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Biomedical subjects

Y Hamada

Publications and source records attributed to Y Hamada.

At least 73 records · Page 4Linked to original sources
PubMed2001

Comparison of the spinal anti-nociceptive effects of ES-242-1 and MK-801, two different NMDA antagonists, in rats.

The purpose of this study was to determine whether ES-242-1, a novel N-methyl-D-aspartate (NMDA) receptor antagonist of microbial origin, has anti-nociception at the spinal level and to evaluate how its anti-nociceptive effect differs from that of MK-801, a non-competitive NMDA receptor antagonist. Agents were injected intrathecally (0.1, 1.0 and 10 microg) through a previously implanted PE tube in rats. Formalin (2%, 100 microl) was injected subcutaneously into the left hindpaw 15 min after each antagonist administration. Licking time as a nociceptive behavior was measured in three stages after formalin-injection, such as early phase (0-9 min), late first phase (10-29 min) and late second phase (30-60 min). In the early phase, the largest dose of ES-242-1 significantly decreased total licking time, although MK-801 did not show any significant reduction. With the treatment of 1.0 and 10 microg MK-801, total licking time in both late first and second phases was significantly suppressed, although the smallest dose (0.1 microg) of ES-242-1 showed a significant reduction in the late second phase. These results indicate that ES-242-1 is highly effective against tonic pain, such as inflammatory pain.

Animals↗
PubMed2001

Physiological and morphometric analyses of neuropathy in sucrose-fed OLETF rats.

To investigate the characteristic features of diabetic neuropathy in type 2 diabetes mellitus, Otsuka Long-Evans Tokushima fatty (OLETF) rats, an animal model of human type 2 diabetes mellitus, and non-diabetic Long-Evans Tokushima Otsuka (LETO) rats were fed with or without sucrose and/or an aldose reductase inhibitor, [5-(3-thienyl) tetrazol-1-yl] acetic acid (TAT), for 24 weeks, and physiological, biochemical and morphological assessments were performed. Sucrose administration caused remarkable hyperglycemia in OLETF rats but not in LETO rats. Sucrose-fed OLETF rats demonstrated delayed nerve conduction velocity, decreased coefficient of variation of R-R interval, reduced sciatic nerve blood flow, increased platelet aggregation activity, a lower concentration of erythrocyte 2,3-diphosphoglycerate, and decreased Na+/K+-ATPase activity in sciatic nerves, compared with the non-sucrose-fed OLETF and LETO rats. TAT prevented all these deficits except hyperglycemia. Sorbitol and fructose accumulation and myo-inositol depletion in tail nerves of sucrose-fed OLETF rats were ameliorated by TAT. Myelinated fiber size and density in sural nerves of sucrose-fed OLETF rats were decreased and increased, respectively, compared with non-sucrose-fed OLETF and LETO rats. These morphological abnormalities were normalized by TAT. These observations suggest that the sucrose-fed OLETF rat developed diabetic neuropathy not only electrophysiologically but also histologically, and that an aldose reductase inhibitor, TAT, possesses therapeutic value for the treatment of diabetic neuropathy.

2,3-Diphosphoglycerate↗
PubMed2001

Clinical significance of enzyme-linked immunosorbent assay for the detection of circulating anti-BP180 autoantibodies in patients with bullous pemphigoid.

The NC16A domain of the 180-kDa bullous pemphigoid antigen (BP180) is the most immunogenic and, probably, pathogenic region in bullous pemphigoid (BP). In the present study, in order to determine whether serum level of circulating anti-BP180 autoantibodies is a valuable serum marker in BP, the immunoreactivity of sera against the NC16A domain of BP180 was measured using enzyme-linked immunosorbent assay (ELISA) in ten patients with BP. Serum levels of anti-BP180 autoantibodies correlated with the clinical course in BP patients, who received various therapeutic agents. The result suggests that this NC16A-ELISA is a useful method for evaluating the clinical course and efficacy of the therapy in patients with BP.

Aged↗
PubMed2001

Evaluation of recombinant interleukin-2 immunotherapy for human hemangiosarcoma in a SCID mice model (WB-SCID).

We treated the patients with cutaneous hemangiosarcoma with recombinant interleukin-2 (rIL-2) immunotherapy that showed clear therapeutic effects. This immunotherapy is popular for the treatment of hemangiosarcoma in Japan. The purpose of this study is to clarify the clinical effects in an animal experiment. After establishing a SCID mouse model of human hemangiosarcoma WB-SCID, we used this model to investigate anti-tumor effects of rIL-2 and LAK cells. We demonstrated that hemangiosarcoma cells are LAK-sensitive, and LAK cells induced by rIL-2 suppress the growth of hemangiosarcoma. Our results may assure the clinical effects of rIL-2 immunotherapy on hemangiosarcoma.

Aged↗
PubMed2001

Anti-fibrogenic effect of an angiotensin converting enzyme inhibitor on chronic carbon tetrachloride-induced hepatic fibrosis in rats.

The tissue renin-angiotensin system has recently been demonstrated to reduce fibrogenesis in various organs. However, little has been clarified regarding its role in hepatic fibrosis. The purpose of this study was to investigate the effect of angiotensin-converting enzyme inhibitors on liver fibrogenesis induced in rats by low-dose chronic carbon tetrachloride administration. We used lisinopril that is absorbed in its active form and not metabolized in the liver to avoid any influence by the administration of the chemical. Carbon tetrachloride was administered twice a week i.p. Twelve and 24 weeks after the start of treatment, expanded periportal fibrosis or portal-portal bridgings and severe fat deposition were observed in the rats treated with carbon tetrachloride alone, and these findings were significantly reduced with the simultaneous treatment with lisinopril. The hydroxyproline content of the liver was significantly lower in the lisinopril-treated group. Angiotensin II up-regulated mRNA of pro alpha (I) collagen and transforming growth factor-beta in isolated hepatic stellate cells. These results suggest that the local tissue renin-angiotensin system plays a role in rat hepatic fibrogenesis induced by chronic carbon tetrachloride administration and that hepatic fibrogenesis is significantly reduced by ACE inhibitors.

Journal Article↗
PubMed2001

The temporal profile of interactions between sensory information from both hands in the secondary somatosensory cortex.

OBJECTIVE: To elucidate the temporal profile of interactions between sensory information from both hands in the somatosensory cortex. METHODS: Somatosensory evoked fields (SEFs), generated by stimulation applied to the right index finger after a preceding stimulation to the left index finger, were recorded using a whole head-type magnetoencephalography (MEG). The paired electrical stimuli were applied with a stimulation onset asynchrony (SOA) of 50, 100, 200, 300, or 400 ms. RESULTS: The mean SEF intensities in the primary somatosensory area (SI) of five subjects, which were evoked approximately 40 ms after the latter of the paired stimuli, were not significantly smaller than that evoked in the control condition when only the right finger was stimulated. In contrast, SEFs in the secondary somatosensory area (SII), generated approximately 100 ms after the stimuli, were suppressed when the paired stimuli were applied at an SOA of 100 ms (P<0.05, t test). In addition, SEFs at approximately 150 ms after the stimuli were significantly suppressed at SOAs of 50, 100 (P<0.05), 200, and 300 ms (P<0.1). CONCLUSION: Within a time window of approximately 300 ms, sensory information from the left finger significantly affected the SEFs generated by sensory inputs from the right finger. This time window may be required for the integration of sensory input.

Adult↗
PubMed2001

Studies on cytotoxic effect of nickel ions on three cultured fibroblasts.

Cytotoxicity of Ni ions on three fibroblasts such as L929, Balb/3T3 clone A31 and MC3T3-E1 were examined by cell count (CC) and Neutral Red assay (NR). Three cells were incubated for 6 days in 1 ml DME medium containing Ni ions which ranged from 0 to 2 mM/l. The results clarified that Ni ions had dose-dependent cytotoxicity. L929 possessed the largest TC50 values (the amount of Ni ion that caused 50% cell death or 50% cell viability) of 0.12 mM/l (CC) and 0.32 mM/l (NR), and Balb/3T3 clone A31 had the least values of 0.05 mM/l (CC) and 0.09 mM/l (NR), whilst MC3T3-E1 had the intermediate values of 0.08 mM/l (CC) and 0.15 mM/l (NR). The dissolution of Ni ions from Ni-containing metallic restorations must be lower than these concentration levels so that body tissues might not be severely damaged.

Journal Article↗
PubMed2001

MRI prior computation and parallel tempering algorithm: a probabilistic resolution of the MEG/EEG inverse problem.

Since the MEG inverse problem is ill-posed and admits many possible solutions, it is not possible to give it a single "true" answer. Therefore, we propose here to use a specific probabilistic algorithm to map the full probability distribution of the MEG sources with Markov Chain Monte Carlo methods. Using a Bayesian approach, the probability of the MEG solutions is expressed as the product of the likelihood by the prior probability. To compute the prior and constrain the MEG inverse problem resolution, MRI data are also acquired and automatically processed to determine the brain position and volume. We then use Parallel Tempering algorithm to estimate the full posterior probability and determine the likely solutions of the inverse problem. We illustrate the method with results obtained from the analysis of somatosensory data. This illustrates both the MRI processing for the prior computation, and how the knowledge of the full posterior probability distribution can be used to estimate the position of the sources, as well as their likely extension.

Adult↗
PubMed2001

Autocrine expression of neurotrophins and their receptors in prostate cancer.

Previously, it has been demonstrated that the neurotrophins and their receptors are present in human prostate tissue, but neither their functional role nor localization is clearly understood. We studied the expression of neurotrophins and their receptors in prostate cancer. Between 1990 and 1999, 48 prostate cancer specimens were obtained from patients undergoing radical prostatectomy, of whom 25 received neoadjuvant hormonal therapy (NHT) and 23 were untreated. The specimens were analyzed immunohistochemically for neurotrophins (nerve growth factor, brain derived neurotrophic factor, neurotrophin 3, neurotrophin 4/5) and their receptors (TrkA, TrkB, TrkC, p75NTR). Immunohistochemical studies revealed that both benign and malignant prostate gland epithelial cells expressed the neurotrophins and their receptors to various degrees, but no obvious immunopositive reaction was observed in stromal cells. In benign epithelial cells, the neurotrophins were localized to secretory cells and the receptors were localized to basal cells. The neurotrophins, TrkA and TrkC were expressed to a similar extent in prostate cancer specimens obtained from patients both with and without NHT. In contrast, the expression of TrkB was down-regulated and the expression of p75NTR was up-regulated in prostate cancer after hormonal therapy. These findings suggest that neurotrophins are secreted by prostate cancer cells in an autocrine fashion. Neurotrophins may be involved, through their receptors, in the escape mechanism from cell death after androgen depletion found in prostate cancer.

Aged↗
PubMed2001

Antiinflammatory effect of heparin-coated circuits with leukocyte-depleting filters in coronary bypass surgery.

Cardiac surgery with cardiopulmonary bypass is associated with a systemic inflammatory response. We examined combined use of heparin coating of the cardiopulmonary bypass circuit and a leukocyte-depleting arterial line filter to reduce this response. Thirty patients were allocated randomly to equal groups with a conventional circuit and arterial line filter (C group), a heparin-coated circuit with a conventional filter (H group), or a heparin-coated circuit with a leukocyte-depleting arterial line filter (HF group). Cytokines and respiratory function were repeatedly measured perioperatively. Plasma interleukin (IL)-6 concentrations in the HF group were lower than in the C group immediately following bypass and operation, at 4 h, and 12 h (p < 0.05). Plasma IL-8 was lower in the HF group than in the C group at 4 h (p < 0.05). The respiratory index was lower immediately after bypass in the HF group than the C group (0.61 +/- 0.2 versus 1.05 +/- 0.4, p < 0.05). Heparin-coated circuits with leukocyte-depleting filters decrease inflammatory responses and improve pulmonary function during operation.

Adult↗
PubMed2001

Disc mobility and arthroscopic condition of the temporomandibular joint associated with long-term mandibular discontinuity.

PURPOSE: The present study aimed to explore disc mobility and arthroscopically diagnosed morphologic changes in the temporomandibular joint (TMJ) associated with long-term mandibular discontinuity. PATIENTS AND METHODS: Twelve patients (24 TMJs) who had undergone mandibulectomy including the unilateral condyle or segmental mandibulectomy without mandibular reconstruction, more than 8 months before this study were examined. The 24 TMJs were classified into 3 groups as follows: group 1, TMJs with a major mandibular fragment including the mandibular body (n = 11); group 2, TMJs with a mandibular ramus including the coronoid process (n = 5); and group 3, TMJs with only a condylar process, a mandibular ramus not including the coronoid process, or without a condyle (n = 8). Disc mobility was evaluated by magnetic resonance imaging, and arthroscopic observation of the superior joint compartment (SJC) was performed in all TMJs. The relationship between disc mobility and the arthroscopic findings was also studied. RESULTS: The frequency of immobile discs differed significantly among groups 1 (0%), 2 (40.0%), and 3 (100%). Arthroscopic findings were normal in all SJCs of group 1. Various types of fibrous adhesions were observed in 40.0% of group 2 and in 75.0% of group 3. The development of fibrous adhesions in the SJC was significantly related to the presence of an immobile disc. CONCLUSIONS: Long-term immobilization of the TMJ in a nonfunctional state seems to promote the development of fibrous adhesions in the SJC. Preservation of the mandibular fragment including the coronoid process, during mandibulectomy appears to contribute to postoperative TMJ mobility. To ensure recovery of a physiologic TMJ after mandibulectomy, it seems important to re-establish TMJ mobility by establishing mandibular continuity as soon as possible.

Humans↗
PubMed2001

Insulin secretion to glucose as well as nonglucose stimuli is impaired in spontaneously diabetic Nagoya-Shibata-Yasuda mice.

To clarify the mechanisms of impaired insulin secretion in Nagoya-Shibata-Yasuda (NSY) mice, an inbred strain of mice with spontaneous development of type 2 (non-insulin-dependent) diabetes mellitus, the insulin response to glucose (5.5 to 27.8 mmol/L) and nonglucose stimuli (glibenclamide, arginine, and BayK8644, a Ca-channel opener) was studied in vitro using isolated islets from male NSY and control C3H/He mice at 36 weeks of age by the batch incubation method. Insulin response to 5.5 mmol/L glucose was not significantly different between NSY and C3H/He mice, but insulin response to a high concentration of glucose (> or = 11.1 mmol/L) was significantly smaller in NSY mice than in control C3H/He mice. The dose-response curve of insulin secretion showed a markedly reduced maximum response, but almost normal glucose sensitivity in NSY islets. Insulin responses to glibenclamide (1 mmol/L), arginine (20 mmol/L), and BayK8644 (0.1 mmol/L) were also significantly smaller in NSY mice than in C3H/He mice. Insulin content of islets, in contrast, was significantly higher in NSY mice than in C3H/He mice. The impaired insulin response to glucose and nonglucose stimuli together with higher insulin content in islets in the NSY mouse suggest that a defect in voltage-dependent Ca(2+)-channel or thereafter in the cascade of insulin secretion may be responsible for impaired insulin secretion in NSY mice. NSY mice, therefore, could be a novel animal model of type 2 diabetes with a defect in insulin secretion at a different site from that in previously known animal models.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed2001

Hypothalamic hamartoma associated with an arachnoid cyst.

A hypothalamic hamartoma associated with an arachnoid cyst in an 8-year-old boy is reported herein. He presented with precocious puberty, and neuroimaging studies demonstrated a solid mass in the prepontine cistern and a huge arachnoid cyst in the left cranial fossa. The mass appeared isointense to the surrounding cerebral cortex on T1-weighted magnetic resonance images, hyperintense on T2-weighted images, and was not enhanced after administration of Gd-DTPA. The patient underwent a left frontotemporal craniotomy and a cyst-peritoneal shunt was inserted. Histological features of the cyst wall and the mass were characteristic of an arachnoid cyst and hamartoma, respectively. While a hypothalamic hamartoma associated with an arachnoid cyst is rare, such a case may help clarify the geneses of both anomalous lesions.

Arachnoid↗
PubMed2001

Preventive effects of lecithinized superoxide dismutase and methylprednisolone on spinal cord injury in rats: transcriptional regulation of inflammatory and neurotrophic genes.

The effects of lecithinized superoxide dismutase (PC-SOD) and/or methylpredisolone (MP) in preventing secondary pathological changes after spinal cord injury (SCI) were investigated in rats with reference to recovery of hindlimb motor function and expression of mRNA of pro-inflammatory and neurotrophic genes. Hindlimb motor function was assessed as the BBB open field locomotor scores. The BBB scores of three groups treated with either PC-SOD (40,000 units/kg), MP (30 mg/kg), or a combination of PC-SOD and MP (PC-SOD+MP) increased with time until 3 days after SCI, and were significantly higher than that of the control group (p < 0.05). Thereafter, the score of the PC-SOD group increased, whereas that of the MP group showed a temporary decrease from day 3 to 5 and then it gradually recovered. The scores in all groups reached a plateau about 18 days after SCI. The PC-SOD+MP group did not show a synergism but a tendency similar to that of the MP group. PC-SOD and MP had down-regulatory effects on mRNA expression of pro-inflammatory substances such as interleukin-1beta (IL-1beta), intercellular adhesion molecule-1 (ICAM-1), and inducible-nitric oxide synthetase (i-NOS) after spinal cord compression at 3, 6, and 24 h, respectively, as judged by a semiquantitative reverse transcription-polymerase chain reaction and on the lipid peroxide (LPO) level 1 h after injury as determined by thiobarbituric acid-reactive substances. The suppression of pro-inflammatory genes expression, especially IL-1beta were greater in the MP group than in the PC-SOD group, while suppression of LPO level was similar in these two groups. PC-SOD+MP treatment augmented the suppression of all three pro-inflammatory genes expression and the decrease of the LPO level. The level of neurotrophin-3 (NT-3) mRNA increased from 6 h after SCI and reached a maximum after 48 h. NT-3 mRNA level was enhanced by PC-SOD treatment, but not by MP treatment. Thus, the effect of MP in suppressing these pro-inflammatory genes expression was more than that of PC-SOD. The difference in motor function in the early and later stage may be partially due to differences in expression of IL-1beta and NT-3 after either treatment, through an IL-1beta-dependent or NT-3-mediated repair response.

Animals↗
PubMed2001

Analysis of the upstream regulatory region of the GTS1 gene required for its oscillatory expression.

The protein level of the GTS1 gene product (Gts1p) fluctuated during the oscillation of energy metabolism in continuous culture of the yeast Saccharomyces cerevisiae. Here, we found that the GTS1 mRNA level oscillated with the same periodicity as the metabolic oscillation, suggesting that the expression of GTS1 was regulated at the transcriptional level. As the 5'-upstream sequence of GTS1 contains two short open-reading frames at -310 and -829 bp from the initiation codon, we determined the GTS1 promoter required for the oscillatory expression. The upstream sequence was truncated into fragments of 183, 355, 1,042, and 1,572 bp, named GTS1pr.183 and so on, and their effects on the expression of lacZ as a reporter gene and the GTS1 gene itself were examined. The beta-galactosidase activity and Gts1p level oscillated in the continuous cultures when genes were expressed under the control of GTS1pr.183 but not GTS1pr.355. The disappearance of the metabolic and cell-cycle oscillations in the GTS1-deleted mutant was rescued by the transformation with GTS1pr.183-GTS1 but not with GTS1pr.355-GTS1. However, the stress-resistance oscillations were not found in the cells transformed with GTS1pr.183-GTS1, differing from the case of GTS1pr.1042-GTS1 reported previously [Wang et al. (2001) FEBS Lett. 489, 81-86]. Thus, we suggest that the 183-bp upstream sequence of GTS1 is basically required for the metabolic oscillation, while the 1,042-bp upstream sequence is required for oscillations of stress resistance.

Biological Clocks↗