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Biomedical subjects

M Takada

Publications and source records attributed to M Takada.

At least 37 records · Page 2Linked to original sources

Organization of prefrontal outflow toward frontal motor-related areas in macaque monkeys.

Linkage between the prefrontal cortex and the primary motor cortex is mediated by nonprimary motor-related areas of the frontal lobe. In an attempt to analyse the organization of the prefrontal outflow from area 46 toward the frontal motor-related areas, we investigated the pattern of projections involving the higher-order motor-related areas, such as the presupplementary motor area (pre-SMA) and the rostral cingulate motor area (CMAr). Tracer injections were made into these motor-related areas (their forelimb representation) on the medial wall that had been identified electrophysiologically. The following data were obtained from a series of tract-tracing experiments in Japanese monkeys. (i) Only a few neurons in area 46 were retrogradely labelled from the pre-SMA and CMAr; (ii) terminal labelling from area 46 occurred sparsely in the pre-SMA and CMAr; (iii) a dual labelling technique revealed that the sites of overlap of anterograde labelling from area 46 and retrograde labelling from the pre-SMA and CMAr were evident in the rostral parts of the dorsal and ventral premotor cortices (PMdr and PMvr); (iv) and tracer injections into the PMdr produced neuronal cell labelling in area 46 and terminal labelling in the pre-SMA and CMAr. The present results indicate that a large portion of the prefrontal signals from area 46 is not directly conveyed to the pre-SMA and CMAr, but rather indirectly by way of the PMdr and PMvr. This suggests that area 46 exerts its major influence on the cortical motor system via these premotor areas.

Animals↗

Concomitant use of buffered and enteric-coated low-dose aspirin products and antisecretory drugs.

OBJECTIVE: Buffered and enteric-coated formulations of low-dose aspirin therapy are although expected to avoid gastrointestinal complications, there are reports that these modified products are associated with such complications. One available option for preventing aspirin-induced gastrointestinal complications is the simultaneous use of the agents that inhibit acid secretion such as H(2)-receptor antagonists and proton pump inhibitors. We compared the frequency of prescriptions for antisecretory drugs between users of either buffered or enteric-coated low-dose aspirin. METHODS: Monthly prescriptions at the National Cardiovascular Center for aspirin products and antisecretory drugs were counted from January 1998 to December 2002. Counting was based on information from a prescription database file compiled from a computerized order entry system. Time-series analyses were performed to determine changes in the frequency of prescriptions for low-dose aspirin products and antisecretory drugs. In addition, the frequency of prescriptions for antisecretory drugs was compared in individuals using either buffered or enteric-coated low-dose aspirin. RESULTS: A significant reduction in the frequency of prescriptions for H(2)-receptor antagonists was observed during 2001 in users of enteric-coated low-dose aspirin compared with users of buffered low-dose aspirin users. In contrast, we observed a significant increase in the frequency of prescriptions for H(2)-receptor antagonists in users of enteric-coated low-dose aspirin during 2002. This change in prescribing H(2)-receptor antagonists in users of enteric-coated low-dose aspirin began in the latter half of 2001. Proton pump inhibitors accounted for 0.31% of prescriptions in users of buffered low-dose aspirin and 0.47% in users of enteric-coated low-dose aspirin, with this difference being statistically significant. CONCLUSION: The findings of the present study do not support the notion that enteric-coated low-dose aspirin reduces the risk of gastrointestinal complications and is safer than buffered low-dose aspirin products. However the usual caution about making inferences from observational retrospective data is appropriate.

Administration, Oral↗

A malar granular cell tumor in a djungarian hamster.

'Granular cell' tumor observed in the malar subcutis of a Djungarian hamster was examined to determine its cellular origin. Histologically, the tumor consisted of a solid growth of oval or spindle-shaped large cells with abundant cytoplasm filled with eosinophilic granules that were periodic acid-Schiff-positive and diastase-resistant. Immunohistochemically, the tumor cells were positive to anti-vimentin and anti-desmin antibodies and a few cells showed positivity to anti-actin antibody as well. They did not react to myoglobin, S-100 protein, and glial fibrillary acidic protein (GFAP). Electron microscopic studies revealed that the tumor cells had pinocytotic vesicles, dense plaque and microfilaments. The first granular cell variant of myogenic tumor reported here in Djungarian hamsters was differentiated from granular cell tumor of Schwann cell origin.

Animals↗

Role of ionotropic glutamatergic and GABAergic inputs on the firing activity of neurons in the external pallidum in awake monkeys.

The neurons in the external segment of the pallidum (GPe) in awake animals maintain a high level of firing activity. The level and pattern of the activity change with the development of basal ganglia disorders including parkinsonism and hemiballism. The GPe projects to most of the nuclei in the basal ganglia. Thus exploring the mechanisms controlling the firing activity is essential for understanding basal ganglia function in normal and pathological conditions. To explore the role of ionotropic glutamatergic and GABAergic inputs to the GPe, unit recordings combined with local injections of receptor antagonists were performed in awake monkeys. Observations on the effects of local application of the alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate antagonist 1,2,3,4-tetrahydro-6-nitro-2, 3-dioxo-benzo[f]quinoxaline-7-sulfonamide, the N-methyl-D-aspartic acid (NMDA) antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid, and the GABAA antagonist gabazine as well as the effects of muscimol blockade of the subthalamic nucleus on the spontaneous firing rate, firing patterns, and cortical stimulation induced responses in the GPe suggested the following: sustained glutamatergic and GABAergic inputs control the level of the spontaneous firing of GPe neurons; both AMPA/kainate and NMDA receptors are activated by glutamatergic inputs; some GPe neurons receive glutamatergic inputs originating from areas other than the subthalamic nucleus; no GPe neurons became silent after a combined application of glutamate and GABA antagonists, suggesting that GPe neurons have intrinsic properties or nonionotropic glutamatergic tonic inputs that sustain a fast oscillatory firing or a combination of a fast and a slow oscillatory firing in GPe neurons.

Animals↗

Comparison of intestinal transit recovery between laparoscopic and open surgery using a rat model.

BACKGROUND: After laparoscopic surgery (LS), patients show faster recovery of intestinal transit than after conventional open surgery (OS). To prove the mechanism of this advantage, we compared the recovery of intestinal transit using steel carbon balls. METHODS: Rats underwent either open laparotomy or were insufflated with carbon dioxide followed by the administration of steel balls (0.6 mm). An abdominal radiograph was taken 12 h after the operation. Compliance of the intestinal walls was analyzed with a computer-driven barostat device. RESULTS: An abdominal radiograph of 12 h after administration of the steel carbon balls showed the balls scattered in the small and large intestine of the LS patients, whereas they remained mostly in the stomach of the OS patients. Compliance of the intestinal walls was sustained at approximately 100 microl/mmHg in the LS patients, whereas it dropped to 94 microl/mmHg in the OS patients with the increase in balloon pressure. Histologically, the extent of serosal edema was more severe in the OS than in the LS patients. In terms of intestinal transit and irritation LS has advantage over OS. CONCLUSIONS: Intestinal transit recovery, as measured by the migration of steel carbon balls, is faster in LS, and gastric emptying is slow in OS.

Animals↗

Characterization of islet-infiltrating immunocytes after pancreas preservation by two-layer (UW/perfluorochemical) cold storage method.

Clinical islet transplantation offers the prospect of good blood glycemic control without major surgical risks. Nevertheless, long-term function of the transplanted islets is seldom appreciated because rejection is followed by the graft failure. Although it has been implicated that islets have high immunogenicity, characterization of the islet-infiltrating immunocytes, such as leukocytes and macrophages, has not been extensively studied. Rat islets were isolated by the collagenase digestion method and separated by handpicking under the microscope. The islets were further dispersed into individual cells for flow cytometric analysis. Monoclonal antibodies directed toward T cells, B cells, and macrophages as well as ICAM-1, and MHC class I and II were used to enumerate cells. Pancreatic islets contained 6.3 +/- 2.9% immunocytes; T cells (39.6 +/- 4.2%), B cells (44.7 +/- 5.8%), and macrophages (1.7 +/- 0.6%). MHC class I was expressed on 85.6 +/- 2.8%, MHC class II on 36.8 +/- 2.9%, and ICAM-1 on 39.9 +/- 7.0%. The results of islets from preserved pancreas also showed the same tendency. As these islet-infiltrating immunocytes within the grafts may contribute to the rejection, one potential strategy to prevent early graft loss might start to eliminate or inactivate the islet-infiltrating immunocytes.

Adenosine↗

Excitatory GABA input directly drives seizure-like rhythmic synchronization in mature hippocampal CA1 pyramidal cells.

GABA, which generally mediates inhibitory synaptic transmissions, occasionally acts as an excitatory transmitter through intense GABA(A) receptor activation even in adult animals. The excitatory effect results from alterations in the gradients of chloride, bicarbonate, and potassium ions, but its functional role still remains a mystery. Here we show that such GABAergic excitation participates in the expression of seizure-like rhythmic synchronization (afterdischarge) in the mature hippocampal CA1 region. Seizure-like afterdischarge was induced by high-frequency synaptic stimulation in the rat hippocampal CA1-isolated slice preparations. The hippocampal afterdischarge was completely blocked by selective antagonists of ionotropic glutamate receptors or of GABA(A) receptor, and also by gap-junction inhibitors. In the CA1 pyramidal cells, oscillatory depolarizing responses during the afterdischarge were largely dependent on chloride conductance, and their reversal potentials (average -38 mV) were very close to those of exogenously applied GABAergic responses. Moreover, intracellular loading of the GABA(A) receptor blocker fluoride abolished the oscillatory responses in the pyramidal cells. Finally, the GABAergic excitation-driven afterdischarge has not been inducible until the second postnatal week. Thus, excitatory GABAergic transmission seems to play an active functional role in the generation of adult hippocampal afterdischarge, in cooperation with glutamatergic transmissions and possible gap junctional communications. Our findings may elucidate the cellular mechanism of neuronal synchronization during seizure activity in temporal lobe epilepsy.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

Phaeohyphomycosis caused by Chaetomium globosum in an allogeneic bone marrow transplant recipient.

Bone marrow transplant recipients are highly susceptible to opportunistic fungal infections. This is the report, of the first case of a Chaetomium systemic infection described in Brazil. A 34 year-old patient with chronic myeloid leukemia underwent an allogeneic sibling matched bone marrow transplant. Seven months later, he developed systemic infection with enlargement of the axillary and cervical lymph nodes. Culture of the aspirates from both lymph nodes yielded Chaetomium globosum. The infection was successfully treated with amphotericin B. The increasing population of immunosupressed patients requires a careful microbiologic investigation for uncommon fungal infections.

Adult↗

Involvement of the entorhinal cortex in the stress response to immobilization, but not to insulin-induced hypoglycaemia.

Although the involvement of the limbic system in the neuroendocrine responses to some stressors has been documented, the specific role of the entorhinal cortex has not been elucidated. In this study, we investigated the involvement of the entorhinal cortex in stress responses. Fos immunoreactivity, a widely used marker for neuronal activation, was detected in the entorhinal cortex of rats subjected to immobilization stress, whereas no marked staining was observed in the entorhinal cortex of the control and insulin-induced hypoglycaemia groups. Lesion of the entorhinal cortex produced by ibotenic acid significantly attenuated the adrenocorticotropic hormone (ACTH) release evoked by immobilization; however, no significant change in ACTH release was observed in insulin-induced hypoglycaemia. No significant difference between entorhinal-lesioned rats and control rats was observed in blood glucose concentrations when subjected to either immobilization or to insulin-induced hypoglycaemia. Together, these results indicate that the entorhinal cortex is closely involved in the stress response to immobilization but not to insulin-induced hypoglycaemia.

Adrenocorticotropic Hormone↗

Shielding experiment of heavy-ion produced neutrons using a tissue-equivalent proportional counter.

A shielding experiment was performed at the HIMAC (Heavy Ion Medical Accelerator in Chiba), of National Institute of Radiological Sciences (NIRS), to measure neutron dose using a spherical TEPC (tissue-equivalent proportional counter) of 12.55 cm inner diameter. Neutrons are produced from a 5 cm thick stopping length Cu target bombarded by 400 MeV/nucleon C6+ ions and penetrate concrete or iron shields of various thicknesses at 0 degree to the beam direction. From this shielding experiment. y-distribution, mean lineal energy, absorbed dose, dose equivalent and mean-quality factor were obtained behind the shield as a function of shield thickness. The neutron dose attenuation lengths were also obtained as 126 g cm(-2) for concrete and 211 g cm(-2) for iron. The measured results were compared with the calculated results using the MARS Monte Carlo code.

Calibration↗

Physicians' prescribing attitudes to combined therapy with statins and fibrates.

OBJECTIVE: To assess the impact of a package insert revision and a drug-drug interaction warning embedded in a computerized prescription ordering system, on physicians' prescribing of concomitant statins and fibrates. METHODS: Data were obtained using a computerized prescription order entry system before and after administrative intervention advising of potentially adverse effects of this combined therapy. The number of prescriptions for statins and fibrates were counted monthly from January 1998 to June 2002 at the National Cardiovascular Center (NCVC). Counting was based on information from a prescription database file compiled from a computerized order entry system. The total number of prescriptions and frequency of requests for statins and fibrates were compared with the timing of either package insert revision or introduction of the warning on a computerized prescription ordering system. In addition, laboratory testing of renal function using serum creatinine (Scr) assays in patients treated with combined statins and fibrates was obtained from medical records at two stages during the study period (stage 1, January 1998 to June 1998; stage 2, January 2002 to June 2002). RESULTS: There were 204 prescriptions for concomitant statins and fibrates at the beginning and 50 prescriptions at end of the study period. The number of prescriptions began to decrease in the latter half of 1999 with the percentage of concomitant use of statins and fibrates showing an evident downward trend from January 2001. This acceleration in the downward trend coincided with the introduction of the computerized warning message. Scr levels were measured in 43.8% of patients in stage 1 and in 48.3% of patients in stage 2 in the past month. The percentage of patients having Scr levels measured in the past 6 months was 85.3% in stage 1 and 84.5% in stage 2. There was no significant difference in the percentages of patients whose Scr levels had been measured between the two stages. CONCLUSION: Revision of package inserts concerning combined therapy of statins and fibrates led to physicians' prescribing fewer of these combinations. A warning message displayed on a computerized prescription order entry system accentuated this effect.

Anticholesteremic Agents↗

[Lung cancer with both sarcoid reaction and metastasis in the mediastinal lymph nodes; report of a case].

A 66-year-old man was admitted to our hospital for detailed investigation of an abnormal shadow on his chest X-ray. Chest radiography and computed tomography(CT) of the chest showed mediastinal lymphadenopathy and a tumor shadow in the left upper lobe. Biopsy of the mediastinal lymph nodes by mediastinoscopy showed that sarcoid nodules existed in all the biopsies nodes. Therefore, the lymphadenopathy was thought to be sarcoidosis or sarcoid reaction accompanied with lung cancer. Left upper lobectomy and dissection of hilar and mediastinal lymph nodes were performed. Although sarcoid nodules were seen in all the dissected lymph nodes, the cancer involved #5 and #14 lymph nodes. He died of brain metastasis 10 months after surgery.

Adenocarcinoma↗

Microdosimetry of epithermal neutron field at the Kyoto University reactor.

Microdosimetric spectra were measured in order to gain the microdosimetric parameters of some epithermal neutron fields. Changes in dose mean lineal energy YD as a function of depth of heavy water showed a trend of softening with heavy water of the beam. The neutron absorbed dose was obtained by using the frequency mean lineal energy. Results show good agreement with measurements with the activation method using gold foil. This study demonstrated how microdosimetric parameters change in radiation quality as a function of heavy water depth.

Deuterium Oxide↗

Microdosimetric distribution of protons, Ep = 19-65 MeV, measured with a low pressure proportional counter.

Microdosimetric measurements of 19, 32, 43, 55, and 65 MeV protons were carried out with the A-150-walled low pressure proportional counter (LPPC). The spectra are deconvoluted into three components, which are energy loss by directly incident protons, secondary electrons, and scattered protons and heavy charged particle (including protons) produced by proton nuclear reactions with the TE wall. Dose-mean lineal energies of protons are large as usual, because larger lineal energies by proton reaction events are affected.

Equipment Design↗

Characterisation of an ultra-miniature counter for microdosimetric measurements in a therapeutic 400 MeV/A carbon beam.

Single event spectra of a clinical carbon beam have been measured by an ultra-miniature tissue-equivalent proportional counter (UMC). In order to cover the energy range of the Bragg peak, the incident energy of the carbon beam was degraded by aluminium plates. Single event spectra for carbon-events incident to the UMC were analysed and selected at several carbon energies using thin scintillation counters. It was found that the dose weighted lineal energy distributions have a doublet peak structure due to incident carbon beam and fragment contributions.

Calibration↗

Endogenous nitric oxide and endothelin-1 in persistent pulmonary hypertension of the newborn.

UNLABELLED: We studied changes in endogenous nitric oxide (NO) synthesis and endothelin-1 (ET-1) production in infants with persistent pulmonary hypertension of the newborn (PPHN). We determined concentrations of serum NO metabolites, i.e., nitrites and nitrates (NOx), and of plasma ET-1 in five infants with PPHN (PPHN group) and in 25 healthy full-term neonates (control group). In both groups, serum NOx concentrations increased over time and plasma ET-1 concentrations decreased with age. The differences in serum NOx concentrations between groups were not significant at < 12 h and 24 h of age; however, they were significantly higher in the PPHN group than in the control group at 5 days of age. The differences in plasma ET-1 concentrations between groups were not significant at 5 days of age, but were significantly higher in the PPHN group than in the control group at < 12 h and 24 h of age. CONCLUSION: Limited endogenous nitric oxide synthesis and elevated endogenous endothelin-1 production during the first few days of life may contribute to pulmonary hypertension in infants with persistent pulmonary hypertension of the newborn.

Age Factors↗

Early phase II study of S-1, a new oral fluoropyrimidine, for advanced non-small-cell lung cancer.

BACKGROUND: The efficacy and safety of S-1, a new oral fluoropyrimidine, were evaluated in patients with non-small-cell lung cancer (NSCLC). The objective of this study was to determine whether the drug should be investigated in a late phase II study. METHODS: Each treatment course consisted of an oral dose of S-1, 50 mg/body or 75 mg/body, twice a day for 28 days followed by a 2-week washout period. RESULTS: Fifty-six eligible patients were enrolled. Five of the 40 previously untreated patients (12.5%; 90% confidence interval, 6.2%-23.5%) showed a partial response (PR), and no tumor response was observed in the 16 previously treated patients. The median survival duration in all eligible patients was 8.4 months, with a 1-year survival rate of 27.3%. The incidences of grade 3 or more severe adverse effects were: anemia, 5.4%; leukopenia, 5.4%; neutropenia, 5.4%; thrombocytopenia, 1.8%; anorexia, 3.6%; diarrhea, 3.6%; and general fatigue, 5.4%. These effects disappeared after cessation of the drug or appropriate treatment. One patient died as a result of aggravated interstitial pneumonitis, but the relationship of this event to S-1 was not clear. CONCLUSION: S-1 showed modest activity with mild toxicity in the treatment of non-small-cell lung cancer. Based on this result, we will progress to the next stage of a late phase II study for advanced NSCLC, and a phase II study of S-1 and cisplatin for advanced gastric cancer. Final results will be reported as they are obtained.

Administration, Oral↗

Structural analysis of high resolution in vitro MR images compared to stained grindings.

The recent advancement of high resolution magnetic resonance imaging has opened up new avenues for the determination of structural characteristics of the trabecular network, which may significantly improve the diagnosis of osteoporosis. An analysis of the calcaneus in healthy women has shown similar age-related changes when comparing structural parameters in high resolution MR images and BMD as measured by DXA [1]. Here we undertook an in vitro study to further compare structural measurements in MR images with those from stained grindings. A 3D gradient echo sequence on a 1.5 T scanner was used to obtain four contiguous sagittal MR images with a slice thickness of 1 mm and an in plane pixel size of 195 microns. Twenty-one stained grindings with a slice thickness of 1 micron each were obtained from a 3 mm thick slab of the same volume investigated by MR. The stack of stained grindings was also used to simulate the influence of variations in slice thickness and in plane resolution. Results for structural parameters derived from the high resolution MR images differed considerably from those derived from the stained grindings because the MR images are heavily influenced by partial volume artifacts. This finding was supported by simulations which also revealed that even at a slice thickness of 500 microns and an in plane pixel size of 13 microns, accurate results could not be obtained when a histomorphometric type analysis was applied. Results also depended strongly on the segmentation method. However, contrary to the stained grindings, images averaged over several slices reveal the three-dimensional network character of the trabecular structure. New efforts should be undertaken to develop analysis strategies that are more adequate for in vivo high resolution images instead of using analysis techniques applied in classical histomorphometry.

Cadaver↗