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N Kato

Publications and source records attributed to N Kato.

At least 649 records · Page 36Linked to original sources
PubMed1993

Immunogenetic and clinical characterization of slowly progressive IDDM.

OBJECTIVE: To examine the clinical and immunogenetic heterogeneity of IDDM. RESEARCH DESIGN AND METHODS: We divided 207 IDDM patients into groups based on the interval from clinical onset to initiation of insulin therapy: group A (< 3 mo, acute clinical-onset group, n = 134), group B (3-12 mo, intermediate group, n = 31), and group C (> or = 13 mo, slowly progressive group, n = 42). Immunogenetic and clinical markers were compared between group A and group C. RESULTS: The mode age of onset was higher in group C (52 yr) than group A (10 yr). Group C had a higher prevalence of islet cell antibodies (42.9%, 18 of 42) than group A (25.4%, 34 of 134, P = 0.05). Serum C-peptide immunoreactivity assayed by radioimmunoassay in response to a 100-g oral glucose tolerance test was significantly higher in group C than in group A. Group C patients were also more likely to have a family history of NIDDM (26.1%, 11 of 42) among their first-degree relatives than group A patients (11.2%, 15 of 134, P = 0.039). The prevalences of family history of IDDM and endocrine autoimmune diseases were not different between groups C and A. The frequency of complications of endocrine autoimmune disease was not different between group A (6.7%, 9 of 134) and group C (2.3%, 1 of 42). Significant associations with two class I major histocompatibility complex antigens (HLA-A24 and -Bw54) and one class II antigen (HLA-DR4) were observed in group A. Group A patients were associated with three diabetogenic HLA-DQ haplotypes including DQA1*0301-DQB1*0401, DQA1*0301-DQB1*0302, and DQA1*0301-DQB1*0303. In contrast, group C lacked the association with class I antigens, although HLA-DR4 and HLA-DQA1*0301-DQB1*0401 were more common in this group than in control subjects. CONCLUSIONS: These results indicate that the clinical subtype with slowly progressive course (slowly progressive IDDM) has distinct findings including late-age onset, high prevalence of islet cell antibodies, preserved beta-cell function, and high family history of NIDDM. An additive effect of class I and class II major histocompatibility complex antigens is suggested as an explanation for the acute clinical manifestations and more severe beta-cell destruction in group A patients.

Adolescent↗
PubMed1993

Experimental murine model for autoimmune myocarditis using Klebsiella pneumoniae O3 lipopolysaccharide as a potent immunological adjuvant.

Experimental autoimmune myocarditis could be produced in mice by repeated injection of syngeneic heart extract together with Klebsiella pneumoniae O3 lipopolysaccharide (KO3 LPS) as a powerful adjuvant. Histological changes in the cardiac lesions were characterized by infiltration with mononuclear cells in the myocardium, degeneration and loss of myocardial fibers, and replacement of granulation tissues. No such cardiac lesions were produced in mice receiving injections of heart extract alone or KO3 LPS alone. Development of the autoantibody and the delayed type-hypersensitivity (DTH) against syngeneic heart extract was found in mice immunized repeatedly with the mixture of heart extract and KO3 LPS. Moreover, definite cardiac lesions were produced in normal recipient mice by transfer of sensitized spleen cells from hyperimmunized mice. Therefore, it was suggested that those cardiac lesions were caused by the autoimmune mechanism. Our methodology provided a new experimental murine model for autoimmune myocarditis.

Adjuvants, Immunologic↗
PubMed1993

Responses of tissue ascorbic acid and of serum cholesterol, alpha-tocopherol, and ceruloplasmin in rats to dietary level of cystine.

The present study was conducted with growing rats to examine effects of addition of 0.3, 1.0, 2.5, and 5% L-cystine to 10 or 25% casein diet on tissue ascorbic acid and on serum cholesterol, alpha-tocopherol, and ceruloplasmin activity. Addition of 0.3-1% cystine to 10% casein diet caused the maximum growth and addition of 5% cystine to 25% casein diet depressed the growth. Increases in liver levels of ascorbic acid and in serum levels of cholesterol and alpha-tocopherol were observed with addition of 5% cystine to 10 and 25% casein diets as compared to the diets without addition of cystine. Addition of 0.3-5% cystine to 10% casein diet and addition of 5% cystine to 25% casein diet caused a decreased activity of serum ceruloplasmin. The changes in liver ascorbic acid, serum cholesterol, and serum alpha-tocopherol and in ceruloplasmin activity by dietary cystine correlated with the changes in liver levels of non-protein sulfhydryl.

Animals↗
PubMed1993

[A case of pulmonary malignant fibrous histiocytoma in which cytokines exhibited high value by subculture].

A case of pulmonary malignant fibrous histiocytoma (PMFH) was experienced, and the tumor was subcultured in nude mice. Tumor cells were resected and cultured in medium containing RPMI 1640 and 10% FCS. As a result, in both the nude mice and in the cytokines, as supernatant in the tumorous cells, cultured using ELISA method or RIA method. IL-1 alpha, beta, TNF-alpha, GM-CSF, and in particular IL-6 and G-CSF, exhibited markedly raised values. Clinically, the leukocyte and platelet counts on admission showed markedly elevated values of 27,500/mm3 and 48.3 x 10(4)/mm3, respectively, and the erythrocyte sedimentation rate was increased of 67 mm in 1 hour. These findings corresponded to the physiological findings of elevated IL-6 and G-CSF levels. We have experienced two further patients with PMFH, in whom serum levels of IL-6 and G-CSF were markedly elevated. Some reports have been published on cytokine-generating tumors, but there is no report about cytokine generation in PMFH. We report this patient's very interesting clinical course, together with elevation of cytokine generation.

Adult↗
PubMed1993

Mechanisms of beta-adrenergic facilitation of LTP in rat visual cortex.

Mechanisms by which the beta-adrenergic agonist isoproterenol facilitates induction of long-term potentiation (LTP) were studied in visual cortex slices of adult rats. The amplitude of postsynaptic potentials elicited by white matter stimulation was not potentiated by tetanization in normal medium, but was in isoproterenol-containing medium, albeit modestly. This LTP induction was prevented by co-application of either an N-methyl-D-aspartate (NMDA) receptor antagonist, D-(-)-2-amino-5-phosphono-pentanoate, or an L-type Ca2+ channel antagonist, nifedipine. In medium containing the L-type Ca2+ channel agonist BAY K8644, but not isoproterenol, tetanization resulted in LTP. These results suggest that, in visual cortex slices from adult rats, LTP induced under isoproterenol perfusion depends on both NMDA receptors and voltage-sensitive Ca2+ channels.

2-Amino-5-phosphonovalerate↗
PubMed1993

Effect of age on the development or progression of albuminuria in non-insulin-dependent diabetes mellitus (NIDDM) without hypertension.

To study the relationship between aging and development of diabetic nephropathy, we studied the time until the development of microalbuminuria in old onset (> 50 years old, n = 21) and young onset (< 40 years old, n = 26), normotensive NIDDM patients. Microalbuminuria which is associated with the early stage of diabetic nephropathy was defined as urinary albumin index (UAI; mg/g.creatinine) of more than 10mg/g.creatinine, using timed overnight urine. In these two groups, there were no significant differences in duration of diabetes, observation periods, glycemic control, systolic diastolic blood pressure, body mass index and creatinine clearance at the time of the last observation. Mean UAI +/- standard deviation of the two groups were 37.5 +/- 78.2 mg/g.cr and 93.0 +/- 127.2 mg/g.cr in the young onset group and the old onset group, and prevalences of microalbuminuria were 38% and 76% in the young onset and old onset group, respectively. Thus, UAI and prevalence of microalbuminuria in the old onset group are significantly higher than those of the young onset group (P < 0.05). These results suggest that aging, in itself, is one of the significant risk factors for the development of diabetic nephropathy in NIDDM patients.

Age of Onset↗
PubMed1993

A murine model of experimental autoimmune lens-induced uveitis using Klebsiella O3 lipopolysaccharide as a potent immunological adjuvant.

Experimental autoimmune uveitis and finally panophthalmitis could be produced in mice by repeated immunization of syngeneic eyeball extract mixed with Klebsiella O3 lipopolysaccharide (KO3 LPS) as a powerful immunological adjuvant. No ocular lesions were produced in mice given eyeball extract emulsified in complete Freund's adjuvant (CFA), KO3 LPS alone or eyeball extract alone. Histopathological changes in the ocular lesions at the early stage after the second or tertiary immunization were characterized by infiltration with inflammatory cells in the ciliary body and iris. The iridocyclitis was followed by extensive infiltration of polymorphonuclear leucocytes (PMN) into the cornea, lens and the surrounding tissues after repeated immunization. Finally, these areas were replaced by granulomatous tissues infiltrated with mononuclear cells. On the other hand, the structure of the retina and sclera was partially preserved. Those mice exhibited production of autoantibodies and development of the delayed-type hypersensitivity (DTH) to syngeneic eyeball extract. Moreover, ocular lesions could be produced in normal recipient mice by transfer of sensitized lymphocytes from hyperimmunized mice. Therefore, it was suggested that the ocular lesions produced by repeated immunization with the mixture of eyeball extract and KO3 LPS were due to the autoimmune mechanism. This might be useful to model immunological phenomena in the pathogenesis of human phacoantigenic uveitis.

Adjuvants, Immunologic↗
PubMed1993

Involvement of protein kinase C in proliferative response of osteoblastic cell lines stimulated with prostaglandin E2.

The proliferative action of prostaglandin E2 in a rat osteoblastic cell line was studied. Prostaglandin E2 has a crucial effect on bone remodeling process and is shown to stimulate protein and DNA synthesis in serum depleted condition. This reaction is completely inhibited by protein kinase C inhibitors, suggesting that protein kinase C activation induced by prostaglandin E2 is involved in the proliferative response of osteoblast cells.

Animals↗
PubMed1993

[Sequence diversity and variability in the putative envelope proteins including hypervariable regions of hepatitis C virus].

Hepatitis C virus (HCV) genomes show sequence diversities among virus isolates. In particular, the putative envelope region encoding gp35 and gp70 shows on extensive sequence diversity in the whole viral genome. We identified two hypervariable regions [HVR1 (27 amino acids) and HVR2 (7 amino acids)] in the N-terminal region of gp70 of the HCV-II genotype. In the HCV-I genotype, extensive diversity of amino acid sequence in HVR1 is also observed in the same region (21 amino acids), but such diversity in HVR2 is not clearly observed like HCV-II genotype. In addition, the alteration of amino acids in HVR1 was also observed in patients with chronic hepatitis. It is suggested mutation in HVR1 is involved in the mechanism of persistent HCV infection.

Amino Acid Sequence↗
PubMed1993

Quantification of hepatitis C virus by competitive reverse transcription-polymerase chain reaction: increase of the virus in advanced liver disease.

We developed a quantitative method of hepatitis C virus RNA by competitive reverse transcription-polymerase chain reaction. With this method, 36 patients with type C chronic liver disease were analyzed for the copy number of circulating hepatitis C virus in 50 microliters of serum. The amounts of hepatitis C virus RNA ranged from 10(1) to 10(7) copies in the 36 patients. The average amount of hepatitis C virus RNA was 10(3.3 +/- 2.2) copies in 12 patients with chronic persistent hepatitis, 10(5.7 +/- 1.6) copies in 12 patients with chronic active hepatitis and 10(6.0 +/- 1.6) copies in 12 patients with cirrhosis (including 4 patients with hepatocellular carcinoma). The amount of hepatitis C virus RNA in serum was significantly less in patients with chronic persistent hepatitis than in patients with chronic active hepatitis or cirrhosis (p < 0.01), and it tended to increase according to the progression of histopathological changes of the liver. Furthermore, it was revealed that the amount of hepatitis C virus RNA became exponentially larger as the term from infection became longer. Quantification of hepatitis C virus RNA by competitive reverse transcription-polymerase chain reaction may have many applications for the study of clinical features of hepatitis C virus infection.

Adult↗
PubMed1992

Characterization of hypervariable regions in the putative envelope protein of hepatitis C virus.

We previously identified two hypervariable regions [HVR1 (27 amino acids) and HVR2 (7 amino acids)] in the putative envelope glycoprotein (gp70) by comparison of the amino acid sequences of many isolates of the HCV-II genotype. To understand the functional features of these HVRs, using the polymerase chain reaction we analyzed the rate of actual sequence variability in the region including HVR1 and HVR2 of HCV isolated successively at intervals of several months from two patients with chronic C-type hepatitis. In both patients, the amino acid sequence of HVR1, but not HVR2, was found to change dramatically during the observation period (about one amino acid per month). However, no alteration of the amino acid sequence of HVR1 of HCV was observed in a patient in the acute phase of chronic hepatitis. Restriction digestion analysis of sequence diversity showed that a HCV genome with a newly introduced mutation in HVR1 often became the predominant population at the next time of examination. Alterations of amino acids in HVR1 occurred sequentially in the two patients in the chronic phase. These findings suggest that mutations in HVR1 are involved in the mechanism of persistent chronic HCV infection.

Alanine Transaminase↗
PubMed1992

Correlation between the serum level of hepatitis C virus RNA and disease activities in acute and chronic hepatitis C.

The influence of viremia on hepatic injury in patients infected with hepatitis C virus was examined by analysis of the relationship between alanine aminotransferase activity and the amount of hepatitis C virus RNA in sequential serum samples from I untreated patient with acute hepatitis C and 3 untreated patients with chronic hepatitis C. Semiquantitative analysis by the competitive-reverse-transcription/polymerase-chain-reaction method indicated that the quantity of hepatitis C virus RNA in the serum affected the disease activities of acute and chronic hepatitis C through their natural clinical courses in all these patients. The nucleotide sequence encoding the putative envelope region of the viral genome in the patient with acute hepatitis C was examined. Blood samples taken serially at 2 times of exacerbation of the hepatitis revealed 2 nucleotide mutations, resulting in changes of predicted amino acid residues. This finding suggests that nucleotide mutations in the envelope region of the viral genome may be responsible for the recurrent hepatic injury attributed to recurrence of viremia in patients with hepatitis C. From these aspects, the serial divergence of the virus genome in infected individuals, especially in the region encoding the viral envelope protein, may possibly play an important role in developing chronic infection of hepatitis C virus.

Amino Acid Sequence↗
PubMed1992

Cloning and sequence analysis of the StsI restriction-modification gene: presence of homology to FokI restriction-modification enzymes.

StsI endonuclease (R.StsI), a type IIs restriction endonuclease found in Streptococcus sanguis 54, recognizes the same sequence as FokI but cleaves at different positions. A DNA fragment that carried the genes for R.StsI and StsI methylase (M.StsI) was cloned from the chromosomal DNA of S.sanguis 54, and its nucleotide sequence was analyzed. The endonuclease gene was 1,806 bp long, corresponding to a protein of 602 amino acid residues (M(r) = 68,388), and the methylase gene was 1,959 bp long, corresponding to a protein of 653 amino acid residues (M(r) = 76,064). The assignment of the endonuclease gene was confirmed by analysis of the N-terminal amino acid sequence. Genes for the two proteins were in a tail-to-tail orientation, separated by a 131-nucleotide intercistronic region. The predicted amino acid sequences between the StsI system and the FokI system showed a 49% identity between the methylases and a 30% identity between the endonucleases. The sequence comparison of M.StsI with various methylases showed that the N-terminal half of M.StsI matches M.NIaIII, and the C-terminal half matches adenine methylases that recognize GATC and GATATC.

Amino Acid Sequence↗
PubMed1992

An analogue of Joro spider toxin selectively suppresses hippocampal epileptic discharges induced by quisqualate.

The anticonvulsant effect of 1-naphthylacetyl spermine, an analogue of Joro spider toxin (JSTX), was studied against seizures induced by quisqualate (QUIS), a non-NMDA agonist, as assessed electrophysiologically and behaviorally in freely moving rats. Electrodes were implanted into right dorsal hippocampus and an injection cannula for drugs into right ventricle. The pretreatment with JSTX analogue significantly inhibited both of QUIS-induced hippocampal discharges (80-11%) and generalized tonic clonic seizures (100-33%) in a dose-dependent manner, whereas JSTX had no effect on seizures induced by quinolinate, a NMDA agonist. The paper provides the first direct evidence that the JSTX analogue exerts a potent and selective suppression of hippocampal epileptic discharges mediated by non-N-methyl-D-aspartate (non-NMDA) receptors.

Animals↗
PubMed1992

A new type of hepatitis C virus in patients in Thailand.

Partial nucleotide sequences in the tentative NS5 region of the hepatitis C viral genome obtained from patients with chronic hepatitis in Thailand were analyzed by reverse transcription followed by the polymerase chain reaction. Of ten samples studied, four showed low homologies to any known type of HCV: the homologies of the nucleotide sequences of these clones with HCV-J, -US, -K2a and -K2b were 66.5-69.1%, 66.5-68.2%, 61.2-64.1% and 64.4-66.2%, respectively, and the homologies of their deduced amino acids sequences were 71.7-75.2%, 71.7-75.2%, 69.0-72.6% and 69.9-73.5%, respectively. These four clones were classified a new distinct type of HCV, named HCV-T. Moreover, the nucleotide and amino acid sequence homologies of the four HCV-T clones showed that the HCV-T type could be classified into two genotypes, HCV-Ta and HCV-Tb.

Amino Acid Sequence↗
PubMed1992

Organization of association projections from area 17 to areas 18 and 19 and to suprasylvian areas in the cat's visual cortex.

Cells in area 17 that are labelled by single, discrete injections of retrogradely transported tracers into extrastriate visual areas are discontinuously distributed in dense patches. In this study we made multiple, closely spaced injections of fluorescent dyes into extrastriate areas, to generate large deposits that would reveal whether the distributions of corticocortical cell bodies in area 17 are truly patchy or appear clustered only after small injections. By injecting a different tracer into each extrastriate area, or group of areas, we examined the spatial relationships between the populations of association cells. All deposits of tracers in areas 18, 19, or suprasylvian cortex, irrespective of size, label cells in a series of clusters in topographically related parts of area 17. We conclude that the complete populations of cells in area 17 that project to areas 18, 19, and the lateral suprasylvian cortex are all genuinely distributed in a patchy fashion. There appears to be a complex relationship between the sets of association cells projecting to different extrastriate regions: they do not completely overlap, only partially, and share some cortical zones but not others. In these experiments, only tiny percentages (2-5%) of labelled cells in the overlapping regions were filled with both tracers, suggesting that very few association cells in area 17 project to more than one of the extrastriate areas we studied. By comparing the dimensions of each injection site and of the labelled region in area 17, we estimated the extent of the convergence from area 17 to areas 18, 19, and posteromedial suprasylvian areas in retinotopic terms. The functional convergence was very similar in these pathways.

Amidines↗