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Biomedical subjects

T Fujisawa

Publications and source records attributed to T Fujisawa.

At least 181 records · Page 10Linked to original sources
PubMed1999

Genetic analysis of late-onset type 2 diabetes in a mouse model of human complex trait.

Type 2 diabetes is a complex trait with both genes and environmental factors contributing to susceptibility. Except for rare subtypes with monogenic inheritance, the genetic basis of type 2 diabetes is unknown because of the complex and heterogeneous nature of the disease. By using the NSY mouse, an inbred mouse model of type 2 diabetes, we genetically dissected late-onset type 2 diabetes and demonstrated age-dependent changes in the genetic control of type 2 diabetes as well as polygenic inheritance. Three major loci (Nidd1nsy, Nidd2nsy, Nidd3nsy) were mapped on mouse chromosomes (Chr) 11, 14, and 6, respectively. The existence of a fourth locus (Nidd4nsy) with an age-dependent effect was suggested by longitudinal, but not cross-sectional, analysis of linkage data. Nidd1nsy and Nidd4nsy appear to affect insulin secretion, whereas Nidd2nsy and Nidd3nsy appear to affect insulin sensitivity. A locus on Chr 6 was significantly linked to epididymal fat weight. A candidate disease gene (Tcf2) on Chr 11, encoding hepatic nuclear factor-1beta, was shown to have a rare sequence variant in the DNA binding domain in the model. The mouse model we used will serve as a useful model for future studies on the etiology of late-onset polygenic type 2 diabetes in humans.

Adipose Tissue↗
PubMed1999

[Investigation about usefulness of serum antibody of Helicobacter pylori and serum pepsinogen I/II ratio as a marker of the judgment after eradication therapy].

To clarify that serum antibody of Helicobacter pylori (H. pylori) and serum pepsinogen I/II ratio are useful or not as a marker of the judgment after eradication therapy, we followed up 84 cases who received eradication therapy comparing with culture and histology (Carnoy's fixation and immunostaining using anti-H. pylori antibody, MIA method). Successful eradication was recognized in 45 of 84 cases (successful group), and remaining 39 cases were unsuccessful (unsuccessful group). Titers of serum H. pylori antibody went down gradually in the successful group, on the other hand, they did not go down constantly and often re-went up in the unsuccessful group. The difference of the various rate of titers in the both groups became clear statistically since 6 months after eradication therapy (p < 0.05). Supposing that cut-off rate of titer was 60% of pre-eradicated titer, sensitivity, specificity, and accuracy were 86.2%, 77.7%, and 84.2%, respectively, at 6 months after eradication therapy. Serum pepsinogen I/II ratio increased regardless of successful or unsuccessful eradication, but the various rate of serum pepsinogen I/II ratio was different in both groups at 1 month and 3 months after eradication therapy (p < 0.05). Serum antibody of H. pylori and serum pepsinogen I/II ratio could be a marker of the judgment after eradication therapy, especially the various rate of serum antibody of H. pylori is useful for the monitor of H. pylori infection in the long term.

Adolescent↗
PubMed1999

[Exhaled nitric oxide of childhood asthma].

Chronic airway inflammation is a central feature of pathology of bronchial asthma. In order to evaluate inflammatory status in asthma, examinations such as bronchoscope or induced sputum test can be done. Because of difficulty of those examinations we need non-invasive and simple measures for childhood asthma. Here we investigated eNO in childhood asthma. Twenty-six of atopic asthma, 13 non-asthmatic atopic children and 12 normal children were enrolled in this study. eNO was measured by chemiluminescence analyzer. eNO was significantly collerated with % FEV 1.0 and blood eosinophil counts (R = -0.494, R = 0.416, respectively). Geometrical mean of eNO in normal, non-asthmatic atopic, asthma without inhaled corticosteroid (ICS) and asthma with ICS was 16.3, 23.7, 71.6, 43.6 ppb, respectively. eNO was significantly higher in asthma than in normals. eNO in patients without ICS were significantly higher than in non-asthmatic atopic. We concluded that eNO might be useful marker for evaluation of airway inflammation in asthmatic children.

Asthma↗
PubMed1999

[An infant of autoimmune hepatitis (type I) with cirrhosis].

A 6 year-old boy with autoimmune hepatitis accompanied with cirrhosis was reported. He was admitted to our hospital because of abdominal distention, high fever, and diarrhea. Laboratory examination revealed abnormalities in hepatic function, cholestasis, anemia, thrombocytopenia, hypoalbuminemia, hypocomplementemia, and low concentration of coagulation factors. Abdominal MRI, and asialoglycoprotein receptor-mediated liver scintigraphy strongly indicated liver cirrhosis. Viral hepatitis, Wilson's disease, and antitrypsin deficiency were excluded serologically. Instead, hypergammaglobulinemia, and positive antinuclear antibody suggested autoimmune hepatitis, and the survey of anti-mitochondrial antibody, anti-smooth muscle antibody, and anti-LKM-1 antibody was negative, indicating type I autoimmune hepatitis. Finally, the histology of liver biopsy specimen indicating the destruction of hepatic lobular architecture, dense mononuclear cell infiltrates, and severe fibrosis confirmed the diagnosis. He was treated firstly with methylprednisolone pulses, and then prednisolone p.o. + azathioprine p.o. All of the abnormal laboratory parameters improved to normal levels, indicating that the immunosuppressive therapy will be effective for the severe AIH with cirrhosis.

Child↗
PubMed1999

[Detection of early hilar lung cancers with fluorescence bronchoscopy].

The development of fluorescence bronchoscopy has made it possible to diagnose locally superficial hilar lung cancers such as carcinoma in situ, and in some cases atypical squamous metaplasia thought to be precancerous lesions. The selection of a treatment modality can be difficult for early hilar lung cancers due to problems associated with multiple lung carcinomas and the large number of heavy smokers afflicted. Many patients also have decreased pulmonary function. If carcinoma in situ and microinvasive carcinomas can be detected early, it may be possible to treat them radically with a less invasive method than surgery, such as endoscopic laser therapy. Centrally arising squamous cell carcinoma of the tracheobronchial tree, especially in heavy smokers, is thought to develop in multiple stages from squamous metaplasia, to atypical squamous metaplasia, followed by carcinoma in situ, and finally invasive cancer. However, it is hoped that preventive medicine for lung cancer will be established whereby patients with localized atypical squamous metaplasia detected by fluorescence bronchoscopy can be carefully monitored and motivated to stop smoking, and also administered chemopreventive agents.

Adult↗
PubMed1999

[The effectiveness of thin-section computed tomography in diagnosing bullous lesions in patients with spontaneous pneumothorax].

We investigated the effectiveness of thin-section computed tomography (CT) for the diagnosis of bullous lesions in patients with spontaneous pneumothorax. The study group consisted of 74 patients. Apical regions of the lung were scanned for lesions by thin-section CT prior to operation. The presence, number, and locations of bullous lesions were assessed. Bullous lesions were also classified into 2 groups according to their shape as demonstrated by CT findings. Operative findings confirmed that 73 of the 74 patients had bullous lesions. Of these, 33 had a single bulla and 40 had multiple bulla. Thin-section CT accurately detected the presence and location of the bullous lesions, accurately identified the number in all but 6 patients with multiple bulla (accuracy: 91.8%), and also classified them accurately by type. Precise evaluations of bullous lesions are crucial to the treatment of patients with spontaneous pneumothorax. The presence of bullous lesions, as well as their location and shape, are important factors in determining whether to operate or not. Such information also allows for a better understanding of the surgical options available. Our study demonstrated that thin-section CT of apical regions of the lung is an effective diagnostic procedure for patients with spontaneous pneumothorax.

Adolescent↗
PubMed1999

Elevated levels of circulating plasma matrix metalloproteinase 9 in non-small cell lung cancer patients.

Elevated expression levels of matrix metalloproteinase (MMP)-2 and MMP-9 have been implicated as playing important roles in tumor invasion and metastasis in various tissues. We investigated the relationship between circulating plasma MMP-9, its expression in tumor samples, and other clinical features in patients with non-small cell lung cancer (NSCLC). A series of 73 patients (45 men and 28 women) who underwent surgery for NSCLC was used in this study. Preoperative plasma concentrations of MMP-9 were examined using a one-step sandwich enzyme immunoassay. Expression levels of MMP-2, MMP-9, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 were measured in 24 tumor samples by immunohistochemistry. The plasma concentration of MMP-9 in NSCLC patients (71.0 +/- 60.2 ng/ml) was significantly elevated compared to that of healthy volunteers (P < 0.0001). MMP-9 concentrations were elevated in 33 of 73 cases (45.2%), compared with a cutoff value of the mean +/- 2 SD in healthy volunteers. There were statistically significant differences in MMP-9 concentration in adenocarcinoma versus squamous cell carcinoma (P = 0.014) and adenocarcinoma versus large cell carcinoma (P = 0.014). Five of 24 patients (20.8%) had positive immunohistochemical MMP staining of the tumor cell cytoplasm, and two cases had positive staining in the surrounding stromal cells. Plasma MMP-9 concentrations were elevated in 45.2% of NSCLC patients; however, this elevation did not seem to correlate with MMP-9 production by cancer and stromal cells. We concluded that the MMP-9 ELISA could be a beneficial adjunct for assessing the tumor burden of NSCLC, especially for types of squamous cell carcinoma and large cell carcinoma.

Aged↗
PubMed1998

The structure and expression of a preprohormone of a neuropeptide, Hym-176 in Hydra magnipapillata.

Hym-176 (APFIFPGPKVamide) is a novel myoactive neuropeptide which was identified in systematic screening of signaling peptides in Hydra magnipapillata. By using PCR and library screening, we cloned and sequenced a full length cDNA which encoded a preprohormone of Hym-176. In the preprohormone, a typical signal sequence, one copy of Hym-176 precursor peptide and one copy of precursor sequence of another novel peptide, Hym-357 (KPAFLFKGYKPamide), were detected. In situ hybridization analysis revealed a strong signal in peduncle neurons. Signals were also detected, though weaker, in neurons in the gastric region and around the mouth. No signals were detected in the two extremities of the body, tentacles and basal disk. The expression pattern is correlated with the distribution of Hym-176 and its myoactive function.

Amino Acid Sequence↗
PubMed1998

Spontaneous emission spectrum in double quantum dot devices

A double quantum dot device is a tunable two-level system for electronic energy states. A dc electron current was used to directly measure the rates for elastic and inelastic transitions between the two levels. For inelastic transitions, energy is exchanged with bosonic degrees of freedom in the environment. The inelastic transition rates are well described by the Einstein coefficients, relating absorption with stimulated and spontaneous emission. The most effectively coupled bosons in the specific environment of the semiconductor device used here were acoustic phonons. The experiments demonstrate the importance of vacuum fluctuations in the environment for quantum dot devices and potential design constraints for their use for preparing long-lived quantum states.

Journal Article↗
PubMed1998

Selective portal blood flow diversion in auxiliary partial orthotopic liver transplantation to induce regeneration of the graft.

Experience with auxiliary partial orthotopic liver transplantation (APOLT) is still very limited and many questions remain to be solved. In this article, we present the case of a 5-year-old girl with ornithine transcarbamylase deficiency who initially did well after APOLT. During a severe rejection episode 16 months after transplantation, she developed encephalopathy and hyperammonemia. Despite a good clinical and histopathological response to antirejection therapy, the graft had become smaller and the native liver had undergone compensatory hypertrophy. After we surgically ligated the right portal branch, the graft recovered and the patient was able to stop her medication 1 month after surgery. We have estimated that the minimum volume of normal liver required to correct the metabolic defect in ornithine transcarbamylase deficiency is 8 cm3/kg. The ligation of the right portal branch was a safe and effective method of inducing a gradual and progressive involution of the hypertrophic native liver and regeneration of the atrophic graft.

Atrophy↗
PubMed1998

High-pressure solution X-ray scattering of protein using a hydrostatic cell with diamond windows.

A hydrostatic high-pressure cell (maximum pressure 700 MPa) with synthetic diamond windows is applied to measure small-angle X-ray scattering of a protein at high pressure. Use of the present cell allows an accurate solvent background correction, providing quantitative analyses. The performance of the present cell for X-ray scattering is shown by using lysozyme as a sample solution. From the Guinier plot, values of the radius of gyration of lysozyme are evaluated to be 15.31 +/- 0.09 A at 1 atm (0.10 MPa) and 14.80 +/- 0.15 A at 400 MPa.

Journal Article↗
PubMed1998

Secretory IgA induces degranulation of IL-3-primed basophils.

We examined whether secretory IgA (sIgA), known to mediate eosinophil stimulation, has an effect on basophil functions. An immobilized preparation of sIgA, but not of monomeric IgA, induced histamine release (approximately 15% of total histamine contents) from human basophils in vitro. sIgA-induced basophil histamine release was totally dependent on pretreatment with IL-3. IL-5 and granulocyte-macrophage CSF also primed basophils for sIgA-mediated release. Exogenous divalent ions, i.e., Ca2+ and Mg2+, were essential for sIgA-mediated basophil degranulation, and the degranulation was completed within 45 min. A newly synthesized lipid mediator, leukotriene C4, was also liberated from IL-3-primed, sIgA-stimulated basophils. Enzyme digestion experiments revealed that the (Fc)2 x secretory component portion of sIgA is important for sIgA-mediated basophil activation, but the functional binding sites of sIgA on basophils were surmised to be different from FcalphaR. These observations reveal the novel finding that sIgA is able to stimulate basophils as well as eosinophils. Since sIgA is the most abundant Ig isotype in the secretions from mucosal tissues, and basophils are active participants in allergic late-phase reactions, sIgA-mediated basophil mediator release is potentially involved in exacerbation of the inflammation associated with allergic disorders.

Basophils↗
PubMed1998

A novel neuropeptide, Hym-176, induces contraction of the ectodermal muscle in Hydra.

During the course of a systematic non-targeting screening of peptide signal molecules in Hydra, we identified a novel myoactive neuropeptide called Hym-176. The primary structure of Hym-176 was determined to be APFIFPGPKVamide. It specifically and reversibly induced contraction of the ectodermal muscle of the hydra body column in vivo. However, it had no effect on the ectodermal muscle of the tentacles. The structure-activity relationship analysis showed that the sequence of FIFPGPKVamide is a minimal requirement for the myoactivity. Removal of an amide group from the C-terminus completely abolished the activity. By using the antibody specific to Hym-176, the tissue localization of the peptide in hydra was determined immunohistochemically. The intense immunoreactivity was found in the peduncle nerve cells, indicating that Hym-176 is a neuropeptide.

Amino Acid Sequence↗
PubMed1998

Identification of a point mutation associated with a silent phenotype of human serum butyrylcholinesterase--a case of familial cholinesterasemia.

A point mutation which caused a silent phenotype of human serum butyrylcholinesterase (BChE) was identified in the DNA of a 47-year-old Japanese woman who visited our hospital complaining of hypertension. The propositus exhibited an unusually low level of BChE activity, whereas her younger sister and her daughter had intermediate levels of BChE activity and her elder sister a normal level. Immunologically, the amount of BChE protein in the serum of the propositus was normal. DNA sequence analysis of the propositus identified a point mutation at codon 199 (GCA --> GTA), resulting in a Ala --> Val substitution. This alteration is one downstream codon from the catalytic active site (Ser, 198). A family study showed her younger sister and her daughter to have the same mutation.

Blotting, Western↗
PubMed1998

Trichromatic Concept at SPring-8 RIKEN Beamline I.

SPring-8 RIKEN beamline I has been designed and developed for structural biology research by the Institute of Physical and Chemical Research (RIKEN). The beamline consists of two experimental stations for protein crystallography and small-angle X-ray scattering. Both types of experiments can be carried out simultaneously, with dichromatic synchrotron radiation emitted from two coaxial undulators with vertical polarization. The branched beams are generated by a transparent diamond crystal. With synchrotron radiation, the multiple-wavelength anomalous-dispersion (MAD) method, which gives phases from a single anomalous scatterer, has been developed. Anomalous scattering contributes a small proportion of the diffraction intensity so that the accuracy of intensity data is important. The protein crystallography branch of RIKEN beamline I has been designed based on a 'trichromatic concept' to optimize MAD data collection. This concept requires the quasi-simultaneous collection, by use of a 'trichromator', of three intensity data sets at three different wavelengths from a single protein crystal without changing any settings. The main feature of the concept is the minimization of systematic errors in the measurement of anomalous diffraction for the MAD method. Initial commissioning of the beamline has provided three different monochromated undulator beams, which were successfully observed on the phosphor screen located at the near end of the trichromator.

Journal Article↗
PubMed1998

Isolation and characterization of a rheumatoid arthritis-specific antigen (RA-A47) from a human chondrocytic cell line (HCS-2/8).

Two types of 47 kDa antigen specifically recognized by sera from rheumatoid arthritis (RA) patients were isolated from the membrane fraction of a human chondrosarcoma-derived chondrocytic cell line (HCS-2/8) by a 2-step procedure: preparative SDS-PAGE and reverse-phase HPLC. An N-terminal amino acid sequence in one of the 47 kDa antigens, named RA-A47, had 81% homology to that deduced from the DNA sequence of the colligin gene which is reported as human hsp47 gene, and 100% homology to that deduced from the DNA sequence of colligin-2 gene, a homologue of colligin. The RA-A47 cross-reacted with a monoclonal antibody raised against chick heat shock protein (Hsp) 47 and bound to gelatin. The expression of the ra-a47 gene was enhanced by heat shock treatment and TGF-beta stimulation. These findings suggest that RA-A47 is a Hsp47-like protein, presumably the product of the colligin-2 gene, and that a collagen-specific molecular chaperone(s) such as Hsp47 and/or RA-A47 is involved in cartilage destruction in RA.

Amino Acid Sequence↗