Biomedical subjects

K Sasai

Publications and source records attributed to K Sasai.

At least 19 recordsLinked to original sources

PubMed2006

The Ras-MAPK pathway downregulates Caveolin-1 in rodent fibroblast but not in human fibroblasts: implications in the resistance to oncogene-mediated transformation.

Normal human diploid fibroblasts (HDFs) are refractory to oncogene-mediated transformations in vitro, compared with rodent fibroblasts. As successful oncogene-mediated transformations of normal HDFs have been reported using the human telomerase catalytic subunit, it has been considered that telomerase activity contributes to the species-specific transformability. However, these transformed HDFs are much less malignant compared with those of rodent cells, suggesting the existence of undefined mechanisms that render HDFs resistant to malignant transformation. Here, cDNA microarray analysis identified caveolin-1 as one of the possible cellular factors involved in such mechanisms. The mitogen-activated protein kinases (MAPK) pathway downregulates Caveolin-1 in rodent fibroblasts, transformed by coexpression of the SV40 early region and activated H-Ras. In contrast, the coexpression of these two oncogenes in HDFs failed to reduce the expression level of Caveolin-1. These results strongly suggest the presence of critical differences in events following the phosphorylation of ERK during the activation process of the MAPK signaling pathway between human and rodent cells, as the ERK protein was similarly phosphorylated in both systems. Furthermore, the small interfering RNA-mediated suppression of Caveolin-1 facilitated the oncogene-mediated transformation of normal HDFs, clearly indicating that the differences in the transformability between human and rodent cells are due, at least in part, to the mechanism responsible for the resistance to Ras-induced Caveolin-1 downregulation in HDFs.

Animals↗

PubMed2006

Survey of Japanese layer farms for Salmonella enteritidis with vaccination- and infection-specific antigens for egg yolk antibodies.

Japanese layer farms were surveyed for Salmonella Enteritidis vaccination and infection with specific antigens for egg yolk antibodies with the use of vaccination-specific antigen Salmonella Enteritidis FliC-specific 9-kDa polypeptide (SEP9) and infection-specific antigen deflagellated Salmonella Enteritidis whole cell (DEWC). The specific antibodies in eggs from 201 commercial layer farms throughout Japan were surveyed. The percentages of farm flocks with a mean enzyme-linked immunosorbent assay (ELISA) titer of over 0.1 were 56.2% (113 of 201) in DEWC-ELISA and 22.3% (45 of 201) in SEP9-ELISA. Flocks indicating high titers in SEP9-ELISA always showed high titers in DEWC-ELISA. Because both specific antibody titers of the vaccinated flocks monitored long term remained high throughout life, flocks with high titers of both ELISAs in this survey must be vaccinated. On the other hand, 34.3% (69 of 201) of flocks had high titers of DEWC-specific antibody alone. Because Salmonella Enteritidis infection induces the DEWC-specific antibody but not the SEP9-specific antibody, detecting only high ELISA titers of DEWC-specific antibody can be an effective monitoring tool for Salmonella Enteritidis exposure rather than vaccination. These results suggest that vaccination programs in Japanese layer farms would be insufficient to control Salmonella Enteritidis infection, and egg screening to detect specific antibodies would be valuable in obtaining the necessary information to control Salmonella Enteritidis infection.

Animals↗

PubMed2005

Brown-Séquard-plus syndrome due to stab injury: a case report.

STUDY DESIGN: Case report. OBJECTIVE: To describe the mechanism of injury in this case and its clinical features. Magnetic resonance (MR) images of hemorrhage in spinal cord injury due to stab wound are discussed. METHODS: We describe the case of a 21-year-old woman who was stabbed in the right side of her neck and developed left-sided Brown-Séquard syndrome plus loss of bilateral proprioceptive sensation. Neither plain radiographs nor computed tomography of the cervical spine demonstrated any foreign bodies or fractures of the cervical spine. T2-weighted cervical MR images confirm spinal cord hemiresection at C5-C6. RESULTS: MR imaging was performed serially at 4 days, 4 weeks, and 8 weeks after trauma. The signal pattern of the spinal cord at the site of injury varied iso, iso, and low on T1-weighted consecutive images. Meanwhile, high signal intensity on T2-weighted images was consistent during the 8 weeks after incidence of trauma. A T2-weighted sagittal image showed a tiny spot of low intensity in the high signal band at the site of penetration, demonstrating hemosiderin formation in the spinal cord. The patient was treated conservatively and, recovered from Frankel grade C to grade D. CONCLUSION: Spinal cord injuries (SCI) following stab wounds are rare. MR imaging is definitely useful for recording and monitoring the pathology of SCI.

Adult↗

PubMed2003

Analysis of cross-reactivity of five new chicken monoclonal antibodies which recognize the apical complex of Eimeria using confocal laser immunofluorescence assay.

For Apicomplexa (members) the host cell invasion is realized with the help of the organelles located at the apical tip of parasites. In this research paper the characterization of five chicken monoclonal antibodies (mabs) produced against Eimeria acervulina sporozoites is described. All mabs reacted with molecules belonging to the apical complex of chicken Eimeria sporozoites. On immunofluorescence assay (IFA) one mab, 8E-1, recognized an apical tip molecule present on all chicken Eimeria sporozoites, two mabs (8D-2 and HE-4) recognized an antigen present on the apical tip of the same two Eimeria species (E. acervulina and E. brunetti), another mab (5D-11) recognized an antigen present on the apical tip of other two species (E. acervulina and E. maxima) while one mab (8C-3) identified antigens present on the sporozoites and sporocysts wall of only E. acervulina. Besides the apical tip antigens, two mabs (HE-4 and 8D-2) recognized some proteins located in the anterior half of the sporozoites. Collectively, these mabs proved that the apical complex of chicken Eimeria sporozoites share one or more antigens that are expected to play a role in host cell recognition and invasion.

Animals↗

PubMed2003

Increased lymphocyte subpopulations and macrophages in the ovaries and oviducts of laying hens infected with Salmonella enterica serovar Enteritidis.

Salmonella enterica serovar Enteritidis (SE) is a causative agent for human food poisoning cases throughout the world. The ovaries and the oviducts of the laying hens are the major sites of SE colonization from which vertical transmission to eggs occurs. In this study, Salmonella-induced changes in T lymphocytes, B lymphocytes and macrophages in the ovaries and oviducts were assessed after primary and secondary experimental inoculations of laying hen with SE. Statistically significant increases in the numbers of T cells (both CD4+ and CD8+) and macrophages were observed 7 to 14 days after primary inoculation, followed by a peak in B-cell numbers from the 14th day post-primary inoculation onwards in the secretory areas of the oviducts. The peak in lymphocyte numbers immediately preceded a decline in the rate of SE recovery from the reproductive tract beginning at day 14. The correlation of decreased Salmonella recovery with elevated lymphocyte and macrophage numbers strongly suggests that local cell-mediated immunity is involved in controlling SE injection in the ovaries and oviducts.

Animals↗

PubMed2003

Neuronal ceroid-lipofuscinosis and hydrocephalus in a chihuahua.

A two-year-old, female chihuahua presented with a six-month history of visual dysfunction. Computed tomography revealed dilation of the lateral ventricles in the central nervous system (CNS). The dog was tentatively diagnosed as having hydrocephalus and a month later was euthanased at the owner's request. The skull was expanded and dome-like in shape and an open fontanelle was observed on postmortem examination. Histologically, swollen neurons possessing yellowish pigment granules in the cytoplasm were observed throughout the CNS. These storage materials stained positively with periodic acid Schiff, Schmorl method for lipofuscin and oil red O for lipid, and showed autofluorescence under fluorescence microscopy. Ultrastructurally, the storage materials consisted of dense lamellar structures. This case was unique in having ceroid-lipofuscinosis in association with hydrocephalus.

Animals↗

PubMed2001

Localized aggressive non-Hodgkin's lymphoma of the nasal cavity: a survey by the Japan Lymphoma Radiation Therapy Group.

PURPOSE: To clarify the role of radiotherapy and chemotherapy in the treatment of patients with localized aggressive non-Hodgkin's lymphomas (NHL) originating in the nasal cavity. METHODS AND MATERIALS: The survey, administered at 25 Japanese institutes in 1998, enabled us to collect the clinical data for 787 patients with localized aggressive NHL who were treated between 1988 and 1992. RESULTS: There were 42 patients (5%) with nasal lymphomas. Twelve of these patients received radiotherapy alone, and 30 were treated with a combination of radiotherapy and chemotherapy. The median radiation dose was 47 Gy (22-66). Twelve patients were reviewed histopathologically according to REAL (Revised European-American Classification of Lymphoid neoplasms) classification. T-cell or natural killer (NK) cell lymphomas were detected in 9 patients (75%), and diffuse large B-cell lymphomas in 3 (25%). The 5-year overall and disease-free survival (DFS) rates of all patients were 57% and 59%, respectively. The 5-year DFS rate for the 30 patients treated with the combined therapy was 64% and that for the 12 patients treated with radiotherapy alone was 46% (p = 0.021). For the 34 patients with stage-modified International Prognostic Index (m-IPI) 0-1, the 5-year DFS rates of those treated with the combined therapy and radiotherapy alone were 68% and 45%, respectively (p = 0.020), but there was no difference in DFS rate among the two groups of patients with m-IPI 2-3. The 5-year local control rates of the patients who received >46 Gy (n = 22) and < or =46 Gy (n = 20) were 95% and 76% (p = 0.087), respectively. There was no significant difference among the 5-year DFS rates (62% vs. 67%) and local control rates (87% vs. 100%) of the patients with T-cell or NK-cell lymphoma and diffuse large B-cell lymphoma. CONCLUSIONS: Patients with nasal lymphomas (m-IPI 0-1) should be treated with combined therapy. For the patients with high risk (m-IPI 2-3), the effectiveness of combined therapy was not clarified because of the small number of the patients. A high radiation dose >46 Gy may need to be used to achieve good local control.

Adolescent↗

PubMed2001

Definitive intraoperative very high-dose radiotherapy for localized osteosarcoma in the extremities.

PURPOSE: To evaluate the outcome and adverse effects in patients with osteosarcoma treated with very high-dose definitive intraoperative radiotherapy (IORT), with the intention of saving the affected limb. METHODS AND MATERIALS: Thirty-nine patients with osteosarcoma in their extremities were treated with definitive IORT. The irradiation field included the tumor plus an adequate wide margin and excluded the major vessels and nerves. Forty-five to 80 Gy of electrons or X-rays were delivered. The median follow-up of the surviving patients was 124 months. RESULTS: The cause-specific and relapse-free 5-year survival rate was 50% and 43%, respectively. Distant metastasis developed in 23 patients; 19 died and 4 were alive for >10 years. Nine local recurrences were found 4-29 months after IORT in the affected limb. No radiation-induced skin reaction or nerve palsy was observed in the patients treated with X-rays. Experiments using phantoms also confirmed that the scatter dose was below the toxic level in the IORT setting with X-rays. CONCLUSIONS: Very high-dose definitive IORT combined with preventive nailing and chemotherapy appeared to be a promising quality-of-life-oriented alternative to treating patients with osteosarcomas in the extremities, although the problem of recurrences from the surrounding unirradiated soft tissue remains to be solved.

Adolescent↗

PubMed2001

Cholesteryl ester transfer protein deficiency causes slow egg embryonation of Schistosoma japonicum.

In our attempt to discover a potential cause for accumulation of cholesteryl ester transfer protein (CETP) deficiency in Eastern Asia, we studied the association of CETP deficiency with pathogenesis of Schistosoma japonicum, a life-threatening parasite peculiar to this region. The eggs of S. japonicum showed slow embryonation when cultured in CETP-deficient human plasma. Restoration of CETP to the deficient plasma rescued it, while inhibition of CETP in normal plasma did not cause slow embryonation of the cultured eggs. The egg embryonation was also retarded in the liver but not in the intestine of wild-type mice in comparison to the CETP-transgenic mice. The granulomatous lesion around the parasite eggs in the liver was less in the wild-type than in the CETP-transgenic mice. Thus, CETP deficiency may act against Schistosomiasis japonica by retarding egg embryonation, a potential cause of liver granulomatosis. It does not seem directly due to the lack of CETP activity in plasma but to abnormal lipoprotein generated by chronic CETP deficiency.

Animals↗

PubMed2001

The effectiveness of an immobilization device in conformal radiotherapy for lung tumor: reduction of respiratory tumor movement and evaluation of the daily setup accuracy.

PURPOSE: To evaluate the daily setup accuracy and the reduction of respiratory tumor movement using a body frame in conformal therapy for solitary lung tumor. METHODS AND MATERIALS: Eighteen patients with a solitary lung tumor underwent conformal therapy using a body frame. The body shell of the frame was shaped to the patient's body contour. The respiratory tumor movement was estimated using fluoroscopy, and if it was greater than 5 mm, pressure was applied to the patient's abdomen with the goal of minimizing tumor movement. CT images were then obtained, and a treatment planning was made. A total dose of 40 or 48 Gy was delivered in 4 fractions. Portal films were obtained at each treatment, and the field displacements between them and the simulation films were measured for daily setup errors. The patients were repositioned if the setup error was greater than 3 mm. Correlations were analyzed between patient characteristics and the tumor movement, or the tumor movement reduction and the daily setup errors. RESULTS: Respiratory tumor movement ranged from 0 to 20 mm (mean 7.7 mm). The abdominal press reduced the tumor movement significantly from a range of 8 to 20 mm to a range of 2 to 11 mm (p = 0.0002). Daily setup errors were within 5 mm in 90%, 100%, and 93% of all verifications in left-right, anterior-posterior, and cranio-caudal directions, respectively. Patient repositioning was performed in 25% of all treatments. No significant correlation was detected between patient characteristics and tumor movement, tumor movement reduction, and the daily setup errors. CONCLUSIONS: The abdominal press was successful in reducing the respiratory tumor movement. Daily setup accuracy using the body frame was acceptable. Verification should be performed at each treatment in hypofractionated conformal therapy.

Adolescent↗

PubMed2001

The critical role of the stem region as a functional domain responsible for the oligomerization and Golgi localization of N-acetylglucosaminyltransferase V. The involvement of a domain homophilic interaction.

We demonstrated that a region in the stem of N-acetylglucosaminyltransferase V (GnT-V), a Golgi resident protein, is not required for enzyme activity but serves as functional domain, responsible for intracellular localization. Deletion of the domain led to complete retention of the kinetic properties but resulted in the cell surface localization of the enzyme as well as its efficient secretion into the medium. The lack of this domain concomitantly abolished the disulfide-mediated oligomerization of GnT-V, which appears to confer the Golgi retention. When the domain was inserted into the stem region of a cell surface-localized type II membrane protein, the resulting chimeric protein was substantially oligomerized and predominantly localized in the intracellular organelle. Furthermore, it was found that the presence of this domain is exclusively responsible for homo-oligomer formation. This homophilic interaction appears to involve a hydrophobic cluster of residues in the alpha-helix of the domain, as indicated by secondary structure predictions. These findings suggest that the domain specifically participates in the Golgi retention of GnT-V, probably via inducing homo-oligomer formation, and would also provide a possible mechanism for the oligomerization, which is critical for localization in the Golgi.

Animals↗

PubMed2001

Meningeal carcinomatosis in patients with breast cancer: report of 8 patients.

BACKGROUND: Meningeal carcinomatosis (MC) is an uncommon but aggressive complication of advanced breast cancer with a recently increasing incidence. Although the prognosis is extremely poor for MC patients, early diagnosis and appropriate treatment are important. SUBJECTS AND METHODS: We reviewed 8 cases of MC from breast cancer at Kyoto University Hospital from 1990 to 1999. The median age was 51.5 years. All patients had widespread systemic metastases when diagnosed with MC. clinical symptoms were categorized into 3 groups: cranial nerve symptoms, spinal nerve symptoms, and other symptoms. Imaging studies were positive for MC in only 4 patients. Initial CSF cytology studies were positive in 4 patients, and repeated CSF cytology yielded positive results in the remaining 4 patients. Thus the median interval between the onset of any clinical symptom of MC and the initiation of treatment was 22.5 days (range 7 to 120 days ). All patients received whole brain radiotherapy (WBRT). Four patients were given intrathecal chemotherapy and/or intrathecal immunotherapy in addition to WBRT. RESULTS: Improvement of cranial nerve symptoms, spinal nerve symptoms, and other symptoms were observed in 3/5, 1/3, and 5/7 patients, respectively. Patients with cranial nerve symptoms who started WBRT within 29 days of the onset of the symptoms showed at least partial recovery whereas patients who started WBRT later showed no recovery. The median survival was 123 days (53 to 310 days). MC was the direct cause of death in 1 of 8 patients. CONCLUSION: When MC is clinically suspected, neither a negative imaging study nor a single negative CSF cytology can rule out MC. Prompt initiation of WBRT with or without intrathecal chemotherapy may be important for recovery from cranial nerve symptoms.

Adult↗

PubMed2001

A case of allergic reaction to surgical metal clips inserted for postoperative boost irradiation in a patient undergoing breast-conserving therapy.

We report a case of a 28-year-old woman with right-sided breast cancer. The patient had been treated for atopic dermatitis since her infancy. She underwent breast-conserving surgery (BCS) in July 1998, and three titanium clips were placed at the margin of the excision cavity at the time of surgery. Two months after surgery, the patient exhibited a rapid exacerbation of atopic dermatitis. Various drugs were suspected to be the cause of the allergic reaction, but the results of a bi-digital O-ring test (BDORT) suggested an allergic reaction to titanium clips. In August 1999, the patient underwent a second operation to remove the titanium clips under local anesthesia. Allergy to surgical titanium clips is a rare complication, but in patients with a history of severe allergic diseases, a preoperative immunologic examination should be performed and the patient's history of metal allergy should be investigated.

Adult↗

PubMed2001

Cholesteryl ester transfer protein and atherosclerosis in Japanese subjects: a study based on coronary angiography.

We undertook a cross-sectional analysis on CETP and atherosclerosis among Japanese subjects, by means of CETP mass assay, its gene polymorphism and coronary angiogram. The 110 consecutive patients who underwent coronary angiography were enrolled into the study except for those over 70 years and taking lipid-lowering drugs. Association was analyzed among plasma lipid and lipoproteins, CETP mass, its gene polymorphisms and the finding in coronary angiography. Four CETP-deficiency heterozygotes were identified and excluded from the analysis. CETP mass level showed neither significant correlation with the coronary score (CS) (r=0.06, P=0.52) nor the difference between the groups eventually diagnosed as coronary heart disease (CHD) positive and CHD negative (2.36+/-0.57 vs. 2.24+/-0.21, P=0.24). CETP mass correlated with the total and LDL cholesterol (r=0.43, P<0.001; r=0.36, P<0.001, respectively) but not with HDL cholesterol (r=0.08, P=0.40). While I405V polymorphism had no impact on CETP mass, HDL cholesterol or CS, CETP mass was low with TaqIB polymorphism (B1B1>B2B2, P<0.05) only in the low CS group (<4). Among the lipid and lipoprotein, HDL cholesterol had a greater impact than LDL cholesterol on coronary atherosclerosis. We concluded that CETP mass in plasma does not correlate with coronary atherosclerosis as whole in the non-CETP-deficient. However, the B2B2 genotype in CETP TaqIB polymorphism, only when it decreases the CETP level, may act as a protective factor against atherosclerosis. It should also be noted that CETP mass in general correlates to total and LDL cholesterol, so that it would be an indirect atherogenic parameter.

Carrier Proteins↗

PubMed2001

Enhancement of the therapeutic outcome of radio-immunotherapy by combination with whole-body mild hyperthermia.

To enhance the effect of radio-immunotherapy for solid cancers, whole-body mild hyperthermia was added, and its effects on the pharmacokinetics of radiolabelled antibody, outcome of radio-immunotherapy, and radiosensitivity of the tumour were investigated. Nude mice bearing human colon cancer xenografts were heated to 40 degrees C for 3 or 6 h. After heating, mice received intravenous (i.v.) injections of [131I]-labelled anti-carcinoembryonic antigen (CEA) monoclonal antibody. Although 6-h heating did not alter the biodistribution of the radiolabelled antibody, and alone did not show any therapeutic effect on tumour growth, when combined with radio-immunotherapy, the therapeutic effect on tumour growth was significantly enhanced. Three-hour heating also significantly enhanced the effect of radio-immunotherapy. Colony formation assay showed that the radiosensitivity of the tumour was significantly enhanced after heating, which was achieved by a reduction of the hypoxic fraction of the tumour. In conclusion, the addition of whole-body mild hyperthermia significantly enhanced the therapeutic effect of radio-immunotherapy by increasing the radiosensitivity of the tumour.

Animals↗

PubMed2001

Non-Hodgkin's lymphoma of the ocular adnexa.

This study investigates the relationship between the clinical features of lymphoma in the ocular adnexal region and the revised European and American lymphoma (REAL) classification. Specimens from 41 patients with ocular adnexal lymphoproliferative disease were reassessed pathologically using the REAL classification. Thirty-two patients with primary non-Hodgkin's lymphomas (NHL) were included in the study, almost all of them having been treated with radiotherapy with or without chemotherapy. Seven of the 32 patients with NHL showed distant recurrence after treatment: 3 out of 26 with extranodal marginal zone B-cell lymphoma, and 4 with other types of NHL. Although the three patients with recurrent marginal zone B-cell lymphomas all survived, other patients with recurrent lymphomas died of disease. The REAL classification provides a good indication of tumor control probability and survival of patients with ocular adnexal NHL. Radiation therapy is an effective treatment modality for extranodal marginal zone B-cell lymphoma of the ocular adnexa.

Adult↗

PubMed2001

Concurrent chemoradiotherapy for oropharyngeal carcinoma.

The clinical results of definitive chemoradiotherapy for oropharyngeal carcinoma were retrospectively analyzed. Thirty-one patients with oropharyngeal carcinoma who received definitive radiation therapy between January 1986 and June 1998 were analyzed. The median age was 61 years. All patients had squamous cell carcinoma. According to the Union International Contre le Cancer 1997 classification system, stage I, II, III, IVA, and IVB were 1,0, 9, 14, and 7, respectively. Regarding the primary site, 23 tumors were in the lateral wall, whereas 2 were in the superior wall, and 3 each were in the anterior and posterior walls. The median total dose was 66 Gy, with a range of 60 Gy to 74.4 Gy. The overall treatment time ranged from 39 days to 113 days, with a median of 50 days. Seven patients underwent hemilateral radical neck dissection. Fourteen patients received concurrent chemotherapy using weekly cisplatin (50 mg/d) at least three times. The 5-year overall and cause-specific survival (CSS) rates were 55% and 62%, respectively. All local recurrences occurred within 2 years. The CSS rate in patients with lateral or superior wall origin was significantly superior to that of patients with anterior or posterior wall origin (p < 0.05). The 3-year CSS rate was 83% for patients treated with concurrent chemoradiotherapy using weekly cisplatin at least 3 times, whereas that was 53% for the remaining patients (p < 0.05). No serious adverse effects were observed. It is concluded that definitive concurrent chemoradiotherapy using weekly cisplatin for oropharyngeal carcinoma appear promising.

Adult↗

PubMed2001

Phase Ia study of a hypoxic cell sensitizer doranidazole (PR-350) in combination with conventional radiotherapy.

A phase Ia study of a 2-nitroimidazole nucleoside analog radiosensitizer doranidazole was conducted to evaluate its toxicity and pharmacokinetics in patients undergoing conventional external beam radiotherapy. Twenty-nine patients, aged 40-74 years, with a WHO performance status of 0-2 and with adequate organ functions, were entered in the study. Single administration of doranidazole was investigated first with 13 patients and then a course of five consecutive daily administrations was tested in 16 patients. Doranidazole was given i.v. 25 min before irradiation. Doranidazole doses of 400, 800, 1300 and 2000 mg/m2 were evaluated in the former study, and daily doses of 800, 1300 and 2000 mg/m2 were investigated in the latter study. All patients tolerated doranidazole administration. Although a transient decrease in the 24-h creatinine clearance rate was observed in five patients (one in the single administration study and four in the repeat administration study), this was not considered to be the dose-limiting toxicity. Other toxicities (hematological and gastrointestinal), which may not be related to doranidazole administration, were also mild and were not dose limiting. No neurotoxicity was observed. The average maximum concentration, area under the time-concentration curve and half-life of doranidazole in serum were 172-194 microg/ml, 502-582 microg x h/l and 4.2-4.6 h, respectively, at 2000 mg/m2. At the tested doses, administration of doranidazole was tolerable and achieved serum concentrations at which reasonable radiosensitization could be expected. A phase Ib/II study to evaluate the feasibility and efficacy of up to 30 repeat administrations seems to be warranted.

Adult↗