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Biomedical subjects

K Ono

Publications and source records attributed to K Ono.

At least 289 records · Page 16Linked to original sources
PubMed1999

ATP-Dependent efflux of CPT-11 and SN-38 by the multidrug resistance protein (MRP) and its inhibition by PAK-104P.

Non-P-glycoprotein-mediated multidrug-resistant C-A120 cells that overexpressed multidrug resistance protein (MRP) were 10.8- and 29. 6-fold more resistant to 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11) and SN-38, respectively, than parental KB-3-1 cells. To see whether MRP is involved in CPT-11 and SN-38 resistance, MRP cDNA was transfected into KB-3-1 cells. The transfectant, KB/MRP, which overexpressed MRP, was resistant to both CPT-11 and SN-38. 2-[4-Diphenylmethyl)-1-piperazinyl]ethyl-5-(trans-4,6-dimethyl-1,3 , 2-dioxaphosphorinan-2-yl)-2, 6-dimethyl-4-(3-nitrophenyl)-3-pyridinecarboxylate P-oxide (PAK-104P) and MK571, which reversed drug resistance in MRP overexpressing multidrug-resistant cells, significantly increased the sensitivity of C-A120 and KB/MRP cells, but not of KB-3-1 cells, to CPT-11 and SN-38. The accumulation of both CPT-11 and SN-38 in C-A120 and KB/MRP cells was lower than that in KB-3-1 cells. The treatment with 10 microM PAK-104P increased the accumulation of CPT-11 and SN-38 in C-A120 and KB/MRP cells to a level similar to that found in KB-3-1 cells. The ATP-dependent efflux of CPT-11 and SN-38 from C-A120 and KB/MRP cells was inhibited by PAK-104P. DNA topoisomerase I expression, activity, and sensitivity to SN-38 were similar in the three cell lines. Furthermore, the conversion of CPT-11 to SN-38 in KB-3-1 and C-A120 cell lines was similar. These findings suggest that MRP transports CPT-11 and SN-38 and is involved in resistance to CPT-11 and SN-38 and that PAK-104P reverses the resistance to CPT-11 and SN-38 in tumors that overexpress MRP.

ATP-Binding Cassette Transporters↗
PubMed1999

[The proliferative response and immunoglobulin production in peripheral blood lymphocytes stimulated with Japanese cedar pollen antigens].

Peripheral blood mononuclear cells taken from 38 normal subjects and 50 Japanese cedar pollinosis patients were cultured with or without mitogens or Japanese cedar pollen antigens to study the proliferative response and immunoglobulin production in periphral blood lymphocytes. When stimulated with Con A or anti-CD 40 mAb, the proliferative responses in the patient group were significantly higher than those in the normal group, and when stimulated with anti-CD 40 mAb, the IgG 2 production was markedly dominant among the IgE and IgG subclass productions in both groups. When stimulated with Japanese cedar pollen antigens, the proliferative responses in the patient group were markedly augmented in comparison with the normal group, and showed a correlation with the serum anti-cedar IgE antibody titers in the patient group. In regard to the immunoglobulin production in peripheral blood lymphocytes stimulated with Japanese cedar pollen antigens, the IgE productions in the patient group were significantly higher than those in the normal group, and showed a weak correlation with the serum anti-cedar IgE antibody titers in the patient group. The IgG productions were, however, slightly enhanced by the stimulation with Japanese cedar pollen antigens in both of the normal and patient groups. While it could not be clearly demonstrated which subclass of IgG was responsible for the enhancement of IgG production, there were some cases of relatively higher responses of IgG 2 or IgG 4 production. Though the IgG 4 productions in the patient group were significantly higher than those in normal group, there was no clear correlation with the serum anti-cedar IgE antibody titers in the patient group. On the other hand, it seems to be noteworthy that a weak negative correlation was recognized between the IgG 2 productions and the IgG 4 productions, and between the IgG 4 productions and the IgE productions. Considering these results in the present study, it was concluded to be difficult to identify a IgG 4 high responder in a course of clinical immunotherapy through the in vitro IgG 4 production or other related reactions as attempted in this study.

Adult↗
PubMed1999

[Efficacy of combination with granisetron and methylprednisolone for nausea, vomiting and appetite loss in remission induction chemotherapy of acute myeloid leukemia--a randomized comparative trial between granisetron alone and granisetron plus methylprednisolone].

The prevention of nausea, vomiting and appetite loss induced by remission induction chemotherapy for acute myeloid leukemia was compared by randomization between granisetron alone and combination with granisetron plus methylprednisolone. Granisetron was administered at 40 micrograms/kg during chemotherapy, and methylprednisolone was administered concomitantly at 125 mg/body for 3 days or more in the combination group. The single and combination groups comprised 14 and 13 patients, respectively, and there was no significant difference between the background of both groups. To evaluate the effect they were scored according to 4 grades, and evaluated every 24 hours from the start of chemotherapy to 5 days after its completion. The complete inhibition rate of vomiting was as high as 71.4% and 92.3% in the single and combination groups, respectively, showing no significant difference. The grade of vomiting was mild in both groups. Nausea was noted in 71.4% and 46.2%, respectively, and the inhibitory effect tended to be higher in the combination group. Appetite loss developed in 92.9% and 41.7%, respectively, and the prevention effect was clearly higher in the combination group. The prevention effects on nausea 7, 8 and 10 days after the start of chemotherapy, on appetite loss 2-10 days after it, and 2-5 days after its completion, were higher in the combination group. Granisetron revealed an excellent inhibitory effect on vomiting induced by remission induction chemotherapy for acute myeloid leukemia, but combination with granisetron and methylprednisolone was considered useful for nausea in the latter half of the treatment period and for appetite loss during the whole period.

Acute Disease↗
PubMed1999

A rapid method for determination of the relative copy number of HTLV-I proviral genome in HTLV-I carriers and adult T-cell leukemia patients by polymerase chain reaction.

Ten adult T-cell leukemia (ATL) patients and 11 asymptomatic human T-cell leukemia virus type I (HTLV-I) carriers were examined by polymerase chain reaction (PCR) assay with a reduced sensitivity to evaluate its utility in detecting the relative copy number of the HTLV-I genome in clinical samples. Differences in the intensities of the PCR products were observed between the acute type ATL patients and ATL patients in remission or carriers. Intense bands were found in all acute type ATL patients (6/6, 100%), while specific bands were seen in only 2 carriers (2/11, 18.2%). The bands found in one of the two patients in remission were weak. One patient, who had acute type ATL, had achieved a remission but later relapsed. Using this technique, we examined the differences in the intensities of the bands of the PCR products in a patient with acute type ATL who had achieved remission but later relapsed. Thus, this technique may be of clinical importance in diagnosing acute ATL and assessing the effect of therapy.

Adult↗
PubMed1999

[Invasive amebiasis at an institution for the mentally retarded in Hyogo Prefecture].

An outbreak of amebiasis caused by Entamoeba histolytica occurred at an institution for mentally retarded persons in Hyogo Prefecture. Twelve out of a total of 49 admitted persons exhibited E. histolytica cysts in their stool, and 13 including persons in whom no cysts had been detected showed positive serological reactions for E. histolytica infection. However, neither the cyst nor the antibody against the organism was detected in the staff members of the institution. Indirect fluorescence antibody test and sandwich enzyme-linked immunosorbent assay with a monoclonal antibody specific for pathogenic strains of E. histolytica revealed that all trophozoite strains grown from cysts in stool samples from five patients were pathogenic. Epidemiological analysis strongly suggested that a patient in the institution had been infected with an organism from a patient outside the institution, and that infection may have spread among the admitted persons due to abnormal behavior. Administration of metronidazole resulted in effective elimination of the cysts from the stool of the cyst-carriers.

Adult↗
PubMed1999

[Economical evaluation for drug consultation at home].

We started drug consultation at patients' homes in October, 1998. The number of drug consultations are 2.65 per month per patient and the consulting time is 2.25 hours per patient. The fee for drug consultation is 550 points twice a month. We evaluate the fee for drug consultation. Our data suggest that this fee needs to be 550 points three times a month.

Aged↗
PubMed1999

[Recent spread of home parenteral nutrition in Japan--the view of an HPN managing company].

Terumo Corporation has developed a nation wide home healthcare management system "Home-Joint," which helps hospitals to safely discharge patients early. Recently, this system mainly has been adopted with HPN (home parenteral nutrition) patients. This report evaluates 472 HPN patients who underwent the "Home-Joint" program in 1998, and also presents some issues from the standpoint of a HPN managing company. I. Profiles of HPN patients Number: 472 (female 43%, male 57%) Age: 1-104 (47% patients over 70) DIAGNOSIS: cancer 54%, others 25%, unknown 21% Infusion devices: ambulatory pump 85%, stationary pump 15%, gravity none. Therapeutic periods: average 65.6 days (1-437) for 300 patients who completed the program. II. HPN trends from 1997 to 1998 1. Increase in patients directly supported by hospitals. 2. Wider patient variation: increase in patients under 70 years old, in non-cancer patients and in longer periods (longer than 2 months). III. Issues 1. Development of hospital-clinic-pharmacy local relationship. 2. Development of devices for easier infusion control. 3. Evaluation of HPN outcome for patients' QOL and for cost-effectiveness. HPN is becoming a popular home healthcare therapy in Japan, and it requires higher level of performance by medical staff and managing companies.

Cooperative Behavior↗
PubMed1998

Transforming growth factor-beta1 increases mRNA levels of osteoclastogenesis inhibitory factor in osteoblastic/stromal cells and inhibits the survival of murine osteoclast-like cells.

Osteoclastogenesis inhibitory factor (OCIF), also termed osteoprotegerin (OPG), is a secreted member of the tumor necrosis factor (TNF) receptor family. It inhibits bone resorption in vivo and osteoclast-like cell (OCL) formation in vitro. To better understand the biological role of OCIF, we first examined the effects of various osteotropic agents on OCIF mRNA levels in mouse calvarial osteoblasts. Northern blot analysis showed that stimulators of OCL formation such as 1,25-(OH)2D3, prostaglandin E2 (PGE2), parathyroid hormone (PTH), and interleukin 1 (IL-1) decreased OCIF mRNA levels. In contrast, transforming growth factor (TGF)-beta1 increased OCIF mRNA levels in primary osteoblasts as well as in osteoblastic/stromal cell lines. Since it was reported that both TGF-beta1 and OCIF not only inhibited OCL formation but also impaired the survival of OCL by inducing apoptosis in vitro, we next examined the possible involvement of OCIF in TGF-beta1-induced impairment of OCL survival. In a mouse bone marrow culture, we confirmed that addition of OCIF or TGF-beta1 decreased the number of surviving OCL. Anti-OCIF IgG, which completely neutralized the effect of OCIF, partially prevented the TGF-beta1-induced decrease in the number of OCL. Our results suggest that (i) downregulation of OCIF expression is one of the mechanisms for the stimulatory effects of 1,25(OH)2D3, PGE2, PTH, and IL-1 on osteoclastogenesis; and (ii) the TGF-beta1-induced apoptosis of OCL is mediated, at least in part, by upregulation of OCIF expression.

Animals↗
PubMed1998

Phospholipase C cDNAs from sponge and hydra: antiquity of genes involved in the inositol phospholipid signaling pathway.

To know whether or not the set of genes involved in the inositol phospholipid signaling pathway already existed in the early evolution of animals, we carried out cloning of cDNAs encoding phospholipase Cs (PLCs) from Ephydatia fluviatilis (freshwater sponge) and Hydra magnipapillata strain 105 (hydra). We isolated two PLC cDNAs, PLC-betaS and PLC-gammaS, from sponge and three cDNAs, PLC-betaH1, PLC-betaH2, and PLC-deltaH, from hydra. From the domain organization and the divergence pattern in the PLC family tree, the sponge PLC-betaS and PLC-gammaS and the hydra PLC-deltaH are possibly homologous to the vertebrate PLC-beta, PLC-gamma and PLC-delta subtypes, respectively. A detailed phylogenetic analysis suggests that the hydra PLC-betaH1 and PLC-betaH2 are homologs of the vertebrate PLC-beta1/2/3/Drosophila PLC21 and the vertebrate PLC-beta4/Drosophila norpA, respectively. A phylogenetic analysis of the PLC family and the protein kinase C (PKC) family, together with that of the G protein alpha subunit (Galpha) family, revealed that the origin of the set of genes G(alpha)q, PLC, PKC involved in the inositol phospholipid signaling pathway is very old, going back to dates before the parazoan-eumetazoan split, the earliest branching among extant animal phyla.

Animals↗
PubMed1998

Electroporation increases the effect of borocaptate (10B-BSH) in neutron capture therapy.

PURPOSE: The cell membrane permeability of borocaptate (10B-BSH) and its extent of accumulation in cells are controversial. This study was performed to elucidate these points. METHODS AND MATERIALS: Two different treatments were applied to SCCVII tumor cells. The first group of tumor cells was incubated in culture medium with 10B-BSH or 10B-enriched boric acid, and was exposed to neutrons from the heavy water facility of the Kyoto University Reactor (KUR). More than 99% of neutrons were thermal neutrons at flux base. The second group was pretreated by electroporation in combination with 10B-BSH, and thereafter the cells were irradiated with neutrons. The cell killing effects of boron neutron capture therapy (BNCT) using BSH were investigated by colony formation assay. RESULTS: Surviving cell fraction decreased exponentially with neutron fluence, and addition of BSH significantly enhanced the cell killing effect of neutron capture therapy (NCT) depending on 10B concentration. The effect of BSH-BNCT also increased with preincubation time of cells in the medium containing BSH. The electroporation of cells with BSH at 10 ppm 10B markedly enhanced BSH-BNCT effects in comparison with that of preincubation alone. The effect of BSH-BNCT with electroporation was equal to that of BNCT using 10B-boric acid at a same 10B concentration (10 ppm). CONCLUSIONS: BSH is suggested to penetrate the cells slowly and remained after washing. Electroporation can introduce BSH into the cells very efficiently, and BSH stays in the cells and is not lost by washing. Therefore, if electroporation is applied to tumors after BSH injection, 10B remains in tumors but is cleared from normal tissues, and selective accumulation of 10B in tumors will be achieved after an adequate waiting time.

Borohydrides↗
PubMed1998

Ancient gene duplication and domain shuffling in the animal cyclic nucleotide phosphodiesterase family.

The animal cyclic nucleotide phosphodiesterases (PDEs) comprise at least seven subtypes, PDE1-7, which differ from each other in domain organization and primary function, and they diverged from an ancestral gene by gene duplication and domain shuffling during animal evolution. To obtain rough estimates for the divergence times of these subtypes, cloning of PDE cDNAs from Ephydatia fluviatilis (freshwater sponge) by RT-PCR was carried out. We obtained four cDNAs, EFPDE1, EFPDE2, EFPDE3, and EFPDE4, which are possibly homologs of the vertebrate PDE1, PDE2, PDE3, and PDE4, respectively, judging from the sequence similarity, domain organization, and branching pattern in the phylogenetic tree. The phylogenetic tree of the PDE family revealed that most gene duplications and domain shufflings that gave rise to different subtypes had been completed in the early evolution of animals before the separation of sponges and eumetazoans.

3',5'-Cyclic-AMP Phosphodiesterases↗
PubMed1998

Osteoclastogenesis inhibitory factor suppresses osteoclast survival by interfering in the interaction of stromal cells with osteoclast.

Osteoclastogenesis inhibitory factor (OCIF) was originally identified as a factor inhibiting osteoclast (OC) formation. The number of OC in rats treated with OCIF decreased, suggesting that OCIF inhibits OC formation in vivo; however, it is also possible that OCIF affects the number of OC by promoting apoptosis of OC. To address this issue, the effects of OCIF on the survival of OC were examined using well established mouse culture systems. OCIF dose-dependently inhibited OC formation in mouse marrow cultures. Addition of OCIF during day 0-3 did not alter the peak levels of OC formation on day 7 and 8. However, the addition of OCIF during day 5 and thereafter resulted in the rapid decrease of the number of OC. OCIF inhibited the survival of OC formed in mouse marrow cultures in dose- and time-dependent manners. The involvement of stromal cells in OC survival was examined using crude and stromal cell-depleted OC populations. OCIF dramatically inhibited the survival of crude OC populations rich with stromal cells. However, in stromal cell-depleted OC populations, OC spontaneously decreased in the absence of OCIF and OCIF did not enhance the decrease further at least up to 48 h. Apoptotic OC were detected in detached cell populations treated with OCIF in mouse marrow cultures and a specific inhibitor for caspase-3 rescued the death of OC. OCIF mutant lacking the death domain homologous regions inhibited OC survival, though the potency was much less than native OCIF. Taken together, OCIF inhibited not only OC recruitment but also OC survival. OCIF inhibited OC survival by interfering the interaction of stromal cells with OC.

Animals↗
PubMed1998

Chloride-sensitive nature of the histamine-induced Ca2+ entry in cultured human aortic endothelial cells.

1. Whole-cell currents and intracellular Ca2+ concentration ([Ca2+]i) were recorded in cultured human aortic endothelial cells (HAECs) to study the mechanisms underlying Cl--sensitive Ca2+ entry. 2. In the absence of histamine the membrane potential ranged between -90 and +5 mV and showed bimodal distribution with peaks at -17.8 and -67.5 mV. 3. Histamine (1-100 microM) activated an outward current, followed by a sustained inward current at -50 mV. The reversal potential (Vrev) was more negative than -60 mV for the initial outward current, and approximately -30 mV for the sustained inward current with normal Tyrode solution and internal solution containing 30 mM Cl-. 4. Vrev of the sustained inward current was hardly affected by varying the external concentrations of K+, Na+ and Ca2+, but was greatly changed by varying the external Cl- concentration ([Cl-]o). The relationship between Vrev and log[Cl-]o showed a slope of -44.8 mV per tenfold increase of [Cl-]o. 5. The Cl- channel blockers 9-anthracene carboxylic acid (1 mM), N-phenylanthranilic acid (0.1 mM) and niflumic acid (0.1 mM) all depressed the histamine-induced inward current. The non-selective cation channel blocker Gd3+ (10 microM) was without effect on the current. 6. In the absence of histamine, [Ca2+]i was not affected by varying the membrane potential. During the continuous presence of histamine, however, hyperpolarization increased and depolarization decreased [Ca2+]i, indicating that Ca2+ entry through the plasma membrane was activated by histamine. 7. Vrev of the histamine-induced Cl- current, measured by the gramicidin-perforated patch clamp method, was -28.4 +/- 6.6 mV (n = 8), which gave an intracellular Cl- concentration of approximately 34 mM. Under the current clamp condition, the membrane potential varied from cell to cell in the control, but application of histamine induced either depolarization or hyperpolarization, depending on the membrane potential before histamine application, and the membrane potential became stable near the equilibrium potential for Cl-. 8. We conclude that the histamine-induced inward current is carried mainly by Cl-. Although Ca2+ entry was also activated, we consider that its amplitude was too small to be resolved by the patch clamp method. The Cl- current may play a functional role in the sustained [Ca2+]i elevation by providing a constant driving force for Ca2+ entry in the presence of histamine.

Anthracenes↗
PubMed1998

Tectal projections to the parvicellular reticular formation and the upper cervical spinal cord in the rat, with special reference to axon collateral innervation.

After Phaseolus vulgaris leucoagglutinin injection into the lateral part of the superior colliculus (SC) in the rat, labeled fibers and axon terminals in the lower brainstem were distributed not only in the medial reticular formation but also in the lateral tegmental field including the parvicellular reticular formation (RFp). More caudally, in the upper cervical spinal cord labeled fibers with bouton-like varicosities were distributed mainly in laminae V, VII and VIII, with relatively sparse distribution in lamina IX. These labeled axons were found bilaterally with a clear-cut contralateral dominance. After combined injections of rhodamine-dextranamine, Fluoro-ruby (FR) into the RFp and Fluoro-gold (FG) into the upper cervical spinal cord on the same side, SC neurons labeled with FR were intermingled with those labeled with FG in the lateral part of the SC contralateral to the injection sites. In the stratum griseum intermediale, some of them were double-labeled with both tracers. Our results suggest that SC neurons innervating both the RFp and the cervical spinal cord may be involved in the coordination of head and mouth movements.

Animals↗
PubMed1998

Developmental appearance of oligodendrocytes in the embryonic chick retina.

The axons of the optic nerve layer are known to be myelinated by oligodendrocytes in the chick retina. The development of the retinal oligodendrocytes has been studied immunohistochemically with antibodies against oligodendrocyte lineage: monoclonal antibodies O4 and O1, and an antibody against myelin basic protein. O4 positive (O4+) cells were first detected in the retina on the tenth day of incubation (embryonic day (E)10, stage 36). The labeled cells were located in the optic nerve layer close to the optic fissure. Most were unipolar in shape, extending a leading process with a growth cone toward the periphery of the retina. By E12, unipolar O4+ cells had spread to the middle of the retina. Many O4+ cells close to the optic fissure showed radial arrangement with extension of processes toward the inner limiting membrane. O1+ oligodendrocytes were first observed in the E14 retina positioned just above (interiorly to) retinal ganglion cells. These labeled cells extended fine processes in the optic nerve layer. Limited numbers of myelin basic protein-positive cells were present by E16 and located interiorly to the retinal ganglion cells. In addition to the oligodendrocyte in the optic nerve layer, a limited number of O4+ cells were observed in the inner nuclear layer by E14, and they became O1+ by E18. Furthermore, explant culture experiments showed E10 to be the youngest stage at which the retina contained oligodendrocyte precursors. An intraventricular inj ection of fluorescent dye 1,1',dioctadecyl-3,3,3',3-tetramethylindocarbocyanine perchlorate (DiI) at E6 yielded O4+/DiI+ cells in the retina at E10, which provided direct evidence to support migration of oligodendrocyte precursor into the retina. The present results demonstrated the sequential appearance of the cells of oligodendrocyte lineage and the detailed morphology of the developing oligodendrocytes in the retina. These morphologic features strongly suggested that retinal oligodendrocytes were derived from the optic nerve and spread by migration through the optic nerve layer.

Animals↗