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Biomedical subjects

M Inoue

Publications and source records attributed to M Inoue.

At least 55 records · Page 3Linked to original sources
PubMed1996

Nucleic acid binding by zinc finger-like motif of human papillomavirus type 16 E7 oncoprotein.

Human papillomavirus (HPV) types 16 and 6b E7 proteins and their chimeric or mutant proteins were analyzed for oligonucleotide-binding activity by surface plasmon resonance-based biomolecular interaction analysis. The results indicated that type 16 E7 protein has stronger nucleic acid-binding activity than that of type 6b E7 protein. In addition, the results also indicated that the zinc finger-like motif in the C-terminal region of the type 16 E7 protein plays an important role in this activity.

Binding Sites↗
PubMed1996

Spinal cord blood flow decreases following microinjection of sodium nitroprusside into the nucleus tractus solitarii of anesthetized rats.

This study was undertaken to examine whether or not nitric oxide (NO) is involved in synaptic transmission in the nucleus tractus solitarius (NTS) during control of the spinal cord circulation. Employing urethane-anesthetized, paralyzed and artificially ventilated rats, sodium nitroprusside (SNP), which produces NO, was microinjected unilaterally into the NTS and the spinal cord blood flow (SCBF) was determined using labeled microspheres. Arterial blood pressure (ABP) was decreased by unilateral microinjection of SNP into the NTS, but its value was kept within the normotensive range by blood transfusion, in order to measure SCBF at normotension. After microinjection of SNP into the NTS, the SCBFs of the cervical, thoracic and lumbar cords decreased significantly from 63 +/- 8 (mean +/- S.E.M.) to 49 +/- 7 (P < 0.05), from 54 +/- 7 to 37 +/- 7 (P < 0.05), and from 77 +/- 9 to 58 +/- 8 (P < 0.05) ml/min/(100 g), respectively (n = 10). Prior microinjection of NG-monomethyl-L-arginine (L-NMMA), an inhibitor of the formation of NO from L-arginine, into the NTS blocked the spinal cord vasoconstrictor response produced by microinjection of L-glutamate into the NTS (n = 10). Prior microinjection of NG-monomethyl-D-arginine (D-NMMA), which does not inhibit the formation of NO from L-arginine, did not block the spinal cord vasoconstrictor response elicited by microinjection of L-glutamate (n = 11). Unilateral microinjection of L-NMMA into the NTS exerted no effect on the spinal cord circulation (n = 9). These findings suggest that NO may be involved in the control of the spinal cord circulation in the NTS.

Animals↗
PubMed1996

Efficacy of in vitro sensitized cells generated by in vivo priming with OK-432 for adoptive immunotherapy of the poorly immunogenic B16-Bl6 melanoma.

We investigated the efficacy of the streptococcal preparation OK-432 as an adjuvant for in vivo priming in induction of sensitized cells for adoptive immunotherapy of the poorly immunogenic B16-BL6 (BL6) melanoma. C57BL/6 (B6) mice were immunized subcutaneously (s.c.) with 3 x 10(6) viable BL6 tumor cells admixed with various doses of OK-432 ranging from 1 to 100 micrograms in the foot-pad. Draining popliteal lymph nodes (LNs) were harvested 7 days after immunization and LN cells were further sensitized with irradiated tumor cells in the presence of 60-300 IU/ml of IL-2 for 11 days. These in vitro sensitized (IVS) cells (2 x 10(6)) were transferred intravenously (i.v.) to B6 mice bearing 4-day pulmonary metastases established by i.v. injection of 2-4 x 10(5) viable BL6 cells. The mice were also received intraperitoneally (i.p.) 4 x 10(4) IU/day of IL-2 for 4 days after adoptive transfer. Transfer of IVS cells from mice immunized by s.c. injection of tumor cells admixed with 10 micrograms of OK-432 significantly reduced the numbers of BL6 pulmonary metastases compared with that of control IVS' cells without the administration of OK-432 (P = 0.003). These effective IVS cells also significantly prolonged the survival of treated animals (P = 0.003). Functional IVS cells required in vitro stimulation with tumor cells. However, addition of OK-432 in the vaccine resulted in no enhancement of in vitro cytotoxicity and no characteristic change of phenotype of IVS cells. These results suggest that in vivo priming of OK-432 facilitates the sensitization of tumor-reactive T-cells. The procedure of in vivo priming with OK-432 may be beneficial in the adoptive immunotherapy of melanoma.

Animals↗
PubMed1996

Non-carcinogenicity of 2,2'--(4-aminophenyl)imino-bisethanol sulfate in a long-term feeding study in Fischer 344 rats.

2,2'-[(4-aminophenyl)imino]bisethanol sulfate (4APE) was administered at dietary levels of 0 (control), 300, 1000 and 3000 ppm to groups of 50 male and 50 female Fischer 344/DuCrj rats for 104 wk. As slight body weight retardation was observed in the male 3000 ppm group in the preliminary 13-wk feeding study, this dose was selected for the highest exposure level. Mean body weights of both sexes in the 3000 ppm group were lower than those of the controls from wk 2 to termination. However, there were no treatment-related clinical signs or adverse effects on survival rate, food consumption or haematology data. Very slight but statistically significant increases in relative thyroid weights were found in males of the 3000 ppm group, but there was no significant treatment-related increase in the incidence of any non-neoplastic or neoplastic lesions. Thus, under the experimental conditions used, 4APE was not carcinogenic in Fischer 344 rats of either sex.

Animals↗
PubMed1996

Influence of preload, afterload, and contractility on myocardial ultrasonic tissue characterization with integrated backscatter.

Influence of hemodynamic changes in preload, afterload and contractility on myocardial integrated backscatter (IB) was studied in 26 adult mongrel dogs by measuring myocardial IB calibrated with the backscatter from the blood during volume infusion (preload alteration), during aortic constriction (afterload alteration), and during dobutamine or propranolol infusion (contractility alteration). Changes in preload, afterload or contractility did not significantly affect the calibrated myocardial IB either in the septum or in the posterior wall. Changes in preload and afterload did not affect the magnitude of cyclic variation in IB. However, dobutamine produced a significant increase in the magnitude of cyclic variation in IB and propranolol significantly decreased the magnitude of cyclic variation in IB. These data indicated that the calibrated myocardial IB is independent of preload, afterload and contractility, and that the magnitude of cyclic variation in IB is influenced by contractility. We may estimate static (related to histological changes such as fibrosis, edema, necrosis, and so on) and dynamic (related to myocardial contraction such as sarcomere length, muscle fiber orientation, and so on) properties of the myocardium more precisely using myocardial IB calibrated with the backscatter from the blood in addition to the magnitude of cyclic variation in IB.

Adrenergic beta-Agonists↗
PubMed1996

Collateral channels that develop after an acute myocardial infarction prevent subsequent left ventricular dilation.

OBJECTIVES: We sought to evaluate the effect of collateral channels that develop late after a first anterior myocardial infarction on left ventricular dilation and function. BACKGROUND: Collateral channels in an infarct-related artery may develop long after occlusion of the artery. Well visualized collateral channels that appear immediately after a myocardial infarction reduce infarct size and preserve left ventricular function. However, the functional significance of collateral channels that develop late after myocardial infarction has not been evaluated in terms of left ventricular function. METHODS: We studied 21 patients with a first anterior myocardial infarction and an infarct-related artery that remained totally occluded after reperfusion therapy and did not reopen within 1 month of infarction. No collateral channels were observed during the acute period. Patients were classified into two groups according to the extend of collateral formation 1 month after infarction: group C, patients with well developed collateral channels (n = 11), and group NC, patients with absent or poorly developed collateral channels (n = 10). Infarct size was determined by peak creatine kinase activity and thallium-201 single-photon emission computed tomography. Global and regional left ventricular function and left ventricular volumes were assessed by left ventriculography. These measurements were identical in both groups 1 month after infarction. Left ventricular function was reevaluated after 2.12 +/- 0.79 years (mean +/- SD). RESULTS: There were no significant changes in global and regional left ventricular function between the two groups during the long-term follow-up period. However, the end-diastolic volume index of group NC increased from 71 +/- 14 to 85 +/- 19 ml/m2, whereas that of group C decreased from 64 +/- 18 to 59 +/- 12 ml/m2. This important change during the long-term follow-up period resulted in a significant difference (p = 0.0006) in the end-diastolic volume index between the groups 2 years after onset (p = 0.002), whereas 1 month after infarction the difference was not significant (p = 0.36). A similar pattern was observed for the end-systolic volume index (group C: 38 +/- 16 to 35 +/- 14 ml/m2; group NC: 45 +/- 12 to 58 +/- 18 ml/m2, p = 0.018). The power of the tests to detect the observed differences showing nonsignificant results ranged from 0.05 to 0.38, whereas the power of the tests indicating a significant difference in end-diastolic and end-systolic volume indexes was >0.88. CONCLUSIONS: Collateral channels that develop after a myocardial infarction do not reduce the infarct size or prevent left ventricular dilation within 1 month of infarction. In contrast, such collateral channels prevent subsequent ventricular dilation and the deterioration of left ventricular function over 2 years. However, our results may have been biased because of the small number of patients.

Aged↗
PubMed1996

Role of nitric oxide in regulation of coronary blood flow during myocardial ischemia in dogs.

OBJECTIVES: This study was undertaken to examine whether nitric oxide released in ischemic myocardium decreases the coronary vascular resistance and attenuates the severity of contractile and metabolic dysfunction. BACKGROUND: Endothelium-derived relaxing factor, recently identified as nitric oxide, is a potent relaxant of coronary smooth muscle. METHODS: The left anterior descending coronary artery was perfused through an extracorporeal bypass tube placed in the carotid artery in 56 open chest dogs. After hemodynamic stabilization, we occluded this bypass tube to decrease coronary blood flow to one third of the control flow. Thereafter, we maintained a constant coronary perfusion pressure (40.9 +/- 3.1 mm Hg). RESULTS: Under ischemic conditions, the coronary arteriovenous differences in nitrate and nitrite (end products of nitric oxide) increased (from 3.5 +/- 0.4 [mean +/- SEM] to 12.9 +/- 2.1 mumol/liter, p < 0.01). NG-Monomethyl L-arginine (3 micrograms/kg body weight per min, intracoronary) decreased the coronary arteriovenous differences in nitrate and nitrite (5.0 +/- 0.9 mumol/liter, p < 0.05) and coronary blood flow (from 29.8 +/- 0.5 to 18.1 +/- 1.1 ml/100 g per min, p < 0.001). Fractional shortening (from 3.7 +/- 1.0 to -1.3 +/- 0.7%, p < 0.001) and lactate extraction ratio (from -44.0 +/- 4.1 to -59.2 +/- 4.9%, p < 0.005) of the perfused area also decreased. These values were restored by the concomitant administration of L-arginine. Blood flow to the endomyocardium was decreased relative to the epimyocardium. A reduction in coronary blood flow and worsening of myocardial contractile and metabolic functions due to the administration of NG-monomethyl L-arginine during ischemia were observed in denervated hearts. A reduction in coronary blood flow in ischemic myocardium was observed with the administration of NW-nitro-L-arginine methyl ester as well, although neither NW-nitro-L-arginine methyl ester nor NG-monomethyl L-arginine changed coronary blood flow and myocardial contractile and metabolic functions in the nonischemic myocardium. The cyclic guanosine monophosphate content of epicardial coronary artery increased due to myocardial ischemia; this increase was attenuated with NG-monomethyl L-arginine treatment. CONCLUSIONS: We conclude that endogenous nitric oxide predominantly decreases the coronary vascular resistance of ischemic endomyocardium, thereby improving myocardial contractility and metabolic function.

Animals↗
PubMed1996

Chronic neutrophilic leukemia with dysplastic features mimicking myelodysplastic syndromes.

A 52-year-old male patient with chronic neutrophilic leukemia (CNL) with dysplastic features is described. He had a 2-year history of anemia followed by marked leukocytosis up to 57.5 x 10(9)/l with 88% segmented neutrophils. Bone marrow aspiration and biopsy showed hypercellular marrow with myeloid hyperplasia and 16% myeloblasts. There were also significant morphological abnormalities which included neutrophils with few granules, hypersegmented nucleus or Pelger-Heut anomaly, and micromegakaryocytes. Cytogenetic analysis disclosed a deletion of the long arm of chromosome 7 (7q-). He was diagnosed as having CNL with dysplastic features and was treated conservatively. However, leukemic transformation to acute myelogenous leukemia occurred within a year and he died 16 months after diagnosis. Neutrophilia is a feature not of myelodysplastic syndromes (MDS) but rather of myeloproliferative disorders such as CNL. However, this patient was considered to have MDS with increased proliferation and differentiation of neutrophilic lineage, because of marked myelodysplasia and poor prognosis.

Diagnosis, Differential↗
PubMed1996

Endothelial dysfunction in the early stage of atherosclerosis precedes appearance of intimal lesions assessable with intravascular ultrasound.

The objective of this study was to clarify whether morphologic evaluation of the in vivo artery with intravascular ultrasound provides as sensitive a marker as endothelial dysfunction or microscopic histologic assessment. Endothelial dysfunction assessed with the changes in the vessel diameter during acetylcholine infusion has been used as a more sensitive marker of atherosclerosis than the angiographic estimates of morphologic structure of the vessel. Recent advent of intravascular ultrasound has provided such high-resolution images of the vessels that morphologic changes in the vessel structure are sensitively and accurately detected. Twenty-two rabbits were divided into three groups: six rabbits fed a cholesterol-rich diet for 2 weeks as the hypercholesterolemia group, eight rabbits fed with the diet for 8 weeks as the atherosclerosis group, and eight rabbits fed a normal diet as the normal group. After evaluating the atherosclerotic lesions by intravascular ultrasound, the cross-sectional area was measured in the baseline and during the infusion of acetylcholine (0.05, 0.5, and 5 micrograms/kg/min) and nitroglycerin (5 micrograms/kg/min). No atherosclerotic lesions were detectable with intravascular ultrasound in any rabbit despite the presence of microscopic intimal lesions in the vessels in the rabbits of the atherosclerosis group. The cross-sectional area increased during acetylcholine infusion in the rabbits of the normal and the hypercholesterolemia groups. In contrast, in the rabbits of the atherosclerosis group, the cross-sectional area did not significantly increase during acetylcholine infusion at the rate of 0.5 microgram/kg/min and even tended to decrease at the rate of 5 micrograms/kg/min (-3.8% +/- 3.7%, P < 0.05 vs the normal group). Dilating responses to nitroglycerin infusion were similar among all three groups. In conclusion, impairment of the endothelium-dependent vasodilating response assessed with intravascular ultrasound in the in vivo vessel precedes the appearance of echographic atherosclerotic findings. Thus intravascular ultrasound, if used in combination with drug intervention to assess endothelial function, would provide even more accurate assessment of the vessels than conventional intravascular ultrasound alone.

Acetylcholine↗
PubMed1996

An imprinted gene p57KIP2 is mutated in Beckwith-Wiedemann syndrome.

p57KIP2 is a potent tight-binding inhibitor of several G1 cyclin/Cdk complexes, and is a negative regulator of cell proliferation. The gene encoding p57KIP2 is located at 11p15.5 (ref. 2), a region implicated in both sporadic cancers and Beckwith-Wiedemann syndrome, a cancer-predisposing syndrome, making it a tumour-suppressor candidate. Several types of childhood tumours including Wilms' tumour, adrenocortical carcinoma and rhabdomyosarcoma exhibit a specific loss of maternal 11p15 alleles, suggesting that genomic imprinting is involved. Genetic analysis of the Beckwith-Wiedemann syndrome indicated maternal carriers, as well as suggesting a role of genomic imprinting. Previously, we and others demonstrated that p57KIP2 is imprinted and that only the maternal allele is expressed in both mice and humans. Here we describe p57KIP2 mutations in patients with Beckwith-Wiedemann syndrome. Among nine patients we examined, two were heterozygous for different mutations in this gene-a missense mutation in the Cdk inhibitory domain resulting in loss of most of the protein, and a frameshift resulting in disruption of the QT domain. The missense mutation was transmitted from the patient's carrier mother, indicating that the expressed maternal allele was mutant and that the repressed paternal allele was normal. Consequently, little or no active p57KIP2 should exist and this probably causes the overgrowth in this BWS patient.

Beckwith-Wiedemann Syndrome↗
PubMed1996

A novel DNA cleaving agent, 2,2'-bis(2-aminoethyl)-4,4'-bithiazole, induces thymocyte apoptosis.

The incubation of rat immature thymocytes with 2,2-bis(2-aminoethyl)-4,4'-bithiazole, which possesses the cleaving activity toward plasmid DNA in the presence of Co2+, resulted in an increase in DNA fragmentation. No DNA fragmentation of the cells was induced by 2,2-bis(3-aminopropyl)-4,4'-bithiazole, which has little cleaving activity toward plasmid DNA. Analysis of fragmented DNA from thymocytes treated with 2,2-bis(2-aminoethyl)-4,4'-bithiazole by agarose gel electrophoresis revealed that the compound produced 50 kbp DNA fragments and caused internucleosomal DNA fragmentation. In addition, the confocal microscopic images of thymocytes treated with the compound showed condensation of chromatin. These results indicate that bithiazole derivative induces thymocyte apoptosis with the biochemical and morphological characteristics through triggering DNA scission.

Animals↗
PubMed1996

Application of clonal analysis. Differential diagnosis for synchronous primary ovarian and endometrial cancers and metastatic cancer.

Simultaneous involvement of the endometrium and the ovary by carcinoma is a familiar problem in the routine practice of surgical pathology. Such cases may be considered either examples of a single primary carcinoma with metastasis or as synchronous primary neoplasms. The distinction between these two possibilities is made based on clinicopathologic observations, and therefore may not be definitive. In the present study, the authors used molecular techniques to analyze the clonal composition of five cases of concurrent adenocarcinomas of the endometrium and ovary that were clinicopathologically diagnosed as synchronous primary tumors. Patterns of X-chromosome inactivation, mutations in the K-ras gene, mutations or allelic loss of the p53 gene, or human papillomavirus detection were identical in both endometrial and ovarian lesions in three of the cases suggesting that those three cases represented single primary tumors with metastases. In both of the other two cases, the patterns of X-chromosome inactivation clearly demonstrated the presence of independent primary tumors. The application of molecular technology may play an important role for the differential diagnosis between synchronous primary carcinomas and a single carcinoma with metastasis.

Adult↗
PubMed1996

Blood pressure variability at annual periodic health examination for employees and cardiovascular risk factors.

The employees with hypertension at the annual periodic health examination (HE) for employees in Japan usually receive a re-examination of blood pressure (BP) on another day and are often found to be normotensive. In this study, we analyzed data from the HE at the workplace to determine whether or not such employees should receive medical care. Two groups of subjects were selected. One group (group 1) was composed of 50 subjects with normotension at the HE (controls). Another group (group 2) was composed of 33 subjects with hypertension at the annual HE but with normotension in re-examinations. Cardiovascular risk factors were significantly higher in group 2 than in group 1: mean values of the body mass index (group 1, 22 +/- 2.7 vs. group 2, 24.3 +/- 3.1 kg/m2, p < 0.01), total cholesterol (group 1, 197 +/- 36 vs. group 2, 222 +/- 42 mg/dl, p < 0.01), and low density lipoprotein (group 1, 118 +/ 32 vs. group 2, 137 +/- 38 mg/dl, p < 0.05). The proportion of the employees with high-normal BP in group 2 (42.5%) was significantly higher than that in group 1 (28.0%) (p < 0.01). These indicate that the employees with hypertension at the annual HE but with normotension in the re-examination require further medical attention and should receive medical supervision. The occupational physician should supervise these employees.

Adult↗
PubMed1996

DNA fragmentation of oocytes in aged mice.

To investigate whether female fertility decreases with age due to poor oocyte quality, we examined the presence of DNA fragmentation in ovulated oocytes from young, mature and aged mice. Oocytes from three age groups of female mice (7-8, 20-24 and 40-48 weeks) were retrieved from the oviducts 15 h after human chorionic gonadotrophin (HCG) injection. Oocytes from each mouse were incubated in a CO2 incubator for 0-60 h in human tubal fluid (HTF). After incubation, each oocyte was stained with the terminal deoxynucleotidyl transferase-mediated dUDP nick-end labelling (TUNEL) method. The rate of DNA fragmentation (interpreted as apoptotic changes) was significantly higher for oocytes from aged mice, and the fertilization rate was significantly lower, compared with oocytes from young and mature mice. Our results suggest that DNA fragmentation of oocytes might be one of the reasons for poor oocyte quality and lower fertility in the aged group.

Aging↗
PubMed1996

Intra- and inter-complex cross-linking of subunits in the quinol oxidase super-complex from thermophilic Bacillus PS3.

Gram-positive thermophilic Bacilli contain quinol-cytochrome c reductase and cytochrome c oxidase as two major respiratory complexes of the electron transfer chain, and these enzymes can be extracted with mild detergents as an associated quinol oxidase super-complex. The reductase is composed of three subunits; cytochrome b6, cytochrome c1, and FeS protein, whereas cytochrome c oxidase consists of four subunits numbered 1 through 4. In order to clarify the interactions between the subunits, the super-complex isolated from Bacillus PS3 was cross-linked with three bifunctional cross-linkers; disuccinimidyl tartrate, 3,3'-dithiobis(succinimidylpropionate), and ethylene glycolbis(sulfosuccinimidylsuccinate). The most prominent cross-linking was observed for the combination of subunit 1 plus 2 in cytochrome c oxidase, and for that of cytochrome b6 plus cytochrome c1 in the reductase. In addition to these intra-complex cross-linkings, inter-complex linking was observed for the combination of cytochrome b6 plus subunit 1 with ethylene glycolbis(sulfosuccinimidylsuccinate), and for the combinations of cytochrome b6 plus subunit 1 and cytochrome b6 plus subunit 2 with 3,3'-dithiobis(succinimidylpropionate). Incubation in the presence of Triton X-100, which was confirmed to cleave the two enzyme complexes, selectively reduced the inter-complex cross-linking, suggesting that the chemical cross-linking reflect the spatial arrangement of subunits in the super-complex.

Bacillus↗