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Biomedical subjects

Y Ozawa

Publications and source records attributed to Y Ozawa.

At least 37 records · Page 2Linked to original sources
PubMed2001

Histone deacetylase 3 associates with and represses the transcription factor GATA-2.

The zinc finger transcription factor GATA-2 plays a critical role in the survival and proliferation of hematopoietic stem cells. This study examined the interaction of GATA-2 with histone deacetylases (HDACs) to define the involvement of HDACs in the regulation of GATA-2 function. GATA-2 directly associates with HDAC3 but not with HDAC1. Consistent with this, HDAC3 suppressed the transcriptional potential of GATA-2, whereas HDAC1 did not affect GATA-2-dependent transcription. Results further demonstrated that GATA-2 and HDAC3 colocalized in the nucleus. These results identify GATA-2 as a nuclear target for HDAC3-mediated repression. Furthermore, GATA-2 also directly associated with HDAC5 but not with other class II HDACs examined, that is, HDAC4 and HDAC6. This is the first demonstration that a tissue-specific transcription factor directly and selectively interacts with HDAC3 and HDAC5 among HDAC family members.

Animals↗
PubMed2001

Expression profile of active genes in human periodontal ligament and isolation of PLAP-1, a novel SLRP family gene.

Periodontal ligament (PDL) is one of the most important tissues in maintaining the homeostasis of tooth and tooth-supporting tissue, periodontium. In this study, we investigated the expression profile of active genes in the human PDL obtained by collecting sequences with a 3'-directed cDNA library, which faithfully represents the composition of the mRNA population. We succeeded in obtaining a total of 1752 cDNA sequences by sequencing randomly selected clones and identified a total of 1318 different species as gene signatures (GS) by their sequence identity, 344 of which were known genes in the GenBank, and 974 of which were new genes. The resulting expression profile showed that collagen type I and type III were the most abundant genes and that osteogenesis-related proteins, such as SPARC/osteonectin and osteoblast specific factor 2, were highly expressed. By comparing the expression profile of PDL with 44 profiles similarly obtained with unrelated human cell/tissue, nine novel genes, which are probably expressed specifically in PDL, were discovered. Among them, we cloned a full-length cDNA of GS5096, which is frequently expressed in freshly-isolated periodontal tissue. We found that it encodes a novel protein, which is a new member of the class I small leucine-rich repeat proteoglycan family, and designated it PLAP-1 (periodontal ligament associated protein-1). PLAP-1 mRNA expression was confirmed in in vitro-maintained PDL cells and was enhanced during the course of the cytodifferentiation of the PDL cells into mineralized tissue-forming cells such as osteoblasts and cementoblasts. These findings suggest the involvement of PLAP-1 in the mineralized matrix formation in PDL tissues.

Amino Acid Sequence↗
PubMed2001

Histone acetylation induced by granulocyte colony-stimulating factor in a map kinase-dependent manner.

Histone acetylation has been shown to affect chromatin structure and gene expression. The mitogen-activated protein (MAP) kinase pathway is activated by a number of cytokines and plays critical roles in hematopoietic cell survival, proliferation, and differentiation. We focused on the part of the MAP kinase cascade and granulocyte colony-stimulating factor (G-CSF)in histone acetylation at one of the critical myeloid differentiation-associated genes, myeloperoxidase (MPO). G-CSF caused rapid acetylation of histone H3 and H4 at the promoter of MPO as revealed by chromatin immunoprecipitation. In addition, CBP and p300 were recruited to the promoter in response to G-CSF. Furthermore, we showed that rapid histone acetylation induced by G-CSF is MAP kinase-dependent. These results illustrate how myeloid-differentiating signals via G-CSF may be coupled with histone acetylation during the process of gene expression.

Acetylation↗
PubMed2001

Reciprocal regulation of tissue-type and urokinase-type plasminogen activators in the differentiation of murine preadipocyte line 3T3-L1 and the hormonal regulation of fibrinolytic factors in the mature adipocytes.

Adipose tissue expresses a variety of genes including tumor necrosis factor alpha and type-1 plasminogen activator inhibitor (PAI-1); and these factors, produced by adipocytes, may be associated with the risk of coronary events in obesity. In this study, we characterized the production of fibrinolytic factors including tissue-type plasminogen activator (tPA), urokinase-type PA (uPA), and PAI-1 in the differentiation of preadipocytes, and examined the hormonal regulation of these fibrinolytic factors in mature adipocytes. Mouse 3T3-L1 preadipocytes were employed as a model of adipocytes. Adipocyte differentiation was induced by insulin, dexamethasone, and 3-isobutyl-1-methyl xanthine (IBMX). alpha-Glycerophosphate dehydrogenase (GPDH) activity and glucose transporter 4 (GLUT4) mRNA, indices for adipocyte maturation, were induced on Day 4, and gradually increased. GPDH activity reached its maximum level on Day 14. The level of tPA, a major PA in preadipocytes, dramatically decreased with differentiation. On the other hand, that of uPA reciprocally increased. PAI-1 production was also dramatically induced concomitant with differentiation. In mature adipocytes, uPA production was dominant (25 microg/ml/24 h vs. 0.8 microg/ml/24 h for tPA). Total PA activity in the mature adipocytes was reduced by insulin or dexamethasone, but not by glucagon. Insulin, IBMX, and dexamethasone significantly decreased both uPA and tPA production, and increased PAI-1 production. Glucagon had no effect on the production of these fibrinolytic factors. Our results reveal that uPA is one of the markers for the differentiation of 3T3-L1 cells and that insulin, IBMX, and dexamethasone are potent regulators of the fibrinolytic activity in differentiated 3T3-L1 cells, reciprocally affecting PA and PAI-1 levels in them.

1-Methyl-3-isobutylxanthine↗
PubMed2001

Influences of venous involvement on postoperative brain damage following the anterior interhemispheric approach.

BACKGROUND: The anterior interhemispheric approach offers us an excellent surgical view for suprasellar lesions. Following this approach, we occasionally encounter postoperative brain damage in the frontal lobes. To assess the determinants of such a complication, we undertook a clinical study. METHOD: Potential causes for such brain damage were evaluated in 28 consecutive patients with suprasellar tumours extirpated using this approach. We focused particularly on the influences of venous involvement during surgery. The draining territory index (DTI) was originally devised for estimating the extent of the draining area of the sacrificed bridging veins. FINDINGS: CT evident brain damage was observed in five of 28 patients (17.8%), but only one patient (3.6%) showed clinically significant postoperative deficits. The patient's age, tumour pathology, tumour character, tumour size, duration of surgery, and radicality of the surgery did not affect the incidence of the brain damage. Of the twelve patients whose bridging veins were sacrificed during surgery, four (33.3%) showed brain damage in the frontal lobes. In contrast, such damage was observed in only one patient out of 16 (6.3%) whose bridging veins were preserved. Among the brain-damaged group, the average DTI of the sacrificed veins was significantly higher than that among the non-brain-damaged group. INTERPRETATION: Venous involvement during surgery significantly aggravated postoperative brain damage following the anterior interhemispheric approach. The DTI was useful in predicting the risk of brain damage, and a large bridging vein with a DTI over 50% should not be sacrificed during surgery.

Adult↗
PubMed2001

Intracoronary electrocardiogram for early detection of myocardial viability during coronary angioplasty in acute myocardial infarction.

PURPOSE: The clinical value of the intracoronary electrocardiogram (ECG) for detecting myocardial viability in acute myocardial infarction was evaluated by thallium-201 scintigraphy and left ventriculogram at the chronic stage. METHODS: Intracoronary ECGs, recorded from the tip of a guidewire during emergency coronary angioplasty, were obtained in 65 patients with reperfused anterior myocardial infarction. Further ST segment elevation of greater than 0.2 mV detected during the balloon inflation was taken as significant. The left ventricular segmental shortening was measured from left ventriculograms recorded at acute and chronic stages. The infarct area was defined as viable when a thallium uptake of more than 50% was detected on thallium-201 myocardial scintigraphy at the chronic stage. RESULTS: During emergency coronary angioplasty, significant ST segment elevation was noted in 45 patients (Group A); however, the ST segment was not significantly elevated in the other 20 patients (Group B). The infarct area of 42 patients in Group A and three patients in Group B was viable on scintigraphy. Improvement left ventricular wall motion of the infarct area was observed in 39 of the 42 patients in Group A and the three patients in Group B. Therefore, intracoronary ECG can predict reversible dysfunction with excellent sensitivity (92.9%) and specificity (73.9%). CONCLUSIONS: The myocardium within an infarct area can be regarded as viable when a further ST segment elevation occurs on intracoronary ECG during emergency coronary angioplasty. It is useful, therefore, to monitor the intracoronary ECG during coronary angioplasty balloon inflation to assess the myocardial viability of the infarct area.

Angioplasty, Balloon, Coronary↗
PubMed2001

Reduced expression of neuropeptides can be related to respiratory disturbances in Rett syndrome.

We immunohistochemically examined neurotransmitter systems, which function in the brainstem and are involved in neuronal organization of respiration, in an autopsy brain from a patient with Rett syndrome (RS). Immunoreactivity (IR) for tyrosine hydroxylase, a functional marker for catecholaminergic neurons, was severely reduced in the locus ceruleus, while that for tryptophan hydroxylase involved in serotonin synthesis was spared in the raphe nuclei. In the brainstem, IR for substance P (SP) was reduced in the parabrachial complex and that for methionine-enkephalin (met-enk) was affected in the parabrachial, hypoglossal, dorsal vagal and solitary nuclei. In addition, expressions of these neuropeptides were also disturbed in the basal ganglia. A widespread altered expression of antagonistic neuropeptides, SP and met-enk, may be involved in the pathogenesis of RS, especially in its respiratory manifestation.

Adolescent↗
PubMed2001

E7070, a novel sulphonamide agent with potent antitumour activity in vitro and in vivo.

E7070 (N-(3-Chloro-7-indolyl)-1,4-benzenedisulphonamide) was selected from our sulphonamide compound collections via antitumour screening and flow cytometric analysis. Following treatment with E7070, the cell cycle progression of P388 murine leukaemia cells was disturbed in the G1 phase. The cell-killing effect on human colon cancer HCT116 cells was found to be time-dependent. In the panel of 42 human tumour cell lines, E7070 showed an antitumour spectrum that was distinct from those of other anticancer drugs used in clinic. Animal tests using human tumour xenograft models demonstrated that E7070 could cause not only tumour growth suppression, but also tumour regression in three of five colorectal and two of two lung cancers. In the HCT116 xenograft model, E7070 was shown to be superior to 5-FU, MMC and CPT-11 (irinotecan). Furthermore, complete regression of advanced LX-1 tumours was observed in 80% of E7070-treated mice. All of these observations have promoted this drug to clinical evaluation.

Animals↗
PubMed2001

Frequency-dependent electrophysiological effect of ibutilide on human atrium and ventricle.

Most of the class III antiarrhythmic agents developed in recent years blocks the rapid component of delayed rectifier potassium current (IKr). IKr blocker shows reverse use-dependency and also may cause torsades de pointes at slower heart rate. Ibutilide fumarate, a novel class III antiarrhythmic agent, increases window Na(+) current at the action potential plateau phase. We studied the rate-dependent effect of ibutilide on the electrophysiological parameters of human atrium and ventricle. Franz catheter and a pacing catheter were placed closely in the high right atrium and right ventricular apex to record monophasic action potentials (MAP) during pacing at cycle length (PCL) of 600 ms and 350 ms in eight patients who underwent electrophysiological study. MAP duration of right atrium (RA-MAPD) and right ventricle (RV-MAPD), effective refractory period of RA and RV (RA-ERP and RV-ERP), intra-atrial conduction time (IACT) and intra-ventricular conduction time (IVCT) were measured before and after intravenous administration of ibutilide (0.01 mg/kg up to 1mg). A conduction time from RA pacing spike to distal coronary sinus potential was used to measure IACT, while QRS duration of surface ECG during RV pacing was used to measure IVCT. Ibutilide prolonged RA-MAPD by 60 ms at PCL 600 ms and by 53 ms at PCL 350 ms; RV-MAPD by 48 ms at PCL 600 ms and by 55 ms at PCL 350 ms. Ibutilide did not affected RA and RV-ERP/MAPD ratio, IACT, and IVCT. Ibutilide prolongs MAPD and ERP of human atrium and ventricle without reverse use-dependency.

Action Potentials↗
PubMed2001

HLA class II alleles and salivary numbers of mutans streptococci and lactobacilli among young adults in Japan.

To investigate the genetic predisposition toward the accumulation of oral microorganisms, the association between the alleles of HLA-DQA1, -DQB1 and -DRB1 and the salivary numbers of mutans streptococci and lactobacilli were examined in 102 young adults in Japan. HLA-DQA1*0102, DQB1*0604, DRB1*0802, and DRB1*1302 were weakly associated with the numbers of lactobacilli in saliva samples (P<0.05). HLA-DQB1*0601 was associated with the salivary numbers of mutans streptococci (P<0.01). Two HLA class II haplotypes, HLA-[DRB1*0802-DQA1*0301-DQB1*0302] and HLA-[DRB1*1302-DQA1*0102-DQB1*0604], were also weakly associated with the salivary numbers of lactobacilli (P<0.05). These observations suggest that HLA class II alleles may be related to the salivary populations of oral microorganisms, such as mutans streptococci and lactobacilli.

Adolescent↗
PubMed2001

Systematic screening of type B human natriuretic peptide receptor gene polymorphisms and association with essential hypertension.

C-type natriuretic peptide (CNP) dilates arteries, lowers blood pressure and inhibits proliferation of vascular smooth muscle cells via the type B natriuretic peptide receptor (NPRB). The CNP-NPRB system may play a crucial role in the development of cardiovascular disease. We recently determined the structure of the human NPRB gene. In the present study, our objectives are to identify the polymorphisms of the NPRB gene and investigate the association of this gene with essential hypertension (EH). We used the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique to study the NPRB gene polymorphism, and conducted an association study using a novel polymorphic marker. PCR-SSCP analysis of all 22 exons was done in 90 subjects, and abnormally-migrating bands were observed in the analyses of exon 11 and intron 18. Direct sequencing of these DNA fragments revealed the following sequence alterations: a C to T transition at nucleotide (nt) 2077 in exon 11 and a 9-bp insertion/deletion (I/D) in intron 18. PCR-restriction fragment length polymorphism analysis (PCR-RFLP) was developed to detect the C2077T transition. PCR-RFLP analyses of healthy subjects revealed that the C2077T polymorphism had complete linkage to GT repeats in intron 2 reported previously. The I/D polymorphism was identified by polyacrylamide gel electrophoresis, and it was not linked to any known polymorphic alleles of this gene. Therefore, the possible association between the I/D polymorphism and EH was investigated. A total of 123 individuals with EH and 123 age-matched normotensive control subjects were studied. Overall distributions of allele frequencies in the two groups were not significantly different. Although the I/D polymorphism in intron 18 of the NPRB gene was not associated with EH, the results of this study, which identified two novel polymorphisms in the human NPRB gene, will facilitate further genetic analysis of this gene and cardiovascular disease.

Adult↗
PubMed2001

Serum alpha-subunit levels in patients with pituitary adenomas.

OBJECTIVE: We investigated preoperative and postoperative serum alpha-subunit levels and the alpha-subunit response to TRH in patients with various types of pituitary tumour and correlated the data with histological findings in order to clarify the significance of alpha-subunit measurement in pituitary adenomas. PATIENTS: We examined 59 patients with pituitary tumours (22 with GH cell adenomas, 30 with clinically nonfunctioning adenomas and seven with other tumours) treated at Toranomon Hospital between 1996 and 1998. RESULTS: The basal alpha-subunit level was supranormal in six out of 22 (27%) patients with a GH cell adenoma and in nine out of 30 (30%) patients with a nonfunctioning adenoma. A paradoxical alpha-subunit response to TRH was found in seven out of 22 (32%) patients with a GH cell adenoma. These seven patients also showed a paradoxical GH response to TRH administration. In addition, paradoxical response to TRH was found in eight out of 30 (27%) patients with a clinically nonfunctioning adenoma. In contrast, patients with other types of pituitary tumour showed neither a supranormal alpha-subunit level nor a paradoxical response to TRH. The supranormal alpha-subunit level and the abnormal response to TRH were normalized in both GH cell adenoma and nonfunctioning adenoma patients after successful surgery. Immunohistochemical studies showed alpha-subunit positive cells in 51% of GH cell adenomas or nonfunctioning adenomas and there was a good concordance with the serum alpha-subunit levels in both GH cell adenoma and nonfunctioning adenoma patients. CONCLUSIONS: These findings suggest that supranormal serum alpha-subunit levels are mainly due to hypersecretion by the tumour itself, while the paradoxical alpha-subunit response to TRH is an associated phenomenon in patients with a GH cell adenoma or nonfunctioning adenoma. The alpha-subunit level and the response to TRH may be useful indicators for assessing the operative outcome, especially in nonfunctioning adenoma patients who have no other definite endocrine markers.

Adenoma↗
PubMed2001

Serum antibodies to human pituitary membrane antigens in patients with autoimmune lymphocytic hypophysitis and infundibuloneurohypophysitis.

OBJECTIVE: Serum antipituitary antibodies were investigated by the immunoblotting method using human anterior pituitary membrane preparation as the antigen. PATIENTS: Thirteen patients with autoimmune lymphocytic hypophysitis, two patients with infundibuloneurohypophysitis, four patients with isolated ACTH deficiency, 21 patients with diabetes mellitus (type 1 and type 2) and 38 healthy subjects were studied. METHODS: Human pituitary membrane antigens were electrophoresed by sodium dodecylsulphate-polyacrimide gel electrophoresis (SDS-PAGE). The antigens were transferred to polyvinylidene difluoride membrane and reacted with the sera followed by incubation with biotinylated anti-human IgG goat serum. RESULTS: Serum antibodies to 68, 49, 43 kD human pituitary membrane antigens were detected in five of 13, one of 12 patients with infundibuloneurohypophysitis and none of four patients with isolated ACTH deficiency. These antibodies were not detectable when human thyroid, liver or rat pituitary preparations were used as the antigen. CONCLUSION: These findings suggest that serum antibodies to 68, 49, 43 kD human anterior pituitary antigen are specific but not so frequently detected in autoimmune lymphocytic hypophysitis.

Adrenocorticotropic Hormone↗
PubMed2001

Increased expression of queuosine synthesizing enzyme, tRNA-guanine transglycosylase, and queuosine levels in tRNA of leukemic cells.

Queuosine is a modified nucleoside located at the first position of the tRNA anticodon, which is synthesized by tRNA-guanine transglycosylase (TGT). Although the levels of queuosine in cancer cells have been reported to be lower than those in normal cells, the expression levels of TGT remain to be determined. We determined the expression levels of a subunit of TGT (TGT60KD). Contrary of our expectations, the results revealed higher levels of expression of TGT60KD than that in normal cells, and the level of queuosine in the tRNA fraction corresponded with that of TGT60KD expression. These results suggest the possibilities that the expression levels of TGT60KD regulate TGT activity and the levels of queuosine, and that TGT60KD plays significant roles in carcinogenesis. To our knowledge, this is a first report of increased expression levels of TGT60KD in human cancer cells.

Humans↗
PubMed2001

Thoracic epidural bupivacaine attenuates supraventricular tachyarrhythmias after pulmonary resection.

UNLABELLED: Supraventricular tachyarrhythmias after pulmonary surgery are well described. Some investigators suggest that tachyarrhythmias after thoracic operations may result from the relative sympathotonic status produced by injury to the cardiac parasympathetic nerves. We examined whether postoperative thoracic sympathetic blockade by thoracic epidural bupivacaine might reduce the tachyarrhythmias after pulmonary resection. Fifty patients with lung cancer were randomized to receive epidural bupivacaine (Group B) or epidural morphine (Group M). Patients in Group B were given 6 to 10 mL of 0.25% bupivacaine epidurally, followed by epidural infusion at 3 to 5 mL/h for 3 days, and patients in Group M were given 2 to 3 mg morphine epidurally, followed by morphine infusion at a rate of 0.2 mg/h. Tachyarrhythmias were diagnosed by using the continuous heart rate trend and arrhythmia trend with a central monitoring system. Postoperative analgesia was not statistically different between groups. However, the incidence of postoperative tachyarrhythmias in Group B was significantly less than in Group M (1 of 23 vs 7 of 25, P = 0.0497, Fisher's exact test). The continuous infusion of thoracic epidural bupivacaine can reduce supraventricular tachyarrhythmias compared with epidural morphine infusion, presumably because of attenuation of the sympathotonic status after pulmonary resection. IMPLICATIONS: We examined whether postoperative thoracic sympathetic blockade by thoracic epidural bupivacaine after pulmonary resection might reduce the tachyarrhythmias that may result from the relative sympathotonic status produced by injury to the cardiac parasympathetic nerves. The continuous infusion of thoracic epidural bupivacaine was shown to reduce supraventricular tachyarrhythmias.

Aged↗