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Biomedical subjects

Y Hirota

Publications and source records attributed to Y Hirota.

At least 127 records · Page 7Linked to original sources
PubMed1997

Chronic administration of aprindine during maintenance hemodialysis.

Aprindine was administered for 12 months to 8 hemodialysis patients suffering from arrhythmias. The serum aprindine concentration ranged from 0.3 to 0.6 microgram/ml, and did not increase with time during the 1-year treatment period. The PQ interval was temporarily prolonged in the first and second months, but the QRS and QT intervals were not changed by chronic aprindine treatment. The changes of the PQ interval in the second month of treatment were directly correlated with the serum aprindine concentration. No alterations of the ECG findings were observed when aprindine was discontinued. The cardiothoracic ratio (chest radiography) and laboratory findings were also not influenced by either aprindine treatment or its withdrawal. In conclusion, aprindine may be safely administered for at least 1 year to arrhythmia patients on maintenance hemodialysis.

Administration, Oral↗
PubMed1996

Natural history and left ventricular response in chronic aortic regurgitation.

This study was aimed at clarifying the natural history and left ventricular response in aortic regurgitation using M-mode echocardiography. We analyzed the history and echocardiographic data on 94 patients, who were divided into 4 stages according to symptoms. The duration of the asymptomatic period, which represents pure volume overload, is long, and the period of minimal symptoms, combined volume and pressure overload, is relatively short. Patients with overt heart failure due to impaired contractility can survive longer than is usually believed, and the factor that predicted the onset of heart failure was a decrease in fractional shortening > 3.8 percentage points.

Adult↗
PubMed1996

Circadian variations of onset of acute myocardial infarction and efficacy of thrombolytic therapy.

OBJECTIVES: The present study investigated whether the onset of acute myocardial infarction and resistance to thrombolysis have similar circadian variations. BACKGROUND: Circadian variations of the onset of acute myocardial infarction and resistance to thrombolysis in the early morning have been reported. Some studies have also reported a secondary peak incidence in late evening; however, it is not known whether the resistance to thrombolysis has a similar circadian variation in these patients. METHODS: Six hundred eight Japanese patients with an acute myocardial infarction were the subjects of the study. Two hundred forty-four of the 608 patients were treated with thrombolysis within 12 h of the onset of symptoms. One hundred thirteen patients received urokinase, and 131 patients received tissue-type plasminogen activator (t-PA) over 60 min. Patency of the infarct-related artery, the primary end point of the study, was evaluated at 60 min after the initiation of thrombolytic therapy, and Thrombolysis in Myocardial Infarction (TIMI) grade 0, 1 or 2 was defined as resistant to thrombolysis. RESULTS: The onset of acute myocardial infarction and resistance to thrombolysis showed circadian variations with early morning and late evening peaks (p<0.001 and p<0.05, respectively). These circadian patterns showed similar distributions as evaluated with Spearman's method (r=0.70, p<0.05), although resistance to thrombolysis showed a phase difference of about 2 h earlier than the infarction incidence. The circadian variation of the resistance to thrombolysis was independent of the types of thrombolytic agents (urokinase or t-PA). CONCLUSIONS: These findings suggest that adjustment of treatment based on the time of the onset of symptoms may be warranted for the patients with acute myocardial infarction.

Aged↗
PubMed1996

Three-exon structure of the gene encoding the rat prion protein and its expression in tissues.

The prion protein (PrP), encoded by a chromosomal gene, is associated with development of the neurodegeneration of prion-induced diseases. Since determination of the complete structure of the gene encoding PrP is important for understanding gene expression in the central nervous system (CNS), the nucleotide (nt) sequence of the isolated whole gene encoding rat PrP (raPrP) was determined. The rat PrP gene (raPrP) spans 16 kilobases (kb) of the rat genome and contains three exons of 19-47 base pairs (bp), 98 bp, and 2 kb separated by two introns of 2.2 kb and 11 kb. The first and second exons are noncoding, while the third exon contains a short 5' untranslated region, the entire 762-bp open reading frame (ORF), and a 3' untranslated region. The putative raPrP promoter in the 5' flanking region contains putative Sp1, AP-1, and AP-2 binding sites without a consensus TATA box. This TATA box-deficient feature, coupled with the presence of a high G+C content and Sp1-binding sites in the raPrP promoter, characterizes it as a housekeeping gene. Analysis of the raPrP cDNA 5'-end showed that raPrP mRNA transcription was initiated at multiple sites. Northern blot analysis showed that the levels of raPrP mRNA varied among rat tissues, with the highest levels found in the brain and placenta. This determination of raPrP nt sequences, including the introns and the 5' and 3' flanking regions, may make it possible to elucidate cis-acting elements that regulate the expression of this gene in different tissues and cell lines.

Amino Acid Sequence↗
PubMed1996

Inhibition of bacterial translocation from the gastrointestinal tract of mice injected with cyclophosphamide.

Effects of intraperitoneal injection of cyclophosphamide, an immunosuppressant, on the degree of bacterial translocation and morphological changes of Peyer's patches (PP) in the intestine were investigated with antibiotic-decontaminated SPF mice and germfree mice monoassociated with Escherichia coli C25. It has been reported that treatment with cyclophosphamide induces bacterial translocation. Cyclophosphamide treatment in this study, however, significantly decreased E. coli C25 translocation from the gastrointestinal tract to the mesenteric lymph nodes (MLN), although the numbers of lymphoid cells, especially B cells, in the PP, MLN, and spleen were remarkably reduced. Four injections of cyclophosphamide at a dose of 100 mg/kg inhibited bacterial translocation more than one injection at a dose of 200 mg/kg in SPF mice. Germfree mice, however, treated with one dose of 200 mg/kg showed the same inhibition of bacterial translocation as those given 100 mg/kg four times. In cyclophosphamide-treated mice, lymph follicles in the PP were obviously smaller than those in control mice, M-cells were similar in appearance to absorption epithelial cells except for short microvilli, and immune cells among the M-cells had disappeared. These data suggested that inhibition of bacterial translocation in mice treated with cyclophosphamide may be the result of morphological and physiological changes of epithelial cells in the gastrointestinal tract, especially M-cells, as a point of entry of invading bacteria, independent of the changes in immunological function.

Animals↗
PubMed1996

Clinical observation of spontaneous anginal attacks and multivessel spasm in variant angina pectoris with normal coronary arteries: evaluation by 24-hour 12-lead electrocardiography with computer analysis.

OBJECTIVES: Using a new, computerized 24-h 12-lead electrocardiographic (ECG) recording and analysis system (the EAGLE system), we sought to evaluate the clinical manifestations of ischemic episodes in patients with variant angina and normal coronary arteries. BACKGROUND: Although the prognosis of variant angina without significant organic stenosis is generally good, the incidence of multivessel spasm, a major prognostic factor, is surprisingly high in provocation tests. METHODS: A total of 122 patients with suspected variant or unstable angina underwent 24-h examination with the EAGLE system and two-channel Holter monitoring. Thirty patients in this group were diagnosed as having variant angina with normal or nearly normal coronary arteries. Twenty-two (73%) of these 30 patients developed anginal attacks with ST segment elevation during monitoring and were enrolled in the study. RESULTS: The 22 patients had a total of 138 episodes of transient ST segment elevation and 13 episodes of ST segment depression. No arrhythmias were observed during ST segment depression, but 26 episodes of ST segment elevation (19%) were associated with arrhythmias: 7 with premature ventricular contractions, 3 with ventricular bigeminy, 3 with complete atrioventricular (AV) block, 1 with complete AV block and couplets of premature ventricular contractions and 12 with marked sinus bradycardia (< 45 beats/min). Ten (45%) of the 22 patients had multivessel spasm. We observed three different patterns of multivessel spasm: 1) spasm at a different site on different occasions (migratory spasm); 2) spasm that sequentially affected two different sites; 3) simultaneous spasm at more than one site. The duration of ST segment elevation was much longer in patients with sequential and simultaneous spasm than in those with single-vessel spasm, and arrhythmias were more frequent during these two types of multivessel spasm. CONCLUSIONS: Although the prognosis of multivessel spasm is believed to be poor, this may not necessarily be so. Anginal attacks due to sequential and simultaneous multivessel spasm seem to be more dangerous than those involving single-vessel spasm or migratory multivessel spasm.

Aged↗
PubMed1996

Peroxynitrite-induced cardiac myocyte injury.

The effects of peroxynitrite (ONOO-) on cultured cardiac myocytes were examined by simultaneous measurements of intracellular Ca2+ ([Ca2+]i) and contractile function. On exposure to 0.2 mM ONOO-, [Ca2+]i increased to beyond the systolic level within 5 min with a concomitant decrease in spontaneous contraction of myocytes followed by complete arrest. Addition of a L-type Ca2+ channel blocker or removal of extracellular Ca2+ prevented the ONOO(-)-induced increase in [Ca2+]i, indicating that the increase in [Ca2+]i was caused by the enhanced influx of Ca2+ through the plasma membrane and not by the enhanced release from sarcoplasmic reticulum (SR). Plasma membrane fluidity and concentration of the thiobarbiturate acid-reactive substance (TBARS) in the cells remained unchanged by the ONOO- treatment. The complete cessation of contraction of myocytes persisted even under the massive increase in [Ca2+]i, which was induced by an additional saponin (5 microM) treatment. In conclusion, ONOO- increases [Ca2+]i in myocytes through disturbance of Ca2+ transport systems in the plasma membrane and impairs contractile protein.

Analysis of Variance↗
PubMed1996

Study of the collection and separation of umbilical cord blood for use in hematopoietic progenitor cell transplantation.

Human umbilical cord blood has been used as an alternative source of cells for repopulating bone marrow in allogenic bone marrow transplantation in children. The number of transplantations of umbilical cord blood cells is increasing worldwide. Umbilical cord blood was collected from 52 subjects at a single collection at the time of delivery, and separated using the red blood cell sedimentation technique. Nucleated cells harvested from the fraction enriched with white blood cells were used for an assay to detect colony-forming unit granulocyte-macrophage (CFU-GM) derived cell colonies and a flow cytometric analysis of CD34+ cells under variable conditions. The number of hematopoietic progenitor cells that might be reconstituted to bone marrow was estimated. The mean duration time from the beginning of delivery to complete collection of cord blood was 9.9 min (range 5 to approximately 20 min). The mean volume of umbilical cord blood for the 52 collections was 69.1 ml (range 15-135 ml), containing 1.001% CD34+ cells (range 0.21% approximately 2.63%) and 4 x 10(5) cells of CFU-GM derived colonies (range 0.2 x 10(5) approximately 10.0 x 10(5) cells) within 24 h at 4 degrees C after delivery of the infant. There was no contamination by the mother's lymphocytes according to cytogenetic analysis using pYNH24, which is a probe with a variable number of tandem repeat markers. These findings indicated that umbilical cord blood can be easily collected using the syringe method and separated by the red blood cell sedimentation technique using 6% hydroxyethylstarch. Within 24 h at 4 degrees C, hematopoietic progenitor cells were well detected using an assay for CFU-GM derived colonies and were measured by flow cytometric analysis. However, the instability of the number of hematopoietic progenitor cells must be resolved for safe transplantation of hematopoietic progenitor cells as a source of cells for repopulating bone marrow in children.

Antigens, CD34↗
PubMed1996

Influence of left atrial function on Doppler transmitral and pulmonary venous flow patterns in dilated and hypertrophic cardiomyopathy: evaluation of left atrial appendage function by transesophageal echocardiography.

Information regarding the relation of left atrial (LA) function to transmitral and pulmonary venous (PV) flow is limited. Using transesophageal echocardiography, we analyzed this relation in 23 patients with dilated cardiomyopathy (DCM) and 25 patients with hypertrophic cardiomyopathy (HCM). Left atrial appendage (LAA) function was assessed as a substitute for overall LA function. Transmitral and PV flow-velocity variables, the LAA emptying flow velocity (LAA-A), and the LAA ejection fraction (LAA-EF) were determined. Each patient group was divided into two subgroups with a normal ( < 15 mm Hg) or elevated ( > or = 15 mm Hg) mean pulmonary wedge pressure (PWP). Transmitral and PV flow patterns as well as LA function were similar in the two subgroups with a normal PWP (11 patients with DCM and 14 patients with HCM). For the subgroups with an elevated PWP, however, the peak velocity ratio of the early filling wave (E) to atrial contraction wave (A) was higher in DCM patients (n = 12) than in HCM patients (n = 11) (2.1 +/- 0.7 vs 1.3 +/- 0.2; p < 0.01). This difference mostly resulted from a lower A velocity in the DCM group than in the HCM group (30 +/- 10 cm/sec vs 43 +/- 7 cm/sec; p < 0.05). In addition, the reverse flow velocity at atrial contraction in the PV was lower in the DCM group than in the HCM group (19 +/- 8 cm/sec vs 37 +/- 8 cm/sec; p < 0.01). These findings were associated with poorer LA systolic function in the DCM group (LAA-A, 35 +/- 13 cm/sec vs 60 +/- 11 cm/sec; LAA-EF, 37% +/- 12% vs 55% +/- 15%, p < 0.05, respectively). Our data suggest that a restrictive transmitral flow pattern develops more easily in DCM than in HCM because LA dysfunction is present in DCM, and that LA contractility plays an important role in determining the atrial contraction wave of transmitral and PV flows with elevated LA pressure.

Atrial Function, Left↗
PubMed1996

The hemagglutination inhibition antibody responses to an inactivated influenza vaccine among healthy adults: with special reference to the prevaccination antibody and its interaction with age.

The immunogenicity of the trivalent split-virus influenza vaccine was investigated among 70 healthy adults (mean age: 48.5, range: 36-68). The vaccine antigens were: A/Yamagata/32/89 (H1N1); A/Beijing/352/89 (H3N2); and B/Bangkok/163/90. Regarding the entire sample, the vaccine induced a tenfold or more rise on the average in the hemagglutination inhibition (HAI) antibody to each antigen. The response rates (greater than or equal to a fourfold rise) were about 90% or more among those with a prevaccination titer < or = 1:64 (equivalent to < or = 1:16 on the Western scale; in Japan, the HAI titers are expressed by the final, and not the initial, dilution of the serum; from hereon our findings will be expressed using the Japanese scale), whereas they were 0-50% at > or = 1:128. Thus, the prevaccination titer was negatively associated with antibody induction. The achievement rates (postvaccination titer > or = 1:128) among those with a prevaccination titer < 1:16 remained at 48-68%. Regarding the analysis of variance, a significant effect on antibody induction was indicated for the prevaccination titer (P < or = 0.002), but not for age (P > or = 0.425). The interaction between the prevaccination titer and age was significant for A/Yamagata (P = 0.030), while it was also suggestive for A/Beijing (P = 0.054): as age increased, those with no preexisting antibody (< 1:16) showed greater titer rises, in contrast to the smaller rises among those with a titer > or = 1:16. Based on the attack survey conducted separately, the vaccine efficacy on influenza-like illnesses with fever < or = 37 degrees C and > or = 37.5 degrees C was calculated to be 16% (95% confidence interval: -66% to 57%) and 37% (-55% to 74%), respectively.

Adult↗
PubMed1996

Aortic counterpulsation may improve late patency of the occluded coronary artery in patients with early failure of thrombolytic therapy.

OBJECTIVES: Using a prospective, randomized design, we tested our hypothesis that the augmentation of diastolic pressure by intraaortic balloon counterpulsation (IABP) would improve the late patency of the occluded coronary artery in patients with early failure of thrombolytic therapy. BACKGROUND: Rescue angioplasty is often performed in patients in whom thrombolysis has failed, although 30% to 60% of the infarct-related arteries that are closed early after thrombolytic therapy will open later with conservative therapy. METHODS: The study included 45 patients in whom thrombolysis had failed, despite treatment with intravenous tissue-type plasminogen activator (alteplase 0.75 mg/kg body weight) delivered over 60 min within 12 h of the onset of symptoms. All patients underwent coronary angiography 60 min after initiation of thrombolytic therapy (baseline), and Thrombolysis in Myocardial Infarction (TIMI) grade 0, 1 or 2 flow was defined as failed thrombolysis. The patients were randomized to groups receiving IABP for 48 h (n = 23) or conservative therapy (n = 22, control subjects) at the end of cardiac catheterization. The late patency of the infarct-related artery, the primary end point of the study, was evaluated 3 weeks after myocardial infarction. Stenosis of the infarct-related artery was measured using a computer-assisted quantitative angiographic system in blinded manner. Data are expressed as mean value +/- SEM. RESULTS: There was no difference with regard to the baseline value for TIMI flow grade between the groups. However, 3 weeks after myocardial infarction, the patients treated with IABP had a significantly higher frequency of TIMI flow grade 3, lower residual percent stenosis and larger minimal lumen diameter of the infarct-related artery than did the control subjects (74% vs. 32%, p < 0.05; 42 +/- 5% vs. 68 +/- 6%, p < 0.01; and 1.6 +/- 0.1 vs. 0.9 +/- 0.2 mm, p < 0.01, respectively). CONCLUSIONS: These findings suggest that in patients with early failure of thrombolytic therapy, IABP may improve late patency of the occluded coronary artery, probably due to augmented perfusion pressure.

Constriction, Pathologic↗
PubMed1996

Identification of putative downstream genes of Oct-3, a pluripotent cell-specific transcription factor.

BACKGROUND: Oct-3, a pluripotent cell-specific POU transcription factor, appears to be a key regulator in pluripotential early embryonic cells and germ cells. In order to study how pluripotency is maintained, it is essential to know what genes are regulated by Oct-3. RESULTS: By employing a subtraction method, we identified several pluripotent cell-specific genes. Based upon expression patterns in various cell lines lacking or possessing Oct-3 function, about half of the genes were placed downstream of Oct-3. These downstream genes included a previously-known gene (Glut-3: a gene for a glucose transporter) and novel genes (226, 383 and 880). Their expression patterns paralleled that of Oct-3: all of these genes were highly expressed in pluripotent cells such as EC/ES cells, but switched off upon differentiation. More importantly, their expression was rescued in 'revertant' cells that ectopically acquired the Oct-3 transactivating function. Furthermore, the expression profiles of Glut-3, 226 and 383 during mouse development also overlapped that of Oct-3. The Glut-3 gene possessed multiple Oct-3 binding sites in its transcriptional regulatory regions, suggesting that at least one of the downstream genes was a direct target of Oct-3. CONCLUSIONS: A large proportion of pluripotent cell-specific genes appear to be downstream targets of Oct-3.

Amino Acid Sequence↗
PubMed1996

p53 antisense oligonucleotide inhibits growth of human colon tumor and normal cell lines.

We examined the relationship between the expression of mutant p53 proteins and tumor cell growth using a p53 antisense oligonucleotide (5'-CCCTGCTCCCCCCTGGCTCC-3'). The oligonucleotide inhibited the growth of three human colon tumor cell lines (DLD-a, SW620 and WiDr), which produce only mutant p53 proteins with different mutation sites. Treatment of DLD-1 cells with the p53 antisense oligonucleotide caused a decrease in the level of p53 mutant protein. Synthesis of DNA in DLD-1 and SW620 cells was inhibited more potently than that of RNA or protein after antisense treatment. Furthermore, these cells were accumulated in the S phase when DNA synthesis was inhibited. Meanwhile, the antisense oligonucleotide also inhibited the growth of three human normal cell lines (WI-38, TIG-1 and Intestine 407). While treatment of WI-38 and TIG-1 cells with the antisense oligonucleotide inhibited synthesis of DNA more potently than that of RNA or protein, these normal cells were accumulated in the G0/G1 phase. These results suggest that p53 proteins, either with or without mutation, play a pivotal role in the growth of tumor and normal cells, but that mutant and wild-type p53 proteins may function differently in cell growth.

Base Sequence↗
PubMed1996

Immunohistochemical study of c-erb B-2 expression in malignant mixed müllerian tumors of the female genital tract.

OBJECTIVE: To study the expression of c-erb B-2 in gynecologic malignancies, especially in malignant mixed müllerian tumors (MMTs). METHODS: Using immunohistochemical techniques, we examined 6 cases of primary MMT, 6 cases of leiomyosarcoma (LMS), 7 cases of endometrial adenocarcinomas, and 10 cases of normal endometria. RESULTS: The expression of c-erb B-2 was observed in the carcinomatous area of all 6 cases of MMT (100%), the sarcomatous area of 5 of 6 cases of MMT (83.3%), in 1 of the 6 cases of LMS (16.7%), in all 7 cases of adenocarcinoma (100%), and in all cases of normal epithelial cells (100%), but was not observed in any of the cases of normal stromal cells (0%). CONCLUSION: The results suggest that the carcinomatous and sarcomatous elements of MMT are similar in their expression of c-erb B-2. MMT differed immunohistochemically from pure sarcoma cells and normal stromal cells, but resembled pure carcinoma cells and normal epithelial cells of the female genital tract.

Adenocarcinoma↗
PubMed1996

Inhibition of Trypanosoma cruzi growth in mammalian cells by purine and pyrimidine analogs.

Trypanosoma cruzi, the causative agent of Chagas' disease, exhibits two different developmental stages in mammals, the amastigote, an intracellular form that proliferates in the cytoplasm of host cells, and the trypomastigote, an extracellular form that circulates in the bloodstream. We have already established an in vitro culture system using mammalian host cells (HeLa) infected with T. cruzi in which the time course of parasite growth is determined quantitatively. We adopted this system for the screening of anti-T. cruzi agents that would ideally prove to be effective against trypanosomes with no toxicity to the host cell. Of the purine analogs tested, allopurinol markedly inhibited the growth of amastigotes in a dose-dependent manner, with no lethal effect on trypomastigotes. 3'-Deoxyinosine and 3'-deoxyadenosine also suppressed T. cruzi growth inside the host cell, with the concentrations causing 50% growth inhibition being 10 and 5 microM, respectively, in contrast to a concentration causing 50% growth inhibition of 3 microM for allopurinol. Among the pyrimidine analogs examined, 3'-azido-3'-deoxythymidine (zidovudine) significantly reduced the growth of the parasite at concentrations as low as 1 microM. The anti-human immunodeficiency virus agents 2',3'-dideoxyinosine and 2',3'-dideoxyadenosine caused a decrease in amastigote growth, while 2',3'-dideoxycytidine and 2',3'-dideoxyuridine had no inhibitory effect. When Swiss 3T3 fibroblasts were used as host cells, allopurinol, 3'-deoxyinosine, 3'-deoxyadenosine, and 3'-azid-3'-deoxythymidine also markedly inhibited T. cruzi proliferation. These results indicate that our culture system is useful as a primary screening method for candidate compounds against T. cruzi on the basis of two criteria, namely, intracellular replication by the parasite and host-cell infection rate.

3T3 Cells↗
PubMed1996

Vertebral bone mineral density in postpartum women.

The purpose of this study was to measure the bone mineral density of the lumbar spine (L2-L4) in healthy postpartum women following term delivery, and to evaluate factors associated with bone mineral density. Using dual energy X-ray absorptiometry, the bone mineral density of the lumbar spine was determined during 1 year in 123 healthy postpartum Japanese women following term delivery. The mean bone mineral density of the lumbar spine was 1.007 +/- 0.108 g/cm2 (range 0.731-1.252 g/cm2). Thus, there were wide inter-individual differences. Also, this result was in agreement with the peak bone mass previously reported for other Japanese women. Multiple regression analysis and linear regression analysis showed that weight and body mass index were each significantly correlated with bone mineral density of the lumbar spine. Age, parity, height, and baby's birth weight were not contributory.

Absorptiometry, Photon↗
PubMed1996

Synthesis and biological activity of four kinds of reversed peptides.

We have synthesized four kinds of reversed peptides of various physiologically active peptides, which inhibit TNF (tumor necrosis factor) cytotoxicity, produce NGF (nerve growth factor), exert antimicrobial activity and inhibit cell attachment, respectively. They were examined for their biological activity in comparison with that of normal peptides, that is, naturally occurring peptides. The reversed peptides induce similar activities, but to a lesser extent than those of the normal peptides, respectively. These results indicate that there may be conformationally ambiguous binding in some of the naturally occurring ligand-protein interactions. This method may be useful as a tool to rapidly generate a novel lead peptide with the desired biological function from a naturally occurring active peptide.

Amino Acid Sequence↗