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N Kato

Publications and source records attributed to N Kato.

At least 379 records · Page 21Linked to original sources

Analysis of the cell tropism of HCV by using in vitro HCV-infected human lymphocytes and hepatocytes.

BACKGROUND/METHODS: We recently established two hepatitis C virus (HCV) replication systems, using MT-2, a human T-cell leukemia virus type I-infected human T-cell line, and PH5CH, a non-neoplastic human hepatocyte line immortalized with simian virus 40 large T antigen. These HCV replication systems were used to assess the infective potencies of seven sera containing more than 10(6) HCV genomes per ml obtained from HCV-positive blood donors. RESULTS: The results showed that these sera had different infectivities for MT-2 and PH5CH cells. One of the seven sera, 1B-1, was more infective for MT-2 cells than PH5CH cells, whereas all the sera except serum 1B-1 were more infective for PH5CH cells than for MT-2 cells. Intracellular HCV RNA could be detected at least 30 days after inoculation with three of the sera. These findings suggested that the infective potency of each serum depends on the type of target cells. To further investigate HCV replication in these cells, we examined the hypervariable region 1 (HVR1) populations of HCV recovered from both MT-2 and PH5CH cells at 8 days postinoculation. The results revealed that the shift to limited HVR1 populations from the quasi-species of HVR1 populations in both cells usually occurred within 8 days after virus inoculation. Furthermore, in two of four sera, the predominant HVR1 populations in MT-2 and PH5CH cells appeared to be different. CONCLUSION: These results suggest that HCV exhibits cell tropism.

Amino Acid Sequence↗

Trimethyltin syndrome as a hippocampal degeneration model: temporal changes and neurochemical features of seizure susceptibility and learning impairment.

The effects of trimethyltin on the hippocampus were investigated in terms of changes in histology, depth electroencephalography, learning acquisition and memory retention, choline acetyltransferase and neuropeptides, and seizure-induced c-fos messenger RNA expression. The results were as follows. (1) Morphologically, trimethyltin produced a progressive loss of hippocampal CA3 and CA4 pyramidal cells, starting from four days after peroral treatment with trimethyltin hydroxide (9 mg/kg), as described previously. (2) Neurophysiologically, the increased seizure susceptibility to pentylenetetrazol treatment reached a maximum at four days post-trimethyltin and then declined after five days post-trimethyltin. The maximal seizure susceptibility at four days post-trimethyltin was confirmed by the immediate and long-lasting appearance of spike discharge in the hippocampus. However, this was not verified by the expression of c-fos messenger RNA in the hippocampus, which was comparable between trimethyltin-treated and control rats. (3) Behaviorally, the time-courses of aggression and learning impairment were similar to that of the seizure susceptibility. (4) Neurochemically, trimethyltin treatment caused changes of neurochemical markers, which were manifested by the elevation of neuropeptide Y content in the entorhinal cortex, and of choline acetyltransferase in the hippocampal CA3 subfield. Trimethyltin may offer potential as a tool for investigations on the relationship between neuronal death in the hippocampus and the development of seizure susceptibility and learning impairment. Alterations in glucocorticoids, glutamate and neuropeptides may all contribute to the manifestation of the trimethyltin syndrome.

Animals↗

Rapid construction of a transcription map for a cosmid contig of Arabidopsis thaliana genome using a novel cDNA selection method.

Significant progress has been made on the random sequencing of cDNAs (ESTs) and the genetic and physical mapping of the Arabidopsis thaliana genome. New techniques are now required to identify and map the expressed genes efficiently on A. thaliana chromosomes. A novel method to construct a transcription map of expressed genes or cDNAs in specific regions of the genome using DNA-latex particles has been developed. The region-specific DNA fragments prepared from six cosmid clones that constitute a contig covering the abi1 locus on chromosome 4 were covalently bound to latex particles. The DNA-latex particles were used for the selection of region-specific cDNAs. Sequence analysis of the cDNA clones revealed that ABI1, RPS2, casein kinase 1 (CK1), nucleosome assembly protein I (NAP) cDNAs and T20837 EST, which are situated within the contig near abi1 locus, were selected. These results indicate that the cDNAs in the specific region of the genome were faithfully selected with this method. Sequence analysis also indicated that 11 selected cDNAs were derived from novel genes located near the abi1 locus and that four of the selected cDNAs encode putative proteins that have sequence similarity to cationic peroxidase, phosphatidylserine decarboxylase 2 (PSD2), trans-caffeoyl CoA 3-O-methyltransferase (CCoAMT), and proteasome subunit XC3.

Arabidopsis↗

Predictors of the efficacy of interferon therapy in chronic hepatitis C virus infection. Tokyo-Chiba Hepatitis Research Group.

BACKGROUND & AIMS: The relative role of virus load and hepatitis C virus (HCV) subtype as predictor of the efficacy of interferon (IFN) therapy is still in dispute. To resolve this issue, a multicenter, randomized, prospective study of 272 patients with chronic hepatitis C but without cirrhosis was conducted. METHODS: The patients were randomly assigned to two different dose groups: 6 million units (MU) or 9 MU IFN three times a week for 6 months. Serum HCV RNA levels and HCV subtypes were determined. RESULTS: HCV RNA negativity rate at the completion of treatment with 9 MU IFN was higher than that with 6 MU (75% vs. 44%; P < 0.05). Virus eradication at 12 months after completion of treatment was higher in the 9 MU group than in the 6 MU group (36% vs. 25%; P < 0.05), especially in patients who had an intermediate virus load (10(4)-10(5) copies/mL by Amplicor monitor assay) (52% vs. 19%; P = 0.029). Virus eradication rate in patients with serotype 2 was higher than in those with serotype 1 for both regimens (6 MU, 53% vs. 15%; 9 MU, 76% vs. 29%; each P < 0.05). CONCLUSIONS: This prospective study showed that virus load, HCV serotype, and IFN dose are important predictors of the virological response to IFN therapy but virus load is the most important factor influencing the efficacy of IFN.

Adult↗

Change of plasma 1,5-anhydro-D-glucitol levels after the onset of diabetes in spontaneous diabetes prone BB/Wor/(/)Tky rats.

Plasma 1,5-anhydro-D-glucitol (AG) is a marker of the diabetic state and also reflects the glycosuria induced by hyperglycemia but not by renal pathology. To investigate the benefits of the AG determination in order to diagnose diabetes in BB/Wor/(/)Tky rats, AG was measured in non-diabetic (n = 104) and diabetic (n = 113) BB/Wor/(/)Tky rats. AG was significantly higher in non-diabetic rats than in diabetic rats (25.2 +/- 9.3 vs 4.1 +/- 7.4 micrograms/ ml, mean +/- SD, p < 0.001). The best cut-off level for AG (8.5 micrograms/ml) was highly specific (100%) for ruling out diabetes and fairly sensitive (82.3%) to detect diabetes. Based on the AG cut-off levels, 90% of false-negative diabetic rats (18/20) were observed within 4 days after the onset of diabetes, which corresponded to 38.3% in diabetic rats (18/47) at that time. The false-negative diabetic rats and positive rats could be effectively distinguished based on the cumulative points given according to the urinary glucose after the onset of diabetes. 1 point for each cross [+] indicating glycosuria using the Testape, i.e. 2 or less points false negative and 4 or more points for diabetic rats in the first 4 days. In conclusion, there is a close inverse relation between the level of plasma AG and the amount of glycosuria detected just after the onset of overt diabetes in BB/Wor/(/)Tky rats.

Animals↗

Comparative in-vitro and in-vivo activity of AM-1155 against anaerobic bacteria.

The in-vitro activity of AM-1155, a 6-fluoro-8-methoxy quinolone, was compared with those of temafloxacin, sparfloxacin, tosufloxacin, ciprofloxacin, ofloxacin and cefmetazole, a cephamycin, against a variety of anaerobic bacteria. Although AM-1155 demonstrated only modest activity against the Bacteroides fragilis group and Prevotella bivia (MIC90s > or =3.13 mg/mL), 76% of the B. fragilis strains tested were inhibited at AM-1155 concentrations of 0.78 mg/L. AM-1155 was highly active against Prevotella intermedia, Porphyromonas gingivalis, Fusobacterium spp., Clostridium perfringens and Mobiluncus spp. (MIC90s < or =0.39 mg/L). An in-vivo study using a mixed infection with AM-1155- and tosufloxacin-susceptible B. fragilis and Escherichia coli strains in rat granuloma pouch was performed. AM-1155 was effective against both organisms whereas tosufloxacin was effective only against E. coli. These results correlated well to the higher pouch levels of AM-1155 than those of tosufloxacin. Clostridium difficile overgrowth was found in the caecum of mice treated with ampicillin both 1 and 7 days after 5 days dosing, but not in AM-1155-treated mice. These results suggest that the clinical efficacy of AM-1155 against infections involving most anaerobic bacteria except for the B. fragilis group and P. bivia should be evaluated further.

Animals↗

Consumption of buckwheat protein lowers plasma cholesterol and raises fecal neutral sterols in cholesterol-Fed rats because of its low digestibility.

Buckwheat protein product (BWP) has a strong hypocholesterolemic activity in rats fed a cholesterol-enriched diet. In this study, we examined the influence of BWP on fecal excretion of sterols and nitrogen in rats fed a diet containing 5 g/kg cholesterol and 1.25 g/kg sodium cholate, and we examined whether the cholesterol-lowering activity of BWP is due to its low digestibility. In Experiment 1, rats fed BWP for 3 wk had significantly lower concentrations of plasma cholesterol and enhanced excretion of fecal total neutral sterols and nitrogen compared with rats fed casein. There was a significant correlation between fecal total neutral sterols and nitrogen (r = 0.89, P < 0.01). Fecal excretion of acidic sterols was unaffected by BWP. In Experiment 2, plasma cholesterol in rats fed trypsin-digested BWP for 2 wk was significantly higher than that in rats fed intact BWP. In Experiment 3, rats were fed BWP, low-molecular-weight fraction of the digest of BWP (LMF ) or high-molecular-weight fraction of the digest of BWP (HMF ) for 3 wk. Plasma cholesterol was lower in the BWP group than in the LMF group (P < 0.05), whereas that in the HMF group was intermediate. The in vitro digestibility of BWP with pepsin and pancreatin was significantly lower than that of casein. The results suggest that the cholesterol-lowering effect of BWP is mediated by higher fecal excretion of neutral sterols and that lower digestibility of BWP is at least partially responsible for the effect.

Animals↗

Follicular lymphomatoid papulosis.

A case of follicular lymphomatoid papulosis (LyP) is reported. The patient was a 60-year-old Japanese woman. Clinically, cutaneous eruptions were reddish, centrally depressed, dome-shaped papules on the extensor aspect of the forearm. Histologically, they exhibited features that fulfilled the disease criteria described by Pierard, et al., i.e., (Am J Dermatopathol 1980;2:173-80), mixed cellular infiltrates including atypical Reed-Sternberg cell-like type-A cells and mycosis cell-like type-B cells surrounding hyperplastic follicular epithelia. The patient also showed many typical nonfollicular LyP papules, i.e., rhythmically recurrent papules which underwent spontaneous involution within a few weeks, over a 10-year period. The coincidental occurrence of a rare variant of follicular LyP and typical LyP in the same individual further suggests that follicular LyP is merely a histological pattern of LyP involving epithelial adnexae.

Cell Nucleus↗

Superparamagnetic iron oxide enhanced magnetic resonance imaging of rat liver with hepatocellular carcinoma and benign hyperplastic nodule.

RATIONALE AND OBJECTIVES: The authors assess the potential of a new superparamagnetic iron oxide (SPIO) in grading hepatocellular carcinoma (HCC) histologically and in differentiating HCC from benign hyperplastic nodule (HPN). METHODS: Nine Wistar rats (with poorly to moderately differentiated HCC, well-differentiated HCC, and HPN) received drinking water containing N-nitrosomorpholine, and were examined by magnetic resonance imaging (4.7 tesla). Spin-echo images (repetition time/echo time, 600/24.5 mseconds) were obtained before and 15 minutes after intravenous administration of 10 mumol Fe/kg of SH U 555A. RESULTS: Poorly to moderately differentiated and well-differentiated HCC showed no significant change in signal-to-noise ratio (SNR) 15 minutes after contrast, whereas HPN showed a significant decrease in SNR. The contrast-to-noise ratio (CNR) between each kind of tumor and adjacent liver parenchyma showed a significant increase at 15 minutes after contrast. CONCLUSIONS: The SPIO discussed in this article may help to differentiate HCC from HPN, but it remains difficult to grade hepatocellular carcinoma histologically.

Animals↗

Depressed contractile response to exercise in diabetic patients in the absence of cardiovascular disease: relationship to adrenergic cardiac dysinnervation.

We investigated the presence of subclinical left ventricular dysfunction by determining left ventricular diastolic filling at rest and the left ventricular ejection fraction (LVEF) response to exercise with radionuclide angiography. The subjects were 40 patients with non-insulin-dependent diabetes who showed no evidence of cardiovascular disease based on clinical findings, electrocardiography and 201T1 perfusion scintigraphy. We also used 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy to investigate whether subclinical left ventricular abnormalities were related to adrenergic cardiac dysinnervation. The change on LVEF in response to exercise (delta LVEF) was < 5% in 1 of 20 normal controls and in 22 of 40 diabetic patients (P < 0.01). The peak filling rate was within normal limits in all controls but was abnormal (< 2.3 EDV s-1) in 5 of 40 patients (P = N.S.). Of the clinical and scintigraphic variables that correlated significantly with delta LVEF, the heart-to-mediastinum 123I-MIBG uptake ratio on the late planar images was the most important and independent predictor. Nearly half of the patients with non-insulin-dependent diabetes without apparent cardiovascular disease exhibited a depressed LVEF response to exercise. This subnormal response was significantly associated with diminished myocardial 123I-MIBG uptake, suggesting a causal relationship.

3-Iodobenzylguanidine↗

Genetic analysis of the hepatitis C virus (HCV) genome from HCV-infected human T cells.

We recently established a cell culture system for the replication of hepatitis C virus (HCV) by using a human T cell leukaemia virus type I-infected cell line, MT-2, and showed that the quasi-species of the hypervariable region 1 observed in the original inoculum became homogeneous in MT-2 cells 10 days after inoculation of HCV. In this study, we obtained HCV cDNA clones covering the whole viral genome by RT-nested PCR using RNA from HCV-infected cloned MT-2C cells, which support viral replication more efficiently, at 12 days after inoculation. A total of 41 distinct HCV cDNA clones covering almost the whole viral genome were also isolated from a cDNA library derived from the original inoculum. Molecular evolutional analyses comparing the sequences of the HCV clones obtained from both sources revealed that the HCV populations became homogeneous in more than half of the compared regions. This finding suggests that limited HCV populations are able to replicate in MT-2C cells. In addition, we isolated cDNA clones containing a 3' X-tail sequence, which was recently identified as a bona fide 3' terminus of the HCV genome, in the HCV-infected MT-2C cells and confirmed that the nucleotide sequence of the 3' X-tail was highly conserved, suggesting its implication in HCV replication. Finally, on the basis of the sequences of HCV cDNA clones obtained from HCV-infected MT-2C cells, we determined the entire nucleotide sequence of the HCV genome containing the 3' X-tail as a candidate for an infectious HCV molecular clone.

Base Sequence↗

Effect of lactulose on short-chain fatty acids and lactate production and on the growth of faecal flora, with special reference to Clostridium difficile.

Lactulose exerts a beneficial effect on hepatic encephalopathy by decreasing toxic short-chain (iC4-nC6) fatty acid (isobutyrate, butyrate, isovalerate, valerate, isocaproate and caproate) production. However, the precise mechanism by which lactulose exerts this effect remains uncertain. This study investigated the effect of lactulose on faecal flora, particularly Clostridium difficile, which produces mostly iC4-nC6 fatty acids. An in-vitro faecal incubation system was used to estimate how lactulose influences production of short-chain (C2-nC6) fatty acids and lactate. Faecal specimens were collected from patients with liver cirrhosis, who carried C. difficile in the colon. Supplementation of lactulose along with blood in faecal specimens decreased iC4-nC6 fatty acids production and increased acetate and lactate production, resulting in increased faecal acidity. These changes were statistically significant when compared with supplementation by blood alone. Quantitative faecal culture demonstrated that lactulose supplementation suppressed the growth of C. difficile and Bacteroides spp. (B. fragilis group), iC4-nC6 fatty acids-producing organisms. These results suggest that decreased faecal levels of iC4-nC6 fatty acids after lactulose supplementation may be related to suppression of iC4-nC6 fatty acids-producing faecal organisms, especially C. difficile.

Aged↗

Antibiotic-loaded hydroxyapatite blocks in the treatment of experimental osteomyelitis in rats.

A novel drug delivery system for osteomyelitis was developed in which a porous hydroxyapatite block (HAB) is loaded with antibiotic by a centrifugation method. In this study, implantation of HABs loaded with the aminoglycoside antibiotic, arbekacin, were tested in established Staphylococcus aureus osteomyelitis in the proximal tibia of rats after debridement of the marrow cavity. The animals were observed for radiographic signs of infection and tissue was examined histologically. The infections were also evaluated by bone cultures. Bacterial counts were statistically lower in rats implanted with an antibiotic-loaded HAB than in those given a drug-free HAB. Radiographical and histological observations also showed beneficial effects of the antibiotic-loaded implant. The results suggest that the centrifugation method for loading HABs provides a simple drug delivery system. These antibiotic-loaded HABs may be useful for filling grafts in osteomyelitis.

Aminoglycosides↗

A linkage map of the rat genome derived from three F2 crosses.

We report the construction of a dense linkage map of the rat genome integrating 767 simple sequence length polymorphism markers, combined over three crosses with high rates of polymorphism. F2 populations from WKY x S (n = 159), BN x S (n = 91), and BN x GK (n = 139) were selected and genotyped for combinations of microsatellite markers. The loci define 21 linkage groups corresponding to the 20 rat autosomal chromosomes and the X chromosome. The map spans a genetic length of 1998 cM. This combined linkage map should facilitate the advancement of genetic studies for a wide variety of rat models characterized for complex phenotypes.

Animals↗

Zeis gland carcinoma.

Sebaceous carcinoma of the Zeis gland of the cilia is a rare malignant tumor. A 90-year-old Japanese man with a Zeis gland carcinoma on the left upper eyelid is reported. The tumor was a 12 x 3-mm, reddish, partially yellow, papillomatous nodule accompanied by loss of several lashes. Histologically, two types of tumor cells, a dark basaloid cell and a larger pale cell, showed lobular and comedo-acinar growth patterns. The carcinoma did not recur during the 8 months following surgery; however, the patient died of gastric carcinoma.

Adenocarcinoma, Sebaceous↗

Hepatitis C virus in pelvic lymph nodes and female reproductive organs.

Based on epidemiological evidence, hepatitis C virus (HCV) is thought to be involved in the etiology of not only hepatocellular carcinoma, but also lymphoproliferative diseases. In addition, our previous studies using recently developed cell culture systems that support HCV replication have indicated that HCV possesses both hepatotropism and lymphotropism. To determine whether HCV is present in extrahepatic organs, we conducted semi-quantitative reverse transcription-polymerase chain reaction for the 5' non-coding region of the HCV genome in surgical specimens (lymph nodes, ovary, uterus, peripheral blood mononuclear cells [PBMCs] and serum) from three patients with gynecological cancer. We found relatively high HCV genome titers in the lymph nodes, not in the sera, irrespective of various titers in PBMCs. These results suggest that lymph nodes may play an important role in the carrier state and the persistence of HCV infection. Moreover, contrary to expectation, high titers of the HCV genome were observed in the ovaries and the uteri, suggesting the feasibility of mother-to-infant and spouse-to-spouse transmissions of HCV.

Adult↗

[Bacteriological study of oral open abscesses].

Although studies of bacteriology of closed oral abscesses have been extensively done, there are few studies on microorganisms involving open oral abscesses. We examined bacteriologically three open abscesses with precaution against bacterial contamination with oral normal flora and saliva, when sampling. The specimens were subjected to aerobic and anaerobic cultures within 2 hours after sampling. All three cases were infected with 5 to 14 species of aerobic and anaerobic bacteria; Streptococcus spp., Prevotella intermedia and other Prevotella spp. were predominant in all three cases. All six Prevotella spp. isolated were beta-lactamase producers, being resistant to beta-lactam antibiotics. These results emphasize the importance of prompt anaerobic culture for the bacteriological study of open oral abscess and the significance of nitrocefin test to detect beta-lactamase produced by oral isolates, especially Prevotella spp.

Abscess↗