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Biomedical subjects

N Kato

Publications and source records attributed to N Kato.

At least 469 records · Page 26Linked to original sources
PubMed1996

Characterization of hepatitis C virus replication in cloned cells obtained from a human T-cell leukemia virus type 1-infected cell line, MT-2.

We recently found that a human T-cell leukemia virus type 1-infected cell line, MT-2, could support the replication of hepatitis C virus (HCV) (N. Kato, T. Nakazawa, T. Mizutani, and K. Shimotohno, Biochem. Biophys. Res. Commun. 206:863-869, 1995). In order to develop a culture system in which HCV replicates more efficiently, we examined the efficiency of HCV replication in cloned MT-2 cell lines by the limiting dilution method. Consequently, we obtained five clones in which intracellular positive-stranded HCV RNA could be detected until at least 21 days postinoculation (p.i.), as opposed to 15 days p.i. in uncloned MT-2 cells. MT-2C, one of the five clones which supported HCV replication up to 30 days p.i., was used for further characterization of HCV replication. Semiquantitative analysis of HCV by PCR revealed that RNA synthesis in infected cells increased after inoculation, reached a maximum level at 4 days p.i., and maintained this level until at least 11 days p.i. The 5' untranslated region of negative-stranded HCV RNA was also detected in the infected cells by two different methods with strand specificity. These results suggest that HCV replicated and multiplied in the MT-2C cells. HCV-infected MT-2C cells that were treated with antibiotics, such as G418 and hygromycin B, sustained HCV RNA for a longer period than did untreated cells. We demonstrated inhibitory effects on HCV replication by an antisense oligonucleotide complementary to the HCV core encoding region and by interferon-alpha. Furthermore, cell-free viral transmission was demonstrated by this culture system. These results suggest that our cell culture system will be useful for studying the mechanism of HCV replication, for screening antiviral agents, and for developing HCV vaccines.

Cell Line, Transformed↗
PubMed1996

Structure of the 3' terminus of the hepatitis C virus genome.

Hepatitis C virus (HCV), a positive-strand RNA virus, has been considered to have a poly(U) stretch at the 3' terminus of the genome. We previously found a novel 98-nucleotide sequence downstream from the poly(U) stretch on the HCV genome by primer extension analysis of the 5' end of the antigenomic-strand RNA in infected liver (T. Tanaka, N. Kato, M.-J. Cho, and K. Shimotohno, Biochem. Biophys. Res. Commun. 215: 744-749, 1995). Here, we show that the novel sequence is a highly conserved 3' tail of the HCV genome. We repeated primer extension analyses with four HCV-infected liver samples and found the 98-nucleotide sequence in all the samples. Furthermore, experiments in which RNA oligonucleotide was ligated to the 3' end of the HCV genome existing in infectious serum revealed nearly identical 3' termini with no extra sequence downstream from the 98-nucleotide sequence, suggesting that this sequence is the tail of the HCV genome. This tail sequence was highly conserved among individuals and even between the two most genetically distant HCV types, II/1b and III/2a. Computer modeling predicted that the tail sequence can form a conserved stem-and-loop structure. These results suggest that the novel 3' tail is a common structure of the HCV genome that plays an important role in initiation of genomic replication.

Base Sequence↗
PubMed1996

Antirheumatic agents. I. Novel methotrexate derivatives bearing an indoline moiety.

Various novel methotrexate (MTX) derivatives bearing an indoline moiety were synthesized and tested for biological activities using human peripheral blood mononuclear cell (hPBMC) and human synovial cells (hSC) derived from patients with rheumatoid arthritis (RA). Compounds having potent activity in vitro were further evaluated using an adjuvant arthritis model in vivo. N-[1-(2,4-Diamino-6-pteridinylmethyl)indoline-5-carbonyl]-L-glutam ic acid 2f showed more potent activities than MTX in vitro and in vivo, and N-[1-(2,4-diamino-6-pteridinylmethyl)-indoline-5-carbonyl]-L-2-ami noadipic acid 2d exhibited fairly good activities in vitro and considerable activity in vivo. Compound 2d was, as expected, not sensitive to folyl-polyglutamate synthetase (FPGS) and did not undergo polyglutamation, a process which may be responsible for a side-effect during MTX therapy.

Animals↗
PubMed1996

Antirheumatic agents. II. Novel methotrexate derivatives bearing an alkyl-substituted benzene ring.

Novel methotrexate (MTX) derivatives with either a mono- or dialkyl-substituted benzene ring were synthesized and initially tested for in vitro anti-proliferative activities using human peripheral blood mononuclear cells (hPBMC) derived from healthy volunteers and synovial cells (hSC) derived from patients with rheumatoid arthritis (RA). Compounds with potent activities were further evaluated in an in vivo adjuvant arthritis model. In comparison with MTX, a glutamate derivative 3a was more potent as a suppressor of the in vitro cell proliferation and the in vivo experimental arthritis, and a homoglutamate derivative, 3e, exhibited fairly good activities in vitro and considerable activity in vivo in a dose-dependent manner. As expected, 3e did not act as a substrate of folylpolyglutamate synthetase (FPGS), and thus did not undergo polyglutamation, which is thought to be responsible for side-effects that occur during MTX therapy.

Antirheumatic Agents↗
PubMed1996

Production of fructosyl lysine oxidase from Fusarium oxysporum S-1F4 on autoclave-browned medium.

In Fusarium oxysporum S-1F4, fructosyl lysine oxidase (FLOD) was induced with N epsilon-fructosyl N alpha-Z-lysine (epsilon-FL), which is a model compound of a glycated protein, and the induction was inhibited by the addition of cycloheximide in the growing cells. FLOD formation was greatly enhanced in an autoclave-browned medium containing glucose and L-lysine. Some Amadori compounds formed from glucose and L-lysine during autoclaving were assumed to induce the enzyme. After optimization of the culture conditions, FLOD produced in the browned medium was comparable to that in the medium with epsilon-FL.

Amino Acids↗
PubMed1996

Buckwheat protein extract suppression of the growth depression in rats induced by feeding amaranth (Food Red No. 2).

Dietary fiber has an ameliorative effect on the toxicity of amaranth (Food Red No. 2). To test the possibility that a buckwheat protein extract (BWPE) has dietary fiber-like activity by virtue of its low digestibility, we examined the influence of BWPE on amaranth toxicity in rats. The results show that BWPE-containing diet suppressed the growth depression induced by the dietary addition of 5% amaranth.

Amaranth Dye↗
PubMed1996

Comparison of the response of serum ceruloplasmin and cholesterol, and of tissue ascorbic acid, metallothionein, and nonprotein sulfhydryl in rats to the dietary level of cystine and cysteine.

The effects were compared of the addition of graded levels of L-cystine and of L-cysteine (0.3, 3, or 5%) to a 10% casein diet on several metabolic parameters in rats. The growth-promoting effect of cystine was equivalent to that of cysteine. Supplementation of these two amino acids elevated serum cholesterol, liver ascorbic acid, liver nonprotein sulfhydryl (SH) and kidney metallothionein, and reduced the activity of serum ceruloplasmin. The responses of serum cholesterol, liver nonprotein SH, and serum ceruloplasmin to cystine were greater than of those to cysteine. When the basal diet was supplemented with 0.3% of these amino acids, the elevation of liver ascorbic acid by cystine supplementation was less than that by cysteine supplementation. However, when supplemented with 5% of these amino acids, the elevation of liver ascorbic acid by cystine was greater than that by cysteine. There was no difference in the influence of cystine and cysteine on kidney metallothionein. This study demonstrates that dietary cystine and cysteine had the same influence on growth, but had a differential influence on such metabolic parameters as liver nonprotein SH, serum ceruloplasmin, serum cholesterol, and tissue ascorbic acid.

Animals↗
PubMed1996

Age-related alteration of pancreatic beta-cell function. Increased proinsulin and proinsulin-to-insulin molar ratio in elderly, but not in obese, subjects without glucose intolerance.

OBJECTIVE: To determine the secretion of insulin, C-peptide, and proinsulin after oral glucose loading in healthy elderly subjects compared with middle-aged subjects with and without obesity and with NIDDM. RESEARCH DESIGN AND METHODS: Subjects fell into four groups: nonobese middle-aged normal control subjects (CNT group; n = 38, 40-64 years old); obese normal subjects (OB group; n = 18, 40-64 years old); nonobese NIDDM subjects (NIDDM group; n = 28, 40-64 years old); and nonobese elderly subjects (OL group; n = 17, 65-92 years old). Insulin, C-peptide, and proinsulin were determined by radioimmunoassay in plasma samples taken at 0, 30, 60, and 120 min during a 75-g oral glucose tolerance test (OGTT). RESULTS: There were no differences in plasma glucose during the OGTT among the three nondiabetic groups. Hyperinsulinemia was significant in the OB and NIDDM groups but not in the OL group. On the other hand, absolute hyperproinsulinemia was significant in the OL and NIDDM groups compared with the CNT group. Increased proinsulin was rather dominant in the OL group, especially late after glucose loading. Molar ratios of proinsulin to insulin or C-peptide thus were significantly higher in the OL and NIDDM groups. CONCLUSIONS: Alteration of pancreatic beta-cell function independent of that seen with NIDDM occurred in relation to aging. This may be a predisposing factor to the development of impaired glucose tolerance or NIDDM in elderly subjects, that is, independent of obesity.

Adult↗
PubMed1996

Feeding of excessive cystine and cysteine enhances defects of dietary copper deficiency in rats by differential mechanisms involving altered iron status.

We have reported that excess cystine feeding exaggerates the defects of dietary copper deficiency in rats by a mechanism not involving oxidative stress and altered copper status. This study was conducted to examine whether this exacerbation is caused by a mechanism involving altered iron status and to compare the influences of cystine and cysteine feeding on the defects of copper deficiency. Male Wistar rats were fed copper-adequate or copper-deficient diet with supplementation of L-cystine or L-cysteine (2%) for 10 days or 21 days. Copper-deficient diet increased heart weight, caused anemia, reduced plasma iron and elevated liver iron. These defects were exacerbated by supplemental cystine. Cysteine feeding also exacerbated the defects of dietary copper deficiency including anemia, increased heart weight, and reduced plasma iron, although cysteine feeding had no influence on liver iron concentration. Supplemental cysteine reduced apparent absorption of iron, while supplemental cystine did not. These results suggest that cystine feeding enhances the defects of copper deficiency by a mechanism involving impaired mobilization of iron from liver into blood, and that cysteine feeding enhances the defects of copper deficiency by a mechanism involving reduced intestinal absorption of iron.

Anemia↗
PubMed1996

[Clinical studies on autologous blood transfusion].

To study the present status of blood transfusion in head and neck surgery, we investigated recent cases of intraoperative transfusion in our department. In addition, we present our autologous blood transfusion cases, presently involved in an ongoing clinical trial for patients with head and neck cancer in our department which began in 1989. 1. Investigation of intraoperative blood transfusion cases There were 37 cases of intraoperative blood transfusion among 677 cases who underwent surgery under general anesthesia during the period from May, 1991 to December, 1993. We divided these 37 cases into three groups according to the amount of intraoperative blood loss: less than 600ml (10 cases), more than 600ml and less than 1200ml (11 cases), and more than 1200ml (16 cases). Average amounts of intraoperative blood transfusion in each group were 195ml, 475ml and 780ml, respectively. As we noted that most of these 37 cases received a blood transfusion of less than 800ml, the majority needing intraoperative blood transfusion during head and neck surgery are potential candidates for autologous blood transfusion. Therefore, we have promoted autologous blood transfusion for intraoperative blood transfusion in head and neck surgery. Thus, the patients undergoing intraoperative autologous blood transfusion increased to seven annually as of 1994. 2. Clinical studies on autologous blood transfusion Among 677 cases of head and neck surgery conducted during a six year period (1989-1994), we experienced ten cases of autologous blood transfusion. For the prevention of anemia due to repeated blood withdrawal, we administered an iron preparation. Patients who preoperatively showed a low value of Hb (less than 11g/ dl) received intravenous drip infusion of erythropoietin. Since some patients selected for autologous blood transfusion, who also received neo-adjuvant chemotherapy and preoperative radiotherapy, exhibited a generally chronic anemia status, an iron preparation and erythropoietin should be preoperatively administered in combination.

Adolescent↗
PubMed1996

[Diagnostic values and limitations of conventional urodynamic studies (uroflowmetry.residual urine measurement.cystometry) in benign prostatic hypertrophy].

PURPOSE AND METHODS: Diagnostic values and limitation of conventional urodynamic study (UDS) were assessed in 380 patients with benign prostatic hypertrophy (BPH), in terms of uroflowmetry, measurement of postvoid residual urine and cystometry. RESULTS: Maximum and average flow rate on uroflowmetry improved with increasing voided volume. Neither maximum nor average flow rate correlated with size of the prostate, subjective symptom (International Prostate Symptom Score) and bothersomeness for prostatism. Pre-TUR maximum flow rate did not predict outcomes on postoperative flow rate and surgical treatment failures. Uroflowmetry did not differentiate between obstruction and weakness of detrusor contraction. The intraindividual variation of postvoid residual urine was great and the volume of residual urine correlated poorly with subjective symptom, size of the prostate, maximum and average flow rate. On filling cystometry, although uninhibited detrusor contraction was much more frequently observed in patients with urge incontinence as compared with continent patients, there was no significant difference in other parameters between the two groups. Every parameter on cystometry did not correlate with nocturnal frequency. Postoperative persistence of urge incontinence did not correlate with the bladder volume at the first desire to void or at the maximum desire to void, an amplitude of uninhibited detrusor contractions, or bladder compliance. In some cases, evaluation of the intravesical pressure on voiding phase and uroflowmetry was diagnostic of apparent obstruction. CONCLUSIONS: In diagnosis of BPH, conventional UDS has limitation for certain and some caution showed be taken in interpretation of the data. However, since conventional UDS provides important and objective information on obstruction and detrusor function, which are independent of subjective symptom and prostate size, these should be necessary in diagnosis, determination of treatment options and evaluation of treatment outcomes in BPH.

Humans↗
PubMed1996

[Percutaneous ethanol injection therapy for small hepatocellular carcinoma].

Hepatocellular carcinoma is different from other solid tumors. Because of concomitant cirrhosis or multiple lesions, most hepatocellular carcinoma is unresectable. Still worse, hepatocellular carcinoma frequently recurs after surgical resection; the 5-year cumulative recurrence rate is 70-90% even after curative hepatectomy. The situation is similar in small hepatocellular carcinoma 2 cm or less in diameter. Thus, non-surgical treatment plays an important role. At present, we think that percutaneous ethanol injection therapy (PEIT) is best for the treatment of hepatocellular carcinoma because of its local curativity, minimal adverse effect on liver function, and the easy feasibility of repeated treatment for recurrence. We have recently treated about 85% of hepatocellular carcinoma cases by PEIT and have achieved satisfactory long-term results. Here we describe our results in PEIT for small hepatocellular carcinoma. By the end of December 1995, we performed PEIT on 410 patients with hepatocellular carcinoma. Among them, 140 patients were diagnosed as having small hepatocellular carcinoma 2 cm or less in diameter. The 1-, 3-, 5-, 7-, and 10-year survival rates of the 140 patients were 93%, 73%, 55%, 51%, and 32%, respectively. Furthermore, in 83 patients who had a single, small hepatocellular carcinoma 2 cm or less in diameter, the 1-, 3-, 5-, 7-, and 10-year survival rates were 92%, 82%, 72%, 66%, and 66%, respectively. Thus PEIT achieved satisfactory long-term survival rates in the treatment of small hepatocellular carcinoma.

Adult↗
PubMed1996

[In vitro activities of sulopenem, a new parenteral penem, against anaerobes].

In vitro activities of sulopenem, a novel parenteral penem, was compared with those of imipenem, flomoxef, cefuzonam, cefoperazone and sulbactam/ampicillin against 66 reference strains (19 genera, 61 species) and 392 recent clinical isolates of anaerobic bacteria and fastidious aerobic bacteria. Sulopenem had a very broad spectrum against anaerobic bacteria. In general, this compound was active against anaerobic reference strains with MICs of < or = 0.78 micrograms/ml, while being the least active against Bifidobacterium spp. and less active than imipenem against Lactobacillus spp. Sulopenem was more active against Bacteroides fragilis isolates than imipenem and had the highest activities against Bacteroides thetaiotaomicron, Prevotella intermedia, Porphyromonas gingivalis, Fusobacterium spp. and Peptostreptococcus spp. among the antibiotics tested. Sulopenem was not hydrolyzed by oxyiminocephalosporinase type 1 produced by B. fragilis GAI-0558, GAI-7955 and GAI-10150 and its stability was comparable to imipenem. Its susceptibilities to hydrolysis by a metallo-beta-lactamase from B. fragilis GAI-30144 was less than imipenem. Sulopenem (120 mg/kg, 3 times a day for 4 days) was as effective as imipenem/cilastatin against a mixed intraabdominal mice infection due to E. coli and B. fragilis. Sulopenem (20 mg/kg twice a day for 5 days) did not induce an overgrowth of Clostridium difficile in the caecum of mice.

Ampicillin↗
PubMed1996

Low calcium (1.25 mmol/L) dialysate can normalize relative hypoparathyroidism in CAPD patients with low bone turnover.

Recently, several reports have suggested that there is a higher incidence of low turnover bone in the absence of aluminium exposure in peritoneal dialysis patients than in hemodialysis patients. Relative hypoparathyroidism with mild hypercalcemia, induced by a positive calcium balance, is considered to be one of the major causes of this disorder. Thus, we recruited 9 continuous ambulatory peritoneal dialysis (CAPD) patients with relative hypoparathyroidism and low bone turnover [intact parathyroid hormone (iPTH) < 50 pg/mL, intact osteocalcin < 10.0 ng/mL] who had been prescribed 1.75 mmol/L calcium (Ca) dialysate for 5.0 +/- 0.3 years. They were then treated by low Ca (1.25 mmol/L) dialysate for nine months without vitamin D and aluminum administration. Intact PTH and bone metabolic markers [intact osteocalcin, alkaline phosphatase (ALP)] were measured every three months. Intact PTH levels increased from 21.1 +/- 3.8 to 159.2 +/- 32.8 pg/mL after the first three months; thereafter, those levels were maintained at around 150 pg/mL. On the other hand, intact osteocalcin levels rose consecutively from 6.7 +/- 1.2 to reach 22.0 +/- 3.8 ng/mL after nine months. Interestingly, the pattern of time course changes between PTH and intact osteocalcin was different. ALP activity did not change during the nine-month period. Corrected serum calcium was significantly decreased (p < 0.001) to approximately 0.25 mmol/L within one month, and the level remained almost the same thereafter. The serum phosphate level did not change without adjusting the original dose of calcium carbonate as a phosphate binder. We concluded that low Ca dialysate (1.25 mmol/L) is effective for the treatment of CAPD-related hypoparathyroidism with low bone turnover.

Aged↗
PubMed1996

[Laparoscopic pelvic lymphadenectomy for localized prostate cancer].

We report the clinical results and efficacy of laparoscopic pelvic lymphadenectomy for localized prostate cancer. This procedure was followed by radical prostatectomy, when metastasis was not found in the frozen section, and by optional treatment, such as transurethral resection (TUR) or castration, other than radical prostatectomy when metastasized nodes were found. We performed transperitoneal laparoscopic lymphadenectomy on 30 patients and extraperitoneal approach on 20 between April, 1992 and September, 1995. The patients were between 52 and 78 years old. Nineteen, patients had stage B1, 17 stage B2 and 14 stage C cancer. Bilateral obturator nodes were dissected. We could not perform laparoscopic lymphadenectomy on two patients because of adhesion. The average operation time and blood loss were 166 minutes and 151 ml, respectively, in the transperitoneal group, while 142 minutes and 126 ml in the extraperitoneal group. The average number of removed nodes was 12 in the transperitoneal group and 10 in the extraperitoneal group. The extraperitoneal approach is a safer and useful procedure. Nodal metastasis were found in 12 patients by frozen section. Additional positive nodes were found in 7 patients by a further study. Two were not harvested laparoscopically and 5 were ascertained only by permanent section. Therefore, the two-staged operation might be preferable. Nodal metastasis was likely to be found in localized prostate cancer patients with clinical stage C, poorly differentiated cancer, or prostatic specific antigen density (PSAD) over 0.5 ng/ml/ml. Laparoscopic pelvic lymphadenectomy might be indicated for these cases.

Aged↗
PubMed1996

[A case of MPO-ANCA related vasculitis with transient leukoencephalopathy and multiple cerebral hemorrhage].

Recently, it has become clear that anti-neutrophil cytoplasmic autoantibody (ANCA) can be detected in patients with idiopathic necrotizing and crescentic glomerulonephritis or necrotizing angitis, and can be used as a serological marker for vasculitic syndrome. Described is a 56-year-old woman who had peripheral neuropathy, intestinal hemorrhage, generalized tonic-clonic convulsions, during the course of a rapidly progressive glomerulonephritis syndrome due to myeloperoxidase (MPO)-ANCA related vasculitis. The cranial MRI showed transient leukoencephalopathy in the parieto-occipital lobes bilaterally. The following MRI revealed multiple cortical and subcortical hemorrhage in the left occipital and right temporal lobe. The neurologic examination showed a slight left hemiparesis and a right homonymous hemianopsia, but, she experienced no subjective symptoms. In the case of MPO-ANCA related vasculitis, there is the possibility of intracranial disorders seen as this case. Thus, MPO-ANCA in related vasculitis should be always considered as a differential diagnosis in cases of transient localized leukoencephalopathy or cortical-subcortical cerebral hemorrhage.

Antibodies, Antineutrophil Cytoplasmic↗