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Biomedical subjects

K Ono

Publications and source records attributed to K Ono.

At least 397 records · Page 22Linked to original sources
PubMed1997

A monoclonal antibody that recognizes ganglioside GD1b in the rat central nervous system.

A monoclonal antibody (MAb), generated by immunizing BALB/c mice with homogenized bovine retinal tissue, was specific to ganglioside GD1b incorporated into liposome membranes. The antibody (MAb-5G6), classified as IgM, immunostained intensely the perikaryon and processes of motoneurons in the cranial motor nuclei and spinal cord. Spinal and trigeminal ganglion cells were also immunopositive to the MAb. Some fiber tract systems, such as the spinal and mesencephalic trigeminal tracts, the solitary tract and the posterior funiculus, were also immunoreactive to the MAb. These findings suggest that MAb-5G6 labeled specifically neurons with axons extending outside of the central nervous system as a peripheral nerve. The immunoreactive substances were visualized under electron microscopy just beneath the postsynaptic membrane and just inside the plasmalemma of the thick dendrites. No axon terminal was immunolabeled by the MAb. In the rat embryos, immunoreactivity to MAb-5G6 was found in the dorsal and ventral root fibers on the 15th embryonic day (E15). However, cell bodies of the spinal ganglion cells and motoneurons were immunostained by MAb-5G6 at a later stage (E20). The ventral commissure fibers in the floor plate of the spinal cord were transiently immunolabeled during E13-15.

Animals↗
PubMed1997

Focal ventricular origin and migration of oligodendrocyte precursors into the chick optic nerve.

During central nervous system (CNS) development, oligodendrocyte precursors originate in specific locations and subsequently migrate to all regions of the CNS. Here, we demonstrate that the chick optic nerve is populated by oligodendrocyte precursors, which initially appeared in a focal region at the ventral midline of the third ventricle at stage 26-27. Oligodendrocyte precursors migrated into the chiasmal end of the nerve by stage 29 and became uniformly distributed by stage 35. Migrating precursors were restricted to the anterior region of the nerve, closely apposed to axons, and had a bipolar morphology. In contrast to the polysialic acid (PSA)-dependent cooperative streaming migration of olfactory neuronal precursors, the migration of oligodendrocyte precursors along the optic nerve appeared axophilic and unaffected by removal of neural cell adhesion molecule (N-CAM)-associated PSA. These data indicate that during development, defined domains of the ventricular zone give rise to distinct cell types that utilize discrete mechanisms to navigate specific migrational pathways.

Animals↗
PubMed1997

Boron neutron capture therapy: preliminary study of BNCT with sodium borocaptate (Na2B1 2H1 1SH) on glioblastoma.

To plan the optimal BNCT using BSH for glioblastoma patients, the 10B concentration in tumor and blood was investigated in 11 newly diagnosed glioblastoma patients. All patients received 20 mg BSH/kg body weight 2.5-16 hrs prior to tumor removal. The quantitative distribution of 10B was determined by prompt gamma ray spectrometry and/or alpha-track autoradiography. 10B distribution in tumors was heterogeneous, +/- 25% of scattering at the microscopic level, and the distribution was also heterogeneous at the tissue level. 10B concentration in blood decreased in bi-exponential decay as a function of the time after the end of the administration. The T/B ratio showed non-exponential increase with large variation. The maximum T/B ratio would be around 1. The tumor/normal brain (T/N) ratio of 10B concentration was 11.0 +/- 3.2. The 10B content in normal brain is originated in vascular 10B in parenchyma, since the 10B content in normal brain to blood (N/B ratio) being compatible with the blood content in parenchyma. These values allow for BNCT, using thermal neutrons, on brain tumors located less than approximately 3.3 cm in depth from the brain surface of neutron incidence, providing that the dose on the normal endothelium is controlled to less than the tolerance limit. In our preliminary study of BNCT, a 31% 3-year survival was achieved over all for 16 glioblastoma patients and a 50% 2-year survival was achieved on 8 glioblastoma patients in our recent dose escalation study based on these data.

Borohydrides↗
PubMed1997

Inhibition of human pancreatic cancer growth in nude mice by boron neutron capture therapy.

Immunoliposomes were prepared by conjugating anti-carcinoembryonic antigen (CEA) monoclonal antibody with liposomes containing [10B]compound. These immunoliposomes were shown to bind selectively to human pancreatic carcinoma cells (AsPC-1) bearing CEA on their surface. The cytotoxic effects of locally injected [10B]compound, multilamellar liposomes containing [10B]compound or [10B]immunoliposomes (anti-CEA) on human pancreatic carcinoma xenografts in nude mice were evaluated with thermal neutron irradiation. After thermal neutron irradiation of mice injected with [10B]solution, 10B-containing liposomes or [10B]immunoliposomes, AsPC-1 tumour growth was suppressed relative to controls. Injection of [10B]immunoliposomes caused the greatest tumour suppression with thermal neutron irradiation in vivo. Histopathologically, hyalinization and necrosis were found in 10B-treated tumours, while tumour tissue injected with saline or saline-containing immunoliposomes showed neither destruction nor necrosis. These results suggest that intratumoral injection of boronated immunoliposomes can increase the retention of 10B atoms by tumour cells, causing tumour growth suppression in vivo upon thermal neutron irradiation. Boron neutron capture therapy (BNCT) with intratumoral injection of immunoliposomes is able to destroy malignant cells in the marginal portion between normal tissues and cancer tissues from the side of 4He generation.

Animals↗
PubMed1997

Reduction of hypoxic cells in solid tumours induced by mild hyperthermia: special reference to differences in changes in the hypoxic fraction between total and quiescent cell populations.

C3H/He mice bearing SCC VII tumours received 5-bromo-2'-deoxyuridine (BrdU) continuously for 5 days via implanted mini-osmotic pumps in order to label all proliferating (P) cells. The tumours were then heated at 40 degrees C for 60 min. At various time points after heating, tumour-bearing mice were irradiated while alive or after being killed. Immediately after irradiation, the tumours were excised, minced and trypsinized. The tumour cell suspensions obtained were incubated with cytochalasin-B (a cytokinesis blocker), and the micronucleus (MN) frequency in cells without BrdU labelling, which could be regarded as quiescent (Q) cells, was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P+Q) tumour cell population was determined from the irradiated tumours that were not pretreated with BrdU. The 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 (P+Q) tumour cells. In general, Q cells contained a greater hypoxic fraction (HF) than the total tumour cell population. Mild heating decreased the HF of Q cells more markedly than in the total cell population, and the minimum values of HFs of both total and Q cell populations were obtained 6 h after heating. Two days after heating, the HF of total tumour cells returned to almost that of unheated tumours. In contrast, the HF of Q cells did not return to the HF level of unheated tumours until 1 week after heating. It was thought that irradiation within 12 h after mild heating might be a potentially promising therapeutic modality for controlling radioresistant Q tumour cells.

Animals↗
PubMed1997

Human T cell responses to recombinant mite antigens of Dermatophagoides farinae.

We studied T cell responses to four glutathione S transferase (GST)-fused mite antigens prepared in our laboratory using peripheral blood lymphocytes from mite-sensitive patients with bronchial asthma. Of the four recombinant antigens, purified GST-Mag3 had the strongest ability to cause patients' lymphocytes to proliferate, and its potency was almost comparable to that of crude mite bodies (Dfb) and faeces (Dff) antigens and a purified major antigen, Der f 2. The responder lymphocytes were mainly T cells, because the proliferative response was depleted by the treatment of lymphocytes with anti-CD3 antibody and complement, but not with anti-CD20 antibody and complement. The responsiveness of lymphocytes to GST-Mag3 correlated with that to Der f 2, but GST-Mag3 displayed slightly higher activity to stimulate lymphocytes than Der f 2. Simultaneously, the levels of Dff- and GST-Mag3-specific IgE antibodies correlated with the responsiveness of lymphocytes to GST-Mag3. These results suggest that Mag3 is a new valuable antigen for the response of T cell proliferation in mite-sensitive patients.

Allergens↗
PubMed1997

Isolation and characterization of matrix associated region DNA fragments in rice (Oryza sativa L.).

To investigate the interactions between chromosomal DNA and nuclear matrices in higher plants, matrix associated regions (MARs) of rice (Oryza sativa L.) DNAs were cloned. First, we prepared nuclear matrices from isolated nuclei by digesting them with EcoRI and then extracting with 2 M NaCl. About 6% of the total DNA remained in the nuclear matrices after this digestion and extraction. The residual DNA fragments in the nuclear matrices were cloned. Some of the cloned DNA fragments showed binding to certain nuclear proteins. One of the MAR fragments contained sequences related to known consensus motifs and a hairpin loop structure. A method is presented for isolation of matrix associated region (MAR) DNAs from plant cells.

Base Sequence↗
PubMed1997

B7-1(CD80)-transfected human glioma cells and interleukin-12 directly stimulate allogeneic CD8+ T cells.

To obtain more effective cytotoxic T lymphocytes (CTLs), we examined the effect of B7 costimulation and interleukin-12 (IL-12) on the induction of allogeneic CTLs. Peripheral blood lymphocytes (PBLs) or positively selected human CD8+ T cells (purity > 99%) from healthy donors were used as effector cells, and B7-1-transfected or nontransfected U251 human glioma cells (U251-B7 or U251-Vec.) were used as stimulator cells. In mixed lymphocyte culture (MLC) with PBLs and U251 cells, nonspecific natural killer (NK) activity was raised by addition of IL-12, and the effect of B7 costimulation was not observed. However, in MLC with CD8+ T cells, efficient proliferation, generation of CTLs, and cytokine production were induced by MLC with U251-B7 in the presence of IL-12. Efficient generation of CTLs was not induced by either MLC with U251-B7 alone or the addition of IL-12 alone. Our results indicate that a combination of B7-1 costimulation and IL-12 is effective for inducing generation of CTLs, and that the CD8+ T cells can be differentiated into CTLs without the help of CD4+ T cells or antigen-presenting cells or both.

B7-1 Antigen↗
PubMed1997

Cell-killing efficiency and number of platinum atoms binding to DNA, RNA and protein molecules of HeLa cells treated with combinations of trans-diaminedichloroplatinum(II) and hyperthermia.

The effect of hyperthermia on the cell-killing efficiency of Pt atoms binding to DNA, RNA and protein molecules was examined. HeLa S-3 cells were treated with 195mPt-radiolabeled trans-diaminedichloro-platinum(II) (TDDP) for 60 min at various temperatures, and the relationship between the lethal effect and the number of Pt atoms binding to DNA, RNA and proteins was examined. The mean lethal concentration (D0) of TDDP for a 60-min treatment at 0, 25, 37, 40, 42 and 44 degrees C was 1714, 1016, 302, 179, 125 and 42.5 microM, respectively. (D0 is defined as the dose that would give an average of one lethal event per member of the population; for further details, see Fig. 1). By using identically treated cells, the numbers of Pt-atoms combined with DNA, RNA and protein molecules were determined in the subcellular fractions. Thus, the D0's given as the drag concentrations were replaced with the number of Pt-atoms combined in each fraction. Then, the cell-killing efficiency of the Pt atom was expressed as the reciprocal of the number of Pt-atoms combined and was calculated for each molecule. The efficiency for DNA was 0.206, 0.273, 0.779, 1.28, 1.77 and 5.14 x 10(3) nucleotides, respectively, for the conditions described above. It seemed that hyperthermia potentially interacted not only with bifunctional, but also with monofunctional bonds. Thus, it was concluded that TDDP was markedly less cytotoxic than cis-diaminedichloroplatinum (CDDP) at 37 degrees C, but was more cytotoxic than CDDP at 44 degrees C.

Cell Death↗
PubMed1997

Augmentation in chemosensitivity of intratumor quiescent cells by combined treatment with nicotinamide and mild hyperthermia.

C3H/He and Balb/c mice bearing SCC VII and EMT6/KU tumors, respectively, received continuous administration of 5-bromo-2'-deoxyuridine (BrdU) for 5 days using implanted mini-osmotic pumps to label all proliferating (P) cells. Nicotinamide was administered intraperitoneally before cisplatin injection and/or tumors were locally heated at 40 degrees C for 60 min immediately after cisplatin injection. The tumors were then excised, minced and trypsinized. The tumor cell suspensions 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 total (P+Q) tumor cells was determined from tumors that had not been pretreated with BrdU labeling. The sensitivity to cisplatin was evaluated in terms of the frequency of induced micronuclei in binuclear tumor cells (MN frequency). In both tumor systems, the MN frequency in Q cells was lower than that in the total cell population. Nicotinamide treatment elevated the MN frequency in total SCC VII cells. Mild heating raised the MN frequency more markedly in Q cells than in total cells. The combination of nicotinamide and mild heat treatment increased the MN frequency more markedly than either treatment alone. In total SCC VII cells, nicotinamide increased 195mPt-cisplatin uptake. Mild heating elevated 195mPt-cisplatin uptake in total EMT6/KU cells. Cisplatin-sensitivity of Q cells was lower than that of total cells in both tumor systems. Nicotinamide sensitized tumor cells including a large acutely hypoxic fraction, such as those of SCC VII tumors, through inhibition of the fluctuations in tumor blood flow. Tumor cells including a large chronically hypoxic fraction such as Q cells were thought to be sensitized by mild heating through an increase in tumor blood flow.

Animals↗
PubMed1997

Effects of bioreductive agents, tirapazamine and mitomycin C, on quiescent cell populations in solid tumors, evaluated by micronucleus assay.

Mice bearing transplantable solid tumors received 10 intraperitoneal administrations of 5-bromo-2'-deoxyuridine (BrdU) to label the proliferating (P) tumor cells, and were then irradiated with 60Co gamma-rays or injected with cis-diamminedichloroplatinum (II) (cisplatin). The tumor cells were isolated and incubated with cytochalasin-B (a cytokinesis blocker). The micronucleus (MN) frequency in the cells without BrdU labeling, which were regarded as quiescent (Q) cells in the tumor, was determined using immunofluorescence staining for BrdU. The MN frequency in the total (P + Q) tumor cell population was determined from tumors that were not pretreated with BrdU. Pretreatment with tirapazamine, a bioreductive agent, could enhance the sensitivity of tumor cells, including Q cells, to radiation more markedly than mitomycin C pretreatment as judged from an in vivo assay immediately after irradiation. Post-irradiation administration of tirapazamine produced a large post-irradiation radiosensitizing effect on both the total and Q tumor cell populations in vivo. Cisplatin treatment combined with tirapazamine demonstrated that tirapazamine also has a chemosensitizing potential for both the total and Q tumor cell populations. We confirmed that the sensitivity of Q cell populations to radiation and chemotherapy using cisplatin can be enhanced by combined treatment with tirapazamine.

Animals↗
PubMed1997

Identification of T-cell epitope sequences on an important mite antigen.

BACKGROUND: T-cell epitopes on Der 1 and Der 2 groups, the major mite allergens, have been intensively analysed, while those on the other important allergens remain to be elucidated. We have cloned four cDNAs coding for important mite allergens on the basis of frequency and capacity of IgE binding. Stimulatory action of glutathione S-transferase-fused Mag1 on lymphocytes from mite-allergic patients was relatively high among them. OBJECTIVE: To identify T-cell epitopes on Mag1, we studied the stimulating activity of truncated Mag1 proteins and synthetic peptides on proliferative response of lymphocytes from mite antigen-immunized mice and mite-sensitive patients. METHODS: Truncated Mag1 proteins were expressed as a fusion protein with beta-galactosidase in Escherichia coli pop2136 carrying a variety of deleted Mag1 inserts. Murine T-cell epitope regions were estimated by the truncated antigen-induced lymphocyte proliferation assay. Overlapping peptides covering the whole sequence of the presumed T-cell epitope regions were synthesized to identify the epitope core sequences using murine and human Mag1-specific T-cell lines. RESULTS: Amino acid range 56-70 on Mag1 molecule showed remarkable stimulatory action on murine T cells, while amino acid ranges 51-65 and 86-100 had potent stimulatory activity on human T cells. CONCLUSIONS: These results suggest that Mag1 is a valuable antigen suitable for studies on T-cell responses and T-cell epitopes in mice and humans.

Animals↗
PubMed1997

Administration of aminoglycosides to hemodialysis patients immediately before dialysis: a new dosing modality.

We describe a new modality for administering aminoglycosides to hemodialysis (HD) patients, namely, a modification of the once-daily regimen which consists of administering the aminoglycosides over 60 min by drip infusion just before each HD session, with a preplanned peak concentration being reached at the beginning of the session and then with a rapidly decreasing concentration being achieved by the start of HD. The area under the concentration-time curve (AUC), i.e., the accumulation of the drug in the body, is thus minimized by this modality. Arbekacin (ABK) was given at a dose of 2 mg/kg of body weight to 10 HD patients infected with methicillin-resistant Staphylococcus aureus (MRSA) for 2 weeks (six sessions in total), resulting in the complete disappearance of MRSA in 5 patients. A high rate of elimination of ABK was attained for each patient while the patient was on HD (range, 0.20 to 0.42 h-1; mean 0.28 +/- 0.08 h-1) by using high-performance dialyzers provided with membranes made of either polymethylmethacrylate, cellulose triacetate (CTA), or ethylene vinyl alcohol. The best results were obtained with the CTA membrane, as revealed by the overall mass transfer coefficient (Ko). The AUC in the simulation model for the variation in the serum ABK concentration in this modality was calculated to be 40% of that of the conventional post-HD dosing modality, suggesting that a much higher dose could be administered to HD patients who receive HD thrice weekly (4 h per session), giving, e.g., 4 mg/kg initially and before the HD sessions, when there is an interval of 68 h from HD session to HD session, and giving 2 mg/kg before the other sessions.

Aged↗
PubMed1997

Characterization of endonuclease III (nth) and endonuclease VIII (nei) mutants of Escherichia coli K-12.

The nth and nei genes of Escherichia coli affect the production of endonuclease III and endonuclease VIII, respectively, glycosylases/apurinic lyases that attack DNA damaged by oxidizing agents. Here, we provide evidence that oxidative lethal lesions are repaired by both endonuclease III and endonuclease VIII and that spontaneous mutagenic lesions are repaired mainly by endonuclease III.

Cloning, Molecular↗
PubMed1997

Active inhibitory effect of nafamostat mesylate against the elevation of plasma myeloperoxidase during hemodialysis.

Plasma levels of myeloperoxidase (MPO) were compared between hemodialysis (HD) sessions using heparin and those using nafamostat mesylate (NM) as an anticoagulant by an enzyme immunoassay established in our laboratory. MPO levels were markedly elevated during the entire HD procedure with heparin. In contrast, MPO levels were scarcely elevated during the HD with NM. On the other hand, polymorphonuclear leukocyte-elastase was markedly elevated during both of these HD procedures. These observations indicated that NM selectively attenuated MPO elevation in vivo during HD. This inhibitory effect of NM was further investigated ex vivo. Blood samples from a normal subject were collected with heparin alone, NM alone and a mixture of heparin and NM. Each sample was then circulated in a closed circuit composed of a dialyzer with a cuprophane membrane. MPO levels with heparin alone were shown to markedly rise in the closed system. In contrast, levels of MPO in the blood samples mixed with NM were not elevated even in the presence of heparin. These ex vivo results indicate that NM has an active inhibitory effect on the elevation of plasma MPO induced by granulocyte activation through a dialysis membrane. Our results demonstrate that clinical use of NM as an anticoagulant serves to selectively suppress MPO elevation considered as a consequence of granulocyte activation during HD.

Adult↗
PubMed1997

Increased expression of interleukin-1 beta and monocyte chemotactic and activating factor/monocyte chemoattractant protein-1 in the hypertrophied and failing heart with pressure overload.

Studies on the effects of proinflammatory cytokines on the heart suggest that they play some roles in the pathogenesis of congestive heart failure (CHF). To determine the involvement of proinflammatory cytokine in cardiac hypertrophy and CHF induced by mechanical overload, we investigated the expression of interleukin (IL)-1 beta and monocyte chemotactic and activating factor (MCAF)/monocyte chemoattractant protein-1 (MCP-1) in the left ventricle (LV) of Dahl salt-sensitive (DS) rats that showed hypertrophy of the LV induced by hypertension and subsequently developed CHF. The IL-1 beta mRNA content in the LV of DS rats increased 3.9-fold when LV hypertrophy developed, and the increase reached 6.2-fold at the CHF stage compared with that of age-matched Dahl salt-resistant (DR) rats. The amount of IL-1 beta in the LV was positively correlated with the LV weight/body weight ratio. Most of the IL-1 beta immunoreactivity was localized in the endothelial cells and interstitial macrophages. The mRNA levels of MCAF in the LV increased 3.6-fold at 11 weeks and reached 4.8-fold at the CHF stage relative to the age-matched DR rats. MCAF protein was localized to the endothelial cells and interstitial macrophages. In DS rats, the number of interstitial macrophages increased diffusely throughout the LV. We suggest that increased chemokine expression, macrophage infiltration, and proinflammatory cytokine expression play some role in the pathogenesis of cardiac hypertrophy and failure induced by chronic mechanical overload.

Animals↗
PubMed1997

Modification of the response of a quiescent cell population within a murine solid tumour to boron neutron capture irradiation: studies with nicotinamide and hyperthermia.

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. 20 min after intraperitoneal injection of sodium borocaptate-10B (BSH), or 3 h after oral administration of dl-p-boronophenylalanine-10B (BPA), the tumours were irradiated with thermal neutrons. To modify the uptake dose of 10B, nicotinamide (NA) was intraperitoneally injected 60 min before the administration of 10B-compounds and/or the tumours were heated to 41.5 degrees C for 20 min immediately before irradiation. After irradiation, the tumours were excised, minced and trypsinized. The tumour cell suspensions were then incubated with cytochalasin-B (a cytokinesis-blocker). The micronucleus (MN) frequency in cells not BrdU-labelled (quiescent (Q) cells) was determined using immunofluorescence staining for BrdU. With or without the administration of 10B-compounds, the sensitivity of Q cells was lower than that of total (P + Q) tumour cells. With thermal neutron irradiation in the presence of either BPA or BSH, the MN frequency in each cell population was increased. A greater increase in the MN frequency of total tumour cells was observed after thermal neutron irradiation in the presence of BPA than in the presence of BSH. The distribution of 10B from BPA into tumour cells was thought to be more dependent on the uptake ability of the tumour cells than that from BSH. Sufficient quantity of 10B from these two 10B-compounds to cause a highly lethal event inside the cancer cell with thermal neutron irradiation could not be delivered to Q cells. When NA and/or heat treatment were combined with 10B-compound administration, NA increased MN frequency in the BSH treated total cells, and heat treatment elevated MN frequency in Q cells. From the viewpoint of cell kill effect, the combined treatment with nicotinamide and heat treatment was more useful than treatment with either nicotinamide or heat treatment alone, not only in the total tumour cells but also in the Q cells.

Animals↗