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Biomedical subjects

Y Kondo

Publications and source records attributed to Y Kondo.

At least 19 recordsLinked to original sources
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

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

Early treatment with cyclosporin A ameliorates the reduction of muscarinic acetylcholine receptors in gerbil hippocampus after transient forebrain ischemia.

Recent evidence has suggested that cyclosporin A (CsA), an immunosuppressive agent, has neuroprotective properties. However, its mechanisms associated with this activity remain unclear. We have previously shown that post-ischemic administration of CsA daily for 14 days prevented the decrease of muscarinic acetylcholine receptor binding in the hippocampus in the gerbil model of 5-min transient forebrain ischemia. In the present study, CsA (5 mg/kg, subcutaneously) was administered to each animal just after, 2 and 6 h after ischemia so as not to exert its immunosuppressive effect. Initial CsA treatment significantly restored the declined muscarinic acetylcholine receptor binding of the hippocampus 14 days after ischemia similar to the previous report. However, CsA did not alter reactive changes of astrocytes and microglia in the CA1 area of the hippocampus, which had been suppressed by daily administration. These results indicate that CsA could positively modulate the hippocampal acetylcholine neurotransmission system broken down through the ischemia-induced pyramidal cell death and its action mechanism may have no relation to the immunosuppressive properties.

Animals↗
PubMed1999

Overt nephrogenic diabetes insipidus in mice lacking the CLC-K1 chloride channel.

CLC-K1 is a kidney-specific chloride channel that mediates transepithelial chloride transport in the thin ascending limb of Henle's loop (tAL) in the inner medulla. Transport of NaCl in the tAL is thought to be a component of urinary concentration in a passive model of the countercurrent multiplication system, but there has been no direct evidence that CLC-K1 is involved in urine concentration. To analyse the physiological function of CLC-K1 in vivo, we generated mice lacking CLC-K1 by targeted gene disruption. Clcnk1-/- mice were physically normal appearance, but produced approximately five times more urine than Clcnk1+/- and Clcnk1+/+ mice. After 24 hours of water deprivation, Clcnk1-/- mice were severely dehydrated and lethargic, with a decrease of approximately 27% in body weight. Intraperitoneal injection of the V2 agonist 1-deamino-8-D-arginine vasopressin (dDAVP) induced a threefold increase in urine osmolarity in Clcnk1+/- and Clcnk1+/+ mice, whereas only a minimal increase was seen in Clcnk1-/- mice, indicating nephrogenic diabetes insipidus. After in vitro perfusion of the tAL, the lumen-to-bath chloride gradient did not produce a diffusion potential in Clcnk1-/- mice in contrast to Clcnk1+/+ and Clcnk1+/- mice. These results establish that CLC-K1 has a role in urine concentration, and that the countercurrent system in the inner medulla is involved in the generation and maintenance of hypertonic medullary interstitium.

Animals↗
PubMed1999

Interstitial invasion of well-differentiated hepatocellular carcinoma and subsequent tumor growth.

Pathological processes of interstitial invasion of hepatocellular carcinoma (HCC) were investigated in 125 autopsy and seven surgical cases, where selection focused on those occurring in well-differentiated HCC. The invasive pattern of well-differentiated HCC was characterized by the formation of streaks of tumor cell cords running along connective tissue fibers, referred to as a streak pattern. These cell cords were unaccompanied by reticulin frameworks and type IV collagen, which are consistent components of HCC parenchyma. The typical streak pattern was observed only in HCC cases and could be useful in differential diagnosis. Following progressive accumulation or proliferation of the tumor cells within the interstitium, many capillaries appeared between the cell cords while collagen fibers tended to disappear. The tumor cell cords then showed branching and were accompanied by reticulin frameworks, type IV collagen and sinusoidal blood spaces. In the setting of interstitial invasion of well-differentiated HCC, it is suggested that interstitial tissue is converted into HCC parenchyma via the aforementioned steps.

Antigens, CD34↗
PubMed1999

Glial cells protect neurons against oxidative stress via transcriptional up-regulation of the glutathione synthesis.

We examined the effects of oxidative stress on rat cultured mesencephalic neurons and glial cells. Glial cells were more resistant to 6-hydroxydopamine (6-OHDA) and H2O2 toxicity than neurons. In glial cells, incubation with 6-OHDA and H2O2 induced a significant increase in the expression of gamma-glutamylcysteine synthetase (the rate-limiting enzyme in glutathione synthesis) mRNA, which correlated well with increased TPA-response element (TRE)-binding activity. Furthermore, a subsequent elevation in cellular total glutathione content was also observed. In neurons, both agents decreased TRE-binding activity, and these cells failed to up-regulate the glutathione synthesis. We also examined the mechanisms of the neuroprotective effects of glial cells using a glia conditioned medium. Neurons maintained in glia conditioned medium up-regulated the level of TRE-binding activity, gamma-glutamylcysteine synthetase mRNA expression, and total glutathione content in response to 6-OHDA or H2O2, and became more resistant to both agents than cells maintained in a normal medium. Neurons maintained in normal medium failed to up-regulate the glutathione synthesis. Our results suggest that transcriptional up-regulation of glutathione synthesis in glial cell appears to mediate brain glial cell resistance against oxidative stress, and that glial cells protect neurons via transcriptional up-regulation of the antioxidant system.

Animals↗
PubMed1999

Nucleotide sequences and taxonomy of satsuma dwarf virus.

The nucleotide sequences of genomic RNA1 (6795 nt) and RNA2 (5345 nt) of satsuma dwarf virus (SDV), a tentative member of the genus Nepovirus, were determined. The deduced genome organization of SDV showed similarities to the organization in como-, faba- and nepoviruses. There is extensive amino acid sequence similarity in the N-terminal regions of the proteins encoded by RNA1 and RNA2, as reported previously only for tomato ringspot nepovirus. However, unlike definitive nepoviruses, which have a single coat protein, SDV has two coat proteins. SDV RNA2 does not contain the long (> 1300 nt) 3' non-coding region characteristic of some nepoviruses. Phylogenetic analysis of SDV RNA polymerase placed SDV apart from como-, faba- and nepoviruses. These unique features suggest that SDV is distinct from the Comovirus, Fabavirus and Nepovirus genera, and needs to be separated into a new genus, probably within the family Comoviridae.

Amino Acid Sequence↗
PubMed1999

Lysophosphatidic acid and mesangial cells: implications for renal diseases.

The last decade has witnessed a phenomenal increase in our understanding of the biological role of lysophosphatidic acid (LPA) and has led to an appreciation of this critical serum-derived growth factor released from platelets. We herein summarize recent observations that collectively support the hypothesis that LPA may play a key role in the pathogenesis of initiation and progression of proliferative glomerulonephritis. LPA synergistically stimulates mesangial cell proliferation in combination with platelet-derived growth factor in primary culture. The mechanism of co-mitogenesis is likely to be mediated by the prolonged activation of mitogen-activated protein kinase which is stimulated by platelet-derived growth factor and LPA through different mechanisms. LPA contracts cultured mesangial cells and has properties in common with other pressor molecules including mobilization of intracellular Ca2+ and promotion of Ca2+ entry through dihydropyridine-sensitive calcium channels. LPA receptor mRNA has been identified in isolated glomeruli dissected from renal biopsy samples of patients with IgA nephropathy. All of these facts have led us to postulate that LPA is produced within glomeruli and that LPA's mitogenic as well as haemodynamic action contribute to the pathological process of mesangial proliferative glomerulonephritis. The possible production of LPA as an autocrine factor from mesangial cells themselves has also been discussed.

Glomerular Mesangium↗
PubMed1999

Apolipoprotein E in cerebrospinal fluid: relation to phenotype and plasma apolipoprotein E concentrations.

BACKGROUND: Apolipoprotein (apo) E may be related to the development of Alzheimer disease, but data on apoE in cerebrospinal fluid (CSF) are limited. The aim of the present study was to measure apoE in CSF and relate its concentrations to apoE phenotype and CSF lipids. METHODS: We adapted an assay for CSF apoE sensitivity using an ELISA. It allowed us to measure CSF apoE with sufficient reproducibility and precision. RESULTS: The within- and between-run CVs were <7%, and the detection limit was 0.025 mg/L. No cross-reaction was found for other apolipoproteins. No significant differences related to sex or apoE phenotype were observed in the CSF apoE concentration. The mean CSF apoE concentration was significantly higher in the 0-5 year group (n = 6; 18.47 +/- 1.14 mg/L, mean +/- SD) than in the >5 year group (n = 34; 8.82 +/- 3.31 mg/L). The mean concentrations of total cholesterol (TC) and phospholipid (PL) in CSF were 2.68 +/- 2.16 and 6.50 +/- 2.84 mg/L (n = 52), respectively. Although no significant differences in TC or PL in the CSF were found with respect to sex or age, the concentrations in subjects with the apoE phenotype E4/E3 were significantly lower than in those with E3/E3 and E3/E2. The concentrations of apoE, TC, and PL in CSF did not correlate with those in plasma. The time-related fluctuations in CSF apoE were independent of those in total protein and IgG. CSF apoE was significantly correlated with TC and PL concentrations in the CSF, but not with the number of cells in the CSF. CONCLUSIONS: These findings support the idea that apoE and lipids are unable to cross the blood-brain barrier and that their concentrations in CSF may reflect production in central nervous tissue.

Adolescent↗
PubMed1999

Small mucosal carcinoma of the stomach with para-aortic lymph node metastasis: a case report and review of the literature.

A 38-year-old woman presented with a mucosal gastric carcinoma measuring 0.7 x 0.5 cm and para-aortic lymph node metastasis. Radiographic and endoscopic studies showed a small depressed lesion on the anterior border of the gastric angle, which was classified as a type II c + III lesion. Histological examination of the biopsy specimen revealed a signet-ring cell carcinoma. Distal gastrectomy with wide lymph node excision was performed. Detailed study of the resected specimen revealed that the tumour was limited to the mucosa, but metastasized to both the perigastric and para-aortic lymph nodes. The patient received adjuvant immunochemotherapy postoperatively. However, multiple bone metastases developed at 3 years and she died 4 years after the operation.

Adult↗
PubMed1998

Stimulatory and inhibitory actions of lysophosphatidylcholine, depending on its fatty acid residue, on the phospholipase C/Ca2+ system in HL-60 leukaemia cells.

We examined the mechanism of action of lysophosphatidylcholine (LPC), which is suggested to be involved in the pathogenesis of atherosclerosis and inflammatory disorders, in HL-60 leukaemia cells. Extracellular 1-palmitoyl LPC increased the intracellular Ca2+ concentration in association with production of inositol phosphate. These actions of LPC were markedly inhibited by treatment of the cells with pertussis toxin and U73122, a phospholipase C inhibitor. The lipid-induced stimulation of the phospholipase C/Ca2+ system was also attenuated in the dibutyryl cAMP-induced differentiated (neutrophil-like) cells, in which phospholipase C activation induced by NaF or formyl-Met-Leu-Phe was enhanced. In contrast with the stimulatory action of 1-palmitoyl LPC, 1-stearoyl LPC was inhibitory for the phospholipase C/Ca2+ system stimulated by NaF as well as by 1-palmitoyl LPC or other Ca2+-mobilizing agonists. In a cell-free system, only an inhibitory effect on phospholipase C activity was observed even by 1-palmitoyl LPC; 1-stearoyl LPC was more inhibitive than 1-palmitoyl LPC. Taken together, these results suggest that atherogenic and inflammatory LPC exerts both stimulatory and inhibitory actions on the phospholipase C/Ca2+ system depending on the species of fatty acid residue of the lipid; the stimulatory effect is possibly mediated through G-protein-coupled receptors; the inhibitory effect might be caused by dysfunction of the components involved in the enzyme system owing to the amphiphilic nature of the lipid. 1-Palmitoyl LPC prefers the former receptor stimulation at least in intact cells, but 1-stearoyl LPC preferentially exerts the latter inhibitory action.

Bucladesine↗