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Biomedical subjects

Y Kondo

Publications and source records attributed to Y Kondo.

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

Higher avidity binding of apolipoprotein (E-AII) complex than of apolipoprotein E monomer to beta-amyloid.

Apolipoprotein E (apoE) is believed to be closely involved in the pathogenesis of Alzheimer's disease (AD) because of its ability to bind to beta-amyloid (Abeta), the primary component of senile plaques. The presence of cystein residues in apoE2 and apoE3 allows these isoforms to form disulfide-linked complexes, such as apo(E-AII) complex and apo(AII-E-AII) complex. A 50-kDa complex [which corresponded to apo(E-AII)-Abeta, because it reacted with any of the three antibodies, anti-apoE, anti-apoAII, or anti-Abeta] was detected by immunoblot analysis in native cerebrospinal fluid (CSF) obtained from nondementia patients with the apoE phenotype E3/E3. However, a band considered to represent apoE-Abeta was not observed. The dissociation constant (Kd) values obtained for the specific binding of recombinant apoE2, apoE3, and apoE4 to Abeta(1-42) were 48.1 +/- 2.2 nM, 63.7 +/- 2.1 nM, and 75.9 +/- 1.8 nM, respectively. In contrast, the binding affinity of the partially purified apo(E3-AII) complex to Abeta(1-42) was very high, the Kd being 5.5 +/- 0.5 nM. No basic difference was observed between lipidated and nonlipidated apoE in terms of the characteristics of the binding of apoE isoforms to Abeta(1-42); however, lipidation reduced the binding capacity of each isoform in a dose-dependent manner. These findings seem consistent with the generally accepted idea that apoE4 is a risk factor for AD, insofar as only apoE4 is unable to form a complex with apoAII owing to its lack of a cystein residue. In addition, it is possible that apoE3 monomer (and possibly apoE2 monomer), like apoE4 but unlike apo(E-AII) complex, can act as a risk factor in the pathogenesis of AD.

Amyloid beta-Peptides↗
PubMed1999

T1 Breast Cancer Associated with Von Recklinghausen's Neurofibromatosis.

A rare case of breast cancer associated with von Recklinghausen s neurofibromatosis is reported. This case and review of the literature illustrate the problems of clinical diagnosis. A 66-year-old woman who had undergone sigmoidectomy for sigmoid colon cancer two years previously, was admitted to the hospital because of a left breast skinretraction in October, 1998. The patient had von Recklinghausen fs disease (neurofibromatosis type 1). The TNM clinical staging was T1cN0M0. Modified radical mastectomy was performed. The histopathological diagnosis of the breast tumor was invasive ductal carcinoma and the skin tumor was neurofibroma. The pTNM pathological staging was pT1cN1aM0. Among patients similar to our case, almost all were staged higher than T2. This may be because multiple neurofibromas obscure breast mass at palpation, leading to delayed detection of the cancer. Systemic and careful exploration is essential for patients with von Recklinghausen's neurofibromatosis to detect breast cancer at an early stage.

Journal Article↗
PubMed1999

Regulatory role of metallothionein in NF-kappaB activation.

Metallothionein (MT), a low molecular weight, cysteine-rich metal binding protein, has been associated with cytoprotection from heavy metals and cellular oxidants. As MT has the ability to scavenge hydroxyl radicals, MT may control intracellular redox status. In the present study, we examined whether MT regulates the activity of nuclear factor-kappaB (NF-kappaB), which is one of the redox-regulated transcription factors, using the MT null embryonic cell lines established from MT null mice. We first found that tumor necrosis factor (TNF)-induced activation of the binding of NF-kappaB protein to DNA in wild type MT+/+ cells was lower than that in MT-/- cells. The NF-kappaB activation in MT-expressing cells established from MT-/- cells by the transfection of mouse MT-1 gene was also significantly lower than that in MT-/- cells. In addition, transfection of the MT gene inhibited TNF-induced IkappaB degradation and suppressed NF-kappaB-dependent gene expression induced by TNF. These results demonstrate that MT may function as a negative regulator of NF-kappaB activity.

Animals↗
PubMed1999

Immunohistochemical localization of connective tissue growth factor in the rat central nervous system.

Connective tissue growth factor (CTGF) is an immediate early growth-responsive gene but its distribution and significance in the central nervous system (CNS) are unknown. We investigated the distribution of CTGF-like immunoreactivity (CTGF-IR) in the rat CNS using a specific antiserum against CTGF oligopeptide. The majority of CTGF-IR was observed in astrocytes. Ependymal cells lining the wall of the cerebral ventricle and tanycytes lining the central canal of the spinal cord showed the strongest CTGF-IR, while there was a diffuse but weak signal in the gray matter of the spinal cord. CTGF-IR was also detected in the cytoplasm of a subpopulation of pyramidal neurons in the cerebral cortex. Our results showed that CTGF-IR is widely distributed in the CNS at both regional and cellular levels, suggesting a complex functional role in the CNS.

Animals↗
PubMed1999

Characterization of T-cell repertoire of the bone marrow in immune-mediated aplastic anemia: evidence for the involvement of antigen-driven T-cell response in cyclosporine-dependent aplastic anemia.

To determine whether the antigen-driven T-cell response is involved in the pathogenesis of aplastic anemia (AA), we examined the complementarity-determining region 3 (CDR3) size distribution of T-cell receptor (TCR) beta-chain (BV) subfamilies in the bone marrow (BM) of untreated AA patients. AA patients who did not respond to immunosuppressive therapy and those who obtained unmaintained remission early after cyclosporine (CyA) or antithymocyte globulin (ATG) therapy exhibited essentially a normal CDR3 size pattern. In contrast, five patients who needed continuous administration of CyA to maintain remission exhibited a skewed CDR3 size pattern in a number (>40%) of BV subfamilies suggestive of clonal predominance. The skewing of CDR3 size distribution became less pronounced in one of the CyA-dependent patients when the patient achieved unmaintained remission after a 4-year therapy with CyA, whereas it persisted longer than 7 years in the other patient requiring maintenance therapy. Sequencing of BV15 cDNA for which the CDR3 size pattern exhibited apparent clonal predominance in all CyA-dependent patients showed high homology of the amino acid sequence of the CDR3 between two different patients. These findings indicate that antigen-driven expansion of T cells is involved in the pathogenesis of AA characterized by CyA-dependent recovery of hematopoiesis.

Adolescent↗
PubMed1999

Oral-facial-digital syndrome with hypothalamic hamartoma, postaxial ray hypoplasia of the limbs, and vagino-cystic communication: a new variant?

We report on a 20-month-old girl with hypothalamic hamartoma, left cerebral atrophy, tongue nodules, oral frenula, micrognathia, hypoplasia of the left ulna, the fibulae, and right tibia, polysyndactyly of the hands and feet, vagino-cystic drainage with hydrometrocolpos, megaloureters, and hydronephrosis, agenesis of urethra, complex partial seizures, and central precocious puberty. The differential diagnosis is discussed. We conclude that the malformation complex in this girl is an oral-facial-digital syndrome, but is different from any of the 11 known subtypes.

Female↗
PubMed1999

Vascular endothelial growth factor-induced tumor angiogenesis and tumorigenicity in relation to metastasis in a HT1080 human fibrosarcoma cell model.

Although vascular endothelial growth factor (VEGF) is well known to be a potent mitogen for vascular endothelial cells, the role of VEGF in a developmental process of tumor angiogenesis and metastatic potential remains poorly understood. The present study was designed to investigate VEGF-induced vascular formation from a spatiotemporal viewpoint and to analyze VEGF-enhanced metastatic potential using stable clones of HT1080 human fibrosarcoma cells transfected with VEGF cDNA (S) or with vector alone (V). Microangiography revealed massive angiogenesis in the S cell-derived tumors and demonstrated that the angiogenesis occurred not in the tumor itself, but rather around the S cell tumor early after inoculation into the thigh muscles of mice. Thereafter, the angiogenesis extended in and around the tumor. The tumorigenicity of the S cells was higher than the V cells in the subcutaneous (s.c.) space, intraperitoneal space, liver and spleen. However, neither S cells nor V cells metastasized to the liver after an intrasplenic injection. Few apoptotic cells were detected in the S cell tumor, but many apoptotic cells were scattered in the V cell tumor. Our results indicate that VEGF facilitates tumorigenicity in various organs, possibly due to inducing angiogenesis in and around the tumor and preventing tumor cells from undergoing apoptosis, and suggest that VEGF may augment metastatic potential, by accelerating proliferative activity after reaching the target organ. Furthermore, VEGF-induced angiogenesis occurred preferentially around the tumor at an early period of tumor development, followed by neovascularization into the tumor.

Animals↗
PubMed1999

Identification and characterization of nuclear pore subcomplexes in mitotic extract of human somatic cells.

In higher eukaryotic cells, it is generally thought that nuclear pore complex disassembles at the beginning of mitosis and reassembles at the end. Using a monoclonal antibody that recognizes nuclear pore antigens, we found that, at mitosis of mammalian somatic Hela cells, the nuclear pore complex disassembles into at least three subcomplexes, termed subcomplexes A, B and C (molecular mass; 2 MDa<, approximately 660 kDa, and approximately 440 kDa, respectively). The direct partial amino acid sequencing of the components of these subcomplexes indicates that the A subcomplex contains CAN/Nup214/p250 and p62 and the B subcomplex also contains p62, indicating that p62 is contained in two different subcomplexes. Subcomplex C was shown to consist of Nup98 and human RAE1, a human homolog of yeast Rae1p/Gle2p. Since Nup98 and Rae1p/Gle2p have been reported to be involved in mRNA export, this suggests that some of the mitotic subcomplex may be formed by functionally related proteins.

Amino Acid Sequence↗
PubMed1999

Amino acid substitutions in NS5A region of GB virus C and response to interferon therapy.

GB virus C (GBV-C) is related to hepatitis C virus (HCV) and has a similar genomic structure. Some predictors for the efficacy of interferon (IFN) therapy on HCV have been reported: genotype, viral load, IFN dose, and the amino acid substitutions in the NS5A region, designated as the interferon sensitivity determining region (ISDR). To evaluate the correlation between the amino acid substitutions in the GBV-C NS5A region and the response to IFN therapy, single-strand conformation polymorphism (SSCP) analysis was performed in the 12 concomitantly GBV-C-and HCV-infected patients who received IFN therapy at three time points: before, end-point, and after the IFN therapy. The region in the GBV-C NS5A studied includes the amino acids that exhibit some homology to the ISDR and the various substitutions. By SSCP analysis, amplicons were separated into 1-4 bands, which indicated the existence of heterogeneity in each host. However, the deduced amino acid sequences in these bands exhibited no characteristic differences among these strains irrespective of response to IFN therapy. Of the 32 strains separated by SSCP, 7 strains were responders, and 25 were nonresponders. The mean amino acid substitution, compared with the consensus sequence of nonresponders, was 1.00+/-0.93 among responders, and 1.40+/-0.85 among non-responders (P= NS). No correlation between the amino acid sequence in the GBV-C NS5A region and response to IFN therapy was found, indicating that the GBV-C NS5A region dose not act as the ISDR.

Adult↗
PubMed1999

Simian virus 40-transformed metallothionein null cells showed increased sensitivity to cadmium but not to zinc, copper, mercury or nickel.

Primary cultured embryonic cells derived from mice with disrupted metallothionein (MT) I and II genes and from control mice were transformed with a plasmid encoding the simian virus 40 (SV40) large T antigen. The resulting MT-/- and MT+/+ cell strains showed similar cell morphology, cell cycle and no significant differences in glutathione levels or in the activities of glutathione-related enzymes and antioxidant enzymes. The MT-/- cells were more sensitive to Cd than MT+/+ cells, though no increase in the sensitivity to Zn, Cu, Hg or Ni were observed in MT-/- cells. MT+/+ cells accumulated more Cd than MT-/- cells but showed less lesion, suggesting the role of MT induced by Cd in MT+/+ cells as a scavenger of toxic Cd ion. These results suggest a dominant protective role of MT against Cd compared with other metals. SV40-transformed MT-/- cells seem to be a useful tool for the investigation of cellular function of MT.

Animals↗
PubMed1999

Reduced uptake and enhanced release of cadmium in cadmium-resistant metallothionein null fibroblasts.

Metallothionein (MT) is known to play a predominant role in the protection of cells from cadmium (Cd) toxicity. To investigate other factors involved in Cd resistance, we established Cd-resistant cell lines from simian virus 40-transformed MT null fibroblasts. Cd-resistant MT null cells, Cd-rA7 and Cd-rB5, developed approximately 10-fold resistance to Cd compared to parental cells, but showed no cross-resistance to Zn, Cu, Hg, Ni, As, cisplatin or H2O2. Accumulation of Cd in the resistant cells was 13-18% of that of parental cells after treatment with Cd for 24 h. A short-term experiment revealed that the rate of Cd incorporation into the Cd-resistant cells was suppressed, and the rate of Cd release was enhanced in the resistant cells compared with that of parental cells. These results indicate that the altered transport of Cd, slow uptake and rapid release, may confer resistance to Cd on the Cd-resistant cells established from MT null fibroblasts.

Animals↗
PubMed1999

High prevalence and phylogenetic analysis of TT-virus infection in Mongolia.

A novel DNA virus, TT-virus (TTV), was isolated from a post-transfusion hepatitis patient in Japan. The prevalence of TTV infection was investigated among patients with chronic liver disease and normal alanine aminotransferase (ALT) volunteers as controls in Mongolia. Polymerase chain reaction (PCR) was employed to detect TTV DNA using specific primers derived from open reading frame 1 (ORF1) of the TTV genome. Nucleotide sequences of samples positive for TTV DNA were determined. The sequences were analyzed by a molecular evolutionary method. Fifty (60.2%) hepatitis patients and 12 (42.9%) volunteers were positive for TTV DNA. The serum ALT levels did not differ significantly between patients with single TTV infection and without TTV, HBV and HCV infection. Similarly, the serum ALT levels did not differ significantly between controls with and without TTV infection. Dual infection of TTV with either HBV or HCV did not affect the ALT levels of hepatitis patients. The molecular evolutionary tree showed that TTV was a heterogeneous virus and all strains could be divided into three genotypes in Mongolia. A new genotype was identified that was distinct from those previously reported.

Adult↗
PubMed1999

Microsatellite instability associated with hepatocarcinogenesis.

BACKGROUND/AIMS: The biological and clinicopathological significance of microsatellite instability in hepatocellular carcinoma still remains to be determined. The aim of this study was to assess the role of microsatellite instability in hepatocarcinogenesis. METHODS: Genomic DNA extracted from 38 fresh samples of hepatocellular carcinoma was amplified by polymerase chain reaction using 29 fluorescence-labeled microsatellite markers and analyzed using a semi-automated laser scanning system. Associations between the incidence of replication error and the clinicopathological features of hepatocellular carcinoma were evaluated. Since reference DNA was extracted from corresponding fresh samples of non-cancerous liver tissue, the incidence of microsatellite instability in non-cancerous liver tissues was not assessed in this study. RESULTS: Four (11%) hepatocellular carcinomas had a replication error in one or two microsatellite markers; they were all poorly differentiated hepatocellular carcinomas. The incidence of replication error correlated significantly with the histological differentiation of the tumor (p<0.05) and with portal vein involvement (p<0.05). All four hepatocellular carcinomas with replication errors showed loss of heterozygosity in one or more of the 29 markers we examined. No replication errors were detected in six markers in the coding regions of the BAX, insulin-like growth factor II receptor, transforming growth factor-beta type II receptor, E2F-4, hMSH3 and hMSH6 genes. CONCLUSIONS: The results of this study indicate that: (1) microsatellite instability is a rare event during hepatocarcinogenesis and may be specifically associated with progression of hepatocellular carcinoma; and (2) frame-shift mutation in the above six genes is not a common mechanism involved in progression of this cancer.

Aged↗
PubMed1999

TT virus infection among blood donors and patients with non-B, non-C liver diseases in Korea.

BACKGROUND/AIMS: A novel virus, designated the TT virus (TTV), was isolated from the serum of a patient with posttransfusion hepatitis of unknown etiology, in Japan. Subsequently, TTV was suggested to be a causative agent in a proportion of cases with cryptogenic hepatitis in Japan. This study aimed to elucidate the significance of TTV infection in cases with cryptogenic liver disease in Korea, a neighbor of Japan. METHODS: The prevalence of TTV infection was studied in 120 patients with liver diseases, including 85 patients diagnosed as having non-B, non-C liver diseases. As controls, 220 blood donors were also examined. TTV DNA was detected by polymerase chain reaction, and the sequence was analyzed by phylogenetic analysis. RESULTS: Fourteen (14.0%) of 100 accepted blood donors, 23 (19.2%) of 120 rejected blood donors, and 15 (17.6%) of 85 patients with non-B, non-C liver diseases were positive for TTV DNA. The prevalences of TTV infection among these groups were not significantly different. Phylogenetic analysis suggested the existence of four major genotypes of TTV The proportions of each genotype among patients with non-B, non-C liver diseases were not different from those among accepted blood donors. CONCLUSIONS: TTV exists in Korea, but the prevalence among patients with non-B, non-C liver diseases was almost the same as that among blood donors. TTV may not be the main causative agent of cryptogenic liver disease in Korea. The relationship between non-B, non-C liver diseases and TTV genotype remains unclear, although TTV can be classified into four genotypes.

Adolescent↗
PubMed1999

Allometry in vestibular responses of anurans.

Frogs and toads turn either their heads or bodies opposite to angular accelerations applied around the yaw axis. Thresholds exist for the minimum angular acceleration that induces this vestibulomotor response in individual frogs. These thresholds were recorded for several anuran species that cover a broad range of sizes and life styles. Interspecific variation in the magnitude of the thresholds, which correlated with the ecology and behavior of the species, was documented. Also an allometric relationship was observed between this threshold and body size; the larger the frog, the lower the threshold. In many species, the threshold value for reflexive vestibulomotor responses to angular acceleration was proportional to the -0.4 (+/-0.2) power of body mass. Physical dimensions of the semicircular canals determine, in part, vestibular sensitivity to angular acceleration. Hence changes with growth in the semicircular canals are believed to contribute to the slope of -0.4. The biological significance of this allometry in vestibular responses is discussed and compared to trends in vestibular sensitivity and semicircular canal morphology of other vertebrate classes.

Acceleration↗
PubMed1999

An adenosine receptor agonist-induced modulation of TSH-dependent cell growth in FRTL-5 thyroid cells mediated by inhibitory G protein, Gi.

Adenosine has been shown to modulate the TSH-induced DNA synthesis in FRTL-5 thyroid cells. The mechanism of this adenosine action has been somewhat controversial because both A1 adenosine receptor-mediated and non-receptor-mediated mechanisms have been proposed. We have now reexamined our preliminary finding of the inhibitory action of a non-metabolizable adenosine derivative, N6-(L-2-phenylisopropyl)adenosine (PIA), on the TSH-induced DNA synthesis to clarify the adenosine-dependent mechanism of cell growth modulation. PIA dose-dependently inhibited the TSH-induced DNA synthesis expressed by [3H]thymidine incorporation into DNA. This adenosine derivative also prevented the TSH-induced entry of the cell cycle to the S phase at 24 h of culture and the increase in cell number at 48 h. These PIA actions on different aspects of TSH-dependent cell growth were abolished by the treatment of the cells with pertussis toxin, suggesting the involvement of Gi in the PIA action mechanism. Dibutyryl cAMP-induced DNA synthesis was not influenced by PIA. In concert with our previous finding that PIA in a similar concentration range inhibited TSH-induced cAMP production through the adenosine A1 receptor, the present results strongly support the idea that the major pathway of adenosine signaling for the inhibition of the TSH-induced cell proliferation is through the A1 adenosine receptor-Gi system.

Adenosine↗