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Biomedical subjects

Y Iwata

Publications and source records attributed to Y Iwata.

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

Morphological and biochemical changes of isolated chicken egg-envelope during sperm penetration: degradation of the 97-kilodalton glycoprotein is involved in sperm-driven hole formation on the egg-envelope.

The chicken egg-envelope is made of two major glycoprotein components, which are designated as gp97 and gp42 (after their molecular masses). To elucidate how these two components are involved in macromolecular organization of the chicken egg-envelope, the isolated egg-envelope was characterized by immunochemical and biochemical methods. The gp97 was suggested to be a homologue of mouse ZPB based on the similarities of N-terminal and internal sequences. Immunoblotting using anti-gp97 monoclonal antibodies and two-dimensional gel electrophoresis with or without mercaptoethanol treatment revealed that gp97 formed a homodimer through disulfide bonds, whereas gp42 did not. Under indirect immunofluorescence microscopy, the anti-gp97 antibody visualized indistinct, small spots on the egg-envelope, whereas the anti-gp42 antibody showed a meshwork of blurry, fibrous structures. The hole formation on the egg-envelope by in vitro sperm penetration was completely inhibited by two anti-gp97 monoclonal antibodies. Interestingly, the anti-gp97 monoclonal antibodies blocked the proteolysis not only of gp97 but also of gp42 during incubation of the egg-envelope with either sperm or the crude chicken acrosin. Taken together, these results indicate that gp97 may play pivotal roles not only in constitution of the macromolecular organization of the egg-envelope but also in triggering hydrolysis of the egg-envelope during sperm penetration.

Amino Acid Sequence↗
PubMed2001

Herpesvirus DNA in peripheral blood mononuclear cells of some patients with Meniere's disease.

Herpes simplex virus-1 (HSV) or varicella zoster virus (VZV) DNA was detected by nested polymerase chain reaction in peripheral blood mononuclear cells of patients with Meniere's disease (one of 28 patients for HSV-1, 2 of 28 patients for VZV) during acute illness (within 5 days after onset). On the other hand, neither HSV-1 DNA or VZV DNA was detected in PBMCs of 50 age- and sex-matched healthy individuals and 50 pregnant women. These findings may imply that reactivation of HSV- 1 or VZV may be associated with the development of some cases of Meniere's disease.

Acute Disease↗
PubMed2001

Usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose for predicting outcome in patients with hepatocellular carcinoma.

OBJECTIVES: The present study was designed to assess the usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) for predicting outcome in patients with hepatocellular carcinoma. METHODS: FDG-PET was performed in 48 patients with hepatocellular carcinoma. For quantitative evaluation, a region of interest (ROI) was placed over the area of maximum activity within the lesion. A background ROI was then placed over the nontumor region of the liver. The average activity within each ROI was subsequently corrected for radioactive decay, and the standardized uptake value (SUV) was calculated by dividing the tissue activity by the injected dose of radioactivity per unit body weight. SUV ratio was expressed as the tumor-to-nontumor ratio of the SUV. RESULTS: The tumor-volume doubling time, as index of the growth rate of hepatocellular carcinoma, correlated significantly with SUV ratio but did not correlate with SUV. On the basis of the SUV ratio, the patients were divided into two groups of similar size: group A, SUV ratio of < or = 1.5; and group B, SUV ratio > 1.5. The cumulative survival rate was significantly lower in group B than in group A. On the basis of the SUV, the patients were divided into two groups of roughly equal size: group C, < or = SUV 2.6; and group D, > SUV 2.6. The cumulative survival rate was similar in these groups. On regression analysis with the Cox proportional hazards model, the SUV ratio and tumor number were significantly related to survival. CONCLUSIONS: These results suggest that FDG-PET is useful not only for the evaluation of the malignancy of hepatocellular carcinoma but also for the prediction of outcome in patients with hepatocellular carcinoma.

Adult↗
PubMed2001

Immunological and PCR analyses for Borna disease virus in psychiatric patients and blood donors in Japan.

The involvement of Borna disease virus (BDV) in psychiatric diseases in humans remains controversial. T-cell memory response and seroprevalence of BDV in patients with psychiatric disorders and blood donors in Japan were evaluated collectively by Western blot (WB) analysis with inhibition test, electrochemiluminescence immunoassay, immunofluorescence assay, and T-cell proliferative response as well as detection of BDV p24 RNA in peripheral blood mononuclear cells (PBMCs). Positive proliferative responses to both BDV p40 and p24 proteins were detected in 9% of patients with mood disorders (4 of 45), 4% of schizophrenic patients (2 of 45), and 2% of blood donors (1 of 45). By WB analysis, the antibody to BDV p40 was detected only in 2% of patients with mood disorders (1 of 45). The BDV p24 antibody was detected in 2% of patients with mood disorders (1 of 45) and 9% of schizophrenic patients. (4 of 45) No plasma reacted with both BDV proteins. The finding of a lower seroprevalence than previously reported suggests the presence of false-positive cases in the previous report. BDV RNA was detected only in 2% of patients with mood disorders (1 of 45). In these three serological assays, T-cell responses, and PCR analysis, there was no significant difference in the prevalence among the three groups. However, we found three psychiatric patients who were positive for both BDV antibodies and T-cell proliferative responses and one patient who was positive for BDV RNA in PBMCs. These findings suggest the usefulness of the proliferative T-cell response and that certain individuals are infected with BDV or a BDV-related virus.

Adolescent↗
PubMed2001

GATA3 abnormalities and the phenotypic spectrum of HDR syndrome.

We report on GATA3 analysis and the phenotypic spectrum in nine Japanese families with the HDR syndrome (hypoparathyroidism, sensorineural deafness, and renal dysplasia) (MIM 146255). Fluorescence in situ hybridisation and microsatellite analyses showed heterozygous gross deletions including GATA3 in four families. Sequence analysis showed heterozygous novel mutations in three families: a missense mutation within the first zinc finger domain at exon 4 (T823A, W275R), an unusual mutation at exon 4 (900insAA plus 901insCCT or C901AACCCT) resulting in a premature stop at codon 357 with loss of the second zinc finger domain, and a nonsense mutation at exon 6 (C1099T, R367X). No GATA3 abnormalities were identified in the remaining two families. The triad of HDR syndrome was variably manifested by patients with GATA3 abnormalities. The results suggest that HDR syndrome is primarily caused by GATA3 haploinsufficiency and is associated with a wide phenotypic spectrum.

Adolescent↗
PubMed2001

Stretch-activated cation channels in skeletal muscle myotubes from sarcoglycan-deficient hamsters.

Deficiency of delta-sarcoglycan (delta-SG), a component of the dystrophin-glycoprotein complex, causes cardiomyopathy and skeletal muscle dystrophy in Bio14.6 hamsters. Using cultured myotubes prepared from skeletal muscle of normal and Bio14.6 hamsters (J2N-k strain), we investigated the possibility that the delta-SG deficiency may lead to alterations in ionic conductances, which may ultimately lead to myocyte damage. In cell-attached patches (with Ba(2+) as the charge carrier), an approximately 20-pS channel was observed in both control and Bio14.6 myotubes. This channel is also permeable to K(+) and Na(+) but not to Cl(-). Channel activity was increased by pressure-induced stretch and was reduced by GdCl(3) (>5 microM). The basal open probability of this channel was fourfold higher in Bio14.6 myotubes, with longer open and shorter closed times. This was mimicked by depolymerization of the actin cytoskeleton. In intact Bio14.6 myotubes, the unidirectional basal Ca(2+) influx was enhanced compared with control. This Ca(2+) influx was sensitive to GdCl(3), signifying that stretch-activated cation channels may have been responsible for Ca(2+) influx in Bio14.6 hamster myotubes. These results suggest a possible mechanism by which cell damage might occur in this animal model of muscular dystrophy.

Actins↗
PubMed2001

Upregulation of fractalkine in human crescentic glomerulonephritis.

BACKGROUND/AIM: To evaluate the importance of fractalkine, a novel member of the CX3C chemokine, and natural killer (NK) cells in human crescentic glomerulonephritis, we determined the presence of fractalkine in the diseased kidneys immunohistochemically, and the correlation among fractalkine, NK cells and the degree of renal damage. METHODS: Twenty-three patients (13 males and 10 females) with primary or secondary crescentic glomerular disease were evaluated in this study. Fractalkine and CD16-positive cells including NK cells were detected immunohistochemically. RESULTS: Fractalkine-positive cells were detected in the interstitium of 23 patients with crescentic glomerulonephritis, while they were not detected in the glomeruli. In addition, CD16-positive cells were detected in both the glomeruli (1.3 +/- 0.2/glomerulus) and interstitium (1.3 +/- 0.2/visual field). The number of fractalkine-positive cells in the interstitium correlated with the number of CD16-positive cells before glucocorticoid therapy (r = 0.43, p = 0.047, n = 23). The number of fractalkine-positive cells in the interstitium before glucocorticoid therapy (0.2 +/- 0.1/visual field) decreased after therapy (0.1 +/- 0.1/visual field, p = 0.050) in 11 cases tested. The number of CD16-positive cells in the diseased kidneys did not change after glucocorticoid therapy. CONCLUSION: These results suggest that the local production of fractalkine may explain the presence of CD16-positive cells including NK cells, which may participate in the interstitial lesions of human crescentic glomerulonephritis before corticoid therapy.

Adult↗
PubMed2001

Serum levels of KL-6 reflect disease activity of interstitial pneumonia associated with ANCA-related vasculitis.

OBJECTIVE: KL-6 is reported to be excreted from the lung alveolar and bronchial epithelial cells and may be a good marker for monitoring disease activity of interstitial pneumonia. This study was designed to ascertain the clinical significance of serum KL-6 levels in interstitial pneumonia associated with anti-neutrophil cytoplasmic antibody (ANCA)-related vasculitis. METHODS: Serum KL-6 levels were determined by an enzyme-linked immunosorbent assay. PATIENTS: We examined 20 healthy subjects, 13 patients with perinuclear (myeloperoxidase, MPO) ANCA-related vasculitis and 12 dermatomyositis (DM)/polymyositis (PM) patients as disease controls in this study. Six out of 13 patients with ANCA-related vasculitis had interstitial pneumonia. RESULTS: Serum levels of KL-6 in ANCA-positive patients with interstitial pneumonia were significantly elevated, while they remained as low as those of healthy subjects in ANCA-positive patients without interstitial pneumonia. Similarly, KL-6 levels in sera were higher in 12 dermatomyositis/polymyositis patients with interstitial pneumonia, while they remained low in DM/PM patients without interstitial pneumonia. Moreover, the elevated serum KL-6 level was reduced during the convalescence induced by glucocorticoid therapy and reflected the disease activity of interstitial pneumonia associated with ANCA-related vasculitis. CONCLUSION: These data suggest that the measurement of serum KL-6 levels may be a good monitoring system for the diagnosis and follow-up of interstitial pneumonia of patients with ANCA-related vasculitis.

Aged↗
PubMed2001

[Effect of interferon therapy on hepatitis B virus related membranous nephropathy associated with focal segmental glomerulosclerosis].

We experienced a 24-year-old Japanese man, who was a hepatitis B virus carrier with nephrotic syndrome. Liver biopsy showed that he was suffering from chronic hepatitis (activity 2, fibrosis 2). Renal biopsy revealed membranous nephropathy(MN) with focal segmental glomerulosclerosis(FGS). Immunofluorescentic findings revealed the presence of HBe antigen along the glomerular capillaries as well as HBe antigenemia in circulation. Therefore, we diagnosed this case as HB virus-related membranous nephropathy associated with FGS lesions. He was treated with interferon(IFN) alpha-2b for over a month and angiotensin converting enzyme inhibitor. These therapies reduced urinary protein excretion from 4-6 g/day to 1-2 g/day, in accordance with a decrease in the titer of HBV DNA polymerase. The second renal biopsy revealed that the histological change from MN to membranoproliferative glomerulonephritis Type III after IFN therapy. These results suggest that IFN therapy might be effective for HB virus-related MN associated with FGS.

Adult↗
PubMed2001

A method for assessing the side chain orientations of histidine, asparagine, and glutamine as well as the protonation forms of histidine in protein structures.

In protein X-ray crystallography, it is sometimes impossible to distinguish N and O in amide side chains and N and C in His side chains, resulting in the 'flipped' conformations in these side chains. We have developed a simple, but effective, approach to assess the side chain orientations of His. Asn, and Gln as well as the protonation forms of His in protein structures. This method finds the most favorable side chain orientation and His form by calculating the van der Waals interaction and hydrogen bonding energies around each residue in question. This evaluation is repeated until consistent results are obtained. Our approach was applied to four proteins and in overall approximately 25% of His, Asn, and Gln were evaluated as 'flipped' and 63% of the imidazole rings were suggested to have a polar hydrogen atom only on N epsilon2. In the individual cases, it was found that our results were comparable to or even better than those obtained by a traditional method. The present approach is therefore quite useful to construct initial protein structures for the molecular modeling studies.

Aldehyde Reductase↗
PubMed2001

Conformational analysis of cyclophostin and designed analogs in comparison with the potent IP3 receptor agonist adenophostin A.

A conformational analysis of 5'-6"-tethered cyclophostin was carried out in comparison with the mother compound, adenophostin A, which has a potent IP3 receptor agonistic activity. The global minimum 3'-endo/anti conformation of cyclophostin elucidated by a molecular dynamics simulation was in accord with NMR spectroscopic data. In contrast, the 2'-endo/syn conformation was dominant with respect to adenophostin A. Despite the constraint introduced by the tether, the spatial arrangement of the three phosphate groups and the adenine moiety, which are essential for the extremely high potency, was changed only moderately in comparison with adenophostin A. The observed high potency of cyclophostin (EC50 = 38 nM) also indicates that it closely resembles the bioactive conformation of adenophostin A (EC50 = 7 nM). These results led us to estimate the probable active conformation of adenophostin A by comparison with the stable conformations of cyclophostin. Finally, two other tethered analogs were designed and are expected to exhibit high potencies comparable to adenophostin A.

Adenosine↗
PubMed2001

Protein structure-based de novo design and synthesis of aldose reductase inhibitors.

Aldose reductase has been implicated in the etiology of diabetic complications. Due to the limited number of currently available drugs for the treatment of diabetic complications, we have carried out a structure-based de novo design and synthesis in an attempt to identify new aldose reductase inhibitors. With the LEGEND program, we have designed 200 chemical structures that fit into the ligand binding site of the crystal structure of the enzyme. After their visual inspection and assessment of synthetic feasibility, four compounds were chosen to be synthesized. These compounds were all found to have reasonable inhibitory activities (IC50 = 17-91 microM), indicating the first successful generation of nonpeptide drug leads that have been obtained using a rational de novo design approach.

Aldehyde Reductase↗
PubMed2000

Visualization, quantification and therapeutic evaluation of angiogenic vessels in cancer by synchrotron microangiography.

The usefulness of a synchrotron microangiography system for depicting, quantitating and therapeutically evaluating angiogenic vessels in cancer is illustrated. In 20 mice transplanted with murine colon cancer, sequential changes in the angiogenic vessels were determined by using synchrotron microangiography, using changes in tumor volume for reference. This system allowed the depiction and quantification of angiogenic vessels in the period from one to four weeks after transplantation. The effects of antiangiogenic therapy were evaluated by using a neutralizing antibody against vascular endothelial growth factor. The neutralizing antibody partially suppressed angiogenesis and tumor growth. Synchrotron microangiography is shown to be useful for the depiction, quantification and evaluation of angiogenic vessels in cancer.

Journal Article↗
PubMed2000

Spirophostins: conformationally restricted analogues of adenophostin A.

The synthesis, biological evaluation, and molecular modeling of two conformationally restricted analogues of adenophostinA (1), denominated as spirophostin (3R)-10 and (3S)-11, as novel ligands for the D-myo-inositol 1,4,5-trisphosphate receptor (IP3R), is presented. These diastereoisomeric spiroketals are synthesized by spiroketalization of D-glucose derivatives (2S)-15 and (2R)-16, separation of the protected isomers (3R)-19 and (3S)-20, followed by phosphorylation and deprotection. The spirophostins (3R)-10 and (3S)-11 display comparable biological activity, with a 3H-IP3-displacing and Ca2+-releasing potency less than IP3 and adenophostin A.

Adenosine↗
PubMed2000

Course before and after percutaneous transhepatic portal vein embolization of a patient with cholangiocarcinoma monitored by scintigraphy with Tc-99m galactosyl human serum albumin.

Percutaneous transhepatic portal vein embolization (PTPE) causes atrophy of the embolized lobe and compensatory hypertrophy of the nonembolized lobe, and improves the safety of hepatectomy. We report a patient with cholangiocarcinoma who underwent embolization of both anterior and posterior branches of the right portal vein before hepatectomy. Scintigraphy with Tc-99m galactosyl human serum albumin was performed before and 4 weeks after PTPE. After PTPE, the right lobe of the liver was atrophied and the left lobe of the liver was enlarged, compared with before PTPE. The receptor index of the entire liver was almost unchanged before and after PTPE, but the right lobe receptor index after PTPE was 23% less than the pre-PTPE value, whereas the left lobe receptor index had increased 37%. Scintigraphy with Tc-99m galactosyl human serum albumin is useful for evaluating segmental functional reserve before and after PTPE.

Aged↗
PubMed2000

Clinical usefulness of positron emission tomography with fluorine-18-fluorodeoxyglucose in the diagnosis of liver tumors.

We studied various liver tumors by positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG-PET) to examine the diagnostic usefulness of this technique. We also examined the relation between findings on FDG-PET and the characteristics of hepatocellular carcinoma. FDG-PET was performed in 78 patients with liver tumors, including 53 with primary liver cancer [48 hepatocellular carcinomas (HCC) and 5 cholangiocellular carcinomas (CCC)], 20 with metastatic liver cancer, 2 with liver hemangioma, and 3 with focal nodular hyperplasia. For quantitative evaluation, a region of interest (ROI) was placed over the entire tumor region, at the level of the maximum diameter of the tumor. A background ROI was then placed over the non-tumor region of the liver. The average activity within each ROI was subsequently corrected for radioactive decay, and the standardized uptake value (SUV) was calculated by dividing the tissue activity by the injected dose of radioactivity per unit body weight. SUV ratio was expressed as the tumor-to-non-tumor ratio of the SUV. The median SUV was significantly lower in HCC than in metastatic live cancer or CCC, and the median SUV ratio was significantly lower in HCC than in metastatic liver cancer or CCC. The median SUV was not higher in multiple HCC than in single HCC, but the median SUV ratio was significantly higher in multiple HCC than in single HCC. The median SUV and the median SUV ratio were significantly higher in the presence of portal vein thrombosis than in the absence of such thrombosis. The Cancer of the Liver Italian Program score and the alpha-fetoprotein value correlated significantly with both the SUV and SUV ratio. These results suggest that FDG-PET is clinically useful not only for the differential diagnosis of liver tumors but also for evaluation of the clinical characteristics of HCC.

Adult↗