/kg (maximum dose, 6.0 MU) daily for 2 weeks and then three times per week for an additional 22 weeks (total dose, 8 MU/kg). IFN treatment was initiated at least 2 years after the completion of treatment for acute leukemia. A complete response was obtained in 5 children (38%). The serum level of anti-hepatitis C virus core antibody was closely related to the response to IFN. IFN therapy was well tolerated by all but 1 of the children, who developed mild transient heart failure 4 months after the initiation of therapy. IFN therapy for children with chronic hepatitis C who had underlying acute leukemia was beneficial. However, further trials are required to confirm the safety and improve the dosage schedule of IFN therapy.

Acute Disease↗
PubMed1996

Association of Trp64Arg mutation of the beta3-adrenergic-receptor with NIDDM and body weight gain.

A possible pathogenic mutation in the beta 3-adrenergic-receptor gene (Trp64Arg) has been reported to be associated with an earlier age of onset of non-insulin-dependent diabetes mellitus (NIDDM) and clinical features of the insulin resistance syndrome in Pima Indian, Finnish and French subjects. Since marked heterogeneity has been reported in the association of mutations of candidate genes with NIDDM between Japanese and other ethnic groups, we investigated the association of Trp64Arg with NIDDM in Japanese subjects. The allele frequency of the mutation (Arg) was slightly, but not significantly, higher in NIDDM than in control subjects (70 out of 342 alleles [20.5%] vs 40 out of 248 [16.1%], respectively, p > 0.2). When our data were combined with those of Pima Indian and Finnish subjects, however, the Arg/Arg genotype was significantly associated with NIDDM as compared with the other two genotypes (p < 0.005, relative risk [RR] 2.13, 95% confidence interval [CI] 1.28-3.55). The Arg allele was also associated with NIDDM (p < 0.05, RR 1.27, 95% CI 1.06-1.52). Japanese subjects homozygous for the mutation had a significantly higher body mass index (mean +/- SD: 25.5 +/- 3.9 kg/m2) than heterozygotes (22.6 +/- 4.1, p < 0.05) and normal homozygotes (22.8 +/- 3.8, p < 0.05). NIDDM patients homozygous for the mutation tended to have an earlier age of onset of NIDDM than those with other genotypes. These data suggest that the Trp64Arg mutation not only contributes to weight gain and age-at-onset of NIDDM but is also associated with susceptibility to NIDDM.

Age of Onset↗
PubMed1996

Mite-specific induction of interleukin-2 receptor on T lymphocytes from children with mite-sensitive asthma: modified immune response with immunotherapy.

BACKGROUND: The efficacy of immunotherapy is still controversial. To elucidate the mechanisms of immunotherapy, we studied mite-specific induction of IL-2 receptor (IL-2R) expression on T lymphocytes from children with mite-sensitive asthma. METHODS: Peripheral blood mononuclear cells were obtained from 28 children with mite-sensitive asthma: 13 had never received house dust immunotherapy (nonimmunotherapy group), 15 had been receiving house dust immunotherapy at the time of the study (immunotherapy group). After a 6-day culture with or without Dermatophagoides farinae (Df) antigen, the expression of IL-2Rp55 (CD25) and p75 on CD4+ or CD8+ T lymphocytes was measured by flow cytometry. RESULTS: The nonimmunotherapy group showed significant Df-specific CD25 induction on CD4+ T lymphocytes (delta CD4+ CD25+) but little induction on CD8+ T lymphocytes (delta CD8+ CD25+). delta CD4+ CD25+ was correlated with the severity of the disease. In the immunotherapy group delta CD8+ CD25+ was significantly higher than in the nonimmunotherapy group or in normal subjects and correlated with Df-specific IgG4 and cumulative doses of house dust extract, whereas delta CD4+ CD25+ was similar in the nonimmunotherapy and the immunotherapy groups. IL-2Rp75 was not induced either on CD4+ or CD8+ T lymphocytes. CONCLUSIONS: Our data suggest that house dust immunotherapy may have induced Df-specific CD8+ T lymphocytes in patients with mite-sensitive asthma and that the efficacy of immunotherapy may be attributed to the generation of Df-specific CD8+ T lymphocytes.

Adolescent↗
PubMed1995

Blood and lymphatic vessel invasion as prognostic factors for patients with primary resected nonsmall cell carcinoma of the lung with intrapulmonary metastases.

BACKGROUND: The new classification of intrapulmonary metastases of lung cancer was proposed by the American Joint Committee on Cancer; however, the prognostic factors are heterogeneous and not yet fully clarified. In this study, the authors evaluated the prognostic factors for and the possible routes of intrapulmonary metastases. METHODS: The factors influencing the prognosis of primary resected nonsmall cell lung carcinomas with intrapulmonary metastasis in the resected specimens were evaluated according to the Cox proportional hazards model using a total of 66 nonsmall cell lung carcinomas. The possible routes of tumor spread via the blood or lymphatic vessels also were evaluated. RESULTS: The overall 5-year survival rate was 26.1%, and the statistical analysis of survival curves revealed a significant difference with regard to N classification (P = 0.042), site of intrapulmonary metastasis (P = 0.012), blood vessel invasion (P = 0.0046), and lymphatic vessel invasion (P = 0.0267); there were no significant differences in relation to age, sex, histology, differentiation, T classification, tumor size, stage, number of intrapulmonary metastases, or size of intrapulmonary metastasis. Multivariate analysis according to the Cox proportional hazards model identified a significant correlation between survival and blood vessel invasion (P = 0.044) and lymphatic vessel invasion (P = 0.042), suggesting independent prognostic significance. The correlation between site of intrapulmonary metastasis and the ratio of blood or lymphatic vessel invasion showed a significantly lower ratio of blood vessel invasion in cases with intrapulmonary metastases at sites central to the primary lesion or in different segment(s) compared with those in cases with intrapulmonary metastases at sites peripheral to the primary lesion or in ipsilateral different lobe(s), suggesting a possible lymphatic vessel route of tumor spread. CONCLUSION: Blood vessel and lymphatic vessel invasion are important clinical factors in evaluating prognosis and the route of tumor spread in primary resected nonsmall cell carcinoma with intrapulmonary metastasis.

Adult↗
PubMed1995

Dispersion state of phospholipids and fluorescence production with peroxidation in organic solvents: investigated by time-resolved fluorescence technique.

Fluorescent substances were found to be produced efficiently when phospholipids containing phosphatidylethanolamine (PE) and linoleic chains were autoxidized in non-polar solvents. By using these fluorescent substances as intrinsic probes, the dispersion state of phospholipids was investigated in various organic solvents. Fluorescence anisotropy decay measurements indicated that the aggregation size of phospholipids was much larger in hexane than in chloroform, methanol and tert-butyl alcohol. The average diameter of phospholipid aggregates in hexane was calculated to be 4-6 nm, which was dependent on the lipid composition. A consistent result was obtained when N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-1,2-dihexadecanoyl-sn-gly cer o-3- phosphoethanolamine (NBD-PE) was used as an extrinsic probe. Comparison of the fluorescence data with small-angle X-ray scattering (SAXS) data suggested that a reverse micellar structure of phospholipids formed in hexane. It was shown that phospholipid aggregation enhanced the extent of peroxidation as well as the production yield of fluorescent substances of phospholipid.

Chromatography, Thin Layer↗
PubMed1995

Structural characterization of the molten globule and native states of apomyoglobin by solution X-ray scattering.

Compactness and shape are two of the critical properties that describe the degree of protein folding. Solution X-ray scattering is an effective technique for measuring these properties quantitatively. Structural characteristics of various conformational states of horse myoglobin were studied in terms of size and shape by solution X-ray scattering. The radius of gyration for native holomyoglobin was 17.5 A, while that of the apomyoglobin native state was 19.7 A. Corresponding to the increase in the radius of gyration, the largest dimension of the molecule also increased from 47.5 A to 62.5 A. Both states are globular in shape. The scattering profiles in the high angle region suggest that the apomyoglobin native state has a distinct tertiary structure, and that packing of alpha-helices in the apomyoglobin native state would be looser than that of holomyoglobin. These observations indicate that the native state of apomyoglobin is expanded from that of holomyoglobin, and that the conformations of the two are not identical. The radii of gyration for the acid-unfolded state and the denaturant-unfolded state were 30 A and 35 A, respectively. Both unfolded states have chain-like conformations without any tertiary structures. The radius of gyration and the largest dimension of the molten globule stabilized by trichloroacetate were 23.1 A and 72.5 A, respectively. The molten globule is expanded from the native state although it is globular, and is much more compact than the unfolded state. The bimodal distance distribution function and scattering profile at high-angle region suggest that the structure of the apomyoglobin molten globule contains a core comprising a cluster of multiple alpha-helices and flaring tail(s), which would be a common structural property of the compact denatured state appearing during the folding process. The compactness of each conformational state is highly correlated with the extent of formation of the alpha-helix.

Apoproteins↗
PubMed1995

A new mitochondrial DNA mutation associated with non-insulin-dependent diabetes mellitus.

Mitochondria play an important role in glucose-induced insulin secretion in pancreatic beta cells. We therefore examined whether patients with NIDDM exhibit genetic variability in mitochondrial DNA (mtDNA), a candidate gene for NIDDM. We sequenced mtDNA in the region encoding tRNALeu and the adjacent region in several diabetic patients with clinical features suggesting mitochondrial DNA mutations. We found a new point mutation at position 3316 that leads to an amino acid change in the ND-1 protein. The frequency of the mutation was screened with PCR-RFLP in 295 NIDDM patients and 406 controls. We found ten NIDDM patients (3.4%) harbored the mutation. Although 4 control subjects had the mutation, the frequency was significantly higher in the NIDDM patients than in the control subjects (p = 0.02). These results suggest that the 3316 mutation is associated with NIDDM.

Base Sequence↗
PubMed1995

Isolation and characterization of a mini-collagen gene encoding a nematocyst capsule protein from a reef-building coral, Acropora donei.

Genomic and cDNA clones of a mcol gene encoding mini-collagen (MCOL), a nematocyst capsule protein, have been isolated from a reef-building coral, Acropora donei (Anthozoa). The gene and its flanking regions, comprising 5382 bp and covering three exons and two introns, were sequenced. Exons 2 and 3 together have an open reading frame which can encode a MCOL of 176 amino acids (aa). The coral MCOL has all the characteristic regions present in the four hydra MCOL specified by the four mcol cDNA clones previously isolated from Hydra magnipapillata (Hydrozoa) by Kurz et al. [J. Cell Biol. 115 (1991) 1159-1169], including a central Gly-Xaa-Yaa region and flanking Pro-rich and Cys-repeat regions. This observation suggests that a mcol family is highly conserved in Anthozoa and Hydrozoa, and also that the characteristic regions present in MCOL are essential for the structure and function of these peptides.

Amino Acid Sequence↗
PubMed1995

A mutation in the glucagon receptor gene (Gly40Ser): heterogeneity in the association with diabetes mellitus.

A possible pathogenic mutation in the glucagon receptor gene causing a Gly to Ser change at codon 40 (Gly40Ser) was reported to be associated and linked with non-insulin-dependent diabetes mellitus (NIDDM), in France and Sardinia. Since the frequency of the mutation (Gly40Ser), about 5% in the French population of familial NIDDM and 8% in randomly chosen diabetic patients in Sardinia, was much higher than that of any of the previously reported mutations in candidate genes, it is important to clarify whether the contribution of this mutation to NIDDM is universal. In this study, we investigated the association of this mutation with diabetes mellitus in a large number of Japanese diabetic patients (383 NIDDM and 53 insulin-dependent diabetic patients) by polymerase chain reaction-restriction fragment length polymorphism analysis. None of the Japanese diabetic patients showed Gly40Ser mutation and the association of this mutation with NIDDM was significantly different (p < 4.10(-5) vs French, p < 3.10(-6) vs Sardinian by Fisher's exact test). The results not only indicate that the mutation plays little, if any, role in susceptibility to diabetes in Japan, but also indicate the genetic heterogeneity in NIDDM and further emphasize the importance of studies on genetic susceptibility to NIDDM and other complex traits in different ethnic groups.

Adolescent↗
PubMed1995

The NSY mouse: a new animal model of spontaneous NIDDM with moderate obesity.

The NSY (Nagoya-Shibata-Yasuda) mouse was established as an inbred strain of mouse with spontaneous development of diabetes mellitus, by selective breeding for glucose intolerance from outbred Jcl:ICR mice. NSY mice spontaneously develop diabetes mellitus in an age-dependent manner. The cumulative incidence of diabetes is 98% in males and 31% in females at 48 weeks of age. Neither severe obesity nor extreme hyperinsulinaemia is observed at any age in these mice. Glucose-stimulated insulin secretion was markedly impaired in NSY mice after 24 weeks of age. In contrast, fasting plasma insulin level was higher in male NSY mice than that in male C3H/He mice (545 +/- 73 vs 350 +/- 40 pmol/l, p < 0.05, at 36 weeks of age). Pancreatic insulin content was higher in male NSY mice than that in male C3H/He mice (76 +/- 8 vs 52 +/- 5 ng/mg wet weight, p < 0.05, at 36 weeks of age). Morphologically, no abnormal findings, such as hypertrophy or inflammatory changes in the pancreatic islets, were observed in NSY mice at any age. These data suggest that functional changes of insulin secretion in response to glucose from pancreatic beta cells may contribute to the development of non-insulin-dependent diabetes mellitus (NIDDM) in the NSY mouse. Although insulin sensitivity was not measured, fasting hyperinsulinaemia in NSY mice suggests that insulin resistance may also contribute to the pathogenesis of NIDDM. Since these findings are similar to the pathophysiologic features of human NIDDM patients, the NSY mouse is considered to be useful for investigating the pathogenesis and genetic predisposition to NIDDM.

Aging↗
PubMed1995

Detection of MspI RFLP in human THY1 gene by the polymerase chain reaction.

THY1 gene encodes a cell surface glycoprotein predominantly expressed in brain and peripheral nerves. Human THY1 gene region on chromosome 11q23 has been implicated in susceptibility to type 1 diabetes (Wong et al., 1991). Two primers derived from the sequences flanking the polymorphic MspI site in intron 2 of the human THY1 gene (Gatti et al., 1988) were selected for RCP to amplify a 566 bp fragment that spans the MspI polymorphism. Polymorphism was detected by MspI digestion of the PCR product.

Base Sequence↗
PubMed1995

Response to interferon therapy in children with chronic hepatitis C.

We evaluated the effect of interferon therapy and investigated factors that may influence the outcome in 18 children with chronic hepatitis C. A complete response was obtained in 10 children (56%). The titer for pretreatment serum virus ribonucleic acid (< or = 10(7) copies/ml) was correlated significantly with a complete response to therapy.

Alanine Transaminase↗
PubMed1995

Absorption of fructose by isolated small intestine of rats is via a specific saturable carrier in the absence of glucose and by the disaccharidase-related transport system in the presence of glucose.

Previous studies have shown that the absorption of fructose is aided by simultaneous ingestion of glucose. The aim of the present study was to reproduce this finding in vitro to better understand the mechanism of the effect of glucose on absorption of fructose. The phenomena could not be reproduced with everted sleeves of rat intestine or brush border vesicles. In a perfused segment of isolated intestine, it was possible to demonstrate that the transport of fructose was accelerated when glucose was present in the perfusion medium. The enhanced transport was inhibited by sucrose and also by acarbazone, an inhibitor of intestinal alpha-disaccharidases. Phlorizin had no effect on the transport of fructose. The results of these studies indicate that there is a specific carrier for fructose saturated with a low concentration of the sugar, and that in the presence of glucose there is joint absorption of the two sugars by the disaccharidase-related transport system.

Animals↗
PubMed1995

New selective media for isolation of clostridia from faecal specimens.

Two selective media, novobiocin-colistin agar (NCA) and colistin-crystal violet agar (CCA), were developed for isolating clostridia from human and animal faeces. The basal medium was modified Eggerth-Gagnon agar. The NCA medium contains novobiocin (8 micrograms ml-1) and colistin (8 micrograms ml-1) and the CCA medium contains colistin (10 micrograms ml-1) and crystal violet (10 micrograms ml-1). Nine faecal specimens were cultured. Clostridia isolated on these media were similar to those on non-selective media, and higher than those isolated after heat treatment. However, more clostridial species were isolated on the new selective media compared with the non-selective medium. These selective agars were particularly useful for enumerating and isolating clostridia from human faeces.

Animals↗
PubMed1995

Comprehensive treatment of advanced neuroblastoma involving autologous bone marrow transplant.

Encouraging results are reported with high-dose chemotherapy and total body irradiation followed by autologous bone marrow transplantation in the treatment of advanced neuroblastoma. However, relapse remains a significant problem. We used high-dose chemotherapy, surgery, intraoperative radiation and an autologous bone marrow transplant treated in vitro to remove tumor cells followed by 13-cis-retinoic acid to treat 36 children with advanced neuroblastoma. This comprehensive treatment appears to improve the survival rate of patients with advanced neuroblastoma, including those with N-myc amplification and bony involvement. The disease-free survival rate was 66% (95% confidence interval, 49-84%) at 3 years. All patients who received 13-cis-retinoic acid developed cheilitis, but no bone marrow depression occurred in these patients. Five patients developed hemolytic uremic syndrome (HUS) post-transplant. This may have been related to the procedure used for total body irradiation. Patients who had their kidneys shielded during this procedure did not develop this syndrome. Patients who received local irradiation at the primary site showed no evidence of relapse in this region, indicating that such therapy may help to prevent a relapse. These data suggest a high rate of 3 year disease-free survival with this treatment strategy. The nonrandomized nature of the study and use of multiple modalities precludes analysis of the specific contribution of each.

Adrenal Gland Neoplasms↗