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Biomedical subjects

S Kashiwazaki

Publications and source records attributed to S Kashiwazaki.

At least 19 recordsLinked to original sources

Antibodies in rabbits immunized with cationized IgG react with histones H3 and H4.

OBJECTIVE: Rabbits immunized with cationized rabbit IgG develop antinuclear antibodies. This study was aimed at identifying the reactive antigens. METHODS: Rabbits were immunized with homotypic or allotypic IgG that were physicochemically altered to produce positively charged dimethylpropanamide (polycationic) side chains. RESULTS: Seven of 11 rabbits injected with cationized IgG produced antinuclear antibodies detected by indirect immunofluorescence. By enzyme-linked immunosorbent assay, these were IgG antibodies reacting with histone (H3-H4)2 tetramer and with individual histone polypeptides H3 and H4. The antihistone antibodies were absorbed by cationized IgG but not by normal IgG. CONCLUSION: Cationized IgG appears to possess antigenic determinants of sufficient similarity to produce antibody responses cross-reactive with histones H3 and H4.

Animals

Production of interleukin 8 by cultured synovial cells in response to interleukin 1 and tumor necrosis factor.

Both interleukin 1 alpha (IL-1 alpha) and tumor necrosis factor alpha (TNF alpha) stimulated the production of interleukin 8 (IL-8) by synovial cells in time and dose dependent manners. Enhanced chemotactic activity of polymorphonuclear cells (PMN) in culture supernatants of synovial cells was neutralized with anti-IL-8 antibody, thus showing synovial cells to be capable of secreting IL-8 which may contribute to PMN accumulation in rheumatoid inflamed joints.

Cells, Cultured

Accelerated purine nucleotide degradation by anaerobic but not by aerobic ergometer muscle exercise.

The exact conditions under which exercise causes purine nucleotide degradation are not well understood. We determined plasma hypoxanthine and uric acid levels serially in eight individuals during ergometer muscle exercise. When the load was increased gradually by 15 W/min, plasma hypoxanthine was elevated only after the status exceeded the anaerobic threshold (AT), as determined by analysis of expired gas. Nonstrenuous ergometer exercise, which kept the status continuously below the AT, induced neither blood lactic acid nor plasma hypoxanthine elevation. These results suggest that the AT is also the threshold for the acceleration of purine nucleotide degradation. Muscle exercise to a degree that does not exceed the AT does not cause major purine nucleotide degradation, and, therefore, is expected to be beneficial for patients with gout and/or hyperuricemia.

Adult

Sequence analysis of the 3'-terminal halves of RNA 1 of two strains of barley mild mosaic virus.

DNA complementary to the 3'-terminal halves of RNA 1 of two strains of barley mild mosaic virus (BaMMV) from Japan, BaMMV-Ka1 and BaMMV-Na1, was cloned and sequenced. The sequences start within a single long open reading frame (ORF), and are followed by 337 and 338 3' non-coding nucleotides, for BaMMV-Ka1 and BaMMV-Na1 respectively. The two strains have 88% nucleotide identity in the ORFs and 92% identity in the non-coding regions. The putative ORF products contain the capsid proteins at the C termini, as indicated by amino acid sequence analysis, and two putative non-structural proteins are arranged in the same manner as in RNA 1 of barley yellow mosaic virus (BaYMV). The deduced capsid proteins of BaMMV-Ka1 and BaMMV-Na1 each contain 251 amino acids and have 94% sequence identity, which is compatible with their close serological relationship. Most of the sequence differences between the two capsid proteins are found in the N-terminal region, and might explain their serological differences. Significant sequence similarities of the capsid proteins of the two BaMMV strains (37 and 35% respectively) with that of BaYMV, and their marginal similarities (21 to 26%) to the capsid proteins of aphid-borne or mite-borne potyviruses support the classification of BaMMV and BaYMV as distinct members of the same virus group, which is separate from the group(s) containing aphidborne or mite-borne potyviruses.

Amino Acid Sequence

Only three mutations account for almost all defective alleles causing adenine phosphoribosyltransferase deficiency in Japanese patients.

We analyzed mutant alleles of adenine phosphoribosyltransferase (APRT) deficiency in Japanese patients. Among 141 defective APRT alleles from 72 different families, 96 (68%), 30 (21%), and 10 (7%) had an ATG to ACG missense mutation at codon 136 (APRT*J allele), TGG to TGA nonsense mutation at codon 98, and duplication of a 4-bp sequence in exon 3, respectively. The disease-causing mutations of only four (3%) of all the alleles among Japanese remain to be elucidated. Thus, a diagnosis can be made for most of the Japanese APRT-deficient patients by identifying only three disease-causing mutations. All of the different alleles with the same mutation had the same haplotype, except for APRT*J alleles, thereby suggesting that alleles with the same mutation in different families were derived from the same ancestral gene. Evidence for a crossover or gene conversion event within the APRT gene was observed in an APRT*J mutant allele. Distribution of mutant alleles encoding APRT deficiency among the Japanese was similar to that seen in cystic fibrosis genes among Caucasians and Tay-Sachs genes among the Ashkenazi Jews.

Adenine Phosphoribosyltransferase

Mixed connective tissue disease associated with protein losing enteropathy: successful treatment with intravenous cyclophosphamide therapy.

A patient with mixed connective tissue disease who developed protein losing enteropathy (PLE) is described. The PLE and other symptoms improved dramatically after monthly intravenous administration of 700 mg/day cyclophosphamide three times combined with oral prednisolone, while they were ineffective to the treatment with intravenous methyl-prednisolone 500 mg per day for 3 days. The serum level of CA125 antigen paralleled the severity of symptoms, signs and laboratory data associated with PLE. Thus, pleural effusion, ascites, edema and hypoalbuminemia improved along with the decrease in the level of CA125, suggesting that CA125 might be a marker of the activity of PLE.

Antigens, Tumor-Associated, Carbohydrate

Adult Still's disease with myocarditis and peritonitis.

A 26-year-old woman had myocarditis and peritonitis during an acute multisystem attack of Still's disease. To our knowledge, these complications are rare manifestations of adult Still's disease. Treatment with high-dose adrenocorticosteroids was rapidly successful in controlling these manifestations.

Adult

[Eosinophilia-myalgia syndrome].

Eosinophilia-myalgia syndrome (EMS) is a newly recognized disease, characterized by peripheral eosinophilia with scleroderma-like features. By July 1991, 1543 cases of EMS, including 31 fatal cases, have been reported. Although epidemiologic studies strongly suggest the association of EMS with ingestion of L-tryptophan (LT) containing a contaminant from a single manufacture, the pathogenesis of this disease is not well understood. The insight obtained from the study of EMS may be applicable to scleroderma or eosinophilic fasciitis. Recent advances in the understanding of clinical and pathologic features of EMS are reviewed.

Adolescent

Detection of myeloid precursors (granulocyte/macrophage colony forming units) in the bone marrow adjacent to rheumatoid arthritis joints.

Various cytokines were recently found to be involved in the pathogenesis of rheumatoid arthritis (RA) and particularly, cytokines with hematopoietic activity have been detected in synovial tissues. We counted the number of myeloid precursors in terms of granulocyte/macrophage colony forming units (CFU-GM) and the number of stromal cell progenitors in terms of fibroblast colony forming units (CFU-F) in the tibial bone marrow adjacent to the joints affected by RA (n = 21), osteoarthritis (OA) (n = 10), and trauma (n = 2) using the colony formation unit assay. We also quantitated the amounts of interleukin 1 beta (IL-1 beta), IL-6, and granulocyte/macrophage colony stimulating factor (GM-CSF) in the culture supernatant of synovial tissue explants of these patients by enzyme linked immunosorbent assay (ELISA). The mean number (+/- SEM) of CFU-GM in patients with RA (7.4 +/- 4.9) was greater than that in patients with OA (0.5 +/- 0.2), while CFU-GM was not detected in trauma patients. The number of CFU-GM in the tibial bone marrow of patients with RA correlated well with the amount of IL-1 beta (r = 0.64, p < 0.01), but not with GM-CSF or with IL-6 from synovial tissues. These findings suggest that active bone marrow is present adjacent to the affected joints in patients with RA and that hematopoietic activity is influenced by IL-1 beta produced in nearby synovial tissues.

Aged

Severe progressive erosive arthritis in multicentric reticulohistiocytosis: possible involvement of cytokines in synovial proliferation.

A case of multicentric reticulohistiocytosis complicated by severe progressive erosive arthritis in a 40-year-old man is described. The diagnosis was confirmed by biopsies of the cutaneous nodule and the synovial tissue of the right knee joint. Destructive changes in the multiple joints rapidly progressed and resulted in severe progressive erosive arthritis. Immunohistochemical staining revealed that the histiocytes reacted positively to interleukin 1 beta and platelet derived growth factor B, leading to the speculation that these cytokines may play a role in the synovial proliferation seen in patients with multicentric reticulohistiocytosis.

Adult

[Abnormal findings of magnetic resonance imaging (MRI) in patients with systemic lupus erythematosus involving the brain].

To elucidate the clinical significance of MRI on CNS-SLE, MRI and CT scans were performed in 35 patients with SLE, of 18 patients who had CNS manifestations at the time of MRI examinations. The investigations were also carried out with 17 patients without CNS-SLE. The rate of detection of abnormal findings on MRI in patients with CNS-SLE was 77.2% (14/18), which was high, as compared with the rate of those on CT scans (50%: 9/18). Especially, all of 4 patients with seizure and 3 patients with encephalopathy showed abnormal MRI findings, although respectively 50% and 33.3% of them had abnormal CT scan findings. MRI findings were classified into 4 groups as below: 1) Large focal are as of increased signal intensity at T2 weighted image. These were observed in 2 of 4 patients with seizure and 1 of 3 patients with encephalopathy, which were completely resolved after treatment. 2) Patchy subcortical foci of increased signal intensity at T2 weighted image. These were observed in 11 of 18 CNS-SLE and 7 of 17 without CNS-SLE, which were not detected by CT scan. 3) All of six patients with cerebral infarctions showed high signal intensity areas at T2 weighted image and low signal intensity areas at T1 weighted image. 4) Normal findings were observed in 4 of 18 CNS-SLE (22.2%). We concluded that MRI is useful for the evaluation of CNS-SLE and provides more information than CT scan.

Adolescent

Preliminary criteria for classification of adult Still's disease.

We have attempted to design classification criteria for adult Still's disease by analyzing the data obtained through a multicenter survey of 90 Japanese patients with this disease and of 267 control patients. The proposed criteria consisted of fever, arthralgia, typical rash, and leukocytosis as major, and sore throat, lymphadenopathy and/or splenomegaly, liver dysfunction, and the absence of rheumatoid factor and antinuclear antibody as minor criteria. Requiring 5 or more criteria including 2 or more major criteria yielded 96.2% sensitivity and 92.1% specificity. However, an exclusion process will be needed for an accurate classification, since this disease is relatively rare.

Adolescent

[Adult Still's disease].

Still's disease was reported to be a type of Juvenile Rheumatoid Arthritis (JRA) by Still in 1897. Adult-onset Still's disease is an important clinical entity inducing fever, skin rash and polyarthritis. Spiking fever and rash are characteristic features for early diagnosis. Although chronic polyarthritis is similar to RA, ankylosis of hand joint is characteristic for Still's disease rather than destructive change. Increased ESR, negative autoantibodies, leukocytosis, liver dysfunction and hyperferritinemja are major laboratory findings. A markedly increased level of serum ferritin can be used, not only as an indicator of disease activity, but also as a diagnostic marker of the disease. For therapy, a moderate dose of steroid is the most effective.

Adolescent

Spontaneous degenerative polyarthritis in male New Zealand black/KN mice.

Histopathologic studies and radiographic analysis revealed that male New Zealand black/KN (NZB/KN) mice develop degenerative polyarthritis in the joints of the forepaw and hindpaw beginning at age 2 months. Deposits of autoantibodies were observed on proliferating collagen fibers, nuclei of chondrocytes, and epidermal cells. Increases in the frequency of positivity for rheumatoid factor and anti-type II collagen antibodies and in the level of serum oxidation activity were noted in these mice. The joint disease in male NZB/KN mice was transferable to female NZB/KN mice and male BALB/c mice by intraperitoneal injection of spleen cells from the male NZB/KN mice. This animal model of arthritis will be extremely useful for analyzing not only the pathogenesis of rheumatoid arthritis, but also new strategies for its treatment, since NZB/KN mice, unlike MRL/lpr mice, do not develop severe lupus nephritis or lymph-adenopathy, and therefore have a longer survival period.

Animals

Nucleotide sequence of barley yellow mosaic virus RNA 2.

The sequence of the 3585 nucleotides [excluding the 3' poly(A) tail] of barley yellow mosaic virus (BaYMV) RNA 2 was obtained by analysis of cDNA clones and by direct RNA sequencing. The first initiation codon at nucleotide 155 was followed by a single long open reading frame encoding a protein of 890 amino acids with an Mr of 98,458. Amino acid sequence comparisons indicated that the BaYMV 98K protein contains a region similar to the C-terminal proteinase domain of the potyvirus helper component (HC) protein towards its N terminus, but that it has no sequences that resemble the N-terminal part of the HC protein or other proteins of potyviruses. The data reveal striking differences in genetic organization between BaYMV RNA 2 and the 5'-terminal region of the potyvirus genome, despite a close genetic relationship between BaYMV RNA 1 and the rest of the potyvirus genome.

Amino Acid Sequence