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Biomedical subjects

K Ono

Publications and source records attributed to K Ono.

At least 433 records · Page 24Linked to original sources
PubMed1997

[Usefulness of continuous venous daily chemotherapy of 5-fluorouracil and low-dose cisplatin for patients undergoing noncurative surgery].

We examined the usefulness of continuous venous daily chemotherapy of 5-FU and low/I dose CDDP for patients undergoing noncurative surgery. Twelve patients with carcinoma (1 esophageal, 6 gastric, 4 colorectal carcinoma cases and 1 carcinoma case of unknown origin) underwent resection of primary lesion and postoperative adjuvant chemotherapy. The schedule for the chemotherapy was as follows: 2-7 courses of 24-hours continuous venous infusion of CDDP (5mg/day on day 1, 2, 3, 4, 5) and 5-FU (250 mg/day on day 1, 2, 3, 4, 5 or 1, 3, 5). Several patients received a bolus infusion of Epirubicin (10 mg/1 week or 30 mg/2 week). Mean total volumes of CDDP and 5-FU were 120 mg and 5.38 g, respectively. Nine cases could be evaluated. Results of the chemotherapy were 1 CR, 1 PR, 3 NC and 4 PD, and the overall response rate was 22%. Side effects were found in 6 cases, but were not so severe. One-year survival rate was 47%, and 50% survival time was 9 months. The prognosis of the patients seemed to be relatively good. These results suggest that continuous chemotherapy of 5-FU and low dose CDDP may be useful for patients undergoing noncurative surgery.

Adult↗
PubMed1997

[A case of esophagopleural fistula successfully cured by conservative therapy after middle and lower lobectomy of right lung].

We experience a case of esophagopleural fistula successfully cured by conservative therapy after the lung cancer operation. A 46-year-old man was received middle and lower lobectomy for adenoid cystic carcinoma of the right lung. Complication of empyema associated with an esophagopleural fistula occurred on postoperative 4th day. Conservative therapy of nothing by mouth, intravenous hyperalimentation and antibiotics was started. Three thoracic drains were inserted and the thoracic irrigation of total 3,000 ml warm saline per day twice on one day was continued. The esophagopleural fistula was closed on 6th week and the patient was discharged on 11th week after the therapy start. This complication is much rare, but recent advance in the diagnostic methods seemed to increase the indication of conservative therapy in future.

Anti-Bacterial Agents↗
PubMed1997

[A case of bloody sputum due to the migration of a temporary cardiac pacing lead into the bronchus].

A 60-year-old man with bloody sputum was admitted to our institute. Prior to the present admission, he had undergone coronary artery bypass graft surgery (GABG) at our institute 20 month earlier. The fiber optic bronchoscopy findings showed the cause of bleeding to be due to the migration of a post surgical temporary myocardial pacing lead which had been cut off at skin level after a CABG. Under general anesthesia we thus removed this migrated lead using both a fiber optic bronchoscope and forceps. The wire lead was easily removed and the patient has since suffered no more instances of bloody sputum.

Bronchi↗
PubMed1997

A comparison of body surface Laplacian and potential maps during paced ventricular activation.

The objective of this study is to evaluate the spatial resolution of body surface Laplacian maps (BSLMs) in localizing ventricular electrical activity by means of computer simulation. A 3-D computer heart-torso model was used to simulate cardiac electrical activity and the body surface maps. A two-site pacing protocol was used to generate two simultaneously activated myocardial events on the anterior epicardial wall and the anterior endocardial wall. Following the pacing, the BSLMs and the body surface potential maps (BSPMs) were calculated and compared with the known activation pattern. As a result, the BSLMs showed superior resolution than the BSPMs for localized initial ventricular activity. In summary, the present study suggests that body surface Laplacian mapping may provide a useful methodology for the clinical diagnosis of cardiac electrical abnormalities.

Body Surface Potential Mapping↗
PubMed1997

Chloride- and voltage-dependent Ca2+ transient in cultured human aortic endothelial cells.

The Cl(-)-sensitive nature of histamine-induced Ca2+ entry was investigated in cultured human aortic endothelial cells by the patch-clamp method, combined with the fluorescence measurement of intracellular Ca2+ concentration ([Ca2+]i). The sustained increase in [Ca2+]i, caused by histamine, was decreased by lowering the external concentration of Cl-. The patch-clamp experiment revealed that [Ca2+]i was dependent on the membrane potential in the presence of histamine, but not in the absence of histamine. The sustained increase in [Ca2+]i was accompanied by activation of the Cl- current, of which the reversal potential was measured to be around -28 mV with physiological internal and external Cl- concentrations. The membrane potential of the endothelial cells varied from -90 to 0 mV in the resting condition and approached the equilibrium potential for Cl- during histamine application. The results indicate that the histamine-induced Cl- current plays a functional role in the sustained increase of intracellular Ca2+ during histamine application by providing a constant driving force for Ca2+ entry across the plasma membrane.

Aorta↗
PubMed1996

Axonal growth-related cell surface molecule, neurin-1, involved in neuron-glia interaction.

We purified and characterized a novel axonal growth-related molecule, neurin-1, which is anchored to the surface membrane via a phosphatidylinositol (PI) linkage. This molecule was detected by a combination of phosphatidylinositol-specific phospholipase C (PI-PLC) treatment from detergent-soluble mouse brain membranes and subsequent Western blot analysis with monoclonal antibody (MAb 2A). Neurin-1 is immunologically distinct from other known axonal growth associated surface glycoproteins. In immunoblots of embryonic mouse brain membrane, the MAb 2A recognized a single band at approximately 68 kDa, and showed that neurin-1 is mainly associated with fiber-containing regions of developing embryonic mouse brain. Expression is immunohistochemically similar to that of cell adhesion molecule L1, but in comparison, neurin-1 appears somewhat later. Late in embryonic development, neurin-1 appeared to be more stage- and region-specific. Its precise localization at the neural cell surface membranes was confirmed by immuno-electron microscopy using labeled and cultured live nerve cells. Neurin-1 was found only on the surface of the axon and growth cone. Neurin-1, otherwise termed PI anchor protein, corresponds closely in function to the other PI-anchored cell adhesion molecules. Anti-neurin-1 antibody (MAb 2A), however, perturbs the axonal growth and neural cell migration from the astrocyte feeder layer cultures. These results suggest that neurin-1 is one of the important cell surface molecules mediated in the neuron and glial cell interaction.

Animals↗
PubMed1996

Neck and shoulder pain after laminoplasty. A noticeable complication.

STUDY DESIGN: The authors retrospectively analyzed the prevalence and features of neck and shoulder pain (axial symptoms) after anterior interbody fusion and laminoplasty in patients with cervical spondylotic myelopathy. OBJECTIVES: To reveal the difference in prevalence of postoperative axial symptoms between anterior interbody fusion and laminoplasty and to clarify the pathogenesis of axial symptoms after laminoplasty. SUMMARY OF BACKGROUND DATA: Outcome of the cervical surgery is evaluated on neurologic status alone; axial symptoms after laminoplasty rarely have been investigated. Such symptoms, however, are often severe enough to interfere with a person's daily activity. METHODS: Ninety-eight patients had surgery for their disability secondary to cervical spondylotic myelopathy. Of those patients, 72 had laminoplasty, and 26 had anterior interbody fusion. The presence or absence of axial symptoms was investigated before and after surgery. The duration, severity, and laterality of symptoms were also recorded. RESULTS: The prevalence of postoperative axial symptoms was significantly higher after laminoplasty than after anterior fusion (60% vs. 19%; P < 0.05). In 18 patients (25%) from the laminoplasty group, the chief complaints after surgery were related to axial symptoms for more than 3 months, whereas in the anterior fusion group, no patient reported having such severe pain after surgery. CONCLUSIONS: The prevalence and severity of axial symptoms after laminoplasty proved to be higher and more serious than has been believed. Such symptoms should be considered in the evaluation of the outcome of cervical spinal surgery.

Adult↗
PubMed1996

Sensitive method for the determination of pulmonary surfactant phospholipid/sphingomyelin ratio in human amniotic fluids for the diagnosis of respiratory distress syndrome by thin-layer chromatography-immunostaining.

By TLC-immunostaining with the monoclonal antibody VJ-41, which preferentially reacted with sphingomyelin (Sm) and disaturated fatty acid-containing phosphatidyl choline (DSPC), Sm and surfactant phospholipid dipalmitoyl PC were only detected in the lipid extracts from human amniotic fluid. The method was useful in the selective and simultaneous determination of surfactant phospholipid and Sm concentrations in the amniotic fluids to determine the level of maturity of the lungs of the fetus. By measuring the density of spots visualized by TLC-immunostaining, we detected Sm at a sensitivity two times higher than that for dipalmitoyl PC using the antibody. More than 50 ng of dipalmitoyl PC and Sm was detected on the same TLC plate and the standard curves were linear up to 1 microgram of phospholipids. The method was applied to determine the surfactant phospholipid/Sm ratio in 20 microliter of the amniotic fluids obtained at delivery, and the amniotic fluids from the women who delivered a baby suffering from respiratory distress syndrome (RDS) were easily discriminated from the normal amniotic fluids. In an analysis of 200 microliter of amniotic fluids from 4 RDS cases and 16 normal baby cases, the mean DSPC/Sm ratios were 0.97 +/- 0.53 and 5.75 +/- 1.29, respectively.

Amniocentesis↗
PubMed1996

Lipid secretory mechanisms in the mammalian harderian gland.

The mammalian Harderian glands are lipid-secreting glands. In an unstimulated condition, the glandular cells frequently exocytose the lipid materials; however, no intracellular calcium ion ([Ca2+]c) changes are detectable. Cholinergic (muscarinic) secretagogues induce secretory activity and increase of [Ca2+]c. A G-protein activator, sodium fluoride, enhances the secretory activity and increase of [Ca2+]c. Removal of extracellular calcium ions inhibits the secretion enhanced by cholinergic stimulation. Under pharmacologic stimulation, glandular cells may show an apocrine-like secretory pattern. Cholinergic stimulation also induces contraction of the myoepithelial cells covering glandular end pieces; however, the reduction in volume of glandular end pieces is not prominent. Catecholamines have no effect on the release of lipid materials. These results indicate the involvement of G-proteins linking with muscarinic receptors and Ca2+ dynamics (increase of [Ca2+]c and Ca2+ influx) in lipid secretion by glandular cells and in contraction of myoepithelial cells of mammalian Harderian glands. However, the increase of [Ca2+]c in Harderian glands was less when compared with other cells--for instance, those which secrete protein.

Animals↗
PubMed1996

Detection of hepatitis C virus RNA from the heart of patients with hypertrophic cardiomyopathy.

We investigated hepatitis C virus (HCV) infection in 35 patients with hypertrophic cardiomyopathy and 40 patients with ischemic heart disease who were consecutively admitted to our hospital. Frequency of positive anti-HCV antibody was significantly higher in patients with hypertrophic cardiomyopathy (6 of 35 patients, 17.1%) than that in patients with ischemic heart disease (1 of 40 patients, 2.5%, p = 0.036). In three of these six patients with hypertrophic cardiomyopathy, HCV RNA was detected in myocardial tissue. In two of these three patients, HCV RNA was detected from biopsy and autopsy specimens of the ventricles, but not in the serum, suggesting that HCV may replicate in myocardial tissue and may be relevant to ventricular hypertrophy. Thus, HCV infection may play a role in the development of hypertrophic cardiomyopathy.

Adolescent↗
PubMed1996

Hydroxylforms of p-boronophenylalanine as potential boron carriers on boron neutron capture therapy for malignant brain tumors.

Hydroxylforms of boronophenylalanine (BPA) were synthesized by conjugation with a cascade of polyols to decrease the BPA uptake of normal parenchyma without affecting uptake into the tumor. We determined their tumor cell killing effect on boron neutron capture therapy (BNCT) against BPA using the human glioma cell line T98G. The thermal neutron doses yielding the D37 (dose used to inhibit 63% colony formation) values of dl-p-BPA(OH)n were 1.45 x 10(12)nvt (n = 1), 1.33 x 10(12)nvt (n = 2), 3.37 x 10(12)nvt (n = 4), and 1.72 x 10(12)nvt (n = 0). The relative tumor cell killing effect on BNCT of dl-p-BPA(OH)n against dl-p-BPA, which was defined as the ratio of D37-BPA to D37-BPA(OH)n, was 1.18 (n = 1) 1.29 (n = 2), and 0.51 (n = 4). The tumor:normal brain ratio of dl-p-BPA(OH)n in 9L rat brain tumor models was improved 1.2- (n = 1) and 1.4-fold (n = 2) against that of dl-p-BPA without a decrease of its uptake into the tumor. The water solubility of BPA(OH)n increased against BPA, and the toxicity represented as the IC50 value of dl-p-BPA(OH)2 was nearly one half that of dl-p-BPA, being established in our previous works. Hydroxylforms of BPA, especially dl-p-BPA(OH)2, might be more suitable boron carriers of BNCT to malignant brain tumors since the radiation injury to the normal parenchyma surrounding the tumor is reduced.

Animals↗
PubMed1996

Increased circulating hepatocyte growth factor in the early stage of acute myocardial infarction.

We measured serum hepatocyte growth factor (HGF) in patients with acute myocardial infarction, angina pectoris, and other heart diseases. In patients with acute myocardial infarction, blood was collected at the time of admission. Serum HGF was elevated within 3 hours in 8 of 10 patients (80%) with acute myocardial infarction after onset of chest pain (9.4 +/- 3.2 ng/mL, mean +/- SEM, values in normal subjects <0.39 ng/mL). Mean value of serum HGF was 11.0 +/-2.6 ng.mL (n=11) in patients who admitted to the hospital between 6 and 9 hours and 13.1 +/- 5.7 ng.mL between 12 and 24 hours after onset. Elevated HGF levels were significantly more frequent than those of creatine kinase within 3 hours, and elevated levels correlated well with those of serum creatine kinase at 6-9 hours after onset of acute myocardial infarction. No increase in serum HGF value was found in patients with angina pectoris or other heart diseases. Thus, measurement of HGF is a sensitive method for early diagnosis of acute myocardial infarction.

Aged↗
PubMed1996

Defective anion transport and marked spherocytosis with membrane instability caused by hereditary total deficiency of red cell band 3 in cattle due to a nonsense mutation.

We studied bovine subjects that exhibited a moderate uncompensated anemia with hereditary spherocytosis inherited in an autosomal incompletely dominant mode and retarded growth. Based on the results of SDS-PAGE, immunoblotting, and electron microscopic analysis by the freeze fracture method, we show here that the proband red cells lacked the band 3 protein completely. Sequence analysis of the proband band 3 cDNA and genomic DNA showed a C --> T substitution resulting in a nonsense mutation (CGA --> TGA; Arg --> Stop) at the position corresponding to codon 646 in human red cell band 3 cDNA. The proband red cells were deficient in spectrin, ankyrin, actin, and protein 4.2, resulting in a distorted and disrupted membrane skeletal network with decreased density. Therefore, the proband red cell membranes were extremely unstable and showed the loss of surface area in several distinct ways such as invagination, vesiculation, and extrusion of microvesicles, leading to the formation of spherocytes. Total deficiency of band 3 also resulted in defective Cl-/HCO3- exchange, causing mild acidosis with decreases in the HCO3- concentration and total CO2 in the proband blood. Our results demonstrate that band 3 indeed contributes to red cell membrane stability, CO2 transport, and acid-base homeostasis, but is not always essential to the survival of this mammal.

Animals↗
PubMed1996

A membrane-bound heparan sulfate proteoglycan that is transiently expressed on growing axons in the rat brain.

Monoclonal antibodies were raised to membrane-bound proteoglycans derived from rat brain and three monoclonal antibodies that recognized a 200-kDa heparan sulfate proteoglycan (designated H5-PG) with a core glycoprotein of 140 kDa were obtained. The expression of H5-PG was spatially and temporally regulated in the central nervous system. In the cerebellar cortex, H5-PG was associated mainly with the actively growing parallel fibers of granule cells. The expression was abruptly down-regulated in parallel with the formation of synapses on dendrites of Purkinje cells. In the cerebral cortex, the proteoglycan was widely distributed throughout the cortex. The temporal pattern of expression was similar to that in the cerebellar cortex; the peak level of expression was observed during the period from postnatal days 0 to 20 when neuritogenesis and synaptogenesis occur most extensively in the rat cerebral cortex. H5-PG in the central nervous system disappeared prior to adulthood except in the olfactory bulb. High-level expression was recognized on the olfactory nerves and glomeruli, where the renewal of both axons and synapses is occurring constantly. The data suggest that H5-PG is a glycoconjugate on axonal surface that is involved in axonal outgrowth and/or synaptogenesis.

Animals↗
PubMed1996

Radiobiological evidence suggesting heterogeneous microdistribution of boron compounds in tumors: its relation to quiescent cell population and tumor cure in neutron capture therapy.

PURPOSE: The heterogeneous microdistribution of boron compounds in tumors and its significance on tumor cure were examined by a radiobiological procedure. The role of quiescent (Q) cells in tumor was especially investigated. METHODS AND MATERIALS: 10B-enriched paraboronophenylalanine (BPA) and mercaptoundecahydrododecaborate (BSH) were administered to SCCVII tumor bearing C3H/He mice by intragastric and i.v. injections, respectively. The continued effects of these boron compounds with thermal irradiations were studied by using colony formation and tumor control assays. Their effects on Q cells were also analyzed by the combined method of micronucleus frequency assay and an identification of proliferating (P) cells by BUdR and anti-BUdR monoclonal antibody. RESULTS: 10B-concentration after BPA (1,500 mg/kg) and BSH (75 mg/kg) administration were 11 ppm at 3 h and 10.5 ppm at 30 min, respectively. Cell survival decreased exponentially with an increment of neutron fluence (phi). The exponential parts of the curves were: -InSF = -0.052+ 13.0x10(13)phi, -InSF = -0.032+7.68X10(-13)phi, and -InSF = -0.0005+2.68x10(-13)phi for BPA-BNCT, BSH-BNCT, and NCT alone, respectively. Fifty percent tumor control was obtained at the influence of 10.2 x 10(12) n/cm2 in BPA-BNCT. On the other hand, 11.4 x 10(12) n/cm2 of neutrons had to be delivered in BSH-BNCT. The normal nuclear division fraction defined as the cell fraction that did not express micronuclei at first mitosis after treatment was investigated. The surviving cell fraction and the normal nuclear division fraction were regarded as equal in NCT alone. However, the normal nuclear division factor following BPA-BNCT was greater than the surviving cell fraction, and the difference increased with an increase in neutron fluence. In Q cells, BSH-BNCT yielded higher micronucleus frequency than BPA-BNCT and NCT alone. The frequencies in Q cells following BPA-BNCT and NCT alone were almost same as that in total cell population after NCT alone. CONCLUSIONS: Our data suggested that BPA distributed in tumors hetergeneously. Q cells especially might not accumulate BPA. To decrease the possible disadvantage of BPA-BNCT, the combination of BPA and BSH or other neutron capture element that emit particles with longer ranges, for example, gadolinium, would have to be investigated.

Animals↗
PubMed1996

Immunomodulation by an adenylate cyclase activator, NKH477, in vivo and vitro.

Cyclic adenosine monophosphate (cAMP) is an intracellular second messenger which modulates T cell function. NKH477 is a direct adenylate cyclase activator derived from forskolin and now under clinical investigation as a positive inotropic agent. While the immunosuppressive effects of forskolin on lymphocytes have been reported, little is known about its effects in vivo. In this study, we investigated whether NKH477 has immunosuppressive effects in mice, namely on cardiac allograft survival, and on the generation of cytotoxic T lymphocytes (CTL), T cell proliferation in mixed lymphocyte reaction (MLR), and production of interleukin-2 (IL-2) in MLR and in mitogen response. We assessed the effects of standard immunosuppressant cyclosporin A (CsA) on IL-2 production and on allograft survival to estimate the intensity of rejection in this acute rejection model. Saline-treated C57BL/6 (H-2b) mice rejected DBA/2 (H-2d) cardiac allografts with a median graft survival time of 10 days. In contrast, median graft survival was prolonged to 12 and 15 days in mice treated with NKH477 at 1 and 3 mg/kg/day, respectively (P < 0.01 vs control). The equivalent dose of CsA (40 mg/kg/day) to the maintenance dose after clinical cardiac transplantation prolonged median graft survival time to 15.5 days, indicating that high dose of NKH477 was as efficacious as lower dose of CsA. Addition of NKH477 to the culture medium suppressed the generation of CTL, T cell proliferation in MLR, and production of IL-2 in MLR and in mitogen response. These results suggest that NKH477 exerts a beneficial effect on murine cardiac allograft survival by modulating T cell function.

Acute Disease↗
PubMed1996

Differential modulation of cytokine production by drugs: implications for therapy in heart failure.

We studied the effects of various phosphodiesterase (PDE) III inhibitors: amrinone, pimobendan and vesnarinone: a PDE IV inhibitor (Ro 20-1724) and a PDE V inhibitor (E-4021) on the production of cytokines which have been shown to depress myocardial function. Recently developed inotropic agents which inhibit PDE III activity have produced short-term hemodynamic benefits in patients with advanced heart failure, but long-term treatment with these agents has an adverse effect on survival. However, vesnarinone, which has been shown to improve survival dramatically, has an immunomodulating effect and inhibits the production of cytokines. Peripheral blood mononuclear cells obtained from healthy human subjects were stimulated with lipopolysaccharide and each PDE inhibitor was added. After 24 h of incubation, tumor necrosis factor alpha (TNF-alpha), interleukin 1 beta (IL-1 beta) and IL-6 in the culture supernatants were measured by an enzyme-linked immunosorbent assay. All three PDE III inhibitors, amrinone, pimobendan and vesnarinone, inhibited TNF-alpha production, but vesnarinone's inhibitory effect was the most prominent. Amrinone and pimobendan enhanced IL-1 beta production, whereas vesnarinone had no effect. Vesnarinone inhibited IL-6 production and pimobendan slightly decreased IL-6 production, whereas amrinone had no significant effect on IL-6 production. The PDE IV inhibitor, Ro 20-1724, decreased the production of IL-1 beta and TNF-alpha and also tended to inhibit IL-6 production; its modulation of cytokine production was similar to the effects of vesnarinone. Because 8Br-cAMP or 8Br-cGMP did not suppress cytokine production, the modulating effects were not considered to result from an increase in cAMP or cGMP. Differential modulation of cytokine production may play a role in the therapeutic effect in heart failure patients who are treated with drugs that have PDE-inhibitory actions. It may be important to study whether the use of dual inhibitors of PDE III and PDE IV is therapeutically more useful for the treatment of heart failure due to their immunomodulating properties.

3',5'-Cyclic-AMP Phosphodiesterases↗