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Biomedical subjects

T Kanai

Publications and source records attributed to T Kanai.

At least 55 records · Page 3Linked to original sources
PubMed2000

Relative biological effectiveness for cell-killing effect on various human cell lines irradiated with heavy-ion medical accelerator in Chiba (HIMAC) carbon-ion beams.

PURPOSE: To clarify the relative biological effectiveness (RBE) values of various human cell lines for carbon-ion beams with 2 different linear energy transfer (LET) beams and to investigate the relationship between the cell-killing effect and the biophysical characters, such as the chromosome number and the area of the cell nucleus, using qualitatively different kinds of radiations. METHODS AND MATERIALS: Sixteen different human cell lines were irradiated with carbon-ion beams, having 2 different LET values (LET(infinity) = 13.3 and approximately 77 keV/microm), accelerated by the Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences in Japan. Cell-killing effect was detected as reproductive cell death using a colony-formation assay. The number of chromosomes was observed in a metaphase spread using the conventional method. The area of the cell nucleus was calculated as an ellipse on photographs using a micrometer. RESULTS: The RBE values calculated by the D(10), which is determined as the dose (Gy) required to reduce the surviving fraction to 10%, relative to X-rays, range from 1.06 to 1.33 for 13-keV/microm-beam and from 2.00 to 3. 01 for approximate 77-keV/microm-beam irradiation on each cell line. There was a good correlation in the D(10) values of each cell line between X-rays and carbon-ion beams. However, the D(10) values did not clearly depend on either the chromosome number or the area of the cell nuclei. CONCLUSION: The RBE values for HIMAC carbon-ion beams are consistent with previous reports using carbon-ion beams with the similar LET values, and the cellular radiosensitivity of different cell lines well correlate among different types of radiation.

Brain Neoplasms↗
PubMed2000

Change in radiosensitivity with fractionated-dose irradiation of carbon-ion beams in five different human cell lines.

PURPOSE: To investigate the change in the surviving fractions by fractionated-dose irradiations with carbon ions, based on the recovery of potentially lethal damage (PLDR) and the change of radiosensitivity by every fractionated-dose irradiation. METHODS AND MATERIALS: One normal human and four human-tumor cell lines were used. Cells were irradiated with carbon ions accelerated by the Heavy Ion Medical Accelerator in Chiba (HIMAC) at National Institute of Radiological Sciences in Japan. The LET values were estimated to be 13.18 keV/microm for low-LET beams and 76.92 +/- 0.20 keV/microm for high-LET beams. Fractionated-dose irradiations were carried out with 5 fractions within a 24-h interval. RESULTS: The surviving fractions for the fractionated-dose irradiation with X-rays and carbon ions decreased exponentially with increasing the number of fractions in the tumor cell lines. In contrast, the surviving fractions for the carbon ions in normal human cells decreased exponentially as well as the tumor cell lines, while it tended to level off from the 3rd to the 5th fraction in the case of using X-rays. CONCLUSION: The change in both the recovery ratio of the PLDR and radiosensitivity by every fractionated-dose irradiation depends on individual cell lines and the quality of radiations.

Carbon↗
PubMed2000

Respiratory gated irradiation system for heavy-ion radiotherapy.

PURPOSE: In order to reduce the treatment margin of the moving target due to breathing, we developed a gated irradiation system for heavy-ion radiotherapy. METHODS AND MATERIALS: The motion of a patient due to respiration is detected by the motion of the body surface around the chest wall. A respiratory sensor was developed using an infrared light spot and a position-sensitive detector. A timing signal to request a beam is generated in response to the respiration waveform, and a carbon beam is extracted from the synchrotron using a RF-knockout method. CT images for treatment planning are taken in synchronization with the respiratory motion. For patient positioning, digitized fluoroscopic images superimposed with the respiration waveform were used. The relation between the respiratory sensor signal and the organ motion was examined using digitized video images from fluoroscopy. The performance of our gated system was demonstrated by using the moving phantom, and dose profiles were measured in the direction of phantom motion. RESULTS: The timing of gate-on is set at the end of the expiratory phase, because the motion of the diaphragm is slower and more reproducible than during the inspiratory phase. The signal of the respiratory sensor shows a phase difference of 120 milliseconds between lower and upper locations on the chest wall. The motion of diaphragm is delayed by 200 milliseconds from the respiration waveform at the lower location. The beam extraction system worked according to the beam on/off logic for gating, and the gated CT scanner performed well. The lateral penumbra size of the dose profile along the moving axis was distinguishably decreased by the gated irradiation. The ratio of the nongated to gated lateral fall-off was 4.3, 3.5, and 2. 0 under the stroke of 40.0, 29.0, and 13.0 mm respectively. CONCLUSION: We developed a total treatment system of gated irradiation for heavy-ion radiotherapy. We found that with this system the target margin along the body axis could be decreased to 5-10 mm although the target moved twice or three times. Over 150 patients with lung or liver cancer had already been treated by this gated irradiation system by the end of July 1999.

Diaphragm↗
PubMed2000

Circulating autoantibodies against purified colonic mucin in ulcerative colitis.

To clarify the role of colonic mucin in the autoimmune process of ulcerative colitis, circulating antibodies against human colonic mucin were investigated. Purified colonic mucin, obtained from human colonic mucosa by gel filtration, using a Bio-Gel A-1.5-m column and CsCl equilibrium density gradient, was divided into soluble mucin (S-mucin) secreted extracellularly and membranous mucin (M-mucin) binding to cell membrane. Sodium dodecylsulfate polyacrylamide gel electrophoresis and Western blotting analysis showed that antibodies in the serum samples of some patients with ulcerative colitis recognized purified S- and M-mucin of >180-kD. By enzyme-linked immunosorbent assay (ELISA), anti-mucin antibodies were detected in 11 of 60 patients with ulcerative colitis (18%). In contrast, the antibodies were not detected in 22 patients with Crohn's disease. The titers of antimucin antibodies against S-mucin and M-mucin were not different in each patient. By ELISA using mucin in which the sugar chains were destroyed by neuraminidase or NaIO4 treatment, it was demonstrated that anti-mucin antibodies recognized the epitopes of either the sugar chain or the core protein exposed through destruction of the sugar chains. We then investigated the relationship between anti-mucin antibodies and the patients' clinical features. Anti-mucin antibodies were detected in 6 of 15 patients with chronic continuous type ulcerative colitis (40%) and in 5 of 26 patients with relapsing-remitting type (19%), but there was no antimucin antibody-positive serum in patients who had had only one attack without any relapse. These results suggest that anti-mucin antibodies could be a disease marker for ulcerative colitis and that immunological abnormalities in colonic mucin contribute to the persistence of colonic mucosal inflammation.

Autoantibodies↗
PubMed2000

Management of pancreatic arteriovenous malformation.

Pancreatic arteriovenous malformations (AVM), while extremely rare, are frequently complicated by gastrointestinal bleeding. The elimination of pancreatic AVM is difficult once portal hypertension has developed. We describe herein a patient with congenital AVM of the pancreatic head presenting with recurrent episodes of melena, in whom pylorus-preserving pancreatoduodenectomy provided a means of definitive management. We also review the literature and focus on the diagnostic and therapeutic approaches. Angiography is always necessary to facilitate tactics of treatment, even if diagnosis has been established by non-invasive imaging modalities. To obtain complete regression, total extirpation of the affected organ, or at least the involved portion, should be performed before this disease leads to the lethal complications of gastrointestinal bleeding and portal hypertension. Transcatheter arterial embolization is the only alternative treatment for the control of hemorrhage.

Adolescent↗
PubMed2000

Epidemiology of childhood burns in the critical care medical center of Kinki University Hospital in Osaka, Japan.

The objective of the present study was to describe the characteristics of pediatric burns in order to prepare a program for the prevention of severe burn injuries in children. We conducted a retrospective study of burn victims aged 15 years or younger who were hospitalized in our Critical Care Medical Center between 1982 and 1997. There were 73 children with burn injuries hospitalized in our center during the study period. The greatest number were children 1 year old. The average % body surface area burned was 21. 5+/-20.5%. The most important causes of pediatric burns were found to be hot bath water and other hot liquids. Hot bath scalds accounted for about half of the pediatric burns occurring in all age groups, and they were often extensive. Non-bath scalds accounted for about one-third of the pediatric burns and were most frequent in children 2 years and younger. All the injuries sustained at home occurred when a family member was in the house. Similar to many reports from overseas, non-bath scalds were one of the most common causes of burns in this study; however, hot bath scalds were the most important cause. These data are being used to develop a prevention program. We also consider it necessary to educate children and their family members about the dangers of burn injuries.

Accidents, Home↗
PubMed2000

Interleukin 18 is a potent proliferative factor for intestinal mucosal lymphocytes in Crohn's disease.

BACKGROUND & AIMS: Crohn's disease (CD) is characterized by a marked accumulation of activated Th1 type CD4(+) T cells and macrophages in inflamed intestinal mucosa. Interleukin (IL)-18 is a recently described cytokine that mainly exists in activated macrophages and shares biological activities with IL-12 in driving the development of Th1 type CD4(+) T cells by inducing interferon gamma. To clarify the role of IL-18 in intestinal inflammation in CD, we assessed the functional role of IL-18 in regulating intestinal mucosal lymphocytes. METHODS: Serum IL-18 concentration was measured by enzyme-linked immunosorbent assay. Expression of IL-18 and IL-18 receptor in human intestinal mucosa was determined using immunohistochemistry and flow cytometry. The functional activity of IL-18 was assessed by the use of recombinant IL-18 to stimulate both the growth of intestinal mucosal lymphocytes and IL-2 receptor induction activity. RESULTS: The serum IL-18 concentration was significantly higher in patients with CD than normal controls. In the inflamed colonic mucosa of CD, many IL-18(+)CD68(+) macrophages had infiltrated the lamina propria. Intestinal mucosal lymphocytes from CD expressed functional IL-18 receptors. Recombinant IL-18 induced significant proliferative responses in freshly isolated mucosal lymphocytes from CD patients, but not from normal controls. IL-18 up-regulated IL-2 receptor expression in mucosal lymphocytes from patients with CD, but not from normal controls. CONCLUSIONS: These findings suggest that infiltrated macrophages in the inflamed intestinal mucosa in CD produce IL-18, and that macrophage-derived IL-18 may serve as a potent regulatory factor for intestinal mucosal lymphocytes, thereby contributing to chronic intestinal inflammation in CD.

Cell Division↗
PubMed2000

Clinical usefulness of microsatellite instability for the prediction of gastric adenoma or adenocarcinoma in patients with chronic gastritis.

To assess a role of microsatellite instability (MSI) in the development of gastric adenocarcinoma or adenoma from chronic gastritis, we analysed mutations of five microsatellite loci in gastritis, adenoma and adenocarcinoma retrospectively. Gastric mucosa was biopsied from the same area in each patient at different periods and examined for MSI. Only one of 55 patients with chronic gastritis revealed MSI-H phenotype and the other 54 patients showed microsatellite stable (MSS) phenotypes. In six of 17 patients with gastric adenoma or well-differentiated adenocarcinoma, MSI-positive phenotypes were demonstrated. Interestingly, all of six patients showing MSI, including three high-level MSI (MSI-H) cases and three low-level (MSH-L) cases, had already revealed MSI at the stage of chronic gastritis. In two of three MSI-H cases, the identical MSI patterns had been observed at the stage of gastritis 1.5-7 years before the final diagnosis of adenocarcinoma. The adjacent gastritis mucosa within 10 mm from the carcinoma demonstrated MSI as well. MSI was not found in any of 35 patients with Helicobacter pylori infection, but found in one of 30 patients without infection. Moreover, two of three cases of gastric adenoma or well-differentiated adenocarcinoma with MSI-H at the stage of chronic gastritis showed no evidence of Helicobacter pylori infection throughout the observation periods. These results indicate that MSI in biopsy specimens at the stage of chronic gastritis may predict the risk of the progression to adenoma and well-differentiated adenocarcinoma, and that Helicobacter pylori infection itself may not induce MSI directly in the gastric mucosa.

Adenocarcinoma↗
PubMed2000

Regulatory effect of interleukin-4 and interleukin-13 on colon cancer cell adhesion.

To assess the role of interleukin-4 (IL-4) and interleukin-13 (IL-13) in colon cancer cell-cell adhesion, we investigated the effect of both cytokines in human colon cancer cell line, colo205 cell-cell adhesion. IL-4 receptor was expressed on the cell surface of colo205, and recombinant IL-4 inhibited colo205 cell-cell adhesion in a dose-dependent fashion without inhibiting cell proliferation. Flow cytometric analysis revealed that monoclonal antibodies (mAbs) directed against E-cadherin and carcinoembryonic antigen (CEA) inhibited colo205 cell-cell adhesion and IL-4 significantly inhibited the expression of E-cadherin and CEA. IL-13 also inhibited colo205 cell-cell adhesion. These results indicated that IL-4 and IL-13 inhibited colon cancer cell-cell adhesion by down-regulation of E-cadherin and CEA molecules. We then investigated the expression of both cytokines from freshly isolated colon cancer tumour-infiltrating lymphocytes (TILs). With reverse transcription-polymerase chain reaction and flow cytometric analysis, we demonstrated that colon TILs expressed IL-4 and IL-13 mRNA and protein. These results suggest that Th 2 type cytokines IL-4 and IL-13 locally-produced from TILs may regulate colon cancer adhesion by down-regulation of adhesion molecules.

Cadherins↗
PubMed2000

Correlation between cell killing and residual chromatin breaks measured by PCC in six human cell lines irradiated with different radiation types.

PURPOSE: To examine the relationship between cell killing and residual chromatin breaks after irradiation with qualitatively different types of radiation in six human cell lines. MATERIALS AND METHODS: Six human tumour cell lines and normal human cells were irradiated with 200 kV X-rays and two carbon-ion beams accelerated by the Heavy Ion Medical Accelerator in Chiba (HIMAC) differing in LET. At the sample position the carbon-ion beams had LET infinity values of 13.1 and 77.5 +/- 0.4 keV/microm. Cell inactivation was documented by a colony assay. Residual chromatin breaks were measured by counting the number of residual chromatin fragments at 24h, detected by the premature chromosome condensation (PCC) technique. RESULTS: The cell lines covered a broad range of radiosensitivity. D10 values ranged from 3.53 to 8.12 Gy for X-rays, 2.56 to 7.41 Gy for the lower LET carbon ions and 1.17 to 3.85 Gy for the higher LET carbon ions. The results for residual chromatin breaks indicate that the more radiosensitive cell lines showed a greater induction of residual chromatin breaks either by X-rays or carbon-ions, and that an X-ray resistant cell line also showed resistance to carbon-ions. Cellular radiosensitivity correlated with the frequency of residual chromatin breaks. CONCLUSION: The detection of residual chromatin breaks by the PCC technique could be used to predict cellular radiosensitivity among qualitatively different types of radiation.

Carbon↗
PubMed2000

Combination therapy with vascular endothelial growth factor neutralizing antibody and mitomycin C on human gastric cancer xenograft.

Antiangiogenic therapy has been proposed as a new strategy for the treatment of solid tumors. To enhance the therapeutic effect of antiangiogenic agents, combination with conventional anticancer therapy should be investigated. In the present study, we investigated the therapeutic effect of the combination of vascular endothelial growth factor neutralizing antibody (VEGF Ab) and mitomycin C (MMC) on MT-2, a human gastric cancer xenograft. When small pieces of MT-2 were transplanted orthotopically into 62 nude mice, liver metastasis developed 6 weeks after transplantation. The VEGF Ab (100 micro g / mouse) was administered i.p. in the VEGF Ab group (n = 14) and the combination group (n = 16) twice a week from day 10 after transplantation. MMC (2 mg / kg) was administered in the MMC group (n = 16) and the combination group (n = 16) on days 10, 17 and 24 after transplantation. Compared with the control group, in which saline solution was administered i.p., all three treatments inhibited tumor growth significantly and the effects of MMC and combination therapy were potent. Liver metastases were also inhibited significantly by the administration of VEGF Ab alone, MMC alone or combination therapy. Liver metastasis developed in 9 mice of the control group, 3 of the VEGF Ab group, and 4 of the MMC group, but no mice had liver metastasis in the combination therapy group. However a significant body weight loss and a decrease in spleen weight were observed in the MMC and combination groups, with no significant difference between the two groups. These results suggest that combination therapy with VEGF Ab and MMC may be a potent therapy for human gastric cancer.

Adenocarcinoma↗
PubMed2000

Analysis of clinical course and long-term prognosis of surgical and nonsurgical patients with intestinal Behçet's disease.

OBJECTIVE: Much remains unknown about the pathogenesis of intestinal Behçet's disease. The majority of these patients are treated with surgical intervention, although it has been recently reported that a number of medical treatments are sometimes effective. Only few studies, however, have ever been undertaken to analyze the long-term prognosis of this disease. In this study, we analyzed the clinical course and the recurrences after initial therapy in patients with intestinal Behçet's disease. METHODS: We investigated 20 patients (surgical group, n = 8; nonsurgical group, n = 12) for whom the clinical courses were known for > or = 2 yr (2-23 yr). RESULTS: The surgical group tended to have higher rates of complications such as ocular and ileal lesions than the nonsurgical group. In the surgical group, 75% of the patients recurred (and were readmitted) within 2 yr, and 37.5% of the patients required reoperation for intestinal obstruction because of ulcer at the anastomosis. The percentage of peripheral CD8+ DR+ lymphocytes in the recurrent group (10.4% +/- 2.5%) was significantly higher than that in the nonrecurrent group (4.3% +/- 1.2%, p < 0.05). CONCLUSIONS: Our results indicate that more extensive disease involving the ileum and ocular lesions are markers of severity and progression to surgical crisis, and that patients requiring surgery suffer more frequent recurrences. Furthermore, an increased percentage of peripheral CD8+ DR+ lymphocytes may be a risk factor for disease recurrence.

Adolescent↗
PubMed2000

Theoretical basis for herbal medicines, Tokishakuyaku-san and Sairei-to, in the treatment of autoimmunity-related recurrent abortion by correcting T helper-1/T helper-2 balance.

PROBLEM AND METHOD OF STUDY: To get insight into the basis for the empirical usage of herbal medicines in the treatment of recurrent abortion, we examined whether Tokishakuyaku-san (Toki) and Sairei-to (Sai) modulate T helper-1 (Th1) and T helper-2 (Th2) cytokine release from peripheral blood mononuclear cells (PBMCs). The effects of these medicines were investigated as related to human leukocyte antigen (HLA)-G, a non-classical HLA class I antigen expressed on trophoblasts and a putative crucial player involved in fetomaternal immune interplay. RESULTS: Toki and Sai increased the release of Th1 group cytokines, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma while preserving the inhibitory effect of HLA-G on the release of these cytokines. As for Th2 group cytokine release, Toki was without effect in modulating interleukin (IL)-4 release, regardless of the presence of HLA-G, whereas Sai nullified the effect of the presence of HLA-G to stimulate the release of IL-4 without affecting its release in the absence of HLA-G. CONCLUSION: Toki and Sai may have therapeutic potential, particularly in autoimmunity-related recurrent abortion where Th2 response is pathologically enhanced, but not in recurrent abortion involving alloimmune fetomaternal derangement, a condition of, rather, an enhanced Thl response.

Abortion, Habitual↗
PubMed2000

Ridge filter design and optimization for the broad-beam three-dimensional irradiation system for heavy-ion radiotherapy.

The broad-beam three-dimensional irradiation system under development at National Institute of Radiological Sciences (NIRS) requires a small ridge filter to spread the initially monoenergetic heavy-ion beam to a small spread-out Bragg peak (SOBP). A large SOBP covering the target volume is then achieved by a superposition of differently weighted and displaced small SOBPs. Two approaches were studied for the definition of a suitable ridge filter and experimental verifications were performed. Both approaches show a good agreement between the calculated and measured dose and lead to a good homogeneity of the biological dose in the target. However, the ridge filter design that produces a Gaussian-shaped spectrum of the particle ranges was found to be more robust to small errors and uncertainties in the beam application. Furthermore, an optimization procedure for two fields was applied to compensate for the missing dose from the fragmentation tail for the case of a simple-geometry target. The optimized biological dose distributions show that a very good homogeneity is achievable in the target.

Cell Line↗
PubMed2000

An n-alkane-responsive promoter element found in the gene encoding the peroxisomal protein of Candida tropicalis does not contain a C(6) zinc cluster DNA-binding motif.

When an asporogenic diploid yeast, Candida tropicalis, is cultivated on n-alkane, the expression of the genes encoding enzymes of the peroxisomal beta-oxidation pathway is highly induced. An upstream activation sequence (UAS) which can induce transcription in response to n-alkane (UAS(ALK)) was identified on the promoter region of the peroxisomal 3-ketoacyl coenzyme A (CoA) thiolase gene of C. tropicalis (CT-T3A). The 29-bp region (from -289 to -261) present upstream of the TATA sequence was sufficient to induce n-alkane-dependent expression of a reporter gene. Besides n-alkane, UAS(ALK)-dependent gene expression also occurred in the cells grown on oleic acid. Several kinds of mutant UAS(ALK) were constructed and tested for their UAS activity. It was clarified that the important nucleotides for UAS(ALK) activity were located within 10-bp region from -273 to -264 (5'-TCCTGCACAC-3'). This region did not contain a CGG triplet and therefore differed from the sequence of the oleate-response element (ORE), which is a UAS found on the promoter region of 3-ketoacyl-CoA thiolase gene of Saccharomyces cerevisiae. Similar sequences to UAS(ALK) were also found on several peroxisomal enzyme-encoding genes of C. tropicalis.

Acetyl-CoA C-Acyltransferase↗
PubMed2000

Inactivation of aerobic and hypoxic cells from three different cell lines by accelerated (3)He-, (12)C- and (20)Ne-ion beams.

The LET-RBE spectra for cell killing for cultured mammalian cells exposed to accelerated heavy ions were investigated to design a spread-out Bragg peak beam for cancer therapy at HIMAC, National Institute of Radiological Sciences, Chiba, prior to clinical trials. Cells that originated from a human salivary gland tumor (HSG cells) as well as V79 and T1 cells were exposed to (3)He-, (12)C- and (20)Ne-ion beams with an LET ranging from approximately 20-600 keV/micrometer under both aerobic and hypoxic conditions. Cell survival curves were fitted by equations from the linear-quadratic model and the target model to obtain survival parameters. RBE, OER, alpha and D(0) were analyzed as a function of LET. The RBE increased with LET, reaching a maximum at around 200 keV/micrometer, then decreased with a further increase in LET. Clear splits of the LET-RBE or -OER spectra were found among ion species and/or cell lines. At a given LET, the RBE value for (3)He ions was higher than that for the other ions. The position of the maximum RBE shifts to higher LET values for heavier ions. The OER value was 3 for X rays but started to decrease at an LET of around 50 keV/micrometer, passed below 2 at around 100 keV/micrometer, and then reached a minimum above 300 keV/micrometer, but the values remained greater than 1. The OER was significantly lower for (3)He ions than the others.

Acceleration↗
PubMed2000

[Development of a multi-layer ion chamber for measurement of depth dose distributions of heavy-ion therapeutic beam for individual patients].

In heavy-ion radiotherapy, an accelerated beam is modified to realize a desired dose distribution in patients. The setup of the beam-modifying devices in the irradiation system is changed according to the patient, and it is important to check the depth dose distributions in the patient. In order to measure dose distributions realized by an irradiation system for heavy-ion radiotherapy, a multi-layer ionization chamber(MLIC) was developed. The MLIC consists of 64 ionization chambers, which are stacked mutually. The interval between each ionization chamber is about 4.1 mm water. There are signal and high voltage plates in the MILC, which are used as electrodes of the ionization chambers and phantom. Depth dose distribution from 5.09 mm to 261.92 mm water can be measured in about 30 seconds using this MLIC. Thus, it is possible to check beam quality in a short amount of time.

Heavy Ion Radiotherapy↗