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Biomedical subjects

Y Okubo

Publications and source records attributed to Y Okubo.

At least 145 records · Page 8Linked to original sources
PubMed1998

CD3-CD4-CD8-CD56-CD19-CD14- cells and CD3+CD8 dull-positive cells produce IL-4 in AIDS patients.

We used flow cytometry to identify the presence of intracellular cytokines (cytoflow) and analyse the production of IL-4 in peripheral blood from AIDS patients who have practically no CD4+ T cells. We found that IL-4 was produced by CD3-CD4-CD8-CD56-CD19-CD14- cells and CD3+CD8 dull-positive cells in AIDS patients. Moreover, CD3-CD4-CD8-CD56-CD19-CD14- cells had helper activity for immunoglobulin synthesis. These findings indicate that instead of CD4+ T helper cells, C3-CD4-CD8-CD56-CD19-CD14- cells and CD3+CD8 dull-positive cells may be an important source of IL-4 in a variety of immune responses for AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1998

Heterogeneity of blood group RhE variants revealed by serological analysis and molecular alteration of the RHCE gene and transcript.

After testing red cells from 12 RhE variants with a panel of anti-E monoclonal antibodies (MoAbs), four patterns of reactivity were detected indicating that the MoAbs may recognize four distinct E epitopes designated epE1, epE2, epE3 and epE4. The variants were classified into four categories (cat EI to EIV) which carried epE1 and epE2, epE1 and epE4, epE1, epE3 and epE4, and all four epitopes, respectively. Molecular analysis of the transcripts and genomic DNA of the variants from cat EI, EII and EIII displayed three distinct genetic alterations. Cat EI variants exhibited a point mutation (T500A) in exon 4 of the RHCE gene that resulted in a Met167Lys substitution in the third extracellular loop of the RhcE protein. Cat EII variant carried a hybrid gene structure characterized by replacement of exons 1-3 (or 2-3) of the RHCE gene by their specific counterparts in the RHD gene. This latter variant was also associated with a weak expression of the RhC antigen. In cat EIII variants there was a partial DNA exchange of exon 5 sequences (nt 697 and 712) between the RHCE and the RHD genes, generating a hybrid Rh cE-D-cE protein carrying the Glu233 and Val238 substitutions. The serological and molecular studies of the RhE variants indicated that: (i) the RhE antigen is a mosaic composed of at least four epitopes and proline at position 226 is necessary but not sufficient for the full expression of the E antigen, (ii) the lack of RhE epitope(s) is associated with heterogenous molecular alterations of the RHCE gene, and (iii) amino-acids located on the third and fourth extracellular loops of the RhCE polypeptide are critical for some RhE epitopes expression.

Antibodies, Monoclonal↗
PubMed1998

Decay-accelerating factor (CD55) deficiency phenotypes in Japanese.

Decay-accelerating factor (DAF, CD55) is a complement regulatory glycoprotein that expresses the Cromer-system blood group antigens. Two, very rare, inherited DAF-deficiency phenotypes, Inab and Dr(a-), were identified in Japanese propositi. Red cells of the Inab phenotype propositus had no Cromer-system antigens and did not bind monoclonal anti-DAF. The Inab propositus was homozygous for a DAF non-sense mutation, converting the Trp53 codon to a stop codon; her parents were heterozygous for this mutation. This is the same mutation as that previously found in the original Inab phenotype propositus. Haemagglutination-inhibition titrations of the serum of the Inab propositus with soluble-recombinant DAF demonstrated that anti-IFC represents a mixture of antibodies to all four DAF short consensus repeat domains. The Dr(a-) individual had very low levels of Cromer-system antigens and DAF on her red cells. Loss of a TaqI restriction site from DAF exon 5 suggested that she has a previously detected mutation, encoding a Ser165Leu substitution. Red cells of the two propositi did not show abnormal levels of lysis in an acid lysis test, but after blocking of CD59 with monoclonal antibody, Inab phenotype red cells showed more lysis than Dr(a-) red cells, and Dr(a-) cells showed substantially more lysis than control cells.

Adult↗
PubMed1998

Implications of brain imaging for the management of schizophrenia.

Positron emission tomography (PET) can be used to explore relationships between central neuroreceptor occupancy, psychotropic drug blood levels and clinical effects. Treatment with conventional neuroleptics induces high (70-90%) dopamine (D2)-receptor occupancy. The risk of extrapyramidal side effects increases at D2-receptor occupancies above 80%. Standard doses of clozapine induced a low (20-67%) D2-receptor occupancy, but very high (85-90%) 5-hydroxytryptamine (5-HT2A)-receptor occupancy. The novel antipsychotics risperidone and olanzapine induced high occupancy of both D2 and 5-HT2A receptors at suggested standard doses. The occurrence of extrapyramidal side effects in some patients in the higher dose ranges does not support the view that 5-HT2A-receptor occupancy completely prevents the development of extrapyramidal side effects. These results emphasize the need for further exploration of the low dose ranges of risperidone and olanzapine. A preliminary analysis of an ongoing PET study showed that a schizophrenic patient treated with sertindole at 20 mg/day had a D2-receptor occupancy of below 70%. Further studies are needed to show whether sertindole is the first new antipsychotic that induces low occupancy in the clinical dose range, suggesting a mechanism of action distinct from that of classical neuroleptics and analogous to that of clozapine.

Antipsychotic Agents↗
PubMed1998

The activities of the Tokyo Center.

The main World Health Organization (WHO) activities of the Tokyo Center are as follows: (1) It performed the research project entitled 'A Bio-Psycho-Social Study on Children with Emotional and Behavioral Problems' in cooperation with the Beijing and Seoul Centers from 1985 to 1987. These results suggested that the deviant behavior of children in the general population had no biological background, but presumably stemmed from psychosocial disadvantages. (2) It has participated in a field trial for the proposed draft for chapter V of the ICD-10 as the Field Trial Coordinating Center in Japan since 1986 and the first Japanese edition of the ICD-10 Classification of Mental and Behavioral Disorders: Clinical Descriptions and Diagnostic Guidelines were published in 1993. (3) It proposed the collaborative project exploratory eye movements in patients with schizophrenia in 1989 and has promoted the project with the cooperation of six centers that included Beijing, Casablanca, Montreal, Munich, Prague and Sapporo. The findings of the present project indicated that exploratory eye movements may be specific to schizophrenia and can be practically used to discriminate schizophrenia without significantly depending on language.

Adolescent↗
PubMed1998

Acetylcholine stimulates alveolar macrophages to release inflammatory cell chemotactic activity.

Neurological transmitters including ACh, substance P (SP), and calcitonin gene-related peptide (CGRP) play an important role in regulating airway tone, and increased bronchial reactivity to cholinergic stimulation is a well-recognized phenomenon in patients with bronchial asthma. We postulated that ACh, SP, and CGRP might stimulate alveolar macrophages (AMs) to release neutrophil, monocyte, and eosinophil chemotactic activities. To test this hypothesis, bovine AMs were isolated by bronchoalveolar lavage and cultured. AMs released chemotactic activities in response to ACh in a dose- and time-dependent manner (P < 0.05). However, SP and CGRP did not stimulate bovine AMs. Checkerboard analysis revealed that these released activities were predominantly chemotactic. Partial characterization and molecular-sieve column chromatography revealed that low-molecular-weight lipid-soluble activity was predominant. Lipoxygenase inhibitors significantly blocked the release of chemotactic activities (P < 0.05). Leukotriene B4- and platelet-activating factor-receptor antagonists blocked the chemotactic activities. Immunoreactive leukotriene B4 significantly increased in supernatant fluids in response to ACh (P < 0.05), but platelet-activating factor did not. The receptor responsible for the release of the chemotactic activities was the muscarinic M3 receptor. These data demonstrate that ACh stimulates AMs to release lipoxygenase-derived chemotactic activities and plays a role in inflammatory cell recruitment into the airway.

Acetylcholine↗
PubMed1998

Predominant implication of IL-5 in acute eosinophilic pneumonia: comparison with chronic eosinophilic pneumonia.

BACKGROUND: Acute eosinophilic pneumonia (AEP) is a rare disease with unknown etiology. To examine pathophysiology of AEP we measured the cell number of eosinophils and eosinophil active cytokines in the peripheral blood and bronchoalveolar lavage fluid (BALF) of AEP patients and compared the levels with those measured in chronic eosinophilic pneumonia (CEP) patients. METHODS: Cell number of eosinophils in peripheral blood and BALF from patients with AEP (n = 3) and CEP (n = 3) were measured. Eosinophil active cytokines in serum and BALF from the patients were measured using ELISA. RESULTS: Eosinophil cell number in peripheral blood was 274-1,377/mm3 in AEP and 526-2,500/mm3 in CEP. The percentages of BALF eosinophils were high in AEP and CEP. Eosinophilia disappeared after methylprednisolone pulse therapy (1 g for 3 days) in AEP, however the cell number of eosinophils gradually increased after methylprednisolone pulse therapy and then spontaneously decreased to within normal range without any further medication. The concentrations of IL-5 in AEP were very high in serum and in BALF, however the concentrations in CEP were low in serum and BALF. CONCLUSION: AEP is a disease in which eosinophil active cytokine IL-5 is predominantly involved; CEP is not. The factors involving eosinophil infiltration to inflammatory loci differ between AEP and CEP.

Acute Disease↗
PubMed1998

Effects of intracellular cyclic AMP modulators on human eosinophil survival, degranulation and CD11b expression.

BACKGROUND: Brochial asthma is characterized by infiltration of inflammatory cells such as lymphocytes and eosinophils. Theophylline is one of the most widely used drugs in the therapy of bronchial asthma, and phosphodiesterase (PDE) inhibition is thought to be an important mechanism of its anti-inflammatory actions. However, the detailed effects of PDE inhibition on eosinophils still remain unclear. METHODS: Eosinophils in peripheral blood obtained from normal subjects and patients with mild off-season allergic rhinitis were purified using CD16 negative selection. The following effects of theophylline (nonselective PDE inhibitor), KF19514 (selective PDE IV inhibitor), mirlinone (selective PDE III inhibitor), procaterol (beta2-adrenoceptor agonist) and N6, 2'-O-dibutyryladenosine 3'5'-cyclic monophosphate (dB-cAMP; AMP analogue) on eosinophils were examined: (1) survival in the presence of interleukin-5, (2) degranulation by granulocyte/macrophage colony-stimulating factor (GM-CSF) or platelet-activating factor (PAF), (3) CD11b expression under GM-CSF or PAF stimulation and (4) intracellular cAMP level. RESULTS: Eosinophil survival was inhibited by theophilline, KF19514 or procaterol. GM-CSF- or PAF-induced degranulation was inhibited by theophylline, KF19514, procaterol or dB-cAMP. CD11b up-regulation by PAF was inhibited by theophylline, KF19514 or dB-cAMP, while GM-CSF-stimulated CD11b up-regulation was not significantly inhibited by any of the drugs tested. The levels of intracellular cAMP were increased by theophylline, KF19514 and procaterol. CONCLUSIONS: Intracellular cAMP is an important factor in the regulation of eosinophil biological functions. PDE IV inhibitors and beta2-agonists are suggested to be useful for the treatment of bronchial asthma through inhibition of eosinophil effector function.

Bucladesine↗
PubMed1998

Serum high molecular weight form of insulin-like growth factor II from patients with non-islet cell tumor hypoglycemia is O-glycosylated.

Non-islet cell tumor hypoglycemia (NICTH) is one of major causes of fasting hypoglycemia. In some patients with NICTH, insulin-like growth factor II (IGF-II) produced by and secreted from the tumors is thought to be a hypoglycemic agent. In patients with NICTH, the major form of IGF-II is high molecular weight form of IGF-II, designated as big IGF-II. The generation of big IGF-II in the NICTH syndrome is unclear. It has been reported that in the patients with NICTH big IGF-II lacks normal E-domain O-linked glycosylation, suggesting that the patient's big IGF-II might be generated by abnormal processing of pro-IGF-II. However, we have found that the apparent size of big IGF-II varies in sera from the patients with NICTH, and that there is a possibility that slower migration pattern of IGF-II might be because of a different size of sugar moiety attached to pro-IGF-II. In the present study using the sera from 10 patients with NICTH, we investigated the effect of O-glycosidase digestion on migration of IGF-II and analyzed the results by Western immunoblot. By Western immunoblot analysis the big IGF-II was reduced in size to 9.5 kDa in the enzyme-treated sera of the 10 patients with NICTH. The migration pattern is similar to that observed in sera of normal subjects after O-glycosidase digestion. These data indicate that big IGF-II from patients with NICTH is O-glycosylated, and the sizes of the sugar moiety are larger than those from normal subjects suggesting abnormal glycosylation in NICTH.

Adult↗
PubMed1998

Muscarinic cholinergic receptors in human narcolepsy: a PET study.

OBJECTIVES: To investigate the function of the muscarinic cholinergic receptor (mAchR) in narcolepsy and the effects of pharmacotherapy on mAchRs. BACKGROUND: Muscarinic neural transmission serves as the main executive system in REM sleep. Studies in canine narcolepsy reported an increase in mAchRs in the pons. METHODS: The mAchRs of 11 drug naive/free patients with narcolepsy and 21 normal controls were investigated using PET with [11C]N-methyl-4-piperidylbenzilate ([11C]NMPB). Measurements were done in the pons, thalamus, striatum, and cerebral cortex. Seven of the 11 patients also underwent additional PET scans after the alleviation of symptoms by pharmacotherapy. RESULTS: There were no differences in [11C]NMPB binding between the control and drug naive/free patients in all areas analyzed. At the time of on-medication PET scan, [11C]NMPB binding in the thalamus was decreased, but only to a small degree compared with that by anticholinergic drugs. CONCLUSION: The present results do not support the notion that the mAchR is the main site of action of pharmacotherapy in the marked clinical improvement of human cataplexy.

Adult↗
PubMed1998

Serum insulin-like growth factor II in 44 patients with non-islet cell tumor hypoglycemia.

Serum insulin-like growth factor II (IGF-II) was characterized by radioimmunoassay and Western immunoblot in 44 patients with non-islet cell tumor hypoglycemia (NICTH). 31 of 44 patients with NICTH had big IGF-II in sera. When the presence of IGF-II in tumors from 20 patients was investigated, IGF-II in tumors was detected in 18 patients and these patients had big IGF-II in sera. In two patients whose tumors did not contain IGF-II, big IGF-II in sera was not detected. In six patients with IGF-II in tumors, hypoglycemia disappeared and the big IGF-II decreased after successful removal of the tumors. These data indicate that the big IGF-II could be related to hypoglycemia, and that the increased serum big IGF-II suggests IGF-II-producing NICTH. Serum IGF-II levels in 31 patients with big IGF-II were greater than those in 13 patients without it (Mean +/- SEM: 723+/-54 vs. 326+/-31 ng/ml), but the elevated IGF-II levels were found in only 13 patients. Serum IGF-I levels were low in all patients with NICTH. In the 13 patients without big IGF-II, serum IGF-II levels were lower than those in the patients with big IGF-II, and serum IGF-I levels were also low. Serum IGF-II/IGF-I ratios in the patients with big IGF-II were elevated and greater than those in the patients without big IGF-II (35.0+/-2.2 vs. 11.5+/-2.4). The present data indicate that IGF-II-producing tumors are not rare in NICTH, and serum big IGF-II and IGF-II/IGF-I ratio are useful for screening patients with IGF-II-producing NICTH.

Adenoma, Islet Cell↗
PubMed1998

Hepatitis C virus 1b(II) infection and development of chronic hepatitis, liver cirrhosis and hepatocellular carcinoma: a case-control study in Japan.

This study was performed to determine the distribution of hepatitis C virus (HCV) genotypes among asymptomatic carriers (ASC) and patients with chronic hepatitis without cirrhosis (NC-CH), liver cirrhosis (LC), and hepatocellular carcinoma (HCC) in the Osaka area, and to assess whether infection with HCV genotype 1b (II) is more likely to develop into hepatocellular carcinoma (HCC) than is that with genotype 2a (III) or genotype 2b (IV). Genotypes of all study subjects were determined by Okamoto's method. HCV genotype 1b was detected in 100 of the 143 ASC (69.9%), 551 of the 726 NC-CH patients (75.9%), 86 of the 103 patients with LC (83.5%), and 153 of the 179 HCC (85.5%) patients. Using unconditional logistic regression analysis, the age- and sex- adjusted odds ratios contrasting NC-CH with ASC, LC with ASC and HCC with ASC were 1.38 [95% confidence interval (CI) = 0.93-2.05], 2.28 (95% CI = 1.12-4.63) and 2.27 (95% CI = 1.02-5.06) respectively. HCV genotype 1b is predominant in both healthy carriers and patients with chronic liver diseases in the Osaka area. The findings from the three case-control studies indicate that type 1b infection is more closely associated with the development of LC and HCC than type 2a or 2b through its role in the progression of chronic liver inflammation to a cirrhotic stage.

Adult↗
PubMed1998

Cyfra 21-1 as a marker of lung cancer.

The utility of cytokeratin fragment (Cyfra) 21-1, a new tumor marker, was investigated in 100 patients with lung cancer. Sandwich enzyme immunoassay detected Cyfra 21-1 in the sera of 60% of patients. Sensitivity of this marker was especially high (86.4%) for squamous cell carcinoma, exceeding that of a similar marker, squamous cell carcinoma antigen (SCC, 54.5%). In contrast, sensitivity of Cyfra 21-1 was relatively low for adenocarcinoma (52.6%) and for small cell carcinoma (50%). We conclude that Cyfra 21-1 is of value in diagnosis of lung cancer, particularly squamous cell carcinoma.

Adult↗
PubMed1998

[Serum levels of carboxyterminal propeptide of type I procollagen (PICP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP) and carboxyterminal parathyroid hormone-related protein (C-PTHrP) in hematological malignancies with bone lesions and hypercalcemia].

We measured the levels of carboxyterminal propeptide of type I procollagen (PICP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP) and carboxyterminal parothyroid hormone-related protein (C-PTHrP) in serum of patients with hematological malignancies. ICTP and C-PTHrP levels in serum of multiple myeloma (MM), non-Hodgkin's lymphoma (NHL) and adult T-cell leukemia (ATL) patients with bone lesions and hypercalcemia were significantly higher than those of patients without bone lesions and hypercalcemia. ICTP and C-PTHrP levels in ATL were significantly higher than in MM and NHL. There was a correlation between ICTP and C-PTHrP in serum of ATL patients, but no correlation in MM and NHL. Serum ICTP levels tended to correlate with serum beta 2-microglobulin and survival in patients with MM. Therefore, ICTP and C-PTHrP levels in serum may be useful in the diagnosis of bone lesions and hypercalcemia in hematological malignancies. In particular, ICTP may be a useful bone resorption marker in MM.

Adult↗
PubMed1998

[A case of paragonimiasis westermani].

A 45-year-old man, who had eaten fried fresh water crabs (Geothelphusa dehaani), was admitted to our hospital because of productive cough and bloodysputum. Blood chemistry showed increased levels of white blood cells and C-reactive protein, but peripheral blood eosinophil counts and serum IgE values were not elevated. Chest roentgenogram and chest computed tomographic scan revealed infiltration of the right middle and left upper lung fields. He was diagnosed as having pneumonia, but his symptoms and radiological examination findings did not improve with antibiotics. The diagnosis of paragonimiasis was confirmed by immunoserological examination and detection of ova in sputum, stool and bronchoalveolar lavage fluid samples. Transbronchial lung biopsy showed infiltration and degranulation of eosinophils. The patient was treated with praziquantel for 3 days at a daily dosage of 75 mg/kg. After uneventful completion of treatment all clinical symptoms and radiological abnormalities disappeared. This is the first case in which ova of paragonimiasis westermani were identified in Nagano prefecture.

Adult↗
PubMed1998

Role of selectin-dependent adhesion in cardiac allograft rejection.

BACKGROUND: Selectins play important roles in the inflammatory responses by eliciting leukocyte rolling. The roles of E- and P-selectins in the acute rejection of cardiac allografts remain unclear. This study was designed to evaluate whether E- and P-selectins participate in the pathophysiology of heart rejection. METHODS: Heterotopic heart transplantation was performed in both mice and rats in full histoincompatibility combinations. Immunohistochemistry, flow-cytometry, and reverse transcriptase- polymerase chain reaction were performed to evaluate E-, P-selectin and sialyl Lewis X (SLeX) expression in rejecting cardiac allografts. The effects of short-term administration of monoclonal antibodies (mAbs) to E- and P-selectins on cardiac allograft survival were also evaluated. RESULTS: Significant prolongation of graft survival was observed in mice treated with either anti-E- or P-selectin mAbs, or both. The enhanced endothelial and mRNA expression of E- and P-selectins was observed in the rejecting cardiac allografts. Some graft- infiltrating mononuclear cells were double-stained with both anti-SLeX and anti-alphabetaT cell receptor mAbs. Flow-cytometric analysis of graft-infiltrating cells also showed enhanced SLeX expression. CONCLUSION: These results suggest that both P- and E-selectins are critically involved in the early development of acute heart rejection.

Animals↗
PubMed1997

Regulation by differential development of Th1 and Th2 cells in peripheral tolerance to cardiac allograft induced by blocking ICAM-1/LFA-1 adhesion.

BACKGROUND: Specific immune tolerance to cardiac allografts is induced by anti-ICAM-1 and anti-LFA-1 MAbs. Although the expression of the Th1 cytokines IL-2 and IFN-gamma is shown to increase in association with acute rejection, the roles of cytokines in the induction of peripheral tolerance by anti-ICAM-1 and anti-LFA-1 MAbs are not yet known. METHODS AND RESULTS: BALB/c hearts were transplanted into C3H/He mice. The MAbs to ICAM-1 and LFA-1 were injected for 3 days after transplantation in some recipients, and others were treated with FK506. IL-2 concentration in the supernatant of splenocytes from MAb-treated mice that were mix-cultured with donor splenocytes was lower than in normal controls. The expression of Th1 cytokines, detected by Northern blot assay, was enhanced in grafts or spleens of nontreated mice, whereas Th2 cytokines were expressed in the spleens of MAb-treated mice. No cytokine expression was enhanced in mice treated with FK506. Also, the induction of tolerance was prevented by the administration of rIL-2 in vivo in 5 of 7 mice, which were rendered tolerant. CONCLUSIONS: These data provide evidence that impairment of IL-2 production is critically involved in this tolerance induction and suggest that predominance of Th2 over Th1 cells is essential for tolerance induction by antiadhesion therapy.

Animals↗