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Biomedical subjects

N Kamatani

Publications and source records attributed to N Kamatani.

At least 19 recordsLinked to original sources
PubMed2001

Activated human T cells directly induce osteoclastogenesis from human monocytes: possible role of T cells in bone destruction in rheumatoid arthritis patients.

OBJECTIVE: To elucidate the direct role of human T cells in the induction of osteoclastogenesis in rheumatoid arthritis (RA), by studying human monocytes and the pathogenetic roles of receptor activator of nuclear factor kappaB ligand (RANKL), RANK, and osteoprotegerin (OPG). METHODS: Synovial tissue obtained at total knee replacement was stained immunohistologically using anti-RANKL, CD3, and CD4 antibodies. Synovial fluid was obtained from patients with RA, osteoarthritis (OA), gout, or trauma. Concentrations of the soluble form of RANKL (sRANKL) and OPG in the synovial fluid were measured by enzyme-linked immunosorbent assay. Activated T cells from peripheral blood mononuclear cells (PBMC) of healthy volunteers were cultured with human monocytes from PBMC. RESULTS: Immunostaining of the synovial tissue of RA patients demonstrated that RANKL-positive cells were detected in a subset of fibroblast-like synoviocytes and infiltrating mononuclear cells. Double immunostaining revealed that RANKL-positive cells were detected in a subset of CD3+ cells and CD4+ cells. An increased concentration of sRANKL and a decreased concentration of OPG were detected in synovial fluid from RA patients. The ratio of the concentration of sRANKL to that of OPG was significantly higher in synovial fluid of RA patients than in synovial fluid of patients with OA or gout. The activated T cells expressing RANKL induced osteoclastogenesis from autologous peripheral monocytes. The role of RANKL in this osteoclastogenetic process was confirmed by dose-dependent inhibition by OPG. CONCLUSION: The present study is the first to demonstrate osteoclastogenesis using human-derived T cells and monocytes. In addition, the present findings suggest that excess production of RANKL by activated T cells increases the level of sRANKL in synovial fluid and may contribute to osteoclastic bone resorption in RA patients.

Antibodies↗
PubMed2001

A novel single-nucleotide polymorphism at the 5'-flanking region of SAA1 associated with risk of type AA amyloidosis secondary to rheumatoid arthritis.

OBJECTIVE: To address whether the gamma haplotype at exon 3 of the SAA1 gene is directly associated with type AA amyloidosis or is merely in linkage with an unknown polymorphism that is primarily associated with disease risk, we examined the SAA1 gene for new polymorphisms. METHODS: We analyzed DNA samples from 44 rheumatoid arthritis (RA) patients with AA amyloidosis (amyloid group), 55 RA patients without AA amyloidosis (RA group), and 58 non-RA healthy subjects (non-RA group). We also examined DNA samples from 50 Caucasians to compare linkage disequilibrium relationships involving SAA1 region polymorphisms between Japanese and Caucasoid populations. RESULTS: We observed 3 novel single-nucleotide polymorphisms (SNPs) in the 5'-flanking region of SAA1: -61C/G, -13T/C, and -2G/A. Comparison of allele frequencies and ratios of individuals with particular alleles between the study groups revealed statistically significant differences between the amyloid and RA groups and between the amyloid and non-RA groups. Statistical analysis revealed that the -13T/C SNP was strongly associated with AA amyloidosis. In addition, we found tight linkage between the -13T allele and the alpha haplotype, rather than the beta haplotype, at exon 3 in the Caucasoid population, while -13T was closely linked to the gamma and beta haplotypes, rather than the alpha haplotype, in the Japanese population. Since the linkage disequilibrium relationship was reversed between the Japanese and Caucasoid populations, different exon 3 haplotypes of SAA1 are found to be associated with the risk of AA amyloidosis in different ethnic groups. CONCLUSION: Our data suggest that the SAA1 -13T allele, rather than SAA1 exon 3 haplotypes, is primarily associated with AA amyloidosis risk.

Amyloidosis↗
PubMed2001

A recurrent large Alu-mediated deletion in the hypoxanthine phosphoribosyltransferase (HPRT1) gene associated with Lesch-Nyhan syndrome.

We identified the identical large genomic deletion in the hypoxanthine phosphoribosyltransferase (HPRT1) gene in two Japanese patients with Lesch-Nyhan (LN) syndrome. This deletion spanned from an Alu sequence in the promoter region to another Alu-sequence in intron 1, a length of 2,969 base pairs including exon 1. In order to ask whether this deletion was a recurrent mutation, we developed a simple alternative method to determine the separate origin of the HPRT1 mutation of the patients as assessed with an apparent mtDNA polymorphism. Considering that an LN syndrome-causing mutation is not transmitted from patient to offspring as LN syndrome is a fatal disease in childhood and that mtDNA is maternally inherited, HPRT1 mutations and mtDNA would be co-transmitted from carrier mother to offspring since both appeared in females. Two bases were different in the hypervariable region I of the mtDNA between the two patients, indicating the separate origin of their mtDNA over at least several thousand years as calculated based on the molecular evolution rate in this region. We thus conclude that the identical deletion found in HPRT1 of the two patients was derived from recurrent events of genomic recombination. Given that the same Alu-mediated deletion of HPRT1 has not been reported among somatic mutations at the same locus, this region of the HPRT1 gene flanked by Alu-sequences is likely a mutational hot spot in the germline but not in somatic cells. In addition, we also report novel LN-syndrome-conferring mutations in intron 6 (IVS6+1G --> C) and intron 8 (IVS7-9T --> G) that resulted in exclusions of exon 6 and exon 8, respectively.

Alternative Splicing↗
PubMed2001

Pancytopenia and colitis with Clostridium difficile in a rheumatoid arthritis patient taking methotrexate, antibiotics and non-steroidal anti-inflammatory drugs.

Methotrexate (MTX) is widely used despite its side-effects. We describe a rheumatoid arthritis (RA) patient taking low-dose MTX who developed severe pancytopenia and colitis with Clostridium difficile after the administration of antibiotics for acute pyelonephritis. Our case suggests that low-dose MTX may seriously interact with antibiotics and that these side-effects should always be considered when RA patients are treated with MTX and antibiotics.

Aged↗
PubMed2001

Clinical features of familial gout and effects of probable genetic association between gout and its related disorders.

We examined whether the age at onset, gender, arthritic manifestations, and tophus formation in familial gout are different from those in nonfamilial gout, and we also examined the contributory effect of genetic association to the concurrence of hypertriglyceridemia, hypercholesterolemia, type 2 diabetes mellitus (DM), hypertension, obesity, and renal insufficiency with gout in Taiwan. A total of 21,373 gout patients' data from Ho-Ping Gout database were analyzed in this study retrospectively. The clinical and laboratory data were compared between familial and nonfamilial gout. Mean age at onset of gout in familial subjects was significantly 7.5 years lower than that of nonfamilial subjects (40.9 +/- 13.4 v 48.4 +/- 14.2 years, P =.0001), while gender, arthritic severity, and tophus formation were not significantly different between these 2 groups. Familial gout had lower serum triglyceride (TG), total cholesterol (TC), and percentage of hypertension than nonfamilial gout (182.4 +/- 125.3 v 195.9 +/- 135.8 mg/dL, P =.0001; 207.5 +/- 42.5 v 210.4 +/- 48.8 mg/dL, P =.0003; and 19.57% v 22.56%, P <.0001, respectively). Their serum creatinine, body mass index (BMI), and percentage of type 2 DM were not significantly different. Our results demonstrate that familial gout is associated with precocious onset. Furthermore, the contributory effect of genetic association to the concurrence of hyperlipidemia and hypertension with gout is less than that of environmental factors, while the effect of genetic association to the concurrence of obesity, type 2 DM, and renal insufficiency with gout is equivalent to that of environmental factors.

Age of Onset↗
PubMed2001

A prospective study of renal disease in patients with early rheumatoid arthritis.

OBJECTIVES: This prospective study was designed to clarify the frequency, causes, and clinical course of renal disease in patients with early rheumatoid arthritis (RA). METHODS: 235 patients (185 women, mean age 49.4 years) with early RA of less than one year's duration were enrolled and assessed monthly. Proteinuria was defined as a positive dipstick result and microscopic haematuria was defined as the presence of > or =5 red blood cells per high power field. Urinary abnormalities lasting three months or longer were defined as persistent abnormalities. RESULTS: At entry, 40 patients exhibited haematuria, two had a raised serum creatinine concentration, and none had proteinuria. During the observation period (average 42 months), persistent haematuria was found in 43, persistent proteinuria in 17, and a raised serum creatinine concentration in 14 patients. Persistent proteinuria was caused by drugs in 14 of 17 patients and disappeared in most cases. Risk factors for drug induced proteinuria included a raised C reactive protein and erythrocyte sedimentation rate and age over 50 at entry. Drugs resulted in a raised serum creatinine concentration in eight of 14 patients. The incidence of haematuria at entry did not differ among patients who had been treated with non-steroidal anti-inflammatory drugs, disease modifying antirheumatic drugs, or no drugs. In some patients with isolated haematuria, the haematuria appeared when the activity of RA was high and resolved when it was low. CONCLUSIONS: This study suggests that a raised serum creatinine concentration or persistent proteinuria in patients with early RA is predominantly drug related whereas, in contrast, isolated haematuria is more directly associated with the activity of the disease process.

Adult↗
PubMed2001

Progressive interstitial renal fibrosis due to Chinese herbs in a patient with calcinosis Raynaud esophageal sclerodactyly telangiectasia (CREST) syndrome.

A 58-year-old woman with calcinosis Raynaud esophageal sclerodactyly telangiectasia (CREST) syndrome presented with slowly progressive renal dysfunction. She was normotensive with normal plasma renin activity and lacking symptoms of vasculitis. Mild proteinuria was of tubular origin, but serological tests and an absence of sicca symptoms excluded the possibility of Sjögren's syndrome. Light microscopic study of renal biopsy showed interstitial fibrosis with ectasia and degeneration of proximal tubule and lymphocyte infiltration. There were no remarkable changes in the glomeruli. Chromatographic analysis of the Chinese herbs regimen that she had been taking for several years demonstrated aristolochic acid. She was diagnosed as Chinese herbs nephropathy. Therapy with oral prednisolone was markedly effective in improving renal function and anemia. To our knowledge, this is the first report of Chinese herbs nephropathy complicating connective tissue disease. It is important to consider the possibility of Chinese herbs nephropathy when patients treated with Chinese herbs develop renal dysfunction.

Aristolochic Acids↗
PubMed2001

[A questionnaire-based survey on the Internet concerning optimal timing for knee surgery in a patient with rheumatoid arthritis].

To investigate the differences between orthopedists and internists in indications for surgical management in patients with rheumatoid arthritis (RA), a questionnaire-based survey was performed on the Internet with the presentation of a case of progressive RA along with serial X-ray films of the knee. Ninety-three doctors (43 orthopedists and 50 internists, average age: 49.2 years) answered the questionnaire. Most of the doctors who viewed the X-ray film showing Larsen's grade IV chose that as the optimal time for total knee arthroplasty. No difference was noted in their choice between orthopedists and internists. Opinions varied widely, however, among younger doctors, but there was agreement among older doctors, suggesting the effect of the study and experience. On the other hand, some doctors recommended arthroscopic synovectomy for knees in the earlier stages of RA, but others did not recommend the arthroscopic surgery itself. Although this new methodology might include possible biases, we believe it should be considered in the research of rheumatology.

Arthritis, Rheumatoid↗
PubMed2001

Cricoarytenoid arthritis with rheumatoid arthritis and systemic lupus erythematosus.

A 56-year-old woman with rheumatoid arthritis (RA) suddenly developed severe respiratory distress and laryngeal stridor, which required endotracheal intubation. She had had RA for 12 years, which had been controlled well with prednisolone (3 mg/day) at the orthopedic clinic. Laryngoscopy revealed cricoarytenoid arthritis. She was finally diagnosed as having overlap syndrome with RA and systemic lupus erythematosus. She was given high dose corticosteroids that improved her clinical symptoms and laryngoscopic findings. She represents the first patient with overlap syndrome who developed an acute airway obstruction due to cricoarytenoid arthritis.

Arthritis, Rheumatoid↗
PubMed2001

[A case of recurrent hemophagocytic syndrome complicated with systemic sclerosis: relationship between disease activity and serum level of IL-18].

Hemophagocytic syndrome (HPS) is characterized by the activation of the mononuclear phagocytic system with prominent hemophagocytosis in the bone marrow and reticuloendothelial systems, and its occurrence is usually associated with variable disorders such as viral infections and malignant lymphoma. Recently, it was reported that HPS also occurred in association with underlying connective tissue disease, especially systemic lupus erythematosus. We report here a case of recurrent HPS complicated with systemic sclerosis. A 32-year-old woman had been diagnosed as systemic sclerosis since 1994. She was admitted due to unknown high fever and severe pancytopenia in 1997, and the diagnosis of HPS was determined because of hemophagocytosis in bone marrow and hyperferritinemia. Her symptoms were improved by immunosuppressive therapies including steroid pulse therapy and oral prednisolone (60 mg/day). She was followed by the treatment of oral prednisolone which was gradually tapered in our out-patient clinic. In August of 1999 high fever and severe anemia were recurred, and she was admitted again to our hospital because of the diagnosis as recurrent HPS. She had been treated with 40 mg/day of oral prednisolone and fever was immediately disappeared and hemoglobin was gradually increased. HPS is considered to be a rare complication with systemic sclerosis, and the etiology has been unknown. IL-18 is a novel cytokine which is a potent inducer of interferon-gamma, and its properties may be a proinflammatory regulation and activation of monocyte/macrophage and histiocyte through the expression of interferon-gamma. Therefore, the significance of IL-18 in the pathophysiology of HPS was recently reported. In this case, we investigated the significance of IL-18 and revealed the levels of serum IL-18 were well correlated with disease activity of HPS.

Adult↗
PubMed2001

Tumor necrosis factor-alpha (TNF-alpha) converting enzyme contributes to production of TNF-alpha in synovial tissues from patients with rheumatoid arthritis.

OBJECTIVE: Expression and function of tumor necrosis factor-alpha (TNF-alpha) converting enzyme (TACE) in synovia of patients with rheumatoid arthritis (RA) were examined to investigate posttranslational regulation of TNF-alpha production by TACE in RA. METHODS: Expression of TACE protein was evaluated by immunohistochemistry. Cytokines and soluble cytokine receptors were measured by ELISA. TACE mRNA was detected by RT-PCR. The enzymatic activity of TACE was measured using TACE-specific fluorogenic substrate. RESULTS: Expression of TACE at protein level in synovial tissue (ST) of patients with RA was significantly stronger than that of patients with osteoarthritis (OA). In RA, TACE was mainly expressed in CD68+ macrophage-like synovial cells. ST from 9 of 9 RA and 3 of 8 OA patients expressed TACE mRNA. RA ST cells possessed significantly higher TACE-like enzymatic activity than OA ST. A synthetic TACE inhibitor significantly reduced the release of TNF-alpha and p75 TNF receptor from RA ST cells. CONCLUSION: TACE is an important regulator of the secretion of TNF-alpha from synovia of patients with RA.

ADAM Proteins↗