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Biomedical subjects

J Takada

Publications and source records attributed to J Takada.

At least 19 recordsLinked to original sources

Postischemic gene transfer of midkine, a neurotrophic factor, protects against focal brain ischemia.

Gene therapy may be a promising approach for treatment of brain ischemia. In this study, we examined the effect of postischemic gene transfer of midkine, a heparin-binding neurotrophic factor, using a focal brain ischemia model with the photothrombotic occlusion method. At 90 min after induction of brain ischemia in spontaneously hypertensive rats, a replication-deficient recombinant adenovirus encoding mouse midkine (AdMK, n=7) or a control vector encoding beta-galactosidase (Adbetagal, n=7) was injected into the lateral ventricle ipsilateral to ischemia. At 2 days after ischemia, we determined infarct volume by 2,3,5-triphenyltetrazolium chloride staining. There were no significant differences in cerebral blood flow 1 h after ischemia between AdMK and Adbetagal groups. Infarct volume of AdMK group was 51+/-27 mm3, which was significantly smaller than that of Adbetagal group (86+/-27 mm3, P<0.05). TUNEL-positive and cleaved caspase-3-positive cells in the periischemic area of AdMK-treated rats were significantly fewer than those in Adbetagal-treated rats, suggesting that the reduction of infarct volume by midkine was partly mediated by its antiapoptotic action. Thus, gene transfer of midkine to the ischemic brain may be effective in the treatment of brain ischemia.

Adenoviridae↗

Long-term results of rotational acetabular osteotomy for dysplasia of the hip in adult ambulatory patients with cerebral palsy.

We performed rotational acetabular osteotomy in order to treat dysplasia of the hip in five ambulatory adults with cerebral palsy. There was one man and four women, with a mean age of 21 years (16 to 27) who were followed up for a mean of 12 years and two months. The mean Sharp angle improved from 52 degrees to 43 degrees , the mean acetabular index from 30.2 degrees to 2.8 degrees , the mean centre-edge angle from -5.6 degrees to 29.2 degrees , and the mean acetabular head index from 49.2 to 88.2. There was no progression of joint degeneration and relief from pain was maintained. Our results suggest that rotational acetabular osteotomy is a valuable option for the treatment of acetabular dysplasia in adults with cerebral palsy who have incapacitating pain in the hip.

Adolescent↗

Deterioration of pre-existing hemiparesis brought about by subsequent ipsilateral lacunar infarction.

Mechanisms of post-stroke recovery are still poorly understood. Recent evidence suggests that cortical reorganisation in the unaffected hemisphere plays an important role. A 59 year old man developed a small lacunar infarct in the left corona radiata, which then caused marked deterioration in a pre-existing left hemiparesis that had resulted from an earlier right putaminal haemorrhage. Functional magnetic resonance imaging showed that the paretic left hand grip activated the ipsilateral left motor areas, but not the right hemispheric motor areas. This suggests that partial recovery of the left hemiparesis had been brought about by cortical reorganisation of the left hemisphere and intensification of the uncrossed corticospinal tract. The subsequent small infarct may have damaged the uncrossed tract, thereby causing the pre-existing hemiparesis to deteriorate even further.

Brain Infarction↗

New in-vivo calibration phantoms and their performance.

New in-vivo calibration phantoms (anthropometric phantoms) were developed to meet the needs for Japanese standard phantoms. Two important characteristics of these phantoms were that (1) they were designed using Japanese body size survey data, and (2) they were designed so that they can be adapted to various positions or geometries. The performance of these phantoms was tested with respect to body size, activity distribution along the axis, and counting efficiency. The actual dimensions of the anthropometric phantoms were compared with the survey data. Most items (31 of 47) indicated good agreement between the actual values and the survey data for the adult anthropometric phantom. The activity distribution for the anthropometric phantoms was compared with that for block phantoms that simulate a uniform activity distribution. The anthropometric phantoms have some gaps in their joints. The measurement results, however, indicated that these gaps did not significantly affect the overall accuracy of the measurements. Differences in counting efficiency between the block phantoms and the anthropometric phantoms for the same age were no more than 6%.

Adult↗

Individual dose reconstruction among residents living in the vicinity of the Semipalatinsk nuclear test site using EPR spectroscopy of tooth enamel.

Individual accumulated doses were determined by EPR spectroscopy of tooth enamel for 26 adult persons residing in territories adjacent to the Semipalatinsk Nuclear Test Site (SNTS). The absorbed dose values due to radiation from nuclear tests were obtained after subtracting the contribution of natural background radiation from the total accumulated dose. The determined dose values ranged up to 250 mGy, except for one person from Semipalatinsk city with a measured dose of 2.8 +/- 0.4 Gy. Increased dose values were determined for the individuals whose teeth were formed before 1962, the end of the atmospheric nuclear tests. These values were found to be significantly larger than those obtained for a group of younger residents of heavily exposed territories and the residents of territories not exposed to radioactive fallout. These increased dose values are consistent with those based on officially registered data for the Northeastern part of Kazakstan adjacent to SNTS, which was exposed to high levels of radioactive fallout from nuclear tests in period 1949-1962.

Adult↗

Glycosidase inhibition by cyclic sulfonium compounds.

Inhibitory activities of various cyclic sulfonium compounds including salacinol against several glycosidases were studied and some compounds showed significant inhibition. The sulfonium ion structure was found to be essential for the inhibitory activity. Specific inhibition of salacinol toward rice alpha-glucosidase was ascribed to the tether arm.

Chromatography, High Pressure Liquid↗

A new halogenated antidiabetic vanadyl complex, bis(5-iodopicolinato)oxovanadium(IV): in vitro and in vivo insulinomimetic evaluations and metallokinetic analysis.

A new vanadyl complex, bis(5-iodopicolinato)oxovanadium(IV), VO(IPA)2, with a VO(N2O2) coordination mode, was prepared by mixing 5-iodopicolinic acid and VOSO4 at pH 5, with the structure characterized by electronic absorption, IR, and EPR spectra. Introduction of the halogen atom on to the ligand enhanced the in vitro insulinomimetic activity (IC50 = 0.45 mM) compared with that of bis(picolinato)oxovanadium(IV) (IC50 = 0.59 mM). The hyperglycemia of streptozotocin-induced insulin-dependent diabetic rats was normalized when VO(IPA)2 was given by daily intraperitoneal injection. The normoglycemic effect continued for more than 14 days after the end of treatment. To understand the insulinomimetic action of VO(IPA)2, the organ distribution of vanadium and the blood disposition of vanadyl species were investigated. In diabetic rats treated with VO(IPA)2, vanadium was distributed in almost all tissues examined, especially in bone, indicating that the action of vanadium is not peripheral. Vanadyl concentrations in the blood of normal rats given VO(IPA)2 remain significantly higher and longer than those given other complexes because of its slower clearance rate. VO(IPA)2 binds with the membrane of erythrocytes, probably owing to its high hydrophobicity in addition to its binding with serum albumin. The longer residence of vanadyl species shows the higher normoglyceric effects of VO(IPA)2 among three complexes with the VO(N2O2) coordination mode. On the basis of these results, VO(IPA)2 is indicated to be a preferred agent to treat insulin-dependent diabetes mellitus in experimental animals.

Adipose Tissue↗

EPR tooth enamel dosimetry: optimization of the automated spectra deconvolution routine.

A computer routine was developed for automatic deconvolution of electron paramagnetic resonance spectra of tooth enamel samples for individual radiation dose reconstruction in the low dose region. The deconvolution routine uses the non-linear least square fit of a model simulating a tooth enamel spectrum by superposition of derivative Gaussian functions to obtain the amplitude of the dosimetric radiation induced signal. The parameters of the model and of the routine were optimized on a dose response level using a criterion of the least standard deviation of the derived radiation induced signal amplitude from the regression line vs. the nominal doses for the series of spectra of samples irradiated in known doses in the range 0-500 mGy. It was found that for the series of spectra of the heterogeneous samples (every sample is prepared from different teeth of different persons), it is essential to vary in the least square fit the parameters describing the shape of the native background signal in order to obtain the best accuracy. In the case of the series of spectra of the homogeneous (pooled) samples, almost the same accuracy of the results was obtained using the procedures with varied and fixed background signal parameters. The standard error of the dose reconstruction by the optimized deconvolution procedure was estimated as about 30 mGy for heterogeneous samples and 20 mGy for homogeneous samples.

Algorithms↗

Adenovirus-mediated gene transfer to ischemic brain: ischemic flow threshold for transgene expression.

BACKGROUND AND PURPOSE: Gene therapy may be a promising approach for treatment of brain ischemia, although protein synthesis is generally inhibited in ischemic conditions. Our goal in this study was to examine effects of brain ischemia on transgene expression of adenovirus-mediated gene transfer to ischemic brain. METHODS: Brain ischemia was produced by photochemical occlusion of the distal middle cerebral artery of spontaneously hypertensive rats (n=15). Ninety minutes after ischemia, adenoviral vectors encoding bacterial beta-galactosidase were injected into ipsilateral (nonischemic [I-n], peri-ischemic [I-p], and ischemic core [I-c] areas) and contralateral parietal (C) cortices. Cerebral blood flow before and during ischemia at each injected area was measured by laser-Doppler flowmetry. Expression of transgene was detected by histochemistry for semiquantitative scoring or by biochemical assay for quantitative analysis. RESULTS: Blood flow to the cortex decreased to 72+/-10% (mean+/-SEM) at I-n, 41+/-6% at I-p, and 23+/-3% at I-c after 10 minutes of ischemia. Expression of the reporter gene was consistently detected at C and I-n at each survival period. The semiquantitative score for transgene expression decreased according to severity of ischemia (C, 2.3; I-n, 2.6; I-p, 1.1; I-c, 0.3; mean values). beta-Galactosidase activity detected by chemiluminescent assay revealed that the values (mean+/-SEM) in the ischemic area (I-p, 15.9+/-9.2 mU/mg protein; I-c, 1.3+/-0.5) were significantly smaller than that of the nonischemic area (C, 45.4+/-6.9). Analysis of cerebral blood flow at I-p revealed that cerebral blood flow threshold for transgene expression was approximately 40% of the resting value. CONCLUSIONS: Adenovirus-mediated gene transfer into the ischemic brain provided effective expression of transgene at the nonischemic and peri-ischemic areas. Gene transfer to the ischemic brain may be a promising approach for treatment of ischemic penumbra.

Adenoviridae↗

Bradykinin mediates the acute effect of an angiotensin-converting enzyme inhibitor on cerebral autoregulation in rats.

BACKGROUND AND PURPOSE: In patients with stroke and long-standing hypertension, the autoregulation curve of cerebral blood flow (CBF) shifts toward higher blood pressure levels. Angiotensin-converting enzyme (ACE) inhibitors reduce blood pressure and shift the autoregulation curve back to normal in hypertensive patients. ACE inhibitors have 2 major pharmacological properties: they inhibit both the production of angiotensin II and the breakdown of kinins. Hence, we investigated whether the effect of an ACE inhibitor on the lower limit of CBF autoregulation is mediated by the potentiation of bradykinin-mediated vasodilatation. METHODS: In 28 male Sprague-Dawley rats, CBF was measured by laser-Doppler flowmetry during stepwise controlled hypotension. The lower limit of CBF autoregulation was defined as the mean arterial pressure at which CBF decreased by 20% of the baseline value. The rats were treated with an ACE inhibitor, captopril, in the captopril group; a bradykinin BK2-receptor antagonist, Hoe140, in the Hoe140 group; and both agents in the captopril+Hoe140 group. Other rats served as a control group. The lower limits of CBF autoregulation were compared among the 4 groups. RESULTS: In the captopril group, the lower limit of CBF autoregulation was 43+/-8 mm Hg (mean+/-SD), which was significantly lower than that in the control group (57+/-14 mm Hg). Inhibition of bradykinin abolished the effect of captopril on the lower limit of CBF autoregulation. Hoe140 alone had no significant effect on the lower limit of CBF autoregulation. CONCLUSIONS: These results suggest that the shift of the lower limit of CBF autoregulation by captopril is mediated, at least in part, by bradykinin.

Angiotensin-Converting Enzyme Inhibitors↗

Directional distribution of radiation around an accident at a uranium fuel factory in Tokai-mura, 1999.

A beta-ray survey was carried out on concrete walls of the boundary and buildings after a criticality accident at a factory of JCO Co. Ltd. at Tokai-mura. A remarkable distribution of beta counts was observed on the walls depending on the complex internal and external structures of buildings surrounding a precipitation vessel containing uranium 23 days after the accident. The directional distribution function, based on the beta counts on the walls, was consistent with data concerning the neutron dose rate measured in several directions during the accident, suggesting an anisotropic neutron distribution to the residential area.

Humans↗

Determination of radionuclides induced by fast neutrons from the JCO criticality accident in Tokai-mura, Japan for estimating neutron doses.

A criticality accident occurred at a uranium conversion facility in Tokai-mura, Japan on September 30, 1999, and fission neutrons were continuously emitted for about 20 hours. Materials of stainless steel or iron, and chemical reagents were collected at places between 2 m and 270 m from the criticality accident site on October 25 and 26, 1999, November 27, 1999 and February 11, 2000. Neutron-induced radionuclides. such as 54Mn and 58Co, in the materials exposed to fast neutrons from the accident were measured to estimate the neutron fluences and energy distributions. Highly sensitive y-ray spectrometry with a well-type Ge detector was performed after radiochemical separation of Mn and Co from the materials. An instrumental neutron activation analysis was mainly applied for determinations of the target elements and chemical yields. The concentrations of 54Mn and 58Co in a mesh screen of stainless steel collected at a location 2.0 m from the accident site were determined. The total number of fission events was evaluated to be 2.5 x 10(18) by Monte-Carlo calculations of neutron transfer by considering the observed values of 54Mn and 58Co. The results presented here are fundamental to estimate the neutron doses at various distances.

Fast Neutrons↗

External doses to 350 m zone residents due to anisotropic radiation from the JCO criticality accident in Tokai-mura.

The validity of a method for individual dose reconstruction based on the anisotropic radiation distribution was confirmed by a comparison with the dose from Na-24 whole-body counting for seven persons at a neighboring company located on the western side of the JCO campus. The successful coincidence between Di (Na-24) and Di (present) also supports the validity of the second version of D(r) reported by the Head Office of Countermeasure. The present dose reconstruction for the 350 m zone at the western side showed an average value of 0.7 mSv and a maximal value of 3.1 mSv, as indoor-dose under the assumption of an effective transmittance of 0.4 for all of the houses. If all of the residents in 350 m zone were indoors during the accident, 83% of them might have received external doses of less than 1 mSv. The radiation exposure to the nearest residential area in the southern-west direction was significantly reduced with phi(theta(i)) between 0.4 and 0.2 by several buildings on the JCO campus. The present study on the public dose confirms that the official report on the public dose (the maximal value of 21 mSv for individual doses) from Head Office of Countermeasure is significantly overestimated due to their isotropic treatment of radiation from the source.

Anisotropy↗

[YAG laser-induced reperfusion of photothrombotic middle cerebral artery occlusion in rats].

The laser-driven photochemical occlusion of middle cerebral artery(MCA) is much easier, and less traumatic than standard electrocautery or even clip methods, while the infarct size is fairly reproducible. This study aimed to establish the system for YAG laser-induced reperfusion of photothrombotic MCA occlusion. Male spontaneously hypertensive rats(5-7 months old, 350-450 g) were anesthetized with halothane, endotracheally intubated, and mechanically ventilated. The photosensitizing dye rose bengal(20 mg/kg body weight) was administered intravenously over 90 sec starting simultaneously with 3 min of krypton laser irradiation(568 nm, 20 mW). The irradiated middle cerebral artery was completely occluded by an intraluminal thrombus. A YAG laser operating at 355 nm(16 mW, 15 Hz) was focused with a cylindrical lens and positioned with a mirror onto the occluded distal MCA. This YAG laser irradiation for approximately 3 min caused reperfusion of the thrombosed distal MCA. We demonstrated a novel method of reperfusion in the photothrombotic MCA occlusion model. This reperfusion model should facilitate study of the therapeutic window for reversibility in thrombotic stroke.

Animals↗

[Consideration of surgical treatment for recurrence after the resection of hepatic metastases from colorectal cancer].

We considered treatment for recurrence following the resection of hepatic metastases from colorectal cancer. The subjects of this study were 15 of 29 patients who had undergone WHF arterial infusion following resection of hepatic metastases from colorectal cancer, in whom there was a recurrence. Of these 15 cases, 6 involved recurrence in a single organ (residual liver, 4; lung, 1; local area, 1), 7 involved two organs (residual liver and lung, 2; residual liver and local area, 2; residual liver and bone, 1; spleen and intra-abdominal lymph node, 1; intra-abdominal lymph node and peritoneum, 1) and 2 involved three organs (lung, bone and abdominal wall, 1; lung, peritoneum and distal lymph node, 1). Reresection was performed in all cases in which recurrence occurred in a single organ. For those cases in which recurrence occurred in two or more organs, reresection and infusion were performed in the 4 cases of recurrence in the residual liver and reresection was performed in the case of recurrence in the spleen and intra-abdominal lymph node (No. 16), the case of local recurrence and the case involving the abdominal wall. The 5-year survival rate of the 29 cases who underwent initial hepatic resection was 61.9%. Five years following resection, the recurrence rate in the residual liver was 38.3%. The survival rates following treatment for recurrence were 76.9, 51.3 and 25.6% for 1, 3 and 5 years, respectively. Of the 8 deaths which have occurred to date, only one was directly related to an increase in hepatic metastases. Following resection of hepatic metastases from colorectal cancer, WHF provides a high rate of prevention as well as a high survival rate. Furthermore, with regard to recurrence following WHF treatment, if the recurrence is in only one organ, there is the possibility of achieving effective treatment by reresection (WHF = 5-FU 1,000 mg/m2 5 hrs qw).

Colorectal Neoplasms↗

Dosimetry studies in Zaborie village.

Dosimetry studies in Zaborie, a territory in Russia highly contaminated by the Chernobyl accident, were carried out in July, 1997. Studies on dosimetry for people are important not only for epidemiology but also for recovery of local social activity. The local contamination of the soil was measured to be 1.5-6.3 MBq/m2 of Cs-137 with 0.7-4 microSv/h of dose rate. A case study for a villager presently 40 years old indicates estimations of 72 and 269 mSv as the expected internal and external doses during 50 years starting in 1997 based on data of a whole-body measurement of Cs-137 and environmental dose rates. Mean values of accumulated external and internal doses for the period from the year 1986 till 1996 are also estimated to be 130 mSv and 16 mSv for Zaborie. The estimation of the 1986-1996 accumulated dose on the basis of large scale ESR teeth enamel dosimetry provides for this village, the value of 180 mSv. For a short term visitor from Japan to this area, external and internal dose are estimated to be 0.13 mSv/9d (during visit in 1997) and 0.024 mSv/50y (during 50 years starting from 1997), respectively.

Adult↗

Calculation of the neutron W value for neutron dosimetry below the MeV energy region.

The effective neutron W value for tissue-equivalent gas in the energy region from 5 keV to 5.7 MeV has been calculated using W values for recoil particles (protons, alpha particles, oxygen, carbon and nitrogen ions), which are produced by incident neutrons. The W value is assumed to be an energy-fluence-average over the W values of the recoil particles. The energy fluence spectra for the recoil particles are calculated by using a continuous slowing down approximation (CSDA). For the W values of recoil particles in the low-energy region, the recently evaluated data by Siebert et al and Taylor et al were used. Results are presented which show that the effective neutron W value depends strongly on energy in the low-energy region. This result indicates that neutron dose measurements using ionization chambers need a considerable correction of the W value in the low-energy region.

Carbon↗

Relationship between the 137Cs whole-body counting results and soil and food contamination in farms near Chernobyl.

We measured the radioactivity in the soil and child food samples from farms near Mogilev (56-270 GBq km(-2) 137Cs), Gomel (36-810 GBq km(-2) 137Cs), and Klincy (59-270 GBq km(-2) 137Cs), who had whole-body 137Cs counting results measured as part of a health examination in the Chernobyl Sasakawa Health and Medical Cooperation Project. Soil contamination on the family farm seems to be the main source of human contamination because most of the people in the area live on small farms and they and their domestic animals eat crops from the farms. A clear correlation was found between the children's whole-body 137Cs counting results and the radioactivity in their food (correlation coefficient: 0.76; confidence level of correlation: 3.2 x 10(-9)). There were also significant correlations between the whole-body 137Cs counting results and both the radioactivity of the soil samples (correlation coefficient: 0.22; confidence level of correlation: 0.0107) and the average contamination level of their current residence (correlation coefficient: 0.20; confidence level of correlation: 0.0174).

Cesium Radioisotopes↗