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Biomedical subjects

Y Okano

Publications and source records attributed to Y Okano.

At least 109 records · Page 6Linked to original sources
PubMed1997

Patent ductus arteriosus with combined valvular disease at age 91.

This report describes a 91-year-old patient with patent ductus arteriosus (PDA) complicated by combined valvular disease (CVD) (aortic and mitral stenosis, and aortic, mitral, pulmonic and tricuspid regurgitation). This patient seems to be the oldest living female with PDA and CVD hitherto reported in the medical literature. The patient developed several bouts of congestive heart failure which were treated medically. She not only has survived without surgical management, but is still enjoying her life at age 91. The features of PDA in the elderly are reviewed.

Aged↗
PubMed1997

Long-term continuous intravenous infusion of prostacyclin for severe primary pulmonary hypertension.

A patient suffering from severe symptomatic primary pulmonary hypertension (PPH) underwent long-term intravenous prostacyclin therapy; the first time for such treatment in Japan. A 26-year-old male had experienced gradually progressive dyspnea for about one year. Despite conventional therapy he suffered repeated syncopal attacks. However, after receiving a permanent central venous access device and a portable infusion pump, he recovered fully and was discharged. This remedy seems to be promising for PPH as has already been proven in Europe and North Americas, although in Japan it is not as yet commercially available and some problems still need to be resolved.

Adult↗
PubMed1997

[Toxicity of low-dose methotrexate in rheumatoid arthritis--clinical characteristics in patients with MTX-induced pancytopenia and interstitial pneumonitis].

Pancytopenia and interstitial pneumonitis are one of the most serious and unpredictable adverse effects of low dose, pulse methotrexate (MTX) in treating rheumatoid arthritis (RA). It is important to investigate the historical, clinical or immunologic features associated with the development of such toxicity, in order to use MTX more appropriately. Two hundred eighty four patients (female 230 male 54) with rheumatoid arthritis had been treated with pulse weekly oral MTX with a mean follow-up of 33.2 months. Adverse effects which required the discontinuation of MTX occurred in 47 patients (16.5%). Gastrointestinal toxicity occurred most frequently (14 patients) and liver dysfunction occurred in 9 patients. Four patients (1.4%) developed pancytopenia, and six patients (2.1%) developed interstitial pneumonitis. All patients who developed pancytopenia were old female with long history of active, deforming rheumatoid arthritis, The cumulative dose of MTX ranged from 15 mg to 760 mg at the time pancytopenia developed. Impaired renal function, hypoalbuminemia, and multiple medication were observed, and antinuclear antibodies were positive in most patients. It should be noted that severe stomatitis preceded or accompanied with pancytopenia in all patients. Blood counts returned to the normal level in 7 to 14 days. All patients who developed interstitial pneumonitis were old female. The cumulative dose ranged from 65 mg to 580 mg. Pre-existance of lung diseases, history of adverse effects of other DMARDs, the presence of Raynaud's phenomenon, and antinuclear antibodies appeared to be risk factors for interstitial pneumonitis. All patients recovered with high dose of corticosteroid and mechanical ventilation. Such clinical characteristics that are associated with MTX-induced pancytopenia or interstitial pneumonitis should be reminded in the treatment of rheumatoid arthritis with MTX.

Aged↗
PubMed1997

Differential expression of low Mr GTP-binding proteins in human megakaryoblastic leukemia cell line, MEG-01, and their possible involvement in the differentiation process.

The expression of various low Mr GTP-binding proteins at various states of differentiation of a human megakaryoblastic leukemia cell line, MEG-01, was analyzed using thermocycle amplification of mRNA and immunoblotting. MEG-01 cells were found to express mRNAs of rap1A, rap1B, rap2B, ralA, rhoA, rac1, rac2, CDC42Hs, rab1, rab3B, rab6, ram and ran, but not rab4, and the proteins of Rap1, Rap2, RhoA, Rac1, Rac2, Rab3B, Rab4, Rab6 and Rab8 were expressed. Differentiation of MEG-01 cells induced by 100 nM 12-O-tetradecanoylphorbol-13-acetate revealed the considerable increases in mRNA expression of rap1B, rab3B, rab4, ram and ran whereas the levels of rap2B, rhoA and rac1 decreased. During the differentiation process, significant changes in protein levels of Rap1, RhoA, Rac1, Rac2, Rab3B, Rab4 and Rab6 were observed among three subcellular (cytosol, Triton X-100-soluble membrane and -insoluble cytoskeleton) fractions. The present investigation may be useful for the study of the megakaryocyte differentiation.

Blood Platelets↗
PubMed1997

[A new approach to assessing rheumatoid arthritis (RA) disease activity using the American College of Rheumatology core set of disease activity measures for RA trials--a multi-center study].

To characterize the American College of Rheumatology core set of disease activity measures for rheumatoid arthritis (RA) clinical trials (ACR core set measures) and the ACR definition of improvement of RA (ACR improvement definition), we studied 42 Japanese patients with active RA who were treated with DMARDs including mizoribine. Each patient's disease activity was assessed at the time of enrollment to the study and after 24 weeks using the ACR core set measures as well as the physical global assessment through the conventional measures. Twenty-five (60%) patients were discerned as showing improved by physicians through the conventional measures. This decision appeared to be based on improvement in Lansbury activity index (LAI) and C-reactive protein (CRP) value. Twelve of the 25 "improved" patients satisfied the ACR improvement definition. The 12 patients showed significant improvement in "outcome" measures including patients assessments of pain, disease activity, and physical function, compared to the 30 patients not satisfying the ACR definition. However, no significant differences were observed between these two groups in "process" measures including LAI, tender joint count, swallen joint count, or CRP value. In conclusion, the ACR core set measures including both process and outcome measures have potential to reflect clinical important changes on "real life" of patients with RA.

Activities of Daily Living↗
PubMed1997

[Chronic eosinophilic pneumonia successfully treated with suplatast tosilate].

The patient was a 45-year-old woman in whom a chest X-ray film obtained on admission showed bilateral infiltrative shadows. A chest CT scan revealed areas of consolidation and ground-glass opacities. Examination of bronchoalveolar lavage fluid revealed many eosinophils, and specimens obtained by transbronchial lung biopsy showed thickened alveolar septa with infiltration of eosinophils. The numbers of eosinophils and the level of IgE in blood were low. The radiographic appearance improved after administration of suplatast tosilate. The level of interleukin 5 was high both in plasma and in bronchoalveolar lavage fluid before treatment, but the level of IL-5 in plasma was low after suplatast tosilate was given. Suplatast tosilate, which suppresses the production of cytokines, may be useful in patients with chronic eosinophilic pneumonia.

Anti-Allergic Agents↗
PubMed1997

Clinical characteristics of patients with rheumatoid arthritis and methotrexate induced pneumonitis.

OBJECTIVE: To determine the clinical features of methotrexate (MTX) pneumonitis in patients treated for rheumatoid arthritis (RA). METHODS: The medical records of 284 patients with RA who had been treated with oral MTX (mean followup 33.2 mo) were reviewed retrospectively. RESULTS: MTX induced interstitial pneumonitis developed in 6 patients (2.1%). The affected patients were significantly older than those without MTX pneumonitis (67.3 +/- 9.8 vs 52.4 +/- 12.6 yrs, respectively; p < 0.005). The cumulative MTX dose ranged from 65 to 580 mg at the time pneumonitis developed. Five of the patients (83%) had preexisting interstitial abnormalities, while only 29 of the 278 patients without MTX pneumonitis (10%) had such abnormalities (p < 0.001). The frequency of adverse effects due to previous treatment with disease modifying antirheumatic drugs (DMARD) was 66.7% in MTX pneumonitis patients and 14.3% in the other 278 patients (p < 0.01). CONCLUSION: Advanced age, preexisting interstitial abnormalities, and previous adverse reactions to DMARD may be associated with MTX pneumonitis. Patients with these characteristics require careful monitoring during MTX therapy.

Adult↗
PubMed1996

Autoantibodies to DNA-dependent protein kinase. Probes for the catalytic subunit.

DNA-dependent protein kinase (DNA-PK) is an important nuclear enzyme which consists of a catalytic subunit known as DNA-PKcs and a regulatory component identified as the Ku autoantigen. In the present study, we surveyed 312 patients in a search for this specificity. 10 sera immunoprecipitated a large polypeptide which exactly comigrated with DNA-PKcs in SDS-PAGE. Immunoblot analysis demonstrated that this polypeptide was recognizable by a rabbit antiserum specific for DNA-PKcs. Although the patient sera did not bind to biochemically purified DNA-PKcs in immunoblots or ELISA, they were able to deplete DNA-PK catalytic activity from extracts of HeLa cells in a dose-dependent manner. We conclude that these antibodies should be useful probes for studies which aim to define the role of DNA-PK in cells. Since six sera simultaneously contained antibodies to the Ku protein, these studies suggest that relatively intact forms of DNA-PK complex act as autoantigenic particles in selected patients.

Antigens, Nuclear↗
PubMed1996

Clinical correlations with HLA type in Japanese patients with connective tissue disease and anti-U1 small nuclear RNP antibodies.

OBJECTIVE: To elucidate the roles of HLA genes in the clinical presentation of patients with connective tissue disease and serum anti-U1 small nuclear RNP antibody. METHODS: HLA class I antigens and HLA class II alleles were determined in 43 Japanese patients with anti-U1 RNP antibody alone, by microcytotoxicity testing and DNA typing, respectively. Prospectively recorded clinical and laboratory features were analyzed in relation to HLA class I and class II types. RESULTS: DQB1*0303 was associated with lupus-related symptoms including fever, malar rash, oral ulcers, hypocomplementemia, and high-titer anti-double-stranded DNA antibody. Other HLA-clinical associations included DR2 with pleuritis, DR4 with hand swelling, and DRB1*0405 with arthritis. CONCLUSION: These HLA-clinical associations explain, in part, the heterogeneous clinical presentation in patients with anti-U1 RNP antibody.

Adolescent↗
PubMed1996

Anti-U5 small nuclear ribonucleoprotein (snRNP) antibodies: a rare anti-U snRNP specificity.

We surveyed for autoantibodies to the U small nuclear ribonucleoproteins (snRNPs) in sera from 1171 patients with various connective tissue diseases by immunoprecipitation assay. We found serum, termed LaJ, which principally recognized the U5 snRNP from one patient with systemic sclerosis-polymyositis overlap syndrome. Anti-LaJ serum immunoprecipitated predominantly U5 snRNA from a 32PO4-labeled HeLa cell extract and at least five U5-specific proteins as well as the Sm core proteins from a [35S]methionine-labeled extract. Anti-LaJ serum immunoprecipitated both U5 snRNA and these five proteins in identical fractions at 15-20S by parallel sucrose gradient, suggesting physical association of these two components. Thus, we concluded that anti-LaJ serum contained antibody specific to the U5 snRNP. Antibodies specific to U5 snRNP were found in a single serum; in contrast, the prevalence of anti-U1 snRNP and anti-Sm antibody was considerably higher. Thus, the specific proteins of the U5 snRNP are rare targets for autoantibodies in patients with connective tissue disease.

Antibodies, Antinuclear↗
PubMed1996

Insulin regulated PKC isoform mRNA in rat adipocytes.

Insulin and 12-O-tetradecanoyl phorbol-13-acetate (TPA) induce both glucose uptake and translocation of protein kinase C (PKC) from cytosol to membrane in insulin-sensitive tissues as previously reported by several investigators. We examined insulin-mediated PKC beta I, beta II, and epsilon translocation from cytosol to cytoskeleton, and expression of PKC alpha, beta I, beta II, gamma, and epsilon isoforms using the reverse transcription polymerase chain reaction (RT-PCR) method during treatment with insulin for 240 min in rat adipocytes. Insulin-induced increases in PKC beta I, beta II, and epsilon were greater in the cytoskeleton fraction than those in the membrane fraction. Insulin induced time-dependent increases in PKC alpha, gamma, epsilon and zeta mRNA levels for up to 240 min (555%, 117%, 236% and 138% increase, respectively). TPA also induced time-dependent increases in PKC alpha and gamma (34% and 500% increase, respectively) but not in PKC zeta. However, PKC beta I mRNA was decreased for up to 60 min and then maintained at under the basal level during stimulation with insulin and TPA. On the other hand, PKC beta II mRNA was markedly increased for up to 240 min. These results suggest that insulin-regulated PKC alpha, gamma and epsilon mRNA levels and PKC beta mRNA alternative splicing may occur in rat adipocytes.

Adipocytes↗
PubMed1996

Antinuclear antibody in systemic sclerosis (scleroderma).

The presence of autoantibodies to intracellular molecules is the hallmark immunologic finding of SSc. Recent sophisticated methods have contributed to characterization of unidentified antigens of ANA in sera from patients with SSc. Antibodies to RNA polymerases are the third major SSc-specific ANA, in addition to anti-topo I and anticentromere antibodies, and it is now possible to identify over 85% of SSc patients. These antibodies have proved helpful in diagnosis of this disease. An immunogenetic predisposition to synthesis of the ANAs has been unveiled. Both antigen-driven and molecular mimicry hypotheses have been proposed for ANA production in SSc. Although the role of ANAs in the pathogenesis of SSc is not yet known, it is logical to assume that the origin of ANAs is linked to the causes of this disease because each antibody is associated with its own unique constellation of clinical features.

Antibodies, Antinuclear↗
PubMed1996

Protein kinase C isozymes in human megakaryoblastic leukemia cell line, MEG-01: possible involvement of the isozymes in the differentiation process of MEG-01 cells.

The expression of the different protein kinase C (PKC) isozymes in various states of differentiation of the human megakaryoblastic leukaemia cell line MEG-01 were analysed using thermocycle amplification of mRNA and immunoblotting. MEG-01 expressed mRNAs of PKC alpha, -beta I, -beta II, -delta, -epsilon, -eta, -theta and -zeta, but not PKC gamma. At the protein molecule level, MEG-01 was observed to express PKC alpha, -beta I, -beta II,- epsilon, -theta and -zeta, but lack -gamma, -delta and -eta. When differentiation of MEG-01 was induced by 100 nm 12-O-tetradecanoyl-phorbol-13-acetate (TPA), rapid translocation from cytosol to membrane fraction and down-regulation of PKC alpha, -epsilon and -theta was observed in 1-2h. On the other hand, PKC beta I and -beta II were observed to translocate not only to the membrane fraction but also to the cytoskeletal fraction in a different manner, and their down-regulation, especially beta II, was very slow. The myristoylated, alanine-rich C kinase substrate (MARCKS) in the membrane fraction of MEG-01 cells was observed to decrease gradually throughout the differentiation process. Additionally, time-course study of TPA treatment indicated that incubation of the cells for 30 min is sufficient for differentiation. These results strongly suggest that the activation of PKC alpha, -epsilon and -theta is involved in the initiation of differentiation, and that PKC beta I and -beta II have important roles in the maintenance of differentiation. Although PKC zeta was resistant to TPA treatment and its translocation was reduced, the amount of this isozyme in the cytosol fraction decreased throughout the differentiation process.

Base Sequence↗
PubMed1996

Upregulatory effects of interleukin-4 and interleukin-13 but not interleukin-10 on granulocyte/macrophage colony-stimulating factor production by human bronchial epithelial cells.

Airway epithelial cells are known to produce a granulocyte/macrophage colony-stimulating factor (GM-CSF), which induces eosinophilic inflammation in bronchial asthma. Interleukin-4 (IL-4), IL-10, and IL-13 produced by Th2 cells are involved in the pathogenesis of bronchial asthma. To assess their contributions to airway inflammation, we examined their effects on GM-CSF production by bronchial epithelial cells. Human bronchial epithelial cells were obtained under bronchoscopy from 21 patients with various respiratory diseases and incubated with or without IL-4, IL-10, or IL-13. Then the GM-CSF concentrations in the cell-free supernatants were measured by enzyme-linked immunosorbent assay. Results showed that IL-4 and IL-13 stimulated GM-CSF production by the epithelial cells dose-dependently, whereas IL-10 did not. The eosinophil survival-stimulating activity in the culture supernatants was closely correlated with GM-CSF concentration and was neutralized by anti-GM-CSF antibody. Thus, IL-4 and IL-13 may contribute to airway inflammation by upregulating GM-CSF production by bronchial epithelial cells.

Adult↗
PubMed1996

Adhesion molecule expression on eosinophils in idiopathic eosinophilic pneumonia.

Idiopathic eosinophilic pneumonia (IEP) is characterized by the accumulation of eosinophils in the alveolar spaces and the interstitium of the lung, frequently accompanied by peripheral eosinophilia. To clarify the roles of adhesion molecules of eosinophils in the pathogenesis of eosinophilic pneumonia, we analysed their expression by eosinophil and T-lymphocyte populations in peripheral blood and bronchoalveolar lavage fluid (BALF) obtained from 11 patients with eosinophilic pneumonia, using flow cytometric methods. Cell differentials in BALF showed increased numbers of eosinophils, the increase correlating with the number of activated T-lymphocytes in BALF. The expressions of CD11a (lymphocyte function-associated antigen-1 (LFA-1)), CD11b (Mac-1), CD18, CD49d (very late activation antigen-4 (VLA-4)), and CD62L (L-selectin) by eosinophils in BALF were all lower than those of eosinophils in peripheral blood. In contrast, CD54 (intercellular adhesion molecule-1 (ICAM-1)) was expressed by eosinophils in BALF, but not by those in peripheral blood. These results indicate that intercellular adhesion molecule-1 expression by eosinophils in bronchoalveolar lavage fluid but not in peripheral blood may be induced by locally activated T-cells or macrophages and may be important in the pathogenesis of idiopathic eosinophilic pneumonia.

Bronchoalveolar Lavage Fluid↗
PubMed1996

A family of multiple endocrine neoplasia type 2A: genetic analysis and clinical features.

Since a heterozygous missense mutation of the RET proto-oncogene in the germline was found to cause multiple endocrine neoplasia type 2A (MEN 2A) in 1993, some 20 different mutations of this gene have been identified in MEN 2A kindreds. We report an MEN 2A family in which serine (AGC) substitutes for cysteine (TGC) at codon 618 in exon 10 of the RET proto-oncogene. The mutation was identified by sequencing PCR products of exons 10 and 11 in the proband. Since this mutation results in creation of a new cleavage site for Alu I restriction enzyme, most of the other members of the family were screened by digestion of the PCR product of exon 10 with this enzyme. Eleven of 20 subjects across four generations examined have the mutation of the RET proto-oncogene, and all of the adult gene carriers except one woman had MTC. Characteristics of this family are 1) pheochromocytoma has been found in only the proband, 2) no obvious hyperparathyroidism has been observed, and 3) the prognosis is favorable, with nobody dying of MEN 2A itself. Genetic analysis of MEN 2A is definitely useful and essential for screening of a MEN 2A family. It is very important to accumulate cases with MEN 2A and investigate the phenotype and the prognosis in each mutation.

Adult↗
PubMed1996

[A case of the "shrinking lung syndrome" in SLE--improvement with corticosteroid therapy].

A 56-year-old Japanese woman had a 8-year history of systemic lupus erythematosus (SLE) with recurrent flares. When she was 48 years old, she was diagnosed as having SLE on the basis of fever, polyarthritis, oral ulcers, leukopenia, and positive anti-DNA antibody. Three years later she developed pericarditis and pleuritis, that were improved with treatment with 30 mg of prednisone a day. With tapering of prednisone dose to 9 mg a day in January 1993, she was admitted due to shortness of breath on exertion. Chest radiograph revealed bilateral elevated diaphragms and sluggish movement with clear lung field. Pulmonary function tests showed restrictive defect with a vital capacity 38% of predicted value. A diagnosis of "shrinking lung syndrome" was made. Simultaneously, blood test revealed leukopenia, elevated red cell sedimentation rate, and elevated anti-DNA antibody titer. Therefore, we suspected this pulmonary involvement was related to lupus flare-up. Treatment with 20 mg of prednisone a day resulted in resolution of the patient's dyspnea and in improvement of her vital capacity. Corticosteroid therapy for acute "shrinking lung syndrome" in active SLE can improve symptoms and pulmonary function.

Acute Disease↗