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Biomedical subjects

K Ono

Publications and source records attributed to K Ono.

At least 199 records · Page 11Linked to original sources
PubMed2000

Ser162-Dependent inactivation of overproduced sucrose-phosphate synthase protein of maize leaf in transgenic rice plants.

To investigate the role of Ser162 in phosphorylation-dependent regulation of maize sucrose-phosphate synthase (SPS) activities in rice, transgenic rice plants expressing wild-type or mutagenized maize SPS were produced. Our results indicate that Ser162 was responsible for overproduction-induced inactivation of SPS protein and for light/ dark modulation of this protein in vivo.

Gene Expression Regulation, Enzymologic↗
PubMed2000

Development of different phenotypes of hypertensive heart failure: systolic versus diastolic failure in Dahl salt-sensitive rats.

OBJECTIVE: There are two phenotypes of heart failure, systolic failure and isolated diastolic heart failure with preserved left ventricular systolic function. Although isolated diastolic heart failure frequently occurs, there are only models for diastolic dysfunction unassociated with heart failure and models with overt diastolic heart failure have not been established. We attempted to develop two different models, i.e. diastolic and systolic failure models, based on hypertension. MATERIALS AND METHODS: Dahl salt-sensitive rats were placed on 8% NaCl diet from 7 weeks old (7-week starting group) or 8 weeks old (8-week starting group). As an age-matched control, Dahl salt-sensitive rats were consistently placed on normal chow. In these rats, echocardiogram was serially recorded, followed by hemodynamic and histological studies. RESULTS: The 7-week starting rats showed a steep elevation in blood pressure and progressive left ventricular hypertrophy, and fell into overt heart failure at approximately 19 weeks. The development of heart failure was not associated with a decrease in left ventricular midwall fractional shortening or an increase in left ventricular end-diastolic dimension as compared with the age-matched control, which mimics the characteristics of clinically observed isolated diastolic heart failure. The 8-week starting rats showed a gradual rise in blood pressure and less progressive left ventricular hypertrophy, and fell into heart failure at approximately 26 weeks with a decrease in mid-wall fractional shortening and an increase in left ventricular end-diastolic dimension. Hemodynamic and histological studies at failing stage revealed comparable elevation of left ventricular end-diastolic pressure and comparable left ventricular fibrosis in both groups. CONCLUSION: These two different models of overt heart failure may be useful as models of isolated diastolic heart failure and systolic heart failure based on the same hypertensive heart disease, respectively, and may contribute to discrimination of the mechanisms of the development of the two different phenotypes of heart failure.

Animals↗
PubMed2000

The effects of boron neutron capture therapy on liver tumors and normal hepatocytes in mice.

To explore the feasibility of employing boron neutron capture therapy (BNCT) to treat liver tumors, the effects of BNCT were investigated by using liver tumor models and normal hepatocytes in mice. Liver tumor models in C3H mice were developed by intrasplenic injection of SCCVII tumor cells. After borocaptate sodium (BSH) and boronophenylalanine (BPA) administration, (10)B concentrations were measured in tumors and liver and the liver was irradiated with thermal neutrons. The effects of BNCT on the tumor and normal hepatocytes were studied by using colony formation assay and micronucleus assay, respectively. To compare the effects of BSH-BNCT and BPA-BNCT, the compound biological effectiveness (CBE) factor was determined. The CBE factors for BSH on the tumor were 4.22 and 2.29 using D(10) and D(0) as endpoints, respectively. Those for BPA were 9.94 and 5.64. In the case of hepatocytes, the CBE factors for BSH and BPA were 0.94 and 4.25, respectively. Tumor-to-liver ratios of boron concentration following BSH and BPA administration were 0.3 and 2.8, respectively. Considering the accumulation ratios of (10)B, the therapeutic gain factors for BSH and BPA were 0.7 - 1.3 and 3.8 - 6.6, respectively. Therefore, it may be feasible to treat liver tumors with BPA-BNCT.

Animals↗
PubMed2000

Usefulness of tirapazamine as a combined agent in chemoradiation and thermo-chemoradiation therapy at mild temperatures: reference to the effect on intratumor quiescent cells.

C3H / He mice bearing SCC VII tumors received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. The mice then received one of six different DNA-damaging agents with or without mild temperature hyperthermia (40 degrees C, 30 min, MTH). These agents were adriamycin (ADM), mitomycin C (MMC), cyclophosphamide (CPA), bleomycin (BLM), cisplatin (CDDP), and tirapazamine (TPZ). After the drug treatment, the tumor-bearing mice were irradiated with a series of doses of gamma-rays. Immediately after irradiation, the tumors were excised, minced and trypsinized. The tumor cell suspensions thus obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labeling ( = quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P + Q) tumor cells was determined from the tumors that had not been pretreated with BrdU. MTH significantly increased the MN frequency of total cells in tumors irradiated with gamma-rays combined with CPA, BLM, CDDP or TPZ, and that of Q cells in tumors irradiated with gamma-rays combined with BLM or TPZ. The sensitivity difference in the MN frequency between total and Q tumor cells was significantly decreased by the combination with TPZ. TPZ combined with radiotherapy and TPZ combined with thermo-radiotherapy at mild temperatures appear to be promising modalities for sensitizing tumor cells in vivo, including Q tumor cells.

Animals↗
PubMed2000

Changes in the sensitivity of intratumor cells during fractionated tirapazamine administration.

Mice bearing solid tumors received 10 intraperitoneal administrations of 5-bromo-2'-deoxyuridine (BrdU) to label the proliferating (P) tumor cells. Then, as a priming treatment, tirapazamine (TPZ) was intraperitoneally administered. Further, 0 through 48 h later, the tumor-bearing mice received TPZ again at various doses. The tumor cells were isolated and incubated with a cytokinesis blocker. The micronucleus (MN) frequencies in cells with and without BrdU labeling, which were regarded as P and quiescent (Q) cells at the priming treatment, respectively, were determined using immunofluorescence staining for BrdU. The MN frequency in the total (P + Q) tumor cells was determined from the tumors that were not pretreated with BrdU. In addition, P cell ratios in the tumors at the second treatment were determined using immunofluorescence staining for P cell nuclear antigen. In each cell fraction, the longer the interval between the two treatments, the higher was the sensitivity to TPZ, except 1 h after the priming treatment. More than 24 h later, total and P cells, especially P cells, showed significantly higher sensitivity to TPZ than in the case of a single TPZ treatment. The longer the period between the two TPZ treatments, the lower was the P cell ratio at the second treatment. These findings were thought to indicate that the use of TPZ in the treatment of solid tumors causes a shift from the P to the Q state in vivo.

Animals↗
PubMed2000

The combined effect of electroporation and borocaptate in boron neutron capture therapy for murine solid tumors.

10 B-Enriched borocaptate (BSH) was administered intraperitoneally to SCCVII tumor-bearing C3H / He mice. Electroporation (EP) was conducted by using a tweezers-type electrode. The (10) B contents in tumors were measured by prompt gamma-ray spectrometry. The colony formation assay was applied to investigate the antitumor effects of boron neutron capture therapy (BNCT) and thereby to estimate the intratumor localization of BSH. The (10) B concentrations in tumors decreased with time following BSH administration, falling to 5.4(0. 1) ppm at 3 h, whereas EP treatment (3 repetitions) 15 min after BSH injection delayed the clearance of BSH from tumors, and the (10) B level remained at 19.4(0.9) ppm at 3 h. The effect of BNCT increased with the (10) B concentration in tumors, and the combination with EP showed a remarkably large cell killing effect even at 3 h after BSH injection. The effect of BNCT, i.e., slope coefficient of the cell survival curve of tumors, without EP was proportional to tumor (10) B level (r = 0.982), and that of BSH-BNCT combined with EP lay close to the same correlation line. However, tumors subjected to EP after BSH injection did not show high radiosensitivity when irradiated after conversion to a single cell suspension by enzymatic digestion. This indicates that the increase of the BNCT effect by EP was a consequence of enclosure of BSH in the interstitial space of tumor tissue and not within tumor cells. This is different from a previous in vitro study. The combination of EP and BNCT may be clinically useful, if a procedure to limit EP to the tumor region becomes available or if an alternative similar method is employed.

Animals↗
PubMed2000

Mechanism of preserved positive lusitropy by cAMP-dependent drugs in heart failure.

In tachycardia-induced heart failure (HF), positive lusitropic effects of milrinone or dobutamine were assessed by evaluating the time constant of left ventricular (LV) pressure decay (tau) and Ca(2+)-ATPase activity of the sarcoplasmic reticulum (SR). The peak value of the positive first derivative of LV pressure (+dP/dt) was less increased, either by dobutamine (2-10 microg x kg(-1) x min(-1)) or by milrinone (4-20 microg/kg), in HF than in control (P < 0.05), whereas tau was shortened to an extent similar to that in control with dobutamine [P = not significant (NS)] and to an even greater extent with milrinone (P < 0.05). Ca(2+)-ATPase activity increased similarly in HF and control with dobutamine (1 microM; +11% in HF vs. +12% in control, P = NS), whereas it increased more with milrinone (1 microM; +19% in HF vs. +11% in control, P < 0.05). Ca(2+)-ATPase activity-cAMP relationships were shifted to the left by milrinone or dobutamine in HF compared with control. Thus, in HF, the sensitivity of Ca(2+)-ATPase activity to cAMP was increased on addition of cAMP-dependent inotropic agents, contributing to the preservation of positive lusitropy.

Animals↗
PubMed2000

Effect of milrinone on left ventricular relaxation and Ca(2+) uptake function of cardiac sarcoplasmic reticulum.

Milrinone, a phosphodiesterase 3 (PDE3) inhibitor, is known to enhance left ventricular (LV) contractility by an inhibition of the breakdown of cAMP through the mechanism inhibiting PDE3. However, it is unclear whether milrinone also exerts positive lusitropy, like dobutamine. Here, we assessed the effects of milrinone on in vivo LV relaxation, as well as the Ca(2+)-ATPase activity and the Ca(2+) uptake function of the cardiac sarcoplasmic reticulum (SR), compared with the effect of dobutamine on those functions. After dobutamine (3 microg x kg(-1) x min(-1)) was administered, the peak value of the first derivative of LV pressure (+dP/dt) increased by 46%, whereas the time constant (tau) of LV pressure decay decreased by 6.9%, respectively. After milrinone (10 microg/kg) was administered, the peak +dP/dt increased to a similar extent as dobutamine (46%), whereas tau decreased much more than dobutamine (19.9%; P < 0.05). In LV crude homogenate, the thapsigargin-sensitive, Ca(2+)-ATPase activity-cAMP relationships was significantly less increased by milrinone compared with dobutamine (P < 0.05), indicating the higher sensitivity of the SR Ca(2+)-ATPase activity on cAMP by milrinone than by dobutamine. In the SR vesicles purified from LV muscles, the addition of cAMP increased the SR Ca(2+) uptake in a dose-dependent fashion, and the PDE3 inhibitors (milrinone and cGMP) significantly augmented this response (P < 0.05). Hence, milrinone substantially improved LV relaxation in association with an acceleration of the SR Ca(2+)-ATPase activity and the SR Ca(2+) uptake. This acceleration might be due to an inhibition of the membrane-bound PDE3 in the SR, leading to a local elevation of cAMP.

Adrenergic beta-Agonists↗
PubMed2000

Role of p38 mitogen-activated protein kinase in neointimal hyperplasia after vascular injury.

p38 mitogen-activated protein kinase (MAPK) is involved in intracellular signals that regulate a variety of cellular responses during inflammation. However, the role of p38 MAPK in atherosclerosis, a chronic inflammatory disorder, remains uncertain. The aim of the present study was to examine the role of p38 MAPK in the development of neointimal hyperplasia in balloon-injured rat carotid arteries. Immunohistochemical studies indicated that p38 MAPK was rapidly activated in the majority of medial cells in injured arterial walls. Rats treated with FR167653, a selective inhibitor of p38 MAPK, at a dosage of 10 mg x kg(-1) x d(-1), had a 29.4% lower intima-to-media ratio than the untreated controls at 14 days after balloon injury (P:<0.05). The percentage of proliferating nuclear antigen-positive cells in the media at 48 hours was significantly lower in the FR167653-treated group than in the control group. Quantitative competitive reverse transcription-polymerase chain reaction analysis revealed that interleukin-1beta mRNA expression in arteries was significantly inhibited by FR167653 (to 18.1% of control, P:<0.05) at 8 hours after balloon injury. Moreover, p38 MAPK activation and interleukin-1beta production by lipopolysaccharide-stimulated vascular smooth muscle cells were inhibited by FR167653 in a concentration-dependent manner in vitro. These results indicate that p38 MAPK is activated in vascular walls after injury and promotes neointimal formation and suggest that selective inhibition of p38 MAPK may be effective in the prevention of restenosis after percutaneous transluminal coronary angioplasty.

Angioplasty, Balloon, Coronary↗
PubMed2000

Hypertrophic cardiomyopathy as a manifestation of cardiac sarcoidosis.

The present study aimed to clarify whether cardiac sarcoidosis causes changes that mimic hypertrophic cardiomyopathy. Eighty-two consecutive patients (35 men, 47 women), who were referred to the Department of Cardiovascular Medicine, with a diagnosis of pulmonary and/or ocular sarcoidosis (average age, 49.5 years, range 20-74), underwent detailed clinical, electrocardiographic, and echocardiographic evaluations; in some patients, right and left heart catheterization, selective coronary artery cineangiography, and right and left endomyocardial biopsies were performed. Over a 15-month period of observation, 6 of these 82 patients (7.3%) were found to have echocardiographic abnormalities: increased thickness of the interventricular septum was found in 4 patients, asymmetric septal hypertrophy in 2, localized septal hypertrophy in 1 and apical hypertrophy in 1 patient. One patient had an 'ace-of-spades' deformity of the left ventricle. Cardiac sardoidosis can mimic, and even present as, hypertrophic cardiomyopathy.

Adult↗
PubMed2000

Evaluation of flow volume and flow patterns in the patent false lumen of chronic aortic dissections using velocity-encoded cine magnetic resonance imaging.

In 21 patients with chronic aortic dissections and proven patent false lumens, the flow volume and flow patterns in the patent false lumens was evaluated using velocity-encoded cine magnetic resonance imaging (VENC-MRI) and the relationship between the flow characteristics and aortic enlargement was retrospectively examined. Flow patterns in the false lumen were divided into 3 groups: pattern A with primarily antegrade flow (n=6), pattern R with primarily retrograde flow (n=3), and pattern B with bidirectional flow (n=12). In group A, the rate of flow volume in the false lumen compared to the total flow volume in true and false lumens (%TFV) and the average rate of enlargement of the maximum diameter of the dissected aorta per year (deltaD) were significantly greater than in groups R and B (%TFV: 74.1+/-0.07 vs 15.2+/-0.03 vs 11.8+/-0.04, p<0.01; deltaD: 3.62+/-0.82 vs 0 vs 0.58+/-0.15 mm/year, p<0.05, respectively). There was a significant correlation between %TFV and deltaD (r=0.79, p<0.0001). Evaluation of flow volume and flow patterns in the patent false lumen using VENC-MRI may be useful for predicting enlargement of the dissected aorta.

Adult↗
PubMed2000

Circulating hepatocyte growth factor as a marker of thrombus formation in unstable angina pectoris.

A new enzyme-linked immunosorbent assay can detect 10 pg/ml of human hepatocyte growth factor (HGF). Circulating HGF was significantly higher in patients with unstable angina (296+/-184 pg/ml, mean+/-SD, n=36) than in healthy volunteers (201+/-64 pg/ml, n=250, p<0.0001). Individual concentrations exceeded the mean control value +2 SD (329 pg/ml) in 12 of the 36 (33%) patients with unstable angina. The present study indicates that this new, sensitive HGF assay can successfully detect thrombosis in patients with unstable angina.

Adolescent↗
PubMed2000

Japanese occupational therapy in community mental health and telehealth.

Help for people with mental health problems in Japan has traditionally centred on inpatient medical care. In a revision of the Mental Health Welfare Law planned for 2001, responsibility for the support of people with mental health problems will be transferred from central government to local government. Furthermore, local government will, in turn, delegate administrative tasks to a 'community life support centre'. We believe that such a centre could be linked to a university with a telehealth network. Connection to the network could benefit people with mental health problems living at home. We also believe that occupational therapists are ideally positioned to play a significant role in community life support centres. With the expected sustained growth in Japanese occupational therapy, it could become a key profession in the rehabilitation of people with mental health problems.

Community Mental Health Centers↗
PubMed2000

Change in oxygenation status in intratumour total and quiescent cells following gamma-ray irradiation, tirapazamine administration, cisplatin injection and bleomycin treatment.

C3H/He mice bearing SCC VII tumours received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps to label all proliferating (P) cells. The mice then received gamma-ray irradiation, or administration of tirapazamine (TPZ), cisplatin or bleomycin. At various time points after each treatment, tumour-bearing mice were irradiated with a series of test doses of gamma-rays, while alive or after being killed, to obtain hypoxic fractions (HFs) in the tumours. Immediately after gamma-ray test irradiation, the tumours were excised, minced and trypsinized. Tumour cell suspensions obtained were incubated with cytochalasin-B, a cytokinesis blocker, and the micronucleus (MN) frequency in cells without BrdU labelling (i.e. quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. MN frequency in the total (P + Q) tumour cells was determined from the tumours that were not pre-treated with BrdU. MN frequency of BrdU-unlabelled cells was then used to calculate the surviving fraction of the unlabelled cells from the regression line for the relationship between the MN frequency and the surviving fraction of total tumour cells. TPZ and cisplatin reduced the HF after treatment, especially in Q cells, and this tendency was particularly marked with TPZ. In contrast, bleomycin increased the HF after treatment. Both reoxygenation following gamma-ray irradiation or bleomycin treatment and a subsequent return to pre-treatment levels of HF following TPZ or cisplatin treatment (rehypoxiation) occurred more rapidly in total (P + Q) cells than in Q cells. Based on our previous report that total (P + Q) and Q cells within this tumour have large acutely and chronically HFs, respectively, we conclude that acute hypoxic cells play a major role in reoxygenation and rehypoxiation in SCC VII tumours.

Animals↗
PubMed2000

Molecular structural analysis of HPRT mutations induced by thermal and epithermal neutrons in Chinese hamster ovary cells.

Chinese hamster ovary (CHO) cells were exposed to thermal and epithermal neutrons, and the occurrence of mutations at the HPRT locus was investigated. The Kyoto University Research Reactor (KUR), which has been improved for use in neutron capture therapy, was the neutron source. Neutron energy spectra ranging from nearly pure thermal to epithermal can be chosen using the spectrum shifters and thermal neutron filters. To determine mutant frequency and cell survival, cells were irradiated with thermal and epithermal neutrons under three conditions: thermal neutron mode, mixed mode with thermal and epithermal neutrons, and epithermal neutron mode. The mutagenicity was different among the three irradiation modes, with the epithermal neutrons showing a mutation frequency about 5-fold that of the thermal neutrons and about 1.5-fold that of the mixed mode. In the thermal neutron and mixed mode, boron did not significantly increase the frequency of the mutants at the same dose. Therefore, the effect of boron as used in boron neutron capture therapy (BNCT) is quantitatively minimal in terms of mutation induction. Over 300 independent neutron-induced mutant clones were isolated from 12 experiments. The molecular structure of HPRT mutations was determined by analysis of all nine exons by multiplex polymerase chain reaction. In the thermal neutron and mixed modes, total and partial deletions were dominant and the fraction of total deletions was increased in the presence of boron. In the epithermal neutron mode, more than half of the mutations observed were total deletions. Our results suggest that there are clear differences between thermal and epithermal neutron beams in their mutagenicity and in the structural pattern of the mutants that they induce. Mapping of deletion breakpoints of 173 partial-deletion mutants showed that regions of introns 3-4, 7/8-9 and 9-0 are sensitive to the induction of mutants by neutron irradiation.

Animals↗
PubMed2000

Selective block of late currents in the DeltaKPQ Na(+) channel mutant by pilsicainide and lidocaine with distinct mechanisms.

The congenital long QT syndrome is an inherited disorder characterized by a delay in cardiac repolarization, leading to lethal cardiac arrhythmias such as torsade de pointes. One form of this disease involves mutations in the voltage-dependent cardiac Na(+) channel, which includes an in-frame deletion of three amino acids (Lys-1505, Pro-1506, and Gln-1507; DeltaKPQ). The potential for selective suppression of the mutant was examined by heterologous expression of DeltaKPQ-Na(+) channels in Chinese hamster fibroblast cells via single-channel recording. In a single-channel cell-attached patch study, DeltaKPQ-Na(+) channels yielded currents that peaked at approximately 1 ms after voltage steps to 0 mV with aberrant late currents, which were composed of burst and isolated openings. The affinity of certain anesthetics (pilsicainide and lidocaine) to the late currents of the mutant channels was examined. It was revealed that 1) pilsicainide (1 microM), an open channel blocker of voltage-dependent Na(+) channels, remarkably decreased the late currents primarily by the shortening of burst duration without suppressing the initial peak current; and 2) lidocaine (1 microM), an inactivated channel blocker, decreased the late currents primarily by the suppression of isolated channel openings. Because the late currents in DeltaKPQ mutants are mainly composed of the burst openings, we conclude that pilsicainide is capable of selectively blocking the late currents in the mutant Na(+) channels that show dominant abnormal burst openings such as in DeltaKPQ mutants.

Animals↗
PubMed2000

[A long-term survivor of extensive-stage small cell lung cancer].

A 53-year-old man was admitted for evaluation of multiple hepatic tumors. A thoracic CT scan revealed a mass lesion in the right middle lobe. Transcutaneous needle aspiration cytology from the lung tumor and transcutaneous hepatic tumor biopsy were performed, from which the cytohistological diagnosis was small cell lung cancer with liver metastasis. The patient was treated with 3 courses of high dose cisplatin with vindesine and mitomycin and 5 courses of carboplatin with etoposide, and achieved a complete response. We herein report a long-term survivor of extensive-stage small cell lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗