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Biomedical subjects

Y Okano

Publications and source records attributed to Y Okano.

At least 127 records · Page 7Linked to original sources
PubMed1996

Isolated pulmonary hypertension in systemic sclerosis with diffuse cutaneous involvement: association with serum anti-U3RNP antibody.

OBJECTIVE: To describe a group of patients with systemic sclerosis (SSc) and diffuse cutaneous (dc) involvement with isolated pulmonary hypertension (IPHT) and to compare them to 2 other SSc patient groups, i.e., one with limited cutaneous (lc) involvement with IPHT and another with dcSSc without IPHT. METHODS: The Pittsburgh Scleroderma Databank was screened to identify appropriate patients. SSc specific serum autoantibodies were determined using published methods. Chi-squared tests and Kaplan-Meier survival analysis were performed. RESULTS: During the period 1975-92, 60 of 580 (10%) consecutive new patients with lcSSc and 14 of 677 (2%) with dcSSc have developed IPHT (p < 0.0001). The patients with IPHT did not differ from their parent dc or lc groups by age, race, sex, or cutaneous manifestations. All 14 patients with dcSSc IPHT had minimal or no pulmonary interstitial fibrosis on chest radiograph. The 12 tested had a striking reduction in DLCO (mean 50% of predicted normal), similar to results for patients with lcSSc with IPHT. Of note, 5 of these 14 patients had survived "scleroderma renal crisis" 1.3 to 10.7 (mean 5.5) years before onset of IPHT. Six of 13 (46%) patients with dcSSc with IPHT were positive for serum anti-U3RNP antibody by immunoprecipitation, and one had the typical nucleolar staining pattern of anti-U3RNP, but was not tested for U3RNP by immunoprecipitation. In contrast, only 13 (6%) of the 244 patients with dcSSc without IPHT (p < 0.0001) had anti-U3RNP antibody. Survival from the first reported symptom consistent with pulmonary hypertension (usually dyspnea on exertion) was uniformly poor in both IPHT groups, with the vast majority of patients dying during the first 2 years. CONCLUSION: Patients with SSc with dc involvement can develop severe, fatal isolated pulmonary arterial hypertension. This complication occurs disproportionately more often in patients with serum anti-U3RNP antibody.

Adult↗
PubMed1995

Delayed improvement in exercise capacity with restoration of sinoatrial node response in patients after combined treatment with surgical repair for organic heart disease and the Maze procedure for atrial fibrillation.

BACKGROUND: Although the Maze procedure successfully restores sinus rhythm in patients with heart disease and atrial fibrillation, it is still uncertain whether an addition of the Maze procedure in cardiac surgery is beneficial for exercise performance of the patients after surgery. METHODS AND RESULTS: The Maze procedure was performed in 25 patients (age, 37 to 70 years) during valve surgery (18 patients) or closure of atrial septal defect (7 patients). A cardiopulmonary exercise test using ramp incremental protocol (15 W/min) was performed before and 1 month, 6 months, and 1 year after surgery. Sinus conversion was obtained in 23 of 25 patients 1 month after surgery. However, sinoatrial (SA) node response to exercise was attenuated by surgery: Mean heart rate (HR) was 83 +/- 13/min at rest, 94 +/- 13/min at 60 W, and 107 +/- 17/min at peak exercise. Peak oxygen uptake (PVO2) was unchanged at this period (before, 17.6 +/- 4.5 mL.min-1.kg-1; 1 month after, 17.5 +/- 4.2 mL.min-1.kg-1). Thereafter, SA node response was restored 6 months after surgery: Mean HR was 84 +/- 13/min at rest, 104 +/- 16/min at 60 W, and 130 +/- 20/min at peak exercise (P < .01 versus 1 month). PVO2 was also improved at this period (20.7 +/- 4.0 mL.min-1.kg-1, P < .01). The increase in PVO2 from 1 month to 6 months after surgery was correlated with the increase in peak HR (y = 0.73x +/- 3.6, r = .79). There were no further changes in heart rate response or PVO2 from 6 months to 1 year after surgery. CONCLUSIONS: Atrial fibrillation was successfully treated by combined treatment with surgical repair for organic heart disease and the Maze procedure. However, SA node response to exercise was attenuated early after surgery. Thus, exercise capacity was improved at the late phase after surgery, which was related to the extent of restoration in SA node response.

Adult↗
PubMed1995

Major histocompatibility complex class II gene associations with anti-U1 small nuclear ribonucleoprotein antibody. Relationship to immunoreactivity with individual constituent proteins.

OBJECTIVE: To better define immunogenetic associations with the anti-U1 ribonucleoprotein (U1 RNP) autoantibody response. METHODS: HLA class II alleles were determined by genotyping in 49 Japanese rheumatic disease patients with anti-U1 RNP antibody and 43 race-matched healthy controls. Immunoreactivities to U1 RNP constituent proteins (70K, A, B/B', and C) were detected by immunoblots using purified HeLa cell Sm antigen, and antibody titer was determined by passive hemagglutination assay. RESULTS: DQB1*0302 was significantly more frequent in anti-U1 RNP-positive patients than in controls (43% versus 14%; odds ratio [OR] = 4.6, corrected P = 0.03). All anti-U1 RNP-positive patients had either a DQB1*0601, *0602, *0301, *0302, or *0303 allele, which share tyrosine at position 30, and the amino acid sequence Thr, Arg, Ala, Glu, Leu, Asp, and Thr at positions 71-77 in the DQB1 beta 1 domain. In contrast, one of these alleles was found in 81% of the controls (OR = 24, P = 0.002). In addition, anti-U1 RNP antibody was associated with unique DQB1*0302; DRB1*0401 haplotype. Anti-70K reactivity and antibody titer were positively associated with a basic amino acid residue, arginine or histidine, at position 13 (DR2 or DR4) and were negatively associated with the amino acid sequence Ile, Leu, Glu, and Asp at positions 67-70, which was present in some of the DR5-, DR6-, and DR8-associated alleles, in the DRB1 beta 1 domain. Anti-C reactivity was strongly associated with DR2, particularly with DRB1*1502. CONCLUSION: The several shared epitopes located on HLA-DRB1 and DQB1 genes control the anti-U1 RNP autoantibody response.

Amino Acid Sequence↗
PubMed1995

Molecular characterization of galactosemia (type 1) mutations in Japanese.

We characterized two novel mutations of the galactose-1-phosphate uridyltransferase (GALT) gene in two Japanese patients with GALT deficiency and identified N314D and R333W mutations, previously found in Caucasians. One novel missense mutation was an G-to-A transition in exon 8, resulting in the substitution of arginine by histidine at the codon 231 (R231H). GALT activity of the R231H mutant construct was reduced to 15% of normal controls in a COS cell expression system. The other was a splicing mutation, an A-to-G transition at the 38th nucleotide in exon 3 (318A-->G), resulting in a 38-bp deletion in the GALT cDNA by activating a cryptic splice acceptor site. In seven Japanese families (14 alleles for classic form and one allele for Duarte variant) with GALT deficiency, the R231H and 318A-->G mutations were found only on both alleles of the proband. The N314D and R333W mutations were found on one allele each. The Q188R was prevalent in the United States but not in Japanese patients. The N314D mutation was associated with the Duarte variant in Japanese persons, as well as in the United States. We speculate that classic galactosemia mutations appear to differ between Japanese and Caucasian patients. Our limited data set on galactosemia mutations in Japanese suggests that the N314D GALT mutation encoding the Duarte variant arose before Asian and Caucasian people diverged and that classic galactosemia mutations arose and/or accumulated after the divergence of Asian and Caucasian populations.

Amino Acid Sequence↗
PubMed1995

A suppressor mutation which suppresses adenylyl cyclase mutations in Neurospora crassa.

A spontaneous suppressor mutant, hah, which suppressed the colonial growth of adenylyl cyclase mutants (cr-1) was isolated. The morphology of cr-1 hah was filamentous, but slightly different from that of wild type on solid medium. The hah strain formed many high aerial hyphae, but did not form any conidia. The expression levels of an adenylyl cyclase gene, nac, in both hah and cr-1 hah were much higher than those in wild type or in cr-1. The level of cAMP in cr-1 was very low but returned to close to the wild-type level in the cr-1 hah suppressed strain, whereas that in the strain carrying hah alone was similar to or a little higher than that in wild type. The hah gene was located 13.3 map units from in1 on the right arm of the linkage group V. The hah mutation was recessive and allele specificity of hah for the suppression of cr-1 mutations was weak.

Adenylyl Cyclases↗
PubMed1995

Percutaneous transvenous mitral commissurotomy immediately restores quick response of VO2 to mild exercise despite insignificant increases in peak VO2.

Percutaneous transvenous mitral commissurotomy (PTMC) increases peak oxygen uptake (VO2) chronically, but not acutely, despite early symptomatic improvements. Analysis of transient VO2 responses to submaximal exercise (an exercise regimen more comparable to the patients' daily activities than that provided by maximal exercise testing), may be sensitive in detecting the acute hemodynamic benefits of PTMC. Since no methods are available to accurately estimate the transient response of VO2, we developed a new technique, using random exercise. In 15 patients who underwent successful PTMC, we repeated the conventional maximal exercise test and the random exercise test before and within a few days after PTMC. For the random exercise test, we intermittently imposed upright bicycle exercise at 50 W, according to a random binary sequence, while measuring breath-by-breath VO2. After determining the transfer function relating workload to VO2, we computed the high resolution VO2 response to a hypothetical step increase in exercise. Despite improvements in resting hemodynamics and New York Heart Association (NYHA) Class, peak VO2 improved insignificantly (952 +/- 271 vs 1,029 +/- 342 ml/min, P = 0.063) shortly after successful PTMC. In contrast, the amplitude of the VO2 step response increased significantly in the early-to-mid portion (28-76s; P < 0.01-0.05). The remaining portion was unchanged. Consequently, the time constant shortened from 64 +/- 26 to 48 +/- 22s (P < 0.05). The maximal Borg scale value during random exercise decreased significantly (13.1 +/- 1.8 vs 11.4 +/- 1.1; P < 0.01). We conclude that the VO2 step response, using the random exercise test, is more sensitive than peak VO2 in detecting the functional improvement that is coupled with the hemodynamic improvement immediately after PTMC.

Adult↗
PubMed1995

Identification of heterotrimeric GTP-binding proteins in human megakaryoblastic leukemia cell line, MEG-01, and their alteration during cellular differentiation.

Various heterotrimeric GTP-binding proteins (G proteins) are possible to have important functions in hematopoietic cells. However, there has been no information regarding their expression in magakaryoblasts and/or megakaryocytes. In the present study, protein contents of seven G protein alpha subunits (Gs alpha, Gi2 alpha, Gi3 alpha, Gz alpha, G11 alpha, Gq alpha and G12 alpha) and beta subunit in a human megakaryoblastic leukemia cell line, MEG-01, were analyzed by immunoblotting. Immature MEG-01 cells expressed the alpha subunits of Gs, Gi2, Gi3, Gz, G11 and G12 at protein molecule level. During the 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced differentiation process, the contents of Gi2 alpha and Gi3 alpha increased, whereas the protein levels of Gz alpha, Gs alpha, G11 alpha and G12 alpha were observed to hardly change. beta subunit was also observed to be present in immature MEG-01 cells and to increase continuously throughout the differentiation process. For the expression of Gi2 alpha and beta subunits, chronic TPA-treatment was required although Rac2, a low M(r) GTP-binding protein, was expressed abundantly by only 30 min-TPA-treatment followed by 3 day-culture.

Blood Platelets↗
PubMed1995

Involvement of protein kinase C in bradykinin-induced intracellular calcium increase in primary cultured human keratinocytes.

Bradykinin (BK) is one of the key mediators of inflammation and a weak mitogen. We have previously demonstrated that BK induced the generation of inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) which caused Ca2+ mobilization in human keratinocytes. In this study, BK-induced Ca2+ responses were examined in primary cultured human keratinocytes by video imaging fluorescence microscopy using fura-2. Intracellular calcium concentration ([Ca2+]i) level increased to a peak within 30 s after BK addition and decreased gradually to the basal level. The existence of the broad shoulder in the [Ca2+]i profile was suggested to be due to the Ca2+ influx from the external medium, because this disappeared in the presence of 0.5 mM EGTA. Pretreatment with phorbol-12-myristate-13-acetate (PMA), a protein kinase C (PKC) activator, significantly resulted in reduction of the descending shoulder of BK-induced increase in [Ca2+]i. A 20-min pretreatment with PKC inhibitors, H-7 or staurosporine, reversed the decrease by PMA in the shoulder of BK-induced Ca2+ response. Furthermore, the BK-induced [45Ca] uptake was inhibited by EGTA and PMA. Ins(1,4,5)P3 generation induced by BK peaked at 20 s and returned to the basal level at 60 s. There were no significant differences in Ins(1,4,5)P3 levels at 20 and 60 s among the cells exposed to BK alone, BK with PMA pretreatment (20 min) and BK with PMA+H-7 pretreatment. These results suggest that the BK-induced Ca2+ influx, which was shown as shoulder, may be negatively modulated by PKC in primary cultured human keratinocytes.

Adult↗
PubMed1995

HLA class II genes associated with anticentromere antibody in Japanese patients with systemic sclerosis (scleroderma).

OBJECTIVE: To define further HLA class II gene associations with anticentromere antibody (ACA), a major serum antinuclear antibody in patients with systemic sclerosis (SSc). METHODS: HLA class II genes were determined using polymerase chain reaction/restriction fragment length polymorphisms in 94 Japanese patients with SSc (22 ACA positive and 72 ACA negative) and 50 race matched normal control subjects. RESULTS: Frequency of DQB1*0501 was increased in ACA positive SSc patients compared with ACA negative SSc patients (36% versus 13%; p = 0.02, odds ratio = 4.0, 95% confidence interval 1.1 to 13.9), but the association of ACA with a polar amino acid at position 26 in the DQB1 beta 1 domain, which was demonstrated in white North Americans, was not observed in Japanese. The DRB1*0101, *0405, and *1302 alleles were associated with high ACA titres, whereas DRB1*1502 was associated with low ACA titres and a low frequency of centromere protein C (CENP-C) reactivity. CONCLUSIONS: These results suggest that the ACA response is associated with multiple HLA class II genes and that ACA positive SSc patients are heterogeneous in terms of immunogenetic background.

Alleles↗
PubMed1995

A frame-shift mutation of the androgen receptor gene in a patient with receptor-negative complete testicular feminization: comparison with a single base substitution in a receptor-reduced incomplete form.

Mutations of the androgen receptor that impair the action of androgens result in abnormal male sexual development. We studied the structure of the androgen receptor gene in a patient with the receptor-negative form of complete testicular feminization and another patient with a receptor-reduced form of incomplete testicular feminization. In the subject with complete testicular feminization, the deletion of a single nucleotide occurred at nucleotide number 1893 at exon 2. The subsequent frame-shift mutation changes the sense of codon 622 from cysteine to a translational stop signal. Codon 622 is exon 3, so the mutation predicts the synthesis of a truncated receptor that lacks the entire androgen-binding domain. Analysis of a subject with incomplete testicular feminization revealed a single substitution (CGT --> CAT) at nucleotide 2675 of exon 7, resulting in the conversion of an arginine at amino acid 840 to a histidine. This mutation in the androgen-binding domain may impair, but not remove, the androgen binding to its receptor. These results suggest that the phenotypes in our subjects are due to the mutations, and that single amino acid substitution and premature termination codon can cause variably severe functional abnormalities.

Adult↗
PubMed1995

[Ocular histopathological studies in leprosy in the silent stage--II. Immunohistochemical studies].

The distribution of leprosy antigen in 21 eyes from 12 autopsy cases of lepromatous leprosy patients (5 eyes from 3 cases in the silent stage, 16 cases from 9 cases in the active stage) were examined with acid-fast staining and immunohistochemistry. Anti-BCG antibody, anti-phenolic glycolipid-I (PGL-I) antibody, and anti-lipoarabinomannan-B (LAM-B) antibody were used as primary antigens. In the active stage, anti-BCG antibody and anti-LAM-B antibody showed almost the same staining pattern. Some cases, which showed negative reaction to acid-fast staining, occasionally showed positive staining pattern with anti-BCG antibody and anti-LAM-B antibody, which had high sensitivity and the advantage of detection of leprosy antigen. Some anti-PGL-I antibody showed a different staining pattern from acid-fast staining, anti-BCG antibody and anti-LAM-B antibody. These findings seemed to be caused by the difference in structure of the epitope. In the silent stage, clinically nonpigmented epithelium of 6 cases from 4 eyes showed positive staining pattern with anti-PGL-I antibody. These findings suggested that leprosy antigen still remained in this stage.

Aged↗
PubMed1995

Possible interaction of haemoglobin with a low Mr GTP-binding protein, ram p25.

Haemoblobin (Hb) was observed to inhibit the GDP/GTP exchange activity of a low M(r) GTP-binding protein, ram p25. Hb also inhibited the [32P]GTP-hydrolysis activity of ram p25. These inhibitory effects of Hb were lost after incubation of Hb at 80 degrees C for 3 min, indicating that the ternary tetrameric structure of Hb is essential for the inhibitory effects on ram p25 activities. Hb did not inhibit [35S]GTP gamma S-binding of nucleotide-free ram p25. Methaemoglobin (MetHb) also inhibited both [3H]GDP-dissociation and [32P]GTP-hydrolysis activities of ram p25 in a very similar manner to Hb. The results strongly suggest that Hb may suppress physiological function(s) of ram p25 in vivo by inhibiting both [32P]GTP-hydrolysis and [3H]GDP-dissociation of ram p25.

Animals↗
PubMed1995

[Electrocardiographic findings in arrhythmogenic right ventricular dysplasia (ARVD) evaluated by body surface mapping].

Electrocardiographic characteristics evaluated by body surface mapping were investigated, comparing with the other clinical findings. Isopotential maps were abnormal at the end of QRS period when the positive area persisted in the anterior middle and lower chest. VAT was also prolonged in these area. Post excitation (Epsilon) waves appeared at that period in accordance with the rapid potential change on upper anterior chest which reflected right ventricular conduction delay. There was no difference in electrophysiologic findings in patients with or without Epsilon waves. Negative potentials were present on the anterior chest in ST-T isopotential, ST-T and QRST isointegral maps in all of the patients. The area of these negative potentials was closely correlated with RV dilatation and dysfunction. It is concluded that Epsilon waves are not the direct counterpart of delayed potentials, but the reflection of the peripheral induction delay, and that primary change seems to play large part of the genesis in negative T waves.

Arrhythmias, Cardiac↗
PubMed1995

[Isochrone map, its implication and clinical usefulness].

Isochrone maps are useful tools to visually detect local abnormal activation (ventricular activation time; VAT) or repolarization (Activation recovery interval; ARI, Recovery time; RT) sequence, displaying the body surface distribution of them in the form of a map. VAT has long been considered as one of the parameters in the electrocardiographic diagnosis for ventricular hypertrophy. But its significance has not been well established, and its clinical usefulness has been limited. We demonstrated the different significance of VAT in concentric and eccentric LVH (LV dilatation) by means of VAT maps. We also revealed the usefulness of VAT maps in evaluating the conduction deficit such as bundle branch block, hemodynamic disorder and severity of arrhythmias complicated by miscellaneous heart diseases.

Body Surface Potential Mapping↗
PubMed1995

FK506 and cyclosporin A inhibit granulocyte/macrophage colony-stimulating factor production by mononuclear cells in asthma.

Bronchial asthma is associated with eosinophilic inflammation and expression of T-cell-derived cytokines, which influence eosinophilic function. FK506, a newly established immunosuppressive agent, may have potential as a therapeutic instrument for asthma because of its suppressive effect on T-cell activation. To assess this, we compared the inhibitory effects of FK506 and cyclosporin A on production of granulocyte/macrophage colony-stimulating factor and interleukin-5 by interleukin-2- or Dermatophagoides farinae-stimulated mononuclear cells from patients with asthma, and their contribution to proliferation and survival of eosinophils in vitro. FK506 inhibited granulocyte/macrophage colony-stimulating factor production by stimulated mononuclear cells from asthma patients at lower concentrations than cyclosporin A. Both drugs inhibited eosinophil proliferation and survival activity from mononuclear cells at comparable concentrations. Interleukin-5 production by stimulated mononuclear cells was also inhibited both by FK506 and cyclosporin A. We conclude that both FK506 and cyclosporin A have potential for therapy of bronchial asthma.

Asthma↗
PubMed1995

Newborn mass screening and molecular genetics of phenylketonuria in east Asia.

Phenylketonuria (PKU) is an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (PAH), and is performed with newborn mass screening. PKU causes irreversible mental retardation that can be prevented by a strict low-phenylalanine diet. More than 100 different mutations have been identified world wide and it has been revealed that PKU is a highly heterogeneous disorder. Here, we describe the progress of the molecular genetics of PKU in East Asia. Approximately 60% of all PKU alleles in East Asians have been characterized with 10 PKU mutations. Two major PKU mutations, R413P and IVS4nt-1, may have originated in different populations, spreading in prehistoric times through the Asian continent due to the founder effect, genetic drift, and bottleneck effect. We found different mutations in Caucasians and East Asians, thus PKU mutations have occurred after ethnic divergence between Caucasians and East Asians. Furthermore, PKU genotype and in vitro PAH activity in expression analysis correlates to the clinical and biochemical phenotypes in East Asians. The molecular defects at the PAH gene regulate the in vivo PAH activities and clinical manifestations.

Alleles↗
PubMed1994

Regulatory mechanism of the ventromedial hypothalamus in enhancing glucose uptake in skeletal muscles.

To evaluate roles of the sympathetic nervous system in enhancing glucose uptake in skeletal muscles in response to electrical stimulation of the ventromedial hypothalamic nucleus (VMH), the effects of guanethidine treatment and adrenal demedullation on the response were examined in rats anesthetized and injected with muscle relaxant, pancuronium bromide. Pretreatment with guanethidine effectively suppressed the increase in the rate constant of glucose uptake, measured by the 2-deoxy-D-[3H]glucose method, in skeletal muscles upon VMH stimulation. However, bilateral adrenodemedullation had no significant effect. These results suggest that the VMH is intimately concerned in the regulation of glucose uptake in skeletal muscles through intermediation of the sympathetic nerves.

Adrenal Medulla↗