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Biomedical subjects

M Hirakata

Publications and source records attributed to M Hirakata.

At least 73 records · Page 4Linked to original sources

Purification and characterization of a novel lactonohydrolase, catalyzing the hydrolysis of aldonate lactones and aromatic lactones, from Fusarium oxysporum.

A novel lactonohydrolase, an enzyme that catalyzes the hydrolysis of aldonate lactones to the corresponding aldonic acids, was purified 10-fold to apparent homogeneity, with a 61% overall recovery, from Fusarium oxysporum AKU 3702, through a purification procedure comprising DEAE-Sephacel, octyl-Sepharose CL-4B and hydroxyapatite chromatographies and crystallization. The molecular mass of the native enzyme, as estimated by high-performance gel-permeation chromatography, is 125 kDa, and the subunit molecular mass is 60 kDa. The enzyme contains 15.4% (by mass) glucose equivalent of carbohydrate, and about 1 mol calcium/subunit. The enzyme hydrolyzes aldonate lactones, such as D-galactono-gamma-lactone and L-mannono-gamma-lactone, stereospecifically. Furthermore, it can catalyze the asymmetric hydrolysis of D-pantoyl lactone, which is a promising chiral building block for the chemical synthesis of D-pantothenate. These reactions are reversible, and the reaction equilibrium at pH 6.0 has a molar ratio of nearly 1:1 with D-pantoyl lactone and D-pantoic acid. The Km and Vmax for D-galactono-gamma-lactone are 3.6 mM and 1440 U/mg, respectively, and those for D-galactonate are 52.6 mM and 216 U/mg, respectively. The enzyme also irreversibly hydrolyzes several aromatic lactones, such as dihydrocoumarin and homogentisic-acid lactone.

Amino Acid Sequence↗

Autoantibodies to small nuclear and cytoplasmic ribonucleoproteins in Japanese patients with inflammatory muscle disease.

OBJECTIVE: To elucidate the profile and clinical significance of autoantibodies to small nuclear and small cytoplasmic ribonucleoproteins in Japanese patients with polymyositis and dermatomyositis (PM/DM). METHODS: Radioimmunoprecipitation assays were performed with sera from 91 patients with various inflammatory muscle diseases and from 254 control patients with other rheumatic diseases. Patients with PM/DM were categorized according to autoantibody specificities, and clinical comparisons were made. RESULTS: Antibodies to aminoacyl transfer RNA (tRNA) synthetases and the signal recognition particle (SRP) were found to be specific for PM/DM: PM/DM patients with antibodies to 3 aminoacyl-tRNA synthetases (histidyl, threonyl, and glycyl) appeared to form a distinct clinical subset, associated with chronic interstitial lung disease, polyarthritis, and myositis, while 3 patients with antibodies that bound the SRP had severe myositis that was resistant to corticosteroid therapy. In general, the frequency and clinical correlations of anti-aminoacyl-tRNA synthetase antibodies in Japanese patients were similar to those in North American populations. In contrast, among this Japanese cohort, the occurrence of anti-PM/Scl appeared to be reduced in frequency, whereas anti-Ku and anti-U2 RNP antibodies were accentuated in patients with overlap syndromes. CONCLUSION: We conclude that racial groups differ somewhat in their characteristic autoimmune responses to individual autoantigens. These differences could reflect variation in immunogenetic background or different etiologic mechanisms which might occur at different geographic locations.

Asian People↗

[Spontaneous remission of dermatomyositis which developed one month after normal delivery].

A case of dermatomyositis which developed one month after normal delivery and subsided spontaneously was reported. A 29-year-old woman gave birth to a healthy child. One month later, she noticed muscular pain and weakness of the upper extremities. On admission, there were diffuse edema of upper eyelids with heliotrope rash. The reddish skin rashes were observed on the extensor surfaces of the PIP and MP joints of fingers. Erythrocyte sedimentation rate was 29 mm/hr. The lactic dehydrogenase (LDH), SGOT, CK levels were 470 (normal 150 to 320 IU/l), 43 (normal 6 to 25 IU/l) and 317 (normal 21 to 110 IU/l) respectively. Autoantibodies to nuclear and cytoplasmic antigens were negative. Rheumatoid factor and anti-DNA antibody were negative. Thyroid function was normal. An electromyogram (EMG) demonstrated small amplitude short-duration polyphasic motor unit potentials. The muscle biopsy specimen from left upper arm showed degenerating muscle fibers and infiltration of inflammatory cells surrounding blood vessels. The skin biopsy revealed the presence of edema and perivascular infiltration of lymphocytes. Based on these clinical features and results of various diagnostic tests, a diagnosis of dermatomyositis was established. After the admission, muscle strength has improved dramatically and the CK returned to normal level without specific drug therapy. She has since been seen as an out patient, and complete remission lasted for two years up to date. Review of the literature disclosed that 13 cases of PM/DM which developed during pregnancy or postpartum have been reported including the present case. Detailed analysis showed that these patients were characterized by mild muscular diseases, rare occurrence of internal organ involvements and good response to steroid therapy. As our case, a spontaneous remission was also observed. Although the mechanism involved in occurrence of inflammatory myositis associated with pregnancy or delivery are not clarified, these patient indicated a presence of subset of PM/DM which do not require intensive drug therapy.

Adult↗

Repeated intestinal ulcerations in a patient with systemic lupus erythematosus and high serum antiphospholipid antibody levels.

We report the case of a patient with SLE who had repeated ulceration of the small intestine requiring emergency surgery. Pathologic examination revealed microthrombosis and vasculitis at the site of the intestinal ulcers. High levels of antiphospholipid antibodies, thrombocytopenia, and prolonged prothrombin time coincided with the episodes of intestinal ulceration. Antiphospholipid antibodies may be involved in the development of thrombosis resulting in the repeated episodes of intestinal ulceration in this patient. This possibility should be considered in patients with SLE who have intestinal ulceration and appropriate antithrombotic medication should be administered.

Adult↗

[A case of anti-phospholipid antibody syndrome presenting chorea as an initial manifestation].

A 20 year old female patient with anti-phospholipid antibody syndrome who presented chorea as an initial symptom is described. At the age of 14, she noticed involuntary movements of upper and lower extremities bilaterally. The CT scan revealed the presence of low density areas in the right caudate nucleus and left putamen. The result of the laboratory tests included antibodies to nuclear antigens (positive FANA and anti-DNA), prolonged PT and APTT, biological false positive for syphilis. Her serum contained antibodies to cardiolipin and phosphatidylserine as demonstrated by specific ELISA assay method. The clinical diagnosis of chorea was made and haloperidol was administered with partial symptomatic improvements. The patient reported here is the first well documented case of anti-phospholipid antibody syndrome presenting chorea as an initial manifestation in the Japanese literature.

Adult↗

[Frequency of anti-centromere antibodies in the anti-mitochondrial antibody positive sera].

Autoantibodies give us useful informations for the understanding of the co-existence of multiple autoimmune diseases in an individual patient. This study was undertaken to clarify the frequency of anti-centromere antibodies in the sera which were positive for anti-mitochondrial antibodies. Serum samples with anti-mitochondrial antibodies were examined on the frozen rat liver section and HEp-2 cells by indirect immunofluorescence. 57 out of 239 anti-mitochondrial antibody positive sera were found to contain specific autoantibodies reactive with centromeric antigens of the HEp-2 chromosomal spreads. The co-existence of anticentromere antibodies with anti-mitochondrial antibodies were significantly more frequent than with other defined autoantibodies. Clinical observation which shows frequent association of CREST syndrome and primary biliary cirrhosis appear to be explained by the frequent occurrence of anti-centromere antibodies and anti-mitochondrial antibodies.

Autoantibodies↗

Pyloric stenosis in a patient with progressive systemic sclerosis.

A 64-year-old Japanese woman with progressive systemic sclerosis (PSS) who developed severe pyloric stenosis is described. The conservative treatments brought only the temporary symptomatic relief, and pyloroplasty became necessary. No ulcerative lesions or tumors were found in the resected stomach or duodenum specimens implicated for stenosis. The histological examinations revealed edema and replacement fibrosis in the pyloric ring. The possible mechanisms of pyloric stenosis are discussed.

Female↗

Coexistence of CREST syndrome and primary biliary cirrhosis. Serological studies of two cases.

Two patients with characteristic features of CREST syndrome and primary biliary cirrhosis are reported. Sera of both patients contained autoantibodies to centromere and mitochondrial antigens. Immunodiffusion analysis identified the specificities of precipitating antibodies to mitochondria of the first case as anti-M-A and M-C, and of the second case as anti-M-A and M-B antibodies. Simultaneous occurrence of 2 marker antibodies in an individual patient indicates that the 2 patients reported here have CREST syndrome and primary biliary cirrhosis, both of which are considered as a distinct clinical entity.

Aged↗

In vitro production of autoantibodies to U1 ribonucleoproteins by peripheral blood mononuclear cells from patients with connective tissue diseases.

Antibodies to U1 ribonucleoproteins produced by peripheral blood mononuclear cells from patients with connective tissue diseases were measured by a sensitive enzyme-linked immunosorbent assay and by immunoblotting. Mononuclear cells from patients with high-titer serum antibodies spontaneously started secreting IgG anti-U1 RNP antibodies on the second day after culture. The amount of anti-U1 RNP in the culture supernatants reached maximum level on day 8. The most effective production of anti-U1 RNP by B cells was observed when they were cultured in the presence of T cells and adherent cells. Mononuclear cells from patients without anti-U1 RNP antibodies or from normal subjects did not produce a measurable amount of anti-U1 RNP. Treatment of mononuclear cells by cycloheximide resulted in complete inhibition of anti-U1 RNP secretion, which indicates that antibody in the culture supernatants reflects the active biologic phenomenon in vitro. The methods described should be useful in the study of the cellular mechanisms involved in antinuclear antibody production of connective tissue diseases.

Antigens↗

Rheumatoid arthritis associated with methotrexate-induced pneumonitis: improvement with i.v. cyclophosphamide therapy.

Pneumonitis is one of the most serious adverse effects associated with low-dose weekly methotrexate (MTX) therapy. Immediate cessation of MTX, and the introduction of oxygen therapy and glucocorticoids usually results in a dramatic improvement in the pulmonary toxicity. We report here a case of MTX-induced pneumonitis in a patient with rheumatoid arthritis (RA). Severe hypoxemia and interstitial infiltration in both lung fields did not respond to the withdrawal of MTX and the administration of oxygen and steroid pulse therapy. When intravenous cyclophosphamide (CYC) pulse therapy was initiated, however, rapid physiologic and radiographic improvement was seen. Our case suggests that CYC treatment may have a beneficial effect on MTX-induced pneumonitis that is resistant to steroid therapy.

Aged↗

A case of polymyositis associated with hepatitis B infection.

This report describes the case of a 47-year old man who developed myositis in association with hepatitis B surface antigen-positive hepatitis. Interestingly, the myositis repeatedly worsened 2 months after the exacerbation of hepatitis in this case, suggesting a close association between hepatitis B infection and myositis. The dose of prednisolone was increased twice in order to treat the exacerbating myositis, resulting in improvement of the muscle symptoms, but the patient eventually died of liver failure. Only 5 other myositis patients with hepatitis B antigenemia have been reported in the literature. We review these cases of the association between hepatitis B infection and myositis.

Anti-Inflammatory Agents↗

A case of systemic lupus erythematosus presenting with rectal ulcers as the initial clinical manifestation of disease.

Gastrointestinal involvement is often seen in patients with systemic lupus erythematosus (SLE). All parts of the gastrointestinal tract may be affected. However, rectal involvement at onset is rare. We describe here a case of SLE in which rectal ulcers due to vasculitis occurred as the initial manifestation of the disease without involvement of any other organ. The ulcers worsened, along with the appearance of lupus nephritis 5 years later When steroid therapy was initiated, there was rapid clinical and radiographic improvement. Our case suggests that rectal ulcer is a rare but important complication of SLE and can represent the initial and sole clinical manifestation of the disease.

Adult↗

Clinical characteristics of Japanese patients with anti-PL-7 (anti-threonyl-tRNA synthetase) autoantibodies.

OBJECTIVE: The clinical and laboratory features of seven Japanese patients with anti-aminoacyl-tRNA synthetase (ARS) autoantibodies against PL-7 (anti-threonyl-tRNA synthetase) were analyzed and compared with previously published findings. METHODS: Serum samples from 1,135 Japanese patients with various autoimmune diseases were screened for anti-PL-7 antibodies using RNA and protein immunoprecipitation assays. The patients whose sera contained anti-PL-7 antibodies were assessed regarding clinical symptoms and clinical course. RESULTS: Sera from seven patients were found to have anti-PL-7 antibodies. These autoantibodies were associated with polymyositis/dermatomyositis (PM/DM) and/or interstitial lung disease (ILD). The clinical diagnoses of these seven patients were PM - systemic sclerosis (SSc) overlap (5 patients), DM (1 patient) and idiopathic pulmonary fibrosis (IPF) (1 patient). All patients had ILD with a chronic course and six also had arthritis (85%) and five sclerodactyly (71%). CONCLUSIONS: These results indicate that anti-PL-7 autoantibodies are closely associated with PM-SSc overlap as well as ILD, arthritis and sclerodactyly in our series of Japanese patients.

Adult↗

Successful treatment of recurrent intracardiac thrombus in Behçet's disease with immunosuppressive therapy.

Behçet's disease (BD) is a chronic multisystem inflammatory disorder characterized by recurrent oral and genital ulcers, skin eruptions and uveitis. Neurological, gastrointestinal, and musculoskeletal systems are also involved. Although venous and arterial vasculitis occur in up to one-third of patients, intracardiac thrombus is a very rare complication. We herein report the case of a 46-year-old man with BD who presented with a large right atrial thrombus. Within a month after surgical removal, the thrombus recurred and was successfully treated with immunosuppressants that included prednisolone and cyclophosphamide.

Behcet Syndrome↗

Thrombocytopenia responsive to warfarin in a patient with systemic sclerosis--systemic lupus erythematosus overlap.

We report a patient with overlapping systemic sclerosis-systemic lupus erythematosus who developed refractory thrombocytopenia and recurrent thromboses. Coagulation and platelet labeling studies revealed that platelets were being consumed by the thrombus formation, and anticoagulation with warfarin dramatically increased the platelet count. This case report suggests that platelet consumption due to thrombus formation is one of the causes of thrombocytopenia in patients with rheumatic disease.

Blood Platelets↗