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Biomedical subjects

N Kamatani

Publications and source records attributed to N Kamatani.

At least 73 records · Page 4Linked to original sources
PubMed2000

Polyglutamation of antifolates is not required for induction of extracellular release of adenosine or expression of their anti-inflammatory effects.

Methotrexate (MTX) exerts an anti-inflammatory effect, reportedly by enhancing the release of adenosine, through an accumulation of 5-amino-4-imidazolecarboxamide ribonucleotide (AICAR). To examine the role of polyglutamation in promoting anti-inflammatory effects by antifolates, we tested whether a new antifolate designed to be resistant to intracellular polyglutamation (MX-68) exhibited anti-inflammatory effects and stimulated adenosine release. Both MX-68 and MTX (at concentrations greater than 0.1 microM) increased the release of adenosine from Daudi cells in vitro. Inhibition of AICAR synthesis suppressed adenosine release by MX-68 and MTX. The anti-inflammatory effects of antifolates were estimated using the murine air pouch model, in which a BALB/c mouse was intraperitoneally injected with MX-68 or MTX once a week for 3 weeks. MX-68 (0.5 mg kg(-1) week(-1)), as well as MTX, inhibited infiltration of leukocytes into the air pouch. This inhibitory effect was suppressed in the presence of an adenosine A(2) receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX). These results suggest that MX-68, like MTX, exerts anti-inflammatory effects through the accumulation of AICAR and release of adenosine. These results suggest that polyglutamation of antifolate is not required for expression of anti-inflammatory effects.

2-Aminoadipic Acid↗
PubMed2000

Increased CD40 expression on muscle cells of polymyositis and dermatomyositis: role of CD40-CD40 ligand interaction in IL-6, IL-8, IL-15, and monocyte chemoattractant protein-1 production.

In polymyositis (PM)/dermatomyositis (DM), T cells infiltrate the muscle tissues and interact with muscle cells via cell surface molecules. Recently, myoblasts have been reported to express CD40, but little is known about the role of CD40 in myoblasts. In the present study we examined the expression and involvement of CD40 and CD40 ligand (CD40L) in the interaction between muscle cells and T cells in PM/DM. Immunohistochemical staining revealed that CD40 was expressed on muscle cells in five of five PM and four of five DM patients, and that infiltrating mononuclear cells (MNCs) expressed CD40L in all cases of PM/DM. These CD40L-expressing MNCs were primarily CD4+ T cells. IFN-gamma, which is known to induce CD40 expression on various types of cells, was also expressed on the MNCs in four of the PM and four of the DM patients. Although cultured human myoblasts (SkMC 2859) did not express CD40 constitutively, IFN-gamma induced CD40 expression in a dose-dependent manner. To clarify the functional roles of CD40-mediated signals, the effects of a trimeric form of recombinant human CD40L on cytokine production were studied in SkMC 2859 that were prestimulated with IFN-gamma to express CD40. Recombinant human CD40L markedly increased the production of IL-6, IL-8, IL-15, and monocyte chemoattractant protein-1 of SkMC 2859. The expression of these humoral factors in muscle cells of PM and DM was demonstrated by immunohistochemistry. These results suggest that interaction between T cells and muscle cells via the CD40-CD40L system contributes to the immunopathogenesis of PM/DM by augmenting inflammation via cytokine production by the muscle cells.

Adjuvants, Immunologic↗
PubMed2000

Serum matrix metalloproteinase 3 as a predictor of the degree of joint destruction during the six months after measurement, in patients with early rheumatoid arthritis.

OBJECTIVE: To evaluate whether matrix metalloproteinase 3 (MMP-3), a proteinase that is expressed in rheumatoid synovial tissue and shows potent activity in degrading the proteoglycan of cartilage, plays a pivotal role in the joint destruction seen in early rheumatoid arthritis (RA). METHODS: In a prospective study of patients with early RA, the relationship between the serum concentration of MMP-3, as determined by a sandwich enzyme immunoassay system, and the progression of joint destruction in patients with early RA, as measured by the Larsen radiologic score, was investigated. RESULTS: Serum MMP-3 levels were elevated in the RA patients compared with healthy controls, not only in the late stage, but also in the early stage of the disease in patients whose duration of RA was <4 months. The serum MMP-3 level at entry into the study had a strong correlation with the Larsen score at 6 months and 12 months after entry (r = 0.58 and r = 0.49, respectively). Similarly, the serum MMP-3 level at 12 months and 24 months after entry showed a positive association with the Larsen score in the subsequent 6-12 months. Suppression of the serum MMP-3 level in the first year led to a decline in joint damage in the second year. CONCLUSION: The serum concentration of MMP-3 is a useful marker for predicting bone damage in the early stage of RA, and the suppression of MMP-3 production may be an effective therapeutic approach for patients with early RA.

Adult↗
PubMed2000

Localization of a gene for familial juvenile hyperuricemic nephropathy causing underexcretion-type gout to 16p12 by genome-wide linkage analysis of a large family.

OBJECTIVE: Familial juvenile hyperuricemic nephropathy (FJHN, MIM 162000) is an autosomal-dominant disease characterized by underexcretion-type hyperuricemia, gout, and chronic renal failure. No loci responsible for this disease or any underexcretion-type hyperuricemia/gout have ever been identified. The aim of the study was to localize a gene responsible for FJHN by linkage analysis. METHODS: A single large family with at least 20 affected members was analyzed. DNA was obtained from 13 affected and 18 non-affected members after lymphoblastoid cell lines were established. Initially, polymorphic data were obtained for 343 microsatellite loci covering all chromosomes except the X chromosome. Parametric linkage analysis was performed using the obtained data with LINKAGE package software. RESULTS: Following a genome-wide search using a set of highly polymorphic microsatellite markers, initial evidence for linkage was obtained for a marker on chromosome 16p. We subsequently genotyped the same subjects for 12 additional markers spanning approximately 30 cM on the short arm of chromosome 16. We obtained a maximum 2-point logarithm of odds (LOD) score of 6.04 at theta = 0 with the marker D16S401; multipoint linkage analysis yielded a maximum LOD score of 6.14 with markers D16S401 and D16S3113, and established a minimum candidate interval of approximately 9 cM. CONCLUSION: A gene for FJHN was localized to a candidate interval of approximately 9 cM at 16p12. These findings will be useful for the presymptomatic diagnosis of FJHN in some families and for testing genetic heterogeneity of FJHN in general.

Chromosome Mapping↗
PubMed2000

Progressive appearance of overlap syndrome together with autoantibodies in a patient with fatal thrombotic microangiopathy.

We describe an extraordinary patient with overlap syndrome (systemic lupus erythematosus, systemic sclerosis, and rheumatoid arthritis) having positive autoantibodies against Sm, double stranded DNA, DNA topoisomerase I, and centromere, together with rheumatoid factor. The patient had multiple organ involvement resulting from thrombotic microangiopathy that mimicked so-called normotensive scleroderma renal crisis, and died mainly of massive pulmonary hemorrhage caused by thrombotic thrombocytopenic purpura. The clinical presentations of the case support the concept of strong associations between disease-specific autoantibodies and clinical features.

Adult↗
PubMed2000

Rapidly progressive glomerulonephritis with D-penicillamine.

We present 3 cases of anti-myeloperoxidase, anti-neutrophil cytoplasmic antibody (MPO-ANCA)-positive rapidly progressive glomerulonephritis developed during the treatment with D-penicillamine (D-PC) for rheumatoid arthritis. Rheumatoid arthritis was diagnosed in these patients, and D-PC was administered to them at doses of 100, 200, and 300 mg per day for 32, 42, and 39 months, respectively. They developed proteinuria, hematuria, renal insufficiency, and anemia, and D-PC was stopped. On admission, MPO-ANCA was strongly positive in their sera. Renal biopsy showed glomerulonephritis with cellular crescents. Immunofluorescence examination revealed deposits of granular IgG, IgM, IgA, C1q, and C3 in the mesangium. The 3 patients were treated with steroid pulse therapy along with administration of anticoagulants, and cyclophosphamide was also used in 2 patients. Their renal function improved gradually and MPO-ANCA disappeared after immunosuppressive treatment.

Adult↗
PubMed2000

Systemic lupus erythematosus with myocardial dysfunction due to microvasculopathy.

A 25-year-old Japanese woman with systemic lupus erythematosus (SLE) had myocardial dysfunction. Heart catheterization showed normal coronary anatomy. Left ventricular cineangiography demonstrated hypokinesis in the anterior and posterior segments. Myocardial scintigraphy revealed patchy defects in the regions unrelated to coronary arteries. These data suggested that the myocardial dysfunction was due to microvasculopthy. In addition, it was speculated that the microvasculopathy was caused by vasculitis but not by thrombi, since she did not have antiphospholipid syndrome. In support of this speculation, corticosteroid therapy without any thrombolytic agents was effective. This report represents the first live patient with SLE in whom myocardial dysfunction due to microvasculopathy has been demonstrated.

Adult↗
PubMed2000

Dermatomyositis with splenic and renal infarctions during corticosteroid therapy.

A 60-year-old woman was admitted to our hospital with complaints of muscle weakness and erythema on her extremities. Gottron's sign, heliotrope rash, elevation of serum myogenic enzymes, electromyography and magnetic resonance imaging findings established a diagnosis of dermatomyositis (DM). She was treated with 60 mg of daily prednisolone. One week later, she suddenly developed splenic and renal infarctions, which were considered to have resulted from vasculopathy associated with DM. Cyclophosphamide and anticoagulants along with increasing the dosage of corticosteroid were effective. This is the first report describing splenic and renal infarctions in a patient with adult-onset DM.

Anti-Inflammatory Agents↗
PubMed2000

[Insulin sensitizer and urate metabolism].

Gout patients often have various characteristics of insulin resistance (IR) syndrome such as glucose intolerance, hyperlipidemia, hypertension and obesity. In addition, epidemiological data suggest that hyperuricemia is associated with higher rates of death due to cardiovascular and cerebrovascular disorders. However, it has not conclusively been shown whether the association between hyperuricemia and increased death rate is secondary to the association between IR and death or hyperuricemia itself is an independent risk of death. It is of interest to examine the effects of insulin sensitizer which was developed recently on serum urate concentration because it may provide a new idea as to the mechanism of the association between IR, hyperuricemia and vascular disorders. In the present paper, we discuss the relevance of IR to hyperuricemia and gout, and show the data of urate and glucose metabolism obtained from control subjects or the patients with hyperuricemia, gout or type 2 diabetes.

Chromans↗
PubMed2000

KL-6 as a novel serum marker for interstitial pneumonia associated with collagen diseases.

OBJECTIVE: To investigate the diagnostic value of the serum concentrations of KL-6, a mucinous glycoprotein expressed on type II pneumocytes, for interstitial pneumonia (IP) in various collagen diseases. METHODS: Serum KL-6 levels were measured by ELISA. RESULTS: The mean values and the positive rates of serum KL-6 levels for patients with rheumatoid arthritis, systemic sclerosis, or polymyositis/dermatomyositis with IP were significantly higher than those without IP. Sensitivity, specificity, positive and negative predictive values of serum KL-6 level for IP associated with collagen diseases were 60.7, 98.9, 97.4, and 77.1%, respectively. The mean serum KL-6 level of patients with active IP was significantly (p = 0.0001) higher than that of patients with inactive IP. Serum KL-6 levels increased with the deterioration of IP, while the successful treatment of IP resulted in a significant decrease of these levels. CONCLUSION: Serum KL-6 concentration levels are a useful marker for diagnosis and evaluation of the disease activity of IP associated with collagen diseases.

Adult↗
PubMed2000

[A case of Sjögren's syndrome and systemic sclerosis complicated with acute pancreatitis].

We report a case of Sjögren's syndrome (SS) and systemic sclerosis (SSc) complicated with acute pancreatitis. A 51-year-old woman had been diagnosed as SS in 1973. She noticed Raynaud's phenomenon in 1977. In 1988, interstitial pneumonia (IP) was pointed out and she was treated with methylprednisolone (mPSL) pulse therapy. Prednisolone (PSL) was gradually tapered to 3-5 mg daily and she visited our outpatient clinic in 1995. On her first admission to our hospital in 1996, she showed xerostomia, keratoconjunctivitis sicca, sclerotic skin changes of her distal extremities and face, thickening of her sublinguinal frenulum, and regurgitative esophagitis. She was positive with anti-SS-A and SS-B antibodies. She was diagnosed as SS and SSc. Radiographic and laboratory data also established the diagnosis of inactive IP, renal tubular acidosis (RTA) and chronic renal failure (CRF). In April 30th 1997, she was admitted to our hospital again with complaints of dyspnea, dysesthesia, epigastralgia and petechia. Active IP and mononeuritis multiplex were diagnosed, and petechia was considered to be associated with vasculopathy. Her serum amylase level was 891 mU/ml on admission and spontaneously increased to 2440 mU/ml on May 12th along with increase of fibrinogen degradation product, D-dimer and alpha 2 plasmin-plasmin inhibitor complex levels. Ultrasonography depicted swelling of her pancreatic head and the diagnosis of acute pancreatitis was made. She was treated with protease inhibitors and intravenous hyperalimentation for acute pancreatitis. mPSL pulse therapy (500 mg/day for 3 days) was instituted for IP and mononeuritis multiplex on May 22, followed by 50 mg of daily PSL. While IP and mononeuritis multiplex gradually improved by the high-dose steroid therapy, serum amylase level raised to more than 4293 mU/ml, suggesting the modification of pancreatitis by the treatment with steroid. Since she did not respond to the conservative therapy for acute pancreatitis, she was treated with plasmapheresis, which turned out to be very effective. However, she was suffered from fungal pneumonia and died of respiratory failure. As far as we know, only three cases of SS with acute pancreatitis have been reported so far. The immunopathological mechanisms of development of acute pancreatitis in our case, especially focusing on the significance of microvasculopathy and hypercoagulability, were discussed.

Acute Disease↗
PubMed2000

[A case of amyopathic dermatomyositis with rapidly progressive interstitial pneumonia].

We report here a case of interstitional pneumonia (IP) associated with amyopathic dermatomyositis (DM). In August, 1998, a 53-year-old Japanese man was admitted to our hospital because of fever, polyarthritis and erythematous heliotrope eruption and Gottron's sign without any symptom of myositis. Serum CK level and EMG were normal. Jo-1 antibody was negative. Chest computed tomography (CT) revealed IP at both lung base areas. The patient was diagnosed as amyopathic DM with IP. When IP rapidly progressed, methylprednisolone pulse therapy and oral high dose prednisolone were not effective. High-dose intravenous cyclophosphamide seemed to be transiently effective, but oral cyclosporine A was not effective. The patient was died of respiratory failure in October 1998. During the course, we measured serum levels of LDH, sIL-2 R, s-ICAM-1 and KL-6, KL-6 could be a sensitive parameter of IP activity.

Antigens↗
PubMed2000

[A case of intestinal Behçet's disease with abnormal ossification complicated by myelodysplastic syndrome, symptoms revealed after the perforation of ileum ulcer].

A 39-year-old man, who had been treated with Etretinate for common wart since he was 29 years old, was admitted to Taga General Hospital complaining of gradually deteriorating lumbago and bilateral hip joints pain in September, 1996. His lower vertebrae and bilateral hip joints showed abnormal ossification on X-ray. The bone scintigraphy indicated the existence of sacroiliitis. His platelet counts were fluctuating between 8 x 10(4) and 9 x 10(4)/mm3. During the follow-up in our out-patient clinic, he was suddenly suffered from severe abdominal pain in August, 1997 and admitted to our hospital. An emergency operation revealed multiple ulcers of his ileum with several perforations. Histological findings of the specimen of the ileum showed simple ulcer. After the operation, he had oral and genital ulcers. He did not have any signs or symptoms of ocular involvement. He was diagnosed as intestinal Behçet's disease. Because he showed gradually pancytopenia for several months after the operation, bone marrow aspiration was performed and a diagnosis of refractory anemia, a type of myelodysplastic syndrome (MDS), with trisomy of chromosome 8 was made. Abnormal ossification of his vertebrae and hip joints were considered to be related to Behçet's disease because an coexistence with sacroiliitis. On the other hand, there is no denying the effects of orally Etretinate administration. Several cases have been reported the association of MDS with Behçet's disease. In this case, the existence of MDS or various symptoms in Behçet's disease became apparent after the perforation of ileum ulcer. This paper discusses possible etiology of the relation between Behçet's disease and MDS, or the characteristic clinical course in this case.

Adult↗