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Biomedical subjects

T Kusama

Publications and source records attributed to T Kusama.

At least 19 recordsLinked to original sources
PubMed2005

A rat model of neurolathyrism: repeated injection of L: -beta-ODAP induces the paraparesis of the hind legs.

Neurolathyrisim is a motor neuron disease characterized by spastic paraparesis in the hind legs, and is caused by grass pea, Lathyrus sativus, which contains the excitotoxic amino acid, 3-N-oxalyl-L: -2,3-diaminopropanoic acid (L: -beta-ODAP), an alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-type glutamatergic receptor agonist. In an attempt to make a useful model of this disease, the CNS distribution and toxicity of L: -beta-ODAP was studied in rat neonates after parenteral administration. L: -beta-ODAP was detected in the spinal cord as well as in the pons/medulla oblongata, though only small amounts in the latter. Repeated injection of L: -beta-ODAP resulted in rats with paraparesis of the legs, though at a low incidence rate of 0.032. These paralyzed rats displayed the severe atrophy of the ventral root of the lumbar cord as well as degenerations of motor neuron. The rats were useful models for the study of motor neuron degeneration in the spinal cord.

Animals↗
PubMed2005

Comparison of a digital flat-panel versus screen-film, photofluorography and storage-phosphor systems by detection of simulated lung adenocarcinoma lesions using hard copy images.

The purpose of this study was to compare hard copy images from a flat-panel detector digital radiography system with conventional radiography, photofluorographic radiography and storage phosphor radiography for the detection of simulated lung adenocarcinoma lesions and also for radiation dose. To test the diagnostic performance of these four systems, the authors used 15 types of lung adenocarcinoma phantom according to Noguchi's classification and an anthropomorphic chest phantom. The visual evaluation of tumour detectability by four radiologists and two general thoracic surgeons was examined with a five-level confidence scale. Lung doses were measured with glass dosemeters for the chest radiology systems under the conditions used by each hospital and centre. Our results indicated that flat-panel detector digital radiography and storage phosphor radiography are not necessarily superior to conventional radiography and photofluorographic radiography for detecting lung adenocarcinomas when only hard copy images are used, and this suggests a need to carefully optimize chest radiography.

Adenocarcinoma↗
PubMed2004

Development of primers for detection of meat and bone meal in ruminant feed and identification of the animal of origin.

The safe use of cattle feed free from meat and bone meal is an important prerequisite to prevent further spread of bovine spongiform encephalopathy. We designed primers to detect very small amounts of meat and bone meal in ruminant feed. Mitochondrial subunit 8 of the ATP synthase gene was used as a target sequence. PCR-based assays revealed amplification of DNA from mammals, ruminants, and individual species using these primers. The method allowed detection of the presence of meat and bone meal in ruminant feed from 0.1 to 0.01%. Sensitivity and effectiveness of the method for detecting prohibited animal proteins in ruminant feed was evaluated.

Animal Feed↗
PubMed2003

Radiation doses to neonates during X ray computed tomography examinations.

As the survival rate of newborns has increased, the number of X ray computed tomography (CT) examinations performed on neonates has been increasing. The exposure doses from CT examinations are known to be higher than those from conventional radiography. Although radiation sensitivity of neonates is higher than that of adults, there are few reports on dose estimates of neonates in CT examinations. Four cylindrical phantoms and one neonatal phantom have been developed to estimate doses to neonates during CT examinations. Using these phantoms and glass dosemeters, absorbed doses were measured. Estimated exposure doses to neonates were higher than those to adults, and our results suggest a need to optimise carefully CT examinations in newborns.

Birth Weight↗
PubMed2003

Neonatal doses from X ray examinations by birth weight in a neonatal intensive care unit.

The aim of this study was to investigate the frequency and type of X ray examinations performed on neonates classified according to their birth weight in a neonatal intensive care unit (NICU). In this study, the radiology records of 2408 neonates who were admitted to the NICU of Oita Prefectural Hospital between January 1994 and September 1999 were investigated. This study revealed that the neonates with earlier gestational ages and lower birth weights required longer NICU stays and more frequent X ray examinations made using a mobile X ray unit. The average number of X ray examinations performed on neonates of less than 750 g birth weight was 26 films per neonate. In regard to computed tomography and fluoroscopy, no significant relationship was found between the birth weight and number of X rays. This study revealed that the entrance-surface dose per neonate was dependent upon the birth weight, while the maximum dose was not dependent upon the birth weight. The average neonatal dose in the NICU was predominantly from computed tomography and fluoroscopy. The individual dose varied widely among neonates.

Abdomen↗
PubMed2001

Inhibition of epidermal growth factor-induced RhoA translocation and invasion of human pancreatic cancer cells by 3-hydroxy-3-methylglutaryl-coenzyme a reductase inhibitors.

3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors prevent the conversion of HMG-CoA to mevalonate and thereby inhibit the synthesis of other products derived from this metabolite. This includes a number of small prenylated GTPases involved in cell growth, motility, and invasion. We studied the effect of HMG-CoA reductase inhibitors (fluvastatin and lovastatin) on in vitro invasion of human pancreatic cancer PANC-1 cells. Epidermal growth factor (EGF) induced a dose-dependent increase of PANC-1 cell invasion in a modified Boyden chamber assay. Stimulation of cancer cells with EGF induced translocation of RhoA from the cytosol to the membrane fraction and actin stress fiber assembly. Furthermore, Clostridium botulinum C3 transferase, a specific inhibitor of Rho, inhibited the ability of EGF to promote invasion, indicating that EGF-induced cancer cell invasion is regulated by Rho signaling. Treatment of PANC-1 cells with fluvastatin markedly attenuated EGF-induced translocation of RhoA from the cytosol to the membrane fraction and actin stress fiber assembly, whereas it did not inhibit the tyrosine phosphorylation of EGF receptor and c-erbB-2. The induction of cancer cell invasion by EGF was inhibited by the addition of fluvastatin or lovastatin in a dose-dependent manner. The effects of fluvastatin or lovastatin on cell morphology and invasion were reversed by the addition of all-trans-geranylgeraniol but not by the addition of all-trans-farnesol. These results suggest that HMG-CoA reductase inhibitors affect RhoA activation by preventing geranylgeranylation, which results in inhibition of EGF-induced invasiveness of human pancreatic cancer cells.

ADP Ribose Transferases↗
PubMed2001

Effects of endothelin-1 and nitric oxide on proliferation of cultured guinea pig bronchial smooth muscle cells.

The proliferative effects of endothelin-1 (ET-1), both alone and in combination with epidermal growth factor (EGF), and the effect of nitric oxide (NO) on the cell proliferation were investigated in cultured guinea pig bronchial smooth muscle cells. ET-1 (10-100 nM) alone augmented cell proliferation, and was additive to the effect of EGF (0.48 nM) in a concentration-dependent manner. An ET(A) antagonist, BQ-123 (10 microM), reduced the cell-proliferative effect of ET-1, whereas an ET(B) antagonist, BQ-788 (10 microM), did not influence the effect. A NO donor, SIN-1 (10 nM-1 microM), reduced the cell-proliferative effect of ET-1 in a concentration-dependent manner. The effect of SIN-1 (1 microM) was partly, but significantly, reversed by a soluble guanylyl cyclase inhibitor, ODQ (1 microM). These results suggest that ET-1 acts not only as a co-mitogen with EGF but also as a mitogen alone, and that its action is mediated through activation of ET(A) receptors. Therefore, ET-1 may contribute to airway remodeling, a pathophysiological hallmark of asthma. In addition, NO, which is produced mainly in the airway epithelium and is partly mediated through cGMP-dependent pathway, may reduce the phenomenon.

Animals↗
PubMed2001

Development of a real-time hand dose monitor for personnel in interventional radiology.

Medical procedures denoted as interventional radiology require operation near an X ray beam, which brings high dose exposures to the operators' hands. For the effectual control of their extremity doses, a prototype of a real-time wrist dosemeter has been developed, hand dose monitor (HDM), based on a single silicon detector. Experiments were performed to test its response to diagnostic X rays. The HDM was highly sensitive and showed a linear response down to doses of a few tens of microsieverts. Though dose rate, energy and angular dependence of the response were observed in some extreme conditions, the HDM was proved to be of practical use if it was appropriately calibrated. Since an HDM enables personnel to check their hand doses on a real-time basis, it would enable medical staff to control the exposure themselves.

Calibration↗
PubMed2001

Radiation exposure to patients during paediatric cardiac catheterisation.

Radiation doses were investigated for 18 infants and children undergoing cardiac catheterisation procedures with thermoluminescence dosemeters. The range of integrated current values used during cardiac catheterisation procedure was wide, from 12.2 to 1195.8 mA.min (mean 604.9). The average was 22.9 mA.min for fluoroscopy, and 616.1 mA.min for cineangiography, and the ratio of cineangiography to fluoroscopy ranged from 10.5 to 89.5 with an average of 34.0. The cineangiographic contribution was estimated to be 90% of the total doses. The entrance surface doses and thyroid doses varied widely. The ratio of maximum to minimum for entrance surface doses was 98.5, for left and right thyroid it was 59.8 and 104.4, respectively. The analysis of the entrance surface doses in three age groups showed that there was no significant difference among them. There was a weak inverse relation between the thyroid dose and the weight of the patient, while no correlation was found between the thyroid dose and the entrance surface dose. The average of entrance surface doses to the patients was 847.3 mGy, which was 1-2 orders of magnitude higher than common X ray examinations.

Adolescent↗
PubMed2001

The combined effects of MRI and X-rays on ICR mouse embryos during organogenesis.

The combined effects of X-rays and magnetic resonance imaging (MRI) on mouse embryos at an early stage of organogenesis were investigated. Pregnant ICR mice were irradiated on day 8 of gestation with X-rays at a dose of 1 Gy and/or MRI at 0.5 T for 1 hour. The mortality rates of the embryos or fetuses, the incidence of external malformations, the fetal body weight and the sex ratio were observed at day 18 of gestation. A significant increase in embryonic mortality was observed after exposure to either 1 Gy of X-radiation or 0.5 T MRI. However, the combined X-rays and MRI did not show a statistically significant increase in embryonic mortality compared with the control. External malformations, such as exencephaly, a cleft palate and anophthalmia, were observed in mice irradiated with X-rays and/or MRI. The incidence of each malformation in all treated groups increased with statistical significance compared with the control mice. The incidence in mice irradiated with both X-rays and MRI was lower than in mice irradiated with only X-rays. The combined effects of the combination of radiation and MRI on the external malformations might be antagonistic. There were no statistically significant differences in fetal death, fetal body weight and sex ratio among all experimental groups.

Abnormalities, Radiation-Induced↗
PubMed2001

Soluble type II transforming growth factor-beta (TGF-beta) receptor inhibits TGF-beta signaling in COLO-357 pancreatic cancer cells in vitro and attenuates tumor formation.

UNLABELLED: Human pancreatic ductal adenocarcinomas overexpress transforming growth factor-betas (TGF-betas). This overexpression has been correlated with decreased patient survival. TGF-betas bind to a type II TGF-beta receptor (TbetaRII) dimer, which heterotetramerizes with a type I TGF-beta receptor (TbetaRI) dimer, thereby activating downstream signaling. PURPOSE AND EXPERIMENTAL DESIGN: To determine whether blocking TGF-beta actions would suppress pancreatic cancer cell growth in vivo, we expressed a soluble TbetaRII, encoding amino acids 1-159 of the extracellular domain in COLO-357 human pancreatic cancer cells. This cell line expresses all of the three mammalian TGF-beta isoforms and is growth inhibited by TGF-beta in vitro. RESULTS: COLO-357 clones expressing soluble TbetaRII were no longer growth inhibited by exogenous TGF-beta1 and exhibited a marked decrease in their invasive capacity in vitro. When injected s.c. into athymic mice, these clones exhibited attenuated growth rates and angiogenesis and decreased levels of plasminogen activator inhibitor-1 mRNA as compared with tumors formed by sham-transfected cells. CONCLUSIONS: These results indicate that endogenous TGF-betas can confer a growth advantage in vivo to a pancreatic cancer cell line that is growth inhibited in vitro and suggest that a soluble receptor approach can be used to block these tumorigenic effects of TGF-betas.

Animals↗
PubMed2000

Two Tandemly Arrayed Transfer-RNA-Derived SINEs of the Medaka (Oryzias latipes).

Two tandemly arrayed short interspersed repetitive element (SINE) sequences were found in medaka (Oryzias latipes). These two SINE sequences, designated SINE1 and SINE2, were flanked by a 180-bp AT-rich region. Both appeared to be derived from transfer RNA. The former exhibited 80% sequence homology to human tRNA(Ala) and the latter exhibited 94% sequence homology to rat tRNA(Ser). SINE1 contained the retroviral U5 region, whereas SINE2 did not. This is the first sequence-level demonstration of the existence of neighboring SINEs in medaka.

Journal Article↗
PubMed2000

Involvement of angiotensin II and endothelin-1 in the development of submandibular gland hypertrophy in response to isoproterenol in rats.

We investigated whether angiotensin II (Ang II) and endothelin-1(ET-1) are involved in submandibular hypertrophy in response to repeated treatment with isoproterenol (ISO) in rats. The immunoreactive Ang II (IRAng II) and immunoreactive ET-1 (IRET-1) contents of ISO-induced hypertrophy were significantly higher than those of control glands. Treatment of isolated gland tissues with ISO (1 microM) or dobutamine (1 microM) caused significant increases in the IRAng II and IRET- 1 contents of the glands compared with controls. These increases were suppressed by pretreatment with enalapril (3 microM) or captopril (3 microM). Treatment with Ang II (10 microM) also caused an increase in IRET-1 content. Our findings suggest that Ang II and ET-1 are involved in the submandibular gland hypertrophy that develops in rats repeatedly treated with ISO, and that these biologically active peptides may act as growth factors. They also imply that the tissue renin-angiotensin system and Ang II specific receptors are present in the submandibular glands.

Adrenergic beta-Agonists↗
PubMed2000

IL-1 induces expression of p21(WAF1) independently of p53 in high-passage human embryonic fibroblasts WI38.

We tested the effect of IL-1 on the expression of p21(WAF1) in human embryonic fibroblasts WI38. Exposure to IL-1 caused induction of p21(WAF1) protein in high-passage WI38 cells but not in early-passage cells. However, IL-1 did not stimulate the transcription of a CAT-reporter gene having two copies of the p53-responsive element on its promoter or the p53-binding capacity of nuclear extracts, although it increased transcriptional rate of p21(WAF1) in these high-passage cells. These results suggest that the induction of p21(WAF1) by IL-1 occurs at the transcriptional level, but p53 function is not required in these cells. Further studies found that IL-1 did not cause cell-cycle arrest, and the overexpression of p21(WAF1) resulted in only a slight delay of cell growth, while the level of p21(WAF1) coprecipitated with cyclin-dependent kinase-2 (Cdk2) was increased by IL-1. Moreover, a kinase assay of Cdk2 immunoprecipitates showed that IL-1 did not reduce the kinase activity, and IL-1 did not affect the status of phosphorylation of the retinoblastoma gene product (Rb). These findings imply that despite the induction of p21(WAF1), this cannot fully account for the growth arrest in high-passage WI38 cells. Thus, IL-1 mediates p21(WAF1) induction through a p53-independent pathway(s) in high-passage WI38 cells, but the cell cycle is regulated independently of p21(WAF1).

Cell Cycle↗
PubMed2000

Reciprocal functions of liver tumor cells and endothelial cells. Involvement of endothelial cell migration and tumor cell proliferation at a primary site in distant metastasis.

BACKGROUND: The mechanism by which tumor cells interact with endothelial cells at the primary site in metastasis remains obscure. MATERIALS AND METHODS: To disclose the precise mechanisms and processes of metastasis and angiogenesis, we investigated the interactions of endothelial cells (CPAE; calf pulmonary arterial endothelial cells) with two mouse liver tumor cell lines, G-5, a highly metastatic clone, and G-1, a poorly metastatic clone, based on the difference in their angiogenic activities in vivo at a primary site. RESULTS: G-5 cell cultured conditioned medium (CM) promoted migration of endothelial cells more than did G-1 cell CM, in migration assay using modified Boyden chambers. Anti-basic FGF antibody inhibited G-5-induced endothelial cell migration. Furthermore, endothelial cells stimulated proliferation of G-5 cells more than that of G-1 cells in coculture assay using Transwell chambers (pore size; 0.4 microm). Pretreated endothelial cells with bFGF enhanced tumor cell proliferation, suggesting the ability of activated endothelial cells to support tumor growth. In addition, incubation with endothelial cell CM also improved the proliferative activity of G-5 cells more than that of G-1 cells in a concentration-dependent fashion, indicating production and secretion of liver tumor cell growth substance by endothelial cells. CONCLUSION: These results provide evidence that liver tumor cells stimulate endothelial cell migration and migrated endothelial cells facilitate liver tumor cell proliferation. Tumor growth at a primary site may initially be dependent on migrated endothelial cells rather than vascularization or blood nutrient supply. This bi-directional paracrine relationship between liver tumor cells and endothelial cells may influence their metastatic ability.

Animals↗
PubMed2000

Synthesis and pharmacological activity of O-(5-isoxazolyl)-L-serine.

A novel isoxazole derivative, O-(5-isoxazolyl)-L-serine (OIS, 1), was synthesized by a Mitsunobu reaction of isoxazolin-5-one (4) with N-Boc-L-serine tert-butyl ester (5) and subsequent deprotection of the coupling product. Its structure was elucidated by spectroscopic analyses. The pharmacological activity of 1 was also examined with cloned glutamate receptors and transporters using a Xenopus oocyte-expressing system showing substrate activity on an excitatory amino acid carrier 1 (EAAC 1) as a glutamate transporter.

ATP-Binding Cassette Transporters↗