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Biomedical subjects

K Miyasaka

Publications and source records attributed to K Miyasaka.

At least 19 recordsLinked to original sources

Association of ghrelin receptor gene polymorphism with bulimia nervosa in a Japanese population.

Eating disorders (EDs) have a highly heterogeneous etiology and multiple genetic factors might contribute to their pathogenesis. Ghrelin, a novel growth hormone-releasing peptide, enhances appetite and increases food intake, and human ghrelin plasma levels are inversely correlated with body mass index. In the present study, we examined the 171T/C polymorphism of the ghrelin receptor (growth hormone secretagogue receptor, GHSR) gene in patients diagnosed with EDs, because the subjects having ghrelin gene polymorphism (Leu72Met) was not detected in a Japanese population, previously. In addition, beta3 adrenergic receptor gene polymorphism (Try64Arg) and cholecystokinin (CCK)-A receptor (R) gene polymorphism (-81A/G, -128G/T), which are both associated with obesity, were investigated. The subjects consisted of 228 Japanese patients with EDs [96 anorexia nervosa (AN), 116 bulimia nervosa (BN) and 16 not otherwise specified (NOS)]. The age- and gender-matched control group consisted of 284 unrelated Japanese subjects. The frequency of the CC type of the GHSR gene was significantly higher in BN subjects than in control subjects (chi(2) = 4.47, p = 0.035, odds ratio = 2.05, Bonferroni correction: p = 0.070), while the frequency in AN subjects was not different from that in controls. The distribution of neither beta3 adrenergic receptor gene nor CCK-AR polymorphism differed between EDs and control subjects. Therefore, the CC type of GHSR gene polymorphism (171T/C) is a risk factor for BN, but not for AN.

Adult↗

Dose-dependency of life span prolongation of F344/DuCrj rats injected with (-)deprenyl.

The effect of (-)deprenyl (D) on prolonging survival has previously been reported in different species of animals. In rats, three studies reported a positive effect, while one study reported a shortening of life spans. In the present study, we attempted to clarify past discrepancies in the results based on the speculation that there exists a certain effective dose range for this effect of the drug. F344/DuCrj rats of both sexes began to receive subcutaneous (s.c.) injections of D at the age of 18 months at a dose of 0.25 mg/kg/injection (inj.), 3 times a week. Control animals were given a vehicle (a saline solution). Average life spans of animals (days) were significantly increased in both male (895 +/- 109.7, n=30; 967.8 +/- 88.6, n=30, control vs. D treated, P<0.01, t-test) and female (924.7 +/- 132.2, n=38; 987.1 +/- 133.4, n=39, P<0.05) rats by 8.1% and 6.7%, respectively. We have previously reported that a dose of 0.5mg/kg/inj. (s.c.) significantly increased the life span of male F344 rats, while a dose of 1.0 mg/kg/inj. somewhat shortened the life span, although the difference was not statistically significant. The results of the present study coupled with our previous reports clearly indicate that a proper dose of D within a certain dose range can significantly increase the life span of animals of both sexes, but that a greater dose becomes less effective and may actually adversely affect the life span of rats. The presence of this effective dose range of D may explain discrepancies in the effect of D on life spans of animals previously reported.

Animals↗

Role of 5-HT1B receptors in entrainment disorder of Otsuka Long Evans Tokushima fatty (OLETF) rats.

The role of 5-HT1A and 5-HT1B receptors in entrainment function was studied in Otsuka Long Evans Tokushima fatty (OLETF) rats and control Long Evans Tokushima Otsuka (LETO) rats. Light-induced (100 lux, 30 min) Fos expression in the suprachiasmatic nucleus was studied. Light-induced Fos expression was significantly decreased in OLETF rats compared to that in LETO rats. The decrease of light-induced Fos expression in OLETF rats was significantly reversed by pretreatment with the 5-HT1B receptor antagonist, isamoltan (3 mg/kg, i.p.). Simultaneous administration of CGS12066B (5 mg/kg, i.p.), a 5-HT1B agonist, blocked the reversal effect of isamoltan on Fos expression. Fos expression was not changed in LETO rats by pretreatment with isamoltan (3 mg/kg, i.p.). The Fos expression in LETO and OLETF rats was significantly decreased by pretreatment with the 5-HT1A antagonist, WAY-100,635. Phase shifts in locomotor activity paralleled the Fos expression. Light-induced phase shifts of locomotor activity in OLETF rats were significantly smaller than those in LETO rats. The phase shifts were significantly increased by isamoltan (3 mg/kg, i.p.) in OLETF rats. These results suggest that 5-HT1B receptors are involved in the reduced entrainment function of OLETF rats.

Animals↗

Recent trends in pediatric fluid therapy.

Virtually all hospitalized pediatric patients require some form of intravenous fluid administration. The foundation of current pediatric fluid therapy practice was formulated in the 1950s when pediatricians were dealing with relatively simple dehydration and normal homeostasis could largely be assumed. Recent advances in pediatric medicine have resulted in increased severity of illness and normal physiology can no longer be assumed. The traditional approach to pediatric fluid therapy has been recently challenged by the syndrome of inappropriate secretion of antidiuretic hormone (SIADH), cerebral salt wasting syndrome (CSWS), diabetic ketoacidosis (DKA) and hyponatremia caused by the inappropriate use of hypotonic solutions, all of which involve unusual sodium and serum osmolarity dynamics causing life threatening central nervous system (CNS) pathophysiology. In this review, we give an overview of the recent understanding of pediatric fluid therapy. The widespread use of acetate in place of lactate as a bicarbonate precursor and the expanding role of nonalbumin plasma expanders in pediatrics are also discussed as they will play a clinical role in the near future.

Child↗

MRI in methotrexate-related leukoencephalopathy: Disseminated necrotising leukoencephalopathy in comparison with mild leukoencephalopathy.

We report two fatal cases of methotrexate (MTX)-induced disseminated necrotising leukoencephalopathy (DNL) in which MRI was repeated from the onset. Initial T2-weighted images showed multiple areas of high signal, mainly in deep cerebral white matter, which on follow-up, spread and coalesced to involve the entire white matter. Small irregular low-signal foci on T2-weighted images were seen within the high-signal lesions. Multiple areas of contrast enhancement corresponded to these low-signal foci. The condition of both patients deteriorated and they died. We compared their MRI findings with those of seven patients with mild MTX-related leukoencephalopathy, six of whom were asymptomatic; one had transient neurological symptoms. They showed no contrast enhancement, but rather mild-to-moderate diffuse high signal in deep white matter, which later disappeared. These findings suggest that multiple low-signal foci on T2-weighted images with contrast enhancement may be characteristic of DNL, and that contrast-enhanced imaging is useful to differentiate this condition from mild leukoencephalopathy.

Adolescent↗

Diffusion-weighted magnetic resonance imaging in early stage of 5-fluorouracil-induced leukoencephalopathy.

We report a case of 5-fluorouracil (5-FU)-induced leukoencephalopathy in which magnetic resonance imaging (MRI) of the brain, including diffusion-weighted imaging (DWI), was performed serially. The initial T2-weighted and FLAIR images showed diffuse mild hyperintensity in bilateral deep cerebral white matter and corpus callosum, which on T1WI appeared as non-enhanced faint hypointensity. Isotropic DWI disclosed the abnormality as well-conspicuous diffuse hyperintensity with decreased ADC. Serial studies revealed that majority of the abnormal signal intensity on these sequences resolved, and the decreased ADC values approached normal. Some hyperintensity remained in the deep cerebral white matter and the splenium, but no further significant ADC change after normalization was noted. Measurement of ADC along the three orthogonal directions showed the presence of directional dependence of diffusion throughout the length of study. These findings suggest that early stage of 5-FU-induced leukoencephalopathy is associated with reversible restricted diffusion and preservation of anisotropy. Diffusion-weighted imaging may be useful for the diagnosis.

Adult↗

Effect of intravenous infusion of NIK-716 in anesthetized pediatric patients.

NIK-716 is a maintenance fluid based on the new concept of containing acetate as a base source and 5% glucose as an energy source. It was administered to pediatric patients under general anesthesia for less invasive surgical operations, and its efficacy was investigated by performing blood chemistry examination and urinalysis before and after administration. For efficacy assessment, the three items selected as efficacy parameters, i) the replacement and maintenance of water (assessment of hydration and urine output); ii) the maintenance of serum electrolytes (Na and K); and iii) the utilization of glucose (blood glucose and urinary glucose), were evaluated based on the results of laboratory examination (hematology, blood chemistry and urinalysis), and overall improvement was rated on the basis of total scores of these assessment items. No adverse events or abnormal laboratory values attributable to the maintenance fluid were observed in any of the 25 children administered NIK-716. In an overall improvement rating, NIK-716 proved markedly effective or effective in 79.2% of the 24 children evaluated. The overall safety rating was judged as 'no problem' in all 25 children. These findings suggest that NIK-716 is a useful and safe maintenance fluid that can be administered to pediatric patients during the course of surgery.

Adolescent↗

Detection of lung tumor movement in real-time tumor-tracking radiotherapy.

PURPOSE: External radiotherapy for lung tumors requires reducing the uncertainty due to setup error and organ motion. We investigated the three-dimensional movement of lung tumors through an inserted internal marker using a real-time tumor-tracking system and evaluated the efficacy of this system at reducing the internal margin. METHODS AND MATERIALS: Four patients with lung cancer were analyzed. A 2.0-mm gold marker was inserted into the tumor. The real-time tumor-tracking system calculates and stores three-dimensional coordinates of the marker 30 times/s. The system can trigger the linear accelerator to irradiate the tumor only when the marker is located within the predetermined "permitted dislocation." The value was set at +/-1 to +/-3 mm according to the patient's characteristics. We analyzed 10,413-14,893 data sets for each of the 4 patients. The range of marker movement during normal breathing (beam-off period) was compared with that during gated irradiation (beam-on period) by Student's t test. RESULTS: The range of marker movement during the beam-off period was 5.5-10.0 mm in the lateral direction (x), 6.8-15.9 mm in the craniocaudal direction (y) and 8.1-14.6 mm in the ventrodorsal direction (z). The range during the beam-on period was reduced to within 5.3 mm in all directions in all 4 patients. A significant difference was found between the mean of the range during the beam-off period and the mean of the range during the beam-on period in the x (p = 0.007), y (p = 0.025), and z (p = 0.002) coordinates, respectively. CONCLUSION: The real-time tumor-tracking radiotherapy system was useful to analyze the movement of an internal marker. Treatment with megavoltage X-rays was properly given when the tumor marker moved into the "permitted dislocation" zone from the planned position.

Aged↗

Overexpression of homeobox gene HOXD3 induces coordinate expression of metastasis-related genes in human lung cancer cells.

Homeobox-containing genes are expressed in spatiotemporal fashion during embryogenesis and act as master transcription-regulating factors which control the expression of a variety of genes involved in morphogenesis. They are also expressed in a tissue-specific manner in normal adult tissues and appear to give cells spatial information in the maintenance of their architectural integrity. We transfected a HOXD3 class I homeobox-containing gene into human lung cancer A549 cells and investigated alterations in gene expressions and phenotypes related to the maintenance of tissue architecture in HOXD3-overexpressing A549 cells. In the HOXD3-overexpressing cell lines, expression of E-cadherin was lost and plakoglobin was strongly repressed, whereas integrin alpha3 and beta3 were up-regulated and N-cadherin and integrin alpha4 were newly expressed. Compared with parental and control transfectant lines, the HOXD3-overexpressing cell lines showed highly motile and invasive activity. Blocking experiments using anti-integrin beta1 and beta3 suggested that the increased haptotaxis of the HOXD3-overexpressing cells to vitronectin resulted from increased expression and activation of integrin alphavbeta3, and that overexpression of the HOXD3 gene converted the integrin beta1-dependent haptotaxis to fibronectin into both integrin beta1- and beta3-dependent one. HOXD3 overexpression increased production of matrix-degrative enzymes including matrix metalloproteinase-2 and urokinase-plasminogen activator. When the tumor cells were intravenously injected into the tail veins of nude mice, HOXD3 transfectants formed a significantly large number of metastatic foci in lungs compared with the control transfectants. These findings suggest that HOXD3 can act as a metastasis-promoting gene in human lung cancer A549 cells.

Antigens, CD↗

Magnetic resonance imaging system for three-dimensional conformal radiotherapy and its impact on gross tumor volume delineation of central nervous system tumors.

PURPOSE: We developed an MRI system for three-dimensional planning in radiotherapy. Its contribution on gross tumor volume (GTV) delineation of central nervous system (CNS) diseases was evaluated. METHODS AND MATERIALS: The MRI system, with corrected distortion, was registered on computed tomography (CT) by means of fiducial/anatomic landmarks. In 41 consecutive patients with various CNS diseases, GTVs determined by MRI/CT registration (MR/CT-GTV) and CT alone (CT-GTV) were compared. Hard copies of diagnostic MRI were shown to doctors when CT-GTV was determined to simulate a conventional planning situation. Multi-observer volumetric analysis was conducted, assessing interobserver deviations among four radiation oncologists and intermethodological deviations between MR/CT-GTV and CT-GTV. RESULTS: Overall, the mean of geometric distortion was significantly reduced from 1.08 mm to 0.3 mm by distortion correction (p < 0.0001). The contribution of the correction was apparent at >12.0 cm radius from the center of the magnetic field. Interobserver deviation was significantly reduced by MR/CT registration (p = 0.005). The improvement was significant for acoustic neurinoma (p = 0.038), astrocytomas (p = 0.043), and lesions at the cerebellum/brainstem (p = 0.008). The regression coefficient between MR/CT-GTV and CT-GTV was <0.9 for cerebellum/brainstem lesions, suggesting that MRI/CT-GTV was smaller than CT-GTV. CONCLUSIONS: This system is feasible for three-dimensional planning and was shown to reduce interobserver deviations in GTV delineation for CNS diseases.

Brain Neoplasms↗

Remote verification in radiotherapy using digitally reconstructed radiography (DRR) and portal images: a pilot study.

PURPOSE: To use digitally reconstructed radiography (DRR) and digitally compressed portal images in distant consultation using a telecommunications network, the verification performance of DRR and digitally compressed portal images on the image console was investigated. METHODS AND MATERIALS: A human thoracic phantom was scanned with computed tomography (CT). Radiotherapy was planned at 5 different anatomic locations. A digitally reconstructed radiograph was made; verification films of the phantom were then taken with 6-MV X-rays. The treatment center was intentionally dislocated. Fifty sets of DRR and portal images were seen by 7 doctors on a conventional view-box (view-box method) to judge whether the treatment center was dislocated. These image sets were digitalized by a film scanner, compressed to 1/10 Joint Photographic Experts Group (JPEG) format, and compared on an image console by the same physicians (image-console method). The verification performance of the image console method was compared with that of the view-box method by means of receiver operating characteristic (ROC) analysis. Clinically, 159 portal-image-sets were verified with the image-console method and the appropriateness of the decision was later assessed by the view-box method. RESULTS: The accuracy of the treatment verification was estimated to be 88.8% by the conventional view-box method and 88.3% by the image-console method. There was no statistically significant difference in the verification performances of the conventional method (Az = 0.86+/-0.02) and the image console method (Az = 0.84+/-0.07). Frequent digital image-processing modification was positively related to the accuracy of verification. Clinically, there were 3 (1.8%) major corrections, 31 (19.5%) minor corrections, and 123 cases with no correction. No further correction was called for by the re-evaluation using the view-box method. CONCLUSION: The verification performance of DRR and digitally compressed portal images on the image console was as accurate as the conventional method. Distant consultation using DRR and portal images through telecommunication is usable in clinical practice.

Humans↗

Intramedullary schwannoma of the spinal cord: report of two cases.

We report magnetic resonance findings in the intramedullary schwannoma of the cervical spinal cord in two patients. In both cases, the solid portions of the tumours enhanced intensely after administration of Gd-DTPA and the enhanced border was sharply delineated from the adjacent spinal cord. Schwannomas should be considered in the differential diagnosis of intramedullary tumours when magnetic resonance images show a strongly enhancing mass with sharply delineated borders.

Adolescent↗

MRI in seven cases of tacrolimus (FK-506) encephalopathy: utility of FLAIR and diffusion-weighted imaging.

We assessed the utility of fluid-attenuated inversion-recovery (FLAIR) and diffusion-weighted (DWI) images in investigation of tacrolimus (FK-506) encephalopathy, and to see whether we could predict its cause from clinical and imaging data. In seven patients with presumed FK-506 toxicity the areas involved on MRI were similar to those in cyclosporin A (CsA) toxicity. The abnormal signal was most evident on FLAIR in all cases. In three of four patients who underwent DWI, no diffusion abnormalities were detected; in the remaining patient, increased diffusion was seen in the deep white matter bilaterally on the apparent diffusion coefficient map, consistent with the findings on T2-weighted spin-echo and FLAIR images. Five of the six patients for whom we had clinical data showed sudden changes in electrolyte or fluid equilibrium due to diarrhoea, a polyuria or oliguria one day before or on the day of onset of the central nervous system disturbances. We speculate that FK-506 encephalopathy is triggered by the disturbance of the electrolyte and/or fluid equilibrium, given a certain serum level of FK-506.

Adolescent↗

Clinical efficacy of telemedicine in emergency radiotherapy for malignant spinal cord compression.

The authors developed a Telecommunication-HElped Radiotherapy Planning and Information SysTem (THERAPIST), then estimated its clinical benefit in radiotherapy in district hospitals where consultation with the university hospital was required. The system consists of a personal computer with an image scanner and a digital camera, set up in district hospitals and directly connected via ISDN to an image server, and a treatment planning device set up in a university hospital. Image data and consultative reports are sent to the server. Radiation oncologists at the university hospital determine a treatment schedule and verify actual treatment fields. From 1998 to 1999, 12 patients with malignant spinal cord compression (MSCC) were treated by emergency radiotherapy with the help of this system. Image quality, transmission time, and cost benefit also were satisfactory for clinical use. The mean time between the onset of symptoms and the start of radiotherapy was reduced significantly from 7.1 days to 0.8 days (P < .05) by the introduction of the system. Five of 6 nonambulant patients became ambulant after the introduction of THERAPIST compared with 2 of 8 before the introduction of THERAPIST. The treatment outcome was significantly better after the introduction of the system (P < .05), and suggested to be beyond the international standard. The telecommunication-helped radiotherapy and information system was useful in emergency radiotherapy in district hospitals for patients with MSCC for whom consultation with experienced radiation oncologists at a university hospital was required.

Cost-Benefit Analysis↗

Effect of Phenyl-P/HEMA acetone primer on wet bonding to EDTA-conditioned dentin.

OBJECTIVES: The purpose of this study was to examine the effect of 2-methacryloyloxyethyl phenyl phosphoric acid (Phenyl-P)/2-hydroxyethyl methacrylate (HEMA) acetone-based primer on moist dentin surfaces that were preconditioned with ethylenediaminetetraacetate (EDTA) to remove the smear layer. METHODS: Bovine dentin were prepared with 180-grit paper, conditioned with 0.5M EDTA (pH 7.4) for 60s followed by water rinsing and then blot drying. Each surface was then primed with Phenyl-P/30 wt% HEMA in acetone for 10s followed by blot drying. A light-cured bonding agent was then applied, cured and trimmed to give dumbbell-shaped specimens. The Phenyl-P concentration ranged from 1 to 20 wt%. During the bonding procedure, no compressed air was used. After storage in water at 37 degrees C for one day, tensile bond strengths were measured and analyzed using one-way ANOVA. Dentin discs treated under the same conditions were observed under a scanning electron microscope (SEM). RESULTS: When the concentration of Phenyl-P was 12 wt%, the highest mean tensile bond strength was obtained (27 MPa). It was significantly higher than that of the 3, 5, 15 or 20 wt% groups (9-11 MPa) (p<0.05). The samples of 1 wt% group were all broken during trimming the dumbbell-shaped specimens. SEM observations showed a 1 microm-thick layer of hybridized dentin after polished cross-sections were chemically challenged with 6N HCl for 30s and then 1% NaOCl for 60 min. SIGNIFICANCE: The experimental Phenyl-P/HEMA acetone primer is effective in bonding resin to EDTA-conditioned dentin. Acetone as a solvent for Phenyl-P/HEMA primer has the clinical advantage of not requiring an air-stream to evaporate the solvent. The experimental bonding procedure can minimize the skin irritation by HEMA.

Acetone↗