Systems to culture hepatitis C virus.
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Cells, Cultured↗
Biomedical subjects
N Kato
Publications and source records attributed to N Kato.
Less invasive therapy using endovascular stent graft repair and video-assisted thoracoscopic surgery for ruptured acute aortic dissection.
We report a 75-year-old man with a ruptured acute thoracic aortic dissecting hematoma treated using endovascular stent grafting and video-assisted thoracoscopic surgery. This less invasive therapy is a good therapeutic option even in ruptured acute aortic dissections, particularly given the difficulty of surgery.
Aged↗
Expansion of transgenic tobacco protoplasts expressing pumpkin ascorbate oxidase is more rapid than that of wild-type protoplasts.
When pumpkin (Cucurbita spp., cv. Ebisu Nankin) ascorbate oxidase cDNA was introduced into cultured cells of tobacco BY-2 (Nicotiana tabacum L. cv. Bright Yellow No. 2) by Agrobacterium-mediated transformation, the transgenic cells expressed and secreted the recombinant pumpkin ascorbate oxidase into the culture medium. These transgenic cells showed no morphological difference from wild-type cells. However, in the presence of applied hormones protoplasts prepared from the transgenic cells elongated more rapidly than those of wild-type cells. We propose that ascorbate oxidase may play a key role in the regulation of cell expansion perhaps by controlling transport processes through the plasma membrane, but not by affecting the cell wall.
Ascorbate Oxidase↗
No evidence for an association between the Glu298Asp polymorphism of the NOS3 gene and Alzheimer's disease.
Recently a significant association of a missense mutation (Glu298Asp) of the endothelial nitric oxide synthase (NOS3) gene with late-onset Alzheimer's disease (LOAD) was reported. We tried to replicate this finding in a Japanese sample of 121 patients with LOAD, 51 with early-onset AD (EOAD), and 165 medical controls. However, the genotype and allelic distributions for the Glu298Asp polymorphism were similar for these three groups, suggesting that the Glu298Asp polymorphism of the NOS3 gene has no relevance to the development of AD in Japanese.
Aged↗
Bacteriological study of 28 patients with intraabdominal infection in Japan.
Intraabdominal infections are usually polymicrobial, including both aerobes and anaerobes. To assess the importance of anaerobes in intraabdominal infection, a bacteriological study was performed. The subjects studied were 28 inpatients with acute abdomen who visited Gifu Red Cross Hospital, Gifu, Japan, between May 1996 and July 1998. Twenty-one patients had abscess or peritonitis caused by perforation of the gastrointestinal tract, 4 had liver abscess, 2 had pelvic abscess, and 1 had retroperitoneal and subcutaneous abscess. Most specimens were cultured within 6 h after sampling. Using the E test, we tested the susceptibilities of isolates to 11 antimicrobial agents. Anaerobes were predominantly recovered from intraabdominal infection caused by perforation of the small bowel, appendix, and large bowel. The anaerobes isolated were resistant to the cephems tested, to which the aerobic strains were susceptible. It is suggested that carbapenems may be the choice for treatment of severe intraabdominal infection, especially that resulting from perforation of the small bowel, appendix, and large bowel.
Abdominal Abscess↗
Aberrant expression of glutathione peroxidase in eutopic and ectopic endometrium in endometriosis and adenomyosis.
OBJECTIVE: To determine the expression of glutathione peroxidase (GPx) in the eutopic and ectopic endometria during the menstrual cycle in endometriosis and adenomyosis. DESIGN: Immunohistochemical identification of GPx in endometrial tissues identified using the polyclonal antibody. SETTING: Department of obstetrics and gynecology in a university hospital. PATIENT(S): One hundred fourteen women divided into three groups: 33 patients with endometriosis, 34 patients with adenomyosis, and 47 fertile control subjects. INTERVENTION(S): Endometrium biopsied throughout the menstrual cycle. MAIN OUTCOME MEASURE(S): Endometrial cells: semiquantitative immunostaining (evaluation nomogram) score. RESULT(S): The analyses revealed phase-dependent changes of GPx expression in the surface and glandular epithelia in the eutopic endometrium during the menstrual cycle in the fertile controls, i.e., the expression was weak in the early proliferative phase, gradually increased, was most marked in the early secretory phase, and decreased thereafter. The expression of GPx in the eutopic endometrium in endometriosis lost the variation during the menstrual cycle. The expression of GPx in adenomyosis was persistently marked over the control levels throughout the menstrual cycle. CONCLUSION(S): The aberrant expression of GPx in the eutopic endometrium throughout the cycle suggests a pathological role in endometriosis and adenomyosis.
Endometriosis↗
Evaluation of the poly(ADP-ribose) polymerase gene in human stroke.
Nitric oxide (NO) and its reactant product, peroxynitrite, have been implied to mediate neuronal damage following cerebral ischemia. However, the cellular targets of these compounds remain unclear. Studies using poly(ADP-ribose) polymerase (PARP) inhibitors and PARP knock-out mice have recently demonstrated that excessive activation of this nuclear enzyme plays an important role in NO-induced neurotoxicity. To evaluate the relevance of this plausible candidate gene to human stroke, we undertook a case-control study in Japanese. Participants comprised 213 cerebral infarction cases and 374 age- and sex-matched controls. As a primary investigation, we screened polymorphic sites of the PARP gene, and newly identified a total of four polymorphisms in 1230-bp 5'-flanking sequence. None of them were, however, located on the known promoter components of the gene. Two bi-allelic polymorphisms selected and a CA-repeat polymorphism were subsequently characterized in the case-control study, but none were significantly associated with cerebral infarction in the present study. Our data thus suggest that the tested PARP polymorphisms do not principally contribute to cerebral infarction, although extensive searches would be required to clarify whether the PARP gene plays an important role in the pathogenesis of human stroke.
Adult↗
Evidence for association between paraoxonase gene polymorphisms and atherosclerotic diseases.
Paraoxonase 1 (PON1) is proposed to have an anti-atherogenic action. Two polymorphisms at the PON1 (M/L55 and Q/R192) have been shown to be associated with coronary artery disease (CAD). This conclusion is not drawn universally, however, and specific ethnic characteristics may be important determinants in this association. Recently two homologues of PON1 - PON2 and PON3 - were identified and Sanghera et al. demonstrated C/S311 polymorphism at PON2 was associated with the risk of CAD. Within that context, we investigated the association between the aforementioned three polymorphisms and CAD and ischemic stroke in a Japanese population. The study population included 431 control subjects, 210 CAD patients, and 235 ischemic stroke patients. Genotype distributions and allele frequencies of M/L55 and C/S311 were similar among the control and patient groups, whereas the R192 allele frequency was significantly higher (P<0.001) in CAD (75%) and ischemic stroke (76%) patients than in control subjects (65%). When confounding influences of other risk factors were controlled for by multivariate analysis, R192 remained an independent risk determinant (additive model: OR (95% CI), P value CAD: 2.01 (1.45-2.79), 0.0001; ischemic stroke: 1.84 (1.34-2.52), 0.0002 (three genotypes into calculation)). Taken together, our data indicate that the Q/R192 is principally associated with both CAD and ischemic stroke in Japanese.
Aged↗
Characterization of antiviral activity of lactoferrin against hepatitis C virus infection in human cultured cells.
We recently found that bovine lactoferrin (bLF), a milk glycoprotein belonging to the iron transporter family, prevented hepatitis C virus (HCV) infection in human hepatocyte PH5CH8 cells, that are susceptible to HCV infection, and demonstrated that the anti-HCV activity of bLF was due to the interaction of bLF and HCV. In this study we further characterized the anti-HCV activity of bLF and the mechanism by which bLF prevents HCV infection. We found that bLF inhibited viral entry to the cells by interacting directly with HCV immediately after mixing of bLF and HCV inoculum. The anti-HCV activity of bLF was lost by heating at 65 degrees C, and other milk proteins (mucin, beta-lactoglobulin and casein) did not prevent HCV infection, indicating that bLF prevented HCV infection in a rather specific manner. Furthermore, we found that bovine lactoferricin, a basic N-terminal loop of bLF that is an important region for antibacterial activity, did not exhibit any anti-HCV activity, suggesting that some other region is involved in anti-HCV activity. We confirmed that prevention of HCV infection by bLF was a general phenomenon, because bLF inhibited HCV infection with all five inocula examined, and bLF inhibited HCV infection in human MT-2C T-cells, that were susceptible to HCV infection. In addition, infection with hepatitis G virus, which is distantly related to HCV, was prevented also by bLF. In conclusion, lactoferrin is a natural glycoprotein which effectively protects against HCV infection in hepatocytes and lymphocytes by neutralizing the virus.
Animals↗
Effects of 15-month aldose reductase inhibition with fidarestat on the experimental diabetic neuropathy in rats.
We examined the effects of long-term treatment with an aldose reductase inhibitor (ARI) fidarestat on functional, morphological and metabolic changes in the peripheral nerve of 15-month diabetic rats induced by streptozotocin (STZ). Slowed F-wave, motor nerve and sensory nerve conduction velocities were corrected dose-dependently in fidarestat-treated diabetic rats. Morphometric analysis of myelinated fibers demonstrated that frequencies of abnormal fibers such as paranodal demyelination and axonal degeneration were reduced to the extent of normal levels by fidarestat-treatment. Axonal atrophy, distorted axon circularity and reduction of myelin sheath thickness were also inhibited. These effects were associated with normalization of increased levels of sorbitol and fructose and decreased level of myo-inositol in the peripheral nerve by fidarestat. Thus, the results demonstrated that long-term treatment with fidarestat substantially inhibited the functional and structural progression of diabetic neuropathy with inhibition of increased polyol pathway flux in diabetic rats.
Aldehyde Reductase↗
Anaplastic large-cell lymphoma associated with acquired ichthyosis.
Anaplastic, CD30(+), large-cell lymphoma (ALCL) is a subtype of non-Hodgkin's lymphoma that accounts for 2% to 8% of all lymphomas. Its most common form is a classical systemic type, which involves multiple nodal and extranodal sites, including the skin. Malignant lymphoproliferative disorders, especially Hodgkin's disease, are known rarely to be associated with acquired ichthyosis, whereas only 1 case of ALCL has been reported to be associated with acquired ichthyosis. We describe a 74-year-old Japanese man with ALCL, involving lymph nodes and the skin, who exhibited acquired ichthyosis. The clinical and histopathologic findings were recorded, and immunophenotyping, T-cell receptor (TCR), and immunoglobulin gene rearrangement were determined. Clinically, right axillary and bilateral inguinal lymph nodes were palpable. The cutaneous eruptions were multiple pinkish and yellow colored, up to thumb-sized nodules, some of which were ulcerated. Histologically, the right axillary lymph node showed proliferation of anaplastic large cells in the paracortical and sinusoidal areas. Both the lymph node and skin showed pleomorphic proliferation of lymphoid cells with a mixture of mononuclear cells having oval, embryo-shaped, reniform, and lobulated nuclei, binucleated Reed-Sternberg-like cells, and multinucleated cells, with giant anaplastic and wreath-shaped nuclei. Immunophenotyping of the neoplastic cells revealed that they were positive for CD30 (Ber-H2), CD15 (Leu-M1), CD45 (LCA), and CD45RO (UCHL-1). Southern blot analysis demonstrated clonal rearrangement of the TCR beta region. In contrast, no novel bands were detected with the immunoglobulin heavy chain JH probe. Several months after the detection of the axillary nodes, an ichthyosiform, scaly eruption developed over almost the entire body of the patient. Histologically, it showed orthokeratotic, slight hyperkeratosis of the epidermis without a granular layer or with only a single layer of cells in the granular layer. Several kinds of lymphoproliferative diseases are associated with acquired ichthyosis, including Hodgkin's disease, multiple myeloma, and lymphomatoid papulosis. This is the second case report of acquired ichthyosis associated with ALCL. Although a common pathomechanism is suspected of underlying the development of acquired ichthyosis in these diseases, it is still unexplained.
Aged↗
Aortoesophageal fistula-relief of massive hematemesis with an endovascular stent-graft.
A 59-year-old man with an esophageal carcinoma developed massive hematemesis due to aortoesophageal fistula after irradiation therapy reached 58 Gy. Emergent treatment with an endovascular stent-graft was successfully performed and the patient followed an uneventful course until he died of pneumonia 4.5 months later, which was caused by a tracheoesophageal fistula. Stent-graft repair is a safe and effective method to treat aortoesophageal fistula and may be an alternative to surgical resection.
Aortic Diseases↗
Altered brain energy metabolism in lithium-resistant bipolar disorder detected by photic stimulated 31P-MR spectroscopy.
BACKGROUND: Previous 31P-MRS (magnetic resonance spectroscopy) studies suggested altered brain energy metabolism in bipolar disorder. This study characterized brain energy metabolism in lithium-resistant bipolar disorder using the photic-stimulation paradigm. METHODS: Subjects were 19 patients with DSM-IV bipolar disorder (nine responders and 10 nonresponders, 13 with bipolar I and six with bipolar II) in the euthymic state and 25 healthy volunteers. Energy metabolism in the occipital region was examined by 31P-MRS during photic stimulation (PS). Six 31P-MR spectra were obtained, one was before PS (Pre), two during 12 min of PS (PS1, PS2), and three after the PS (Post 1, Post 2, Post 3). RESULTS: Significant effect of diagnosis (lithium-responsive bipolar disorder, lithium-resistant bipolar disorder, and control) was found for the phosphocreatine peak area ratio during the course of the photic stimulation (P < 0.05 by repeated measures ANOVA). The phosphocreatine peak area ratio was significantly decreased at Post 1 and Post 2 compared with Pre in lithium-resistant bipolar patients (P = 0.01 and P = 0.01 by Dunnett's multiple comparison). CONCLUSIONS: The finding that phosphocreatine decreased after photic stimulation may be compatible with mitochondrial dysfunction. It is possible that mitochondrial function is impaired in lithium-resistant bipolar disorder.
Adult↗
Sustained viral response is rarely achieved in patients with high viral load of HCV RNA by excessive interferon therapy.
Adequate dosing of interferon (IFN) and its cost-effectiveness for sustained virological response were evaluated in relation to viral load and subtype. Prospective analysis of IFN therapy on 326 patients with chronic hepatitis C free from cirrhosis was performed using 9 or 6 million unit (MU) of IFN for six months daily and/or three times a week. Sustained virological response was achieved in 50-94% of patients with < or =2 x 10(4) copies/ml (competitive RT-PCR) or <100 x 10(3) copies/ml (Amplicor monitor) of HCV RNA by 468-1206 MU of IFN, but response was only 0-25% of the patients with > or =2 x 10(5.5) copies/ml (competitive RT-PCR) or >200 x 10(3) copies/ml (Amplicor monitor), even with 468-1206 MU of IFN. A high sustained rate was demonstrated in patients with 100-200 x 10(3) copies/ml of HCV RNA by 901-1206 MU of IFN, in comparison to that with < or =900 MU of IFN. Multivariate analysis showed that IFN dose had a significant value for the efficacy of IFN therapy in patients presenting 100-200 x 10(3) copies/ml of HCV RNA. Cost efficacy analysis indicated that it cost approximately $10,000, $26,000, and $50,000-227,000 for one person-viral eradication in the patients with <100, 100-200, and >200 x 10(3) copies/ml, respectively. High-dose IFN is only cost effective in patients with intermediate viral loads, and IFN therapy could be recommended in patients with <200 x 10(3) copies/ml of HCV RNA.
Adolescent↗
Estimation of nitrate metabolism in intestinal tract by measuring breath nitrous oxide concentration in Chinese and Japanese.
We have previously reported that ingestion of vegetables containing high nitrate (NO3-) increases breath nitrous oxide (N2O) concentration, probably due to denitrification. In the present study, we estimated NO3- metabolism in the intestine by determining exhaled breath N2O concentration after the ingestion of vegetables by 16 healthy Chinese and Japanese. Breath samples were collected at 15-min intervals for 4 hr after subjects ingested 180 g of vegetable juice or 50 g of lettuce. Breath N2O concentration was measured by an IR-PAS analyzer. Lettuce but not vegetable juice increased N2O concentrations similarly in Japanese and Chinese. In control subjects who ingested nothing, there were significant differences between Chinese and Japanese in peak N2O concentrations (334 +/- 91 vs 140 +/- 24 ppb, P = 0.027) and total excretions (535 +/- 143 vs 214 +/- 36 microg, P = 0.036). Although the reason for this difference is unclear, Chinese subjects could produce breath N2O from other metabolic pathways than denitrification of dietary NO3.
Adult↗
Mitochondrial dysfunction in bipolar disorder.
Mitochondrial dysfunction is implicated in bipolar disorder based on the following lines of evidence: 1) Abnormal brain energy metabolism measured by 31P-magnetic resonance spectroscopy, that is, decreased intracellular pH, decreased phosphocreatine (PCr), and enhanced response of PCr to photic stimulation. 2) Possible role of maternal inheritance in the transmission of bipolar disorder. 3) Increased levels of the 4977-bp deletion in mitochondrial DNA (mtDNA) in autopsied brains. 4) Comorbidity of affective disorders in certain types of mitochondrial disorders, such as autosomal inherited chronic progressive external ophthalmoplegia and mitochondrial diabetes mellitus with the 3243 mutation. Based on these findings, we searched for mtDNA mutations/ polymorphisms associated with bipolar disorder and found that 5178C and 10398A polymorphisms in mtDNA were risk factors for bipolar disorder. The 5178C genotype was associated with lower brain intracellular pH. mtDNA variations may play a part in the pathophysiology of bipolar disorder through alteration of intracellular calcium signaling systems. The mitochondrial dysfunction hypothesis, which comprehensively accounts for the pathophysiology of bipolar disorder, is proposed.
Adenosine Triphosphate↗
Iron enhances hepatitis C virus replication in cultured human hepatocytes.
BACKGROUND: Iron overload in the presence of increasing concentrations of iron is one of the indicators of poor response to interferon therapy in chronic hepatitis C. In order to analyze the effect of iron on hepatitis C virus (HCV) replication, we measured replication in an HCV-infected cell line. METHODS AND RESULTS: Cells from a non-neoplastic HCV-infected human hepatocyte line (PH5CH8) susceptible to HCV infection and supportive of HCV replication were used in this study. The replication of HCV RNA was measured by reverse transcription-nested polymerase chain reaction (RT-nested PCR). PH5CH8 cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. PH5CH8 cells were incubated with 0, 1, 10, 50, and 100 microM of FeSO4 at 37 degrees C with 5% CO2. Forty-eight hours after iron supplementation, the quantity of HCV RNA in the cells incubated in 50 and 100 microM of FeSO4 was approximately ten times that of the cells with no iron supplementation. Similar changes were observed beginning at 12 h from supplementation with FeSO4 and continued for at least 72 h after supplementation. MTT assay indicated that iron did not have cytotoxic effects on the PH5CH8 cells. CONCLUSION: Iron enhances HCV replication in a hepatocyte cell line. The results suggest that iron deposition in hepatocytes could facilitate HCV infection in the liver.
Cell Line, Transformed↗
Poor association of TT virus viremia with hepatocellular carcinoma.
AIM: The aim of this study was to clarify the relationship between TT virus (TTV) infection and the development of hepatocellular carcinoma. METHODS: TTV from serum was examined in 224 patients with hepatocellular carcinoma (HCC) and 106 patients with chronic liver disease (CLD) but without HCC who were admitted to our hospital between 1995-1997. As controls, 48 patients without liver disease were also examined. TTV DNA was detected using nested PCR method after extraction of DNA from serum. RESULTS: TTV DNA was detected in 29/224 (13%) of patients with HCC; in 14% (4/28) of HCC patients negative for both hepatitis B virus surface antigen (HBsAg) and anti-hepatitis C virus antibody (anti-HCV), in 9% (2/22) of HCC patients positive for HBsAg, and in 12% (21/170) of HCC patients positive for anti-HCV. The prevalence of TTV DNA in HCC patients (13%) was not significantly higher than in CLD patients (22%). There were no significant differences in age, gender, liver function, tumor biology (size, TNM classification), other viral markers, or amount of alcohol intake between TTV-positive and -negative HCC patients. Only a history of blood transfusion was significantly more frequent in TTV-positive HCC patients than in TTV-negative cases (p= 0.02). Coinfection with TTV did not correlate with the severity of HCV-positive liver disease. There was no significant difference in prognosis between TTV-positive and -negative HCC patients. CONCLUSIONS: TTV does not seem to contribute to the development of HCC from chronic liver disease and is not correlated with severity of liver disease.
Aged↗