[Obesity in the elderly].
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Activities of Daily Living↗
Biomedical subjects
K Sasai
Publications and source records attributed to K Sasai.
[Clinical study of cervical radiculopathy after laminoplasty for cervical myelopathy].
We have retrospectively determined the preoperative risk factors in cervical radiculopathy after laminoplasty for cervical myelopathy using preoperative neuroradiographical findings and electrophysiological studies. Of the 67 patients who underwent laminoplasty, 10 patients (14.9%) postoperatively showed cervical radioculopathy. The preoperative radiographical findings had included cervical lordosis, intraspinal cord centering, and anterior protrusion of the apex of the superior articular process. Needle electromyography, somatosensory evoked potentials (SEPs), sensory nerve action potentials (SNAP) were preoperatively examined in 42 cases. There was no relationship between the postoperative radiculopathy and the preoperative radiographical findings. Six (100%) of 6 cases preoperatively diagnosed as C5 radiculopathy (postganglionic type) with Erb-P 14 interpeak latency of dermatomal SEPs and SNAP, developed postoperative C5 radiculopathy. One (25%) of 4 cases preoperatively diagnosed as C6 radiculopathy developed postoperative C6 radiculopathy. No case preoperatively diagnosed as C7 or C8 radiculopathy developed postoperative radiculopathy. This study suggested that an important risk factor for postoperative radiculopathy was subclinical C5 radiculopathy (postganglionic type) that could be preoperatively evaluated using electrophysiological studies.
Adult↗
Prediction of human cell radiosensitivity: comparison of clonogenic assay with chromosome aberrations scored using premature chromosome condensation with fluorescence in situ hybridization.
PURPOSE: The purpose of the present investigation was to determine whether chromosome aberrations scored by premature chromosome condensation (PCC) and fluorescence in situ hybridization (FISH) can predict the radiosensitivity of human cell lines, thereby providing a possible means of assessing the in situ radiosensitivity of normal tissues and the radiocurability of individual human cancers. METHODS AND MATERIALS: We used four cells lines of different radiosensitivity: normal human fibroblasts (AG1522), ataxia-telangiectasia fibroblasts (AT2052), a human fibrosarcoma cell line (HT1080), and a human melanoma cell line (melanoma 903). These were irradiated in plateau phase with a range of doses and assessed both for clonogenic cell survival and for aberrations in a single chromosome (number 4) immediately after, and 24 h after irradiation. RESULTS: The initial number of breaks in chromosome 4 was proportional to irradiation dose and was identical for all the different human cell lines, irrespective of radiosensitivity. On the other hand, the number of chromosome 4 breaks remaining 24 h after irradiation reflected the radiosensitivity of the cells such that the relationship between residual chromosome aberrations and cell survival was the same for the different cell lines. CONCLUSIONS: These results suggest that the scoring of chromosome aberrations in interphase using FISH with PCC holds considerable promise for predicting the radiosensitivity of normal and tumor tissues in situ.
Ataxia Telangiectasia↗
Combined cytokinesis-block micronucleus and chromosomal aberration assay for the evaluation of radiosensitizers at low radiation doses.
PURPOSE: Several methods have been tried for evaluating the efficacy of hypoxic cell radiosensitizers at clinically relevant low radiation doses (1-4 Gy). The cytokinesis-block micronucleus assay is known to be useful for both the in vitro and in vivo evaluation of radiosensitizers, while the chromosomal aberration assay has been commonly used to assess the mutagenicity of various agents. In the present study, the chromosomal aberration assay and the cytokinesis-block micronucleus assay were performed simultaneously to assess the radiosensitizing effect of etanidazole and KU-2285 at low radiation doses. The correlation between the two assays was also evaluated. METHODS AND MATERIALS: In vitro study: EMT-6 cells were irradiated at a dose of 1-3 Gy under hypoxic conditions with or without the drugs at 1 mM. In vivo-in vitro study: EMT-6 tumor-bearing BALB/c mice received 2-4 Gy of radiation with or without administration of the drugs at 200 mg/kg. Single-cell suspensions were then obtained in both studies and were used for the cytokinesis-block micronucleus assay and the chromosomal aberration assay. The micronucleus frequency in binucleate cells was evaluated in the former assay, and the frequency of chromosomal aberrations in metaphase cells was evaluated in the latter assay. RESULTS: In vitro study: the sensitizer enhancement ratios of etanidazole and KU-2285 were 1.73 and 2.21, respectively, in the micronucleus assay, and 1.41 and 1.79 in the chromosomal aberration assay. In vivo-in vitro study: the sensitizer enhancement ratios of etanidazole and KU-2285 were 1.18 and 1.31, respectively, in the micronucleus assay, and 1.16 and 1.42 in the chromosomal aberration assay. In both studies, a linear correlation was observed between the micronucleus frequency and the chromosomal aberration frequency. The background (i.e., the frequency at 0 Gy) of the latter assay was considerably lower than that of the former assay, especially in the vivo study. CONCLUSIONS: The chromosomal aberration assay has not yet been established as a method for evaluating the effect of radiosensitizers. However, a combination of the cytokinesis-block micronucleus assay and the chromosomal aberration assay seems to be useful for assessing radiosensitizers at low radiation doses for the following reasons: a) the chromosomal aberration assay is as sensitive as the micronucleus assay and possibly more specific, because chromosomal aberrations can be observed before cells pass through the first metaphase after irradiation and, thus, reflect quite acute damage, even though they reflect only a part of the total damage; b) the combined assay provides relatively more information for the time and labor required.
Aerobiosis↗
Discrepancies between measured changes of radiobiological hypoxic fraction and oxygen tension monitoring using two assay systems.
PURPOSE: This study was conducted to assess the ability of computerized pO2 histography to measure changes in tumor oxygenation produced by low oxygen breathing. METHODS AND MATERIALS: Female syngeneic C3H/Km mice bearing SCC VII/St carcinomas were used in these experiments. Changes in tumor oxygenation produced by the mice breathing 10% oxygen were assessed with computerized pO2 histography, 3H-misonidazole binding, and the paired survival curve assay of radiosensitivity. RESULTS: The hypoxic cell fraction of the tumors in mice breathing 10% oxygen was 3.1 times higher than that of tumors in mice breathing normal air determined by an in vivo-in vitro clonogenic assay. Binding of radiolabeled misonidazole to the tumors in mice breathing 10% oxygen was also significantly higher than that to tumors in mice breathing normal air (p < 0.05). In addition, oxygen tension histograms for normal tissue showed a dramatic shift to a lower oxygen tension when the mice were breathing 10% oxygen. However, under identical conditions, there was only a minimal shift in the oxygen tension of tumor tissue. Although the number of oxygen tension readings in the relatively oxic class in tumor tissue was lower when the mice were breathing 10% oxygen than when breathing normal air, there was not a significant decrease in the median pO2 value for the tumor. The number of pO2 readings lower than 5 mmHg in the tumor was not affected by the 10% oxygen breathing. CONCLUSION: These findings indicate that increases in radiobiological hypoxic fraction produced by lower blood oxygen levels may not correlate well with the results of polarographic measurements of tumor pO2 levels.
Animals↗
Fluorinated 2-nitroimidazole derivative hypoxic cell radiosensitizers: radiosensitizing activities and pharmacokinetics.
PURPOSE: To assess the effects of incorporation of a CF2 group into the side chain of a 2-nitroimidazole derivative, we evaluated the in vitro and in vivo radiosensitizing activities of KU-2285 (a 2-nitroimidazole derivative with an N1-substituent of -CH2CF2CONH(CH2)nOH, n = 2) and its related compounds in comparison with those of comparable nonfluorinated compounds. The pharmacokinetics of these compounds in murine tumors was also tested. METHODS AND MATERIALS: KU-2285, KU-3202 (n = 3) and KU-3207 (n = 4) are fluorinated 2-nitroimidazole derivative compounds with similar structures. Etanidazole (a 2-nitroimidazole derivative with an N1-substituent of -CH2CONH(CH2)nOH, n = 2) and its related compounds, KU-3205 (n = 3) and KU-3206 (n = 4) were also tested. The in vitro radiosensitizing activities of each compound for hypoxic cells was evaluated with a standard colony formation method. The in vivo radiosensitizing activities of these compounds were tested in female C3H/He mice bearing SCCVII tumors using an in vivo/in vitro clonogenic assay. The pharmacokinetic studies were performed in C3H/He mice bearing the SCCVII tumor. Samples were analyzed by reverse-phase high-performance liquid chromatography. RESULTS: The in vitro radiosensitizing activities of fluorinated 2-nitroimidazoles were higher than those of the nonfluorinated compounds. Although the in vivo radiosensitizing activity of KU-2285 was higher than that of etanidazole (p < 0.05), other fluorinated 2-nitroimidazoles showed less radiosensitizing activity than the comparable nonfluorinated compounds. The compound was eliminated from serum more rapidly with the increase in the number of CH2 group in the side chain of the compound in each series. CONCLUSION: Although the in vitro sensitizing activity of the fluorinated compounds was higher than that of the comparable nonfluorinated compounds, the in vivo radiosensitizing activity of all fluorinated compounds but KU-2285 was lower than that of comparable etanidazole group compounds, probably due to their lower molecular concentrations in tumor and rapid elimination.
Animals↗
Reoxygenation in the SCCVII tumor after KU-2285 sensitization plus single or fractionated irradiation.
PURPOSE: Because reoxygenation of solid tumors after irradiation with a hypoxic cell sensitizer has never previously been investigated, we assessed the reoxygenation in SCCVII tumors after treatment with KU-2285 plus single or fractionated irradiation. METHODS AND MATERIALS: KU-2285 (100 mg/kg) was injected intraperitoneally into C3H mice bearing 1-cm SCCVII tumors at 30 min before a single dose of 12 Gy or three fractions of 5 Gy at 12 h intervals. Changes of the hypoxic fraction (HF) were then evaluated by the paired survival curve method. RESULTS: Since the radiosensitizing effect of KU-2285 was relatively persistent, the HF was only evaluable after 6 h of irradiation. The HF of untreated SCCVII tumors was 9.1%. After treatment with KU-2285 and 12 Gy, the HF was 25% at 6 h, 32% at 12 h, 24% at 24 h, and 7.6% at 72 h. The HF was lower at 6 h than that after radiation alone, but was similar at later periods. After three fractions of 5 Gy with or without KU-2285, the HF was 33% at 6 h in both groups, while it was 12% and 13% at 24 h for tumors pretreated with KU-2285 and those receiving radiation alone, respectively. However, a sensitizing effect of KU-2285 was indicated by the downward shift of the survival curves for tumors irradiated after exposure to this agent. CONCLUSION: Reoxygenation occurred quite efficiently in tumors receiving KU-2285 and 12 Gy. After fractionated irradiation, however, reoxygenation was similar in the KU-2285-pretreatment and irradiation alone groups.
Animals↗
Comparison of radiosensitizing effect of KU-2285 and SR-2508 at low drug concentrations and doses.
PURPOSE: Since the radiosensitizing effect of KU-2285 at relatively low dose levels is not known, we investigated its efficacy at such low concentrations or doses achievable in humans with oral administration of 0.3-1.0 g/m2. METHODS AND MATERIALS: KU-2285 was tested in comparison with SR-2508 at low concentrations (0.05-0.25 mM) in vitro by the cytokinesis-block micronucleus assay and by the colony formation assay, and at low drug doses (12.5-50 mg/kg) in vivo by the in vivo-in vitro assay and by the growth delay assay using SCC VII tumors in C3H/He mice. RESULTS: In the cytokinesis-block micronucleus assay, the sensitizer enhancement ratio (SER) for KU-2285 and SR-2508 was 1.43 and 1.17 at 0.05 mM, 1.75 and 1.27 at 0.10 mM, and 2.14 and 1.69 at 0.25 mM, respectively. In the colony formation assay, the SER for KU-2285 was also greater than that for SR-2508. In the in vivo-in vitro assay, the SER for KU-2285 and SR-2508 was 1.11 and 1.04 at 12.5 mg/kg, 1.21 and 1.04 at 25 mg/kg, and 1.26 and 1.18 at 50 mg/kg, respectively. In the growth delay assay at 50 mg/kg, no tumor regrowth was observed in four of the 18 mice treated with KU-2285 + 25 Gy, although the growth delay time for the remaining mice was similar to that for SR-2508 + 25 Gy. CONCLUSION: KU-2285 was more effective than SR-2508 both at low drug concentrations in vitro and at low drug doses in vivo. These promising findings suggest the potential superiority of KU-2285 over SR-2508 as a radiosensitizer for clinical use.
Animals↗
Radiosensitizing activity and pharmacokinetics of multiple dose administered KU-2285 in peripheral nerve tissue in mice.
PURPOSE: In a clinical trial in which a 2-nitroimidazole radiosensitizer was administered repeatedly, the dose-limiting toxicity was found to be peripheral neuropathy. In the present study, the in vivo radiosensitizing activity of KU-2285 in combination with radiation dose fractionation, and the pharmacokinetics of cumulative dosing of KU-2285 in the peripheral nerves were examined. METHODS AND MATERIALS: The ability of three nitroimidazoles, misonidazole (MISO), etanidazole (SR-2508) and KU-2285, to sensitize SCCVII tumors to radiation treatment has been compared for drug doses in the range 0-200 mg/kg. Single radiation doses or two different fractionation schedules (6 Gy/fractions x three fractions/48 h or 5 Gy/fractions x five fractions/48 h) were used; the tumor cell survival was determined using an in vivo/in vitro colony assay. The pharmacokinetics in the sciatic nerves were undertaken, when KU-2285 or etanidazole were injected at a dose of 200 mg/kg intravenously one, two, three or four times at 2-h intervals. RESULTS: At less than 100 mg/kg, KU-2285 sensitized SCCVII tumors more than MISO and SR-2508 by fractionated irradiation. Evaluation of pharmacokinetics in the peripheral nerves showed that the apparent biological half-life of SR-2508 increased with the increases in the number of administrations, whereas that of KU-2285 became shorter. CONCLUSION: Since most clinical radiotherapy is given in small multiple fractions, KU-2285 appears to be a hypoxic cell radiosensitizer that could be useful in such regimens, and that poses no risk of chronic peripheral neurotoxicity.
Animals↗
Fecal IgE levels in infants at 1 month of age as indicator of atopic disease.
Fecal IgE levels were investigated in 165 asymptomatic infants at 1 month of age under two nutritional regimens, breast-feeding and formula feeding, and the possibility of predicting by fecal IgE levels the onset of atopic disease was studied in these infants. IgE levels were measured by time-resolved fluoroimmunometric assay. IgE antibodies are detectable in fecal extracts, and we have already reported that IgE levels are increased in food-allergy patients after administration of food allergens, and this increase in fecal IgE levels may be a specific consequence of the local immune response to food-allergen stimulation in the gut mucosa. The presence of atopic disease and the feeding method during the nursing period were surveyed by questionnaire in 89 of these 165 infants when they were 18 months old. In an analysis of the present results, IgE values above 0.015 U/ml, the lower limit of measurement, were considered to be high. Forty-eight (29%) of the 165 subjects showed a high fecal IgE level. Thirty-seven (35%) of 105 formula-fed infants had high fecal IgE levels, whereas only 11 (18%) of 60 breast-fed infants had high levels (P < 0.05). With respect to atopic family history, 30 (39%) of the 77 infants with atopic family history had high fecal IgE levels, as compared with 18 (20%) of the 88 infants without atopic family history (P < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Biomarkers↗
Long-term changes in the haversian systems following high-dose irradiation. An ultrastructural and quantitative histomorphological study.
The effects of high-dose irradiation on the morphology of haversian bone were studied, over a fifty-two-week period, in seventy-seven adult rabbits, after the administration of a single dose of radiation (therapeutic x-ray; twenty-five, fifty, or 100 gray) to one knee joint. The specimens of bone were examined with microangiography, light and transmission electron microscopy, and histomorphometry. Analysis was performed on the haversian bone in the subchondral bone plate of weight-bearing portions of the femoral condyles. Microangiography demonstrated dilatation of the microvasculature four weeks after irradiation. Beginning at twelve weeks, there was a marked decrease in vascularity; no obvious recovery of the subchondral bone had occurred by fifty-two weeks. At four weeks, morphological analysis revealed two changes in the haversian canals: simple occlusion of the haversian vessels with loss of cells in the canal, and dilatation of the capillaries with abnormal resorption of the perivascular bone matrix by osteoclasts. The abnormal bone resorption was not coupled with subsequent new-bone formation, resulting in increased porosity. Beginning at four weeks, a progressive decrease in the number of haversian vessels and in cellularity became prominent. The decrease in cellularity involved all types of cells, including endothelial cells, pericytes, perivascular mesenchymal cells, osteoblasts, osteocytes, and osteoclasts. The loss of perivascular cells was often but not always associated with occlusion of the haversian vessels. Histomorphometry revealed both time-dependent and dose-dependent decreases in capillary density (the number of intraosseous capillaries per unit area) and in the number of osteocytes in the subchondral bone plate. The porosity of the same areas showed a significant increase by four weeks (p < 0.001 after administration of twenty-five gray and p < 0.01 after administration of both fifty and 100 gray), but between twelve and fifty-two weeks, there was only a slight additional increase. Statistical analysis revealed significant correlations between capillary density and osteocyte survival (p < 0.001) and between capillary density and porosity (p < 0.001). The portion of the subchondral bone plate that was located farthest from the non-irradiated normal bone showed progressive damage and no sign of recovery at fifty-two weeks.
Animals↗
Development and characterization of chicken-chicken B cell hybridomas secreting monoclonal antibodies that detect sporozoite and merozoite antigens of Eimeria.
Chicken-chicken B cell hybridomas that secrete monoclonal antibodies (mAb) detecting antigens located at the anterior tip of the sporozoites of Eimeria acervulina have been produced. Peripheral blood lymphocytes (PBL) obtained from chickens infected with E. acervulina were fused with a thymidine-kinase deficient (TK-) chicken B cell line. Hybridomas secreting mAb binding to the sporozoite antigens of E. acervulina were selected using an ELISA. Two stable hybridomas, whose mAb were designated as P11 and P66, respectively, were obtained and their binding characteristics were assessed. The mAb P11 detects the sporozoite but not the merozoite antigens of E. acervulina and Eimeria tenella. The P66 mAb recognizes a cross-reactive antigen of sporozoite and merozoite of E. acervulina but not E. tenella. Flow cytometric analysis of the hybridomas secreting the P11 and P66 mAb showed expression of surface IgM and IgG, respectively. Western blot analysis under reducing conditions showed that mAb P11 recognized a sporozoite protein of 43 kDa. Both mAb recognized antigens located at the anterior end of the sporozoites by indirect immunofluorescence staining. This study shows the development of chicken B cell hybridomas that secrete coccidia-specific mAb.
Animals↗
In vivo radiosensitization efficacy of KU-2285 and etanidazole at clinically relevant low radiation doses.
PURPOSE: The in vivo radiosensitization efficacy of KU-2285 at clinically relevant low radiation doses (2-4 Gy) was compared with that of etanidazole using four types of assays with EMT6, SCCVII, and C3H mammary tumors. METHODS AND MATERIALS: The in vivo-in vitro cytokinesis-block micronucleus assay and the chromosomal aberration assay were used to assess the sensitizing effect at single doses of 2-4 Gy. After in vivo treatment for tumors, tumor cells were cultured in the presence of cytochalasin B for the former assay or demecolcine for the latter assay, and the micronucleus frequency in binucleate cells and the chromosomal frequency in metaphase cells were evaluated after 42 hr and 3 hr of culture. In addition, an in vivo-in vitro colony assay and a growth delay assay were performed using fractionated irradiation regimens (4 Gy x 5). RESULTS: The sensitizer enhancement ratio for 100-400 mg/kg of KU-2285 was between 1.12 and 1.42. KU-2285 was a more efficient sensitizer than etanidazole in 3 of 9 experiments and as efficient as etanidazole in the remaining six experiments. CONCLUSION: Both the micronucleus assay and the chromosomal aberration assay appeared to be very useful in evaluating the in vivo sensitizing effect at low radiation doses. KU-2285 had a definite radiosensitizing effect even at low radiation doses, and clinical trials of KU-2285 may be warranted.
Animals↗
[Effect of lipiodol on MR images evaluation by dynamic MR imaging with intraarterial lipiodol injection in the rabbit VX-2 tumor].
We evaluated the effect of lipiodol on the MR image by using dynamic MR imaging (MRI) with an intraarterial lipiodol injection in the VX-2 tumor. The signal intensity of the tumor had been risen gradually during the dynamic MRI, using T 1-weighted Spin Echo techniques. The high intensity areas on the dynamic MRI nearly corresponded with the lipiodol accumulated areas on CT. On the micrograph, no necrosis or degeneration of the tumor cell was visible. We conclude that the presence of lipiodol will affect the signal intensity of T 1-weighted MR images.
Animals↗
[Evaluation of early MR imaging of the liver in rabbits after ethanol injection].
Seven days after ethanol injection, MR images of the liver in 5 rabbits were evaluated by T1, T2-weighted SE and TURBO-FLASH dynamic images. Necrotic area was visualized as low-intensity on T1-weighted images and high-intensity on T2-weighted images. These findings were similar to the tumor that was not treated, so it is necessary to be careful for evaluation of therapeutic efficacy. Necrotic area was not meanwhile enhanced on TURBO-FLASH dynamic images, therefore, dynamic study seemed to be useful for therapeutic efficacy after ethanol injection.
Animals↗
Increase of mannose residues, as Salmonella typhimurium-adhering factor, on the cecal mucosa of germ-free chickens infected with Eimeria tenella.
To study increase of the Salmonella population in the cecum of chickens infected with Eimeria tenella, quantitative changes in mannose residues on the cecal mucosa were investigated. Inhibition of S typhimurium adherence to the cecum by a 2% carbohydrate (D-mannose, D-galactose, L-fucose, alpha-methyl-D-glucoside) in phosphate-buffered saline solution was examined. Only D-mannose had inhibitory effects. Whereas, D-galactose had somewhat enhancing effects on adherence of S typhimurium to the cecal mucosa of uninfected germ-free chickens. In infected and uninfected chickens, D-mannose inhibited adherence of S typhimurium. D-Mannose significantly (P < 0.05) increased adherence of Bacteroides sp. In infected and uninfected chickens, D-mannose did not have any effect on adherence of Clostridium perfringens and Bifidobacterium thermophilum. Under microscopic observation, only concanavalin A and Lens culinaris agglutinin, of 8 lectins examined, were recognized as lectin-positive staining lines or spots in the cecal mucosa, indicating presence of mannose residues on the cecal mucosa. In E tenella-infected chickens, lectin-positive staining was seen strongly on the coarse surface of damaged cells and at the bottom of the crypts. These results indicate that coccidial infection may induce increase of mannose residues on the intestinal surface and allow adhesion of more salmonellae to the intestine.
Animals↗
Increase in T cells expressing the gamma/delta receptor and CD4+CD8+ double-positive T cells in primary immunodeficiency complicated by human T-cell lymphotropic virus type I infection.
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CD4 Antigens↗
[Detection of intrahepatic lipids by 1H-MRS--studies by breath-holding & 1 cm3 VOI].
The authors performed 1H-MR spectroscopy (MRS) to depict lipids in the liver of 10 healthy volunteers. Spectra were obtained by a 1.5 T-MR unit, with STEAM from 1 x 1 x 1 cm3 VOI. Lipid peaks were depicted in 7 of the 10 volunteers by breath-holding 1H-MRS study, while in only 4 on normal breathing. The existence of lipids could not be depicted through chemical shift imaging adopting in-phase & opposed images. This suggests a clinical utility of 1H-MRS, particularly through breath-holding studies, in depicting lipids from 1 x 1 x 1 cm3 VOI in the liver in vivo.
Humans↗