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Biomedical subjects

T Odaka

Publications and source records attributed to T Odaka.

At least 19 recordsLinked to original sources

Induction of apoptosis by beta radiation from tritium compounds in mouse embryonic brain cells.

Induction of apoptosis by tritium exposure was investigated in both cultured embryonic mid brain cells and brain sections of embryos and of newborns in mice. In the cultures of mid brain cells, addition of methyl-3H-thymidine (3H-TdR) (21 kBq mL(-1)) and tritiated water (5.616 MBq mL(-1)) induced late appearances and low percentages of apoptosis when compared to x-irradiation at the ID50 dose, the inhibitory dose that reduced cellular differentiation by 50% of the control. A significant increase in p53 protein was detected about 2 h before the marked appearance of apoptosis. The pregnant mice were given an intraperitoneal injection of tritiated water at the concentration of 481.8 kBq g(-1) of body weight on gestation day 12.5, by which treatment behavioral changes in the offspring occurred. Increased apoptotic cells were observed in the neural tube of embryos from 1 d after the injection to 1 wk postnatal age. Apoptosis induced by x-rays appeared 2 h after irradiation, with a peak at 4 h. Increase of apoptotic cells was also found in the brain cortexes of newborns. The percentage of apoptosis in the brain was higher in the prenatal tritiated water exposed mice than in the prenatal x-irradiated mice. Possible mechanisms on apoptosis and its relation to the higher relative biological effectiveness value of tritium beta-rays are discussed.

Animals

Adaptive response in embryogenesis: II. Retardation of postnatal development of prenatally irradiated mice.

We previously reported that a priming dose of 0.3 Gy on gestation day 11 significantly increased the rate of living fetuses and reduced the incidence of congenital malformations caused by exposure to 5 Gy X rays on gestation day 12 in ICR mice. In the present study, postnatal development of the live offspring was investigated using a set of developmental and behavioral parameters. The offspring of the mice irradiated with 0.3 Gy generally showed a delay in the appearance of most of the physiological markers, impaired acquisition of neonatal reflexes, and alteration of adult behavior. However, an increase in body weight in the females was observed 4 weeks postnatally. In the offspring primed with 0.3 Gy followed by a challenging dose of 5 Gy prenatally, a high postnatal mortality was found, and all the survivors had various radiation-induced detrimental effects. The results indicated that the priming dose was advantageous to survival itself, but was disadvantageous to the health of survivor. The results also suggested that studying the whole animal can show the extent of the effects of radiation, i.e. quality of life, in a way that cellular or molecular studies cannot.

Abnormalities, Radiation-Induced

Radiation-induced apoptosis and limb teratogenesis in embryonic mice.

In utero irradiation of the fetus during the period of organogenesis induces a dramatic increase in malformation. However, the mechanisms underlying the teratogenesis remain to be elucidated. In the present study, the correlation between radiation-induced apoptosis and limb malformation was examined in mice. The mice were exposed to X rays in utero on day 11 of gestation during the period of organogenesis of limb buds. A marked increase in the number of apoptotic cells in the predigital regions in the forelimb buds was detected 4 h after irradiation. The preinterdigital regions of the forelimb buds did not show such an increase at the same time. Aphlangy and ectrodactyly were the main types of anomalies observed on day 19 in the limbs of the fetuses irradiated with 5 Gy. The increases in prenatal death and teratogenesis in limb digits in living fetuses were dependent on dose. The possible mechanisms involved are discussed.

Abnormalities, Radiation-Induced

Non-fluorescent chromosome painting using the peroxidase/diaminobenzidine (DAB) reaction.

PURPOSE: To develop and validate non-fluorescent chromosome painting for bright-field microscopy using the peroxidase/diaminobenzidine (DAB) reaction. MATERIALS AND METHODS: Peripheral blood lymphocytes were taken from patients with uterine cancer who had received heavy-ion radiation therapy. Chromosome slides were treated with RNase and pepsin, denatured mildly, hybridized with a biotinylated DNA probe specific for whole-chromosome 4 and stained using the peroxidase/DAB reaction with an avidin-biotin amplification. The slides were analysed under a bright-field microscope and an atomic force microscope. The detection rate of chromosome aberrations by DAB painting was compared with that obtained by dual analysis of Giemsa staining and FISH painting. RESULTS: When chromosomes 4 were painted, 11.5% of unstable aberrations were detected by DAB painting, while 10.8% of them were found by dual analysis of Giemsa staining and FISH painting. CONCLUSION: A DAB painting method that can effectively detect rearranged aberrations was established. It has advantages over FISH painting: the preparations can be analysed by bright-field microscope, can be preserved permanently and are suitable for analysis by an automated system.

3,3'-Diaminobenzidine

Trimethoprim resistance and susceptibility genes in Staphylococcus epidermidis.

Genes encoding trimethoprim (TMP)-resistant and -susceptible dihydrofolate reductases (DHFR) in Staphylococcus epidermidis isolated in Saitama Prefecture were compared with the TMP-resistant DHFR gene of S. aureus, dfrA. The nucleotide sequences of TMPr and TMPs genes in five S. epidermidis isolates tested could be divided into three types: type 1, identical with the TMPr gene dfrA that had been found in S. aureus; type 3, identical with the TMPs gene dfrC in S. epidermidis; and type 2, having only two nucleotide substitutions to dfrC with no amino acid change. TMPr isolates carried either one of the type 2 or type 3 sequences in addition to the type 1 sequence. A Southern hybridization analysis revealed that, in TMPr S. epidermidis, the type 1 sequence was located on a 5.5 kb EcoRI-EcoRV restriction fragment together with the sequence for the gentamicin (GM)-resistant gene, while the type 2 or type 3 sequence was located on the 1.0 kb EcoRI-EcoRV fragment. No plasmid-carrying dfrA-homologous sequence was detected in the S. epidermidis isolates we tested. These results suggest that the TMPr and GMr genes are closely linked and located on the chromosome in S. epidermidis isolated in Japan.

Amino Acid Sequence

Adaptive response in embryogenesis: I. Dose and timing of radiation for reduction of prenatal death and congenital malformation during the late period of organogenesis.

An adaptive response was demonstrated during embryogenesis in mice. Whole-body irradiation at a dose of 0-50 cGy was given to condition pregnant ICR mice on day 9 to day 11 of gestation. Then their whole bodies were exposed to a challenging dose of 5 Gy on the next day. The numbers of living fetuses, prenatal deaths and living fetuses with external gross malformations were determined on day 19. A conditioning dose of 30 cGy on day 11 significantly increased the rate of living fetuses and reduced the incidence of congenital malformations induced by a 5-Gy dose on day 12. This indicates the existence of a critical dose and timing for administering a conditioning dose for radioadaptation during the late period of organogenesis in mice. The possible mechanisms involved are discussed.

Abnormalities, Radiation-Induced

A study of learning splice sites of DNA sequence by neural networks.

To predict of splice sites in DNA sequence, we developed a neural network system with back propagation. This system has a flexible network definition language which can describe any network structure. Three types of neural network were defined using the system for the prediction of splice sites. The neural networks are trained by the arrangements of bases around the splice sites of DNA sequences. The results of simulation showed the excellent ability of the neural networks to predict splice sites by applying and testing the arrangements of DNA sequences. This system also were used to predict the effects of point mutations on the splicing of the IX factor gene which may cause hereditary disease.

Algorithms

Disposition and metabolism of the new oral antidiabetic drug troglitazone in rats, mice and dogs.

The pharmacokinetics of troglitazone (CAS 97322-87-7, CS-045), a new oral antidiabetic drug for the treatment of non-insulin-dependent diabetes mellitus (NIDDM), were investigated in rats, mice and dogs following oral and intravenous administration of 14C-labeled troglitazone at doses of 5 mg/kg. The absorption rates, calculated from the AUC ratios of total radioactivity after oral and intravenous administration, or from the biliary excretion rate after intraduodenal administration in rats were both as high as 75%. High uptake by the liver, one of the pharmacological target organs, was demonstrated in both rats and mice. Furthermore, in the KK mouse, an obese NIDDM model animal, the radioactivity was incorporated selectively as troglitazone itself to muscle, the peripheral target organ. Troglitazone reversibly bound to serum albumin with a high ratio (> 99%). Troglitazone was mostly metabolized to the conjugates: sulfate (M 1) and glucuronide (M 2). The oxidized metabolite, a quinone-type metabolite (M 3), was found to be further metabolized to the sulfate (U 2). The biliary excretion rates of these conjugates were high in each animal, and the occurrence of enterohepatic circulation of the conjugates was also suggested. Sex differences in pharmacokinetics were observed in rats; i.e. females showed a higher plasma concentration of troglitazone, and a lower concentration of M 1, than males, and they excreted the sex-related metabolite, a hydroxylated M 1 (U 1), in the bile.

Administration, Oral

A quantitative color recognition measurement system using multimedia computer environment.

We developed a quantitative measurement system that tests the degree of dysgnosia resulting from Obsessive-Compulsive Disorder (OCD). The system outputs a stimulation word that had been set in advance using the voice output facility of the personal computer, then displays a color chart and waits for input from the subject. When the subject touches the CRT screen or clicks the mouse, the system records the response time and coordinates of input position. There were 30 stimulation words in the system. After 30 measurements of response time and input coordinates, the system outputs a results file that includes each response time and input coordinates. This test is easier and simpler than other psychological tests such as MMPI. The influence of the examiner can be reduced to the minimum with this system because it is a computer-based automatic measurement system. To use the computer system, an examiner can easily standardize the environment of the illumination, etc. Moreover, the system can save labor in testing, and can manage large amounts of data easily using the file management facility.

Association

Interspecific complementation between mouse and Chinese hamster cell mutants hypersensitive to ionizing radiation.

Interspecific and intraspecific hybrids were formed between mouse and Chinese hamster cell mutants hypersensitive to ionizing radiation and their radiosensitivities were examined. Chinese hamster cell mutants irs1, irs2 and irs3 and mouse mammary carcinoma cell mutants SX9 and SX10 have been found to belong to five different complementation groups. A radiosensitive mouse lymphoma cell line L5178Y-S has been demonstrated to be different from the X-ray sensitive mouse cell mutants M10 and LX830, both of which are derived from L5178Y cells, in their complementation groups. L5178Y-S is also distinct from SX9 and SX10.

Animals

The study of tumor necrosis factor beta gene polymorphism in lung cancer patients.

BACKGROUND: In recent years numerous reports have discussed the relationship between the human leukocyte antigen and lung cancer. However, the genetic background of lung cancer has not yet been precisely clarified. METHODS: To investigate the genetic background of lung cancer, the human leukocyte antigens in 159 normal healthy control subjects and 102 lung cancer patients were studied, and restriction fragment length polymorphism analysis of the tumor necrosis factor (TNF) beta gene in 165 normal healthy control subjects and 135 lung cancer patients was performed. RESULTS: Lung cancer patients showed a high frequency of human leukocyte antigen B61; however, no statistical difference was found. In the lung cancer patients, the TNF beta 10.5/10.5-kb allele was found at a low frequency, 38.5%, compared to 53.3% in normal controls (chi 2 = 7.51, P = 0.011, corrected P = 0.033, relative risk = 0.77). In the relationship between the histologic types and the TNF beta gene, the TNF beta 10.5/10.5-kb allele showed low frequencies: 38.5% in adenocarcinoma, 38.2% in squamous cell carcinoma, and 27.8% in small cell carcinoma, although no statistical difference was shown. In relation to the postoperative survival period, the TNF beta 10.5/10.5-kb allele was associated with prolonged survival. CONCLUSIONS: The TNF beta 10.5/10.5-kb allele may be associated with resistance to lung cancer and with a better prognosis.

Adenocarcinoma

A visual data analysis system for the medical image processing.

We developed a visual data analysis system that can easily manage a large volume of medical imaging data. This system can analyze sets of imaging data using general image processing methods, so that various kinds of medical imaging data such as ECG charts, X ray image films, and MRI images, can be processed. The system has a graphical user interface (GUI). A physician who is novice at the system can manipulate the imaging data intuitively by pull down menus, pop up menus and buttons within the window system. The system can run on a standard UNIX workstation which is faster and more powerful than most personal computers. The system needs an X window system/Motif and C compiler. These are standard system programs already available on most UNIX workstations. The source code of the system can be retrieved from our anonymous ftp site via Internet.

Computer Graphics

A general purpose neural network simulator system for medical data processing.

We developed a general purpose neural network simulator system for medical data processing. This system has a flexible network definition language. Users can define arbitrary hierarchical neural networks using the definition language to analyze medical data that contains some complex patterns. The learning algorithm used in this system is back propagation. Learning curves are displayed on multiple windows. This is a general purpose system, so it can be used for various kinds of medical data processing such as one dimensional signal processing or two dimensional image processing. The system can run on a standard UNIX workstation, which is faster and more powerful than most personal computers. The system needs an X window system/Motif and C compiler. These are standard system programs already available on most UNIX workstations. The source code of the system can be retrieved from our anonymous ftp site via Internet.

Algorithms

A flexible random allocation program for multi-institutional clinical trials.

This paper describes a flexible random allocation program that assigns treatments to patients according to their prognostic factors in multi-institutional clinical trials. The source lists are available in the appendix of this paper. This program is based on Pocock and Simon's minimization method and Zelen's method for institution balancing. The numbers of institutions, treatments, and prognostic factors can be set arbitrarily. The maximum number of institutions, treatments, or prognostic factors that can be accommodated by the program is limited only by the size of the main memory. For example, an IBM-PC with a 640KB main memory can run a program of 1500 institutions, 4 treatments and 20 prognostic factors.

Humans

Two cases of eosinophilic pustular folliculitis treated by acemetacin.

The report deals with two cases of eosinophilic pustular folliculitis in a 45-year-old man and a 25-year-old woman. After their conditions failed to respond to oral and topical corticosteroids, minocycline, anti-allergic drugs, aspirin and several types of nonsteroidal anti-inflammatory drugs, good results were obtained with acemetacin.

Adult

Patient registration and treatment allocation in multicenter clinical trials using a FAX-OCR system.

This article describes the design and results of implementation of an automated patient registration and treatment allocation system (RETAS) used in multicenter clinical trials. RETAS was developed using a FAX-OCR system by which handwritten Japanese and English characters, as well as numericals and forms with check boxes, are sent from participating institutions by Fax, processed using an optical character reader, and then transmitted to a host computer at a statistical center. Based on the facsimile data, RETAS can automatically review eligibility, collect patient identification data and provide a randomized treatment allocation. RETAS permits uninterrupted, unattended operation at a statistical center, 24 hours a day, 7 days a week. Therefore, it drastically decreases the workload of personnel at the statistical center needed to support central telephone registration coverage. Consequently, staff members are free to focus on patient registration, treatment allocation, and follow-up of patients. The treatment allocation procedure in this system is based on Pocock and Simon's minimization method combined with Zelen's method for institution balancing. By this system it was possible to balance treatment numbers for each level of various prognostic factors over an entire trial and, at the same time, balance the allocation of treatments within an institution. The system currently supports the protocol of a clinical trial for Adjuvant Chemo-Endocrine Therapy for Breast Cancer in West Japan.

Computer Systems

Temperature-sensitive mouse cell factors for strand-specific initiation of poliovirus RNA synthesis.

Two cell lines, TgSVA and TgSVB, were established from the kidneys of transgenic mice carrying the human gene encoding poliovirus receptor. The cells were highly susceptible to poliovirus infection, and a large amount of infectious particles was produced in the infected cells at 37 degrees C. However, the virus yield was greatly reduced at 40 degrees C. This phenomenon was common to all mouse cells tested. To identify the temperature-sensitive step(s) of the virus infection cycle, different steps of the infection cycle were examined for temperature sensitivity. The results strongly suggested that the growth restriction observed at 40 degrees C was due to reduced efficiency of the initiation process of virus-specific RNA synthesis. Furthermore, this restriction appeared to occur only on the synthesis of positive-strand RNA. Virus-specific RNA synthesis in crude replication complexes was not affected by the nonpermissive temperature of 40 degrees C. In vitro uridylylation of VPg seemed to be temperature sensitive only after prolonged incubation at 40 degrees C. These results indicate that a specific host factor(s) is involved in the efficient initiation process of positive-strand RNA synthesis of poliovirus and that the host factor(s) is temperature sensitive in TgSVA and TgSVB cells.

Adsorption