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T Doi

Publications and source records attributed to T Doi.

At least 91 records · Page 5Linked to original sources
PubMed2000

Kindling phenomena induced by the repeated short-term high potassium stimuli in the ventral hippocampus of rats: on-line monitoring of extracellular glutamate overflow.

We observed in this study that transient periodic stimuli in response to high potassium (40 mM, 5 min at 40-min intervals, 13-15 stimuli) perfusion in the ventral hippocampus of rats led to the appearance of a kindling-like phenomenon. In this kindling-like phenomenon, we confirmed the augmentation of glutamate release and the prolongation of spike discharge. Changes in the extracellular glutamate levels before and after the stimuli were monitored by the application of in vivo microdialysis combined with on-line enzyme fluorometric detection of glutamate. This kindling-like phenomenon was not observed when microdialysis was carried out using a Ca++-free medium. The augmentation of glutamate release and the prolongation of spike discharge with epileptic convulsions are completely Ca++ dependent. These data show that repeated short-term increases in extracellular glutamate levels results in the enhancement of excitatory neuronal systems, causing an excessive propagation of seizure activity and culminating in secondary generalized seizures.

Action Potentials↗
PubMed2000

CD44 expression in soft tissue sarcomas.

Recent studies have shown that expression of alternatively splicing variants of CD44 is correlated with prognosis for several kinds of malignant tumors. However, little is known about the expression of CD44 standard and variant isoforms in soft tissue sarcomas. In this study 47 cases of soft tissue sarcoma [18 malignant fibrous histiocytomas (MFHs), 13 synovial sarcomas (SSs), 7 malignant schwannomas (MSs), and 9 liposarcomas (LSs)] were examined immunohistochemically. The monoclonal antibodies to the standard form of CD44 (CD44H) and variant exons of CD44v3, 4, 5, 6, 7, 9, and v10 were used. We analyzed the membranous expression pattern of CD44H and CD44 variant exons and assessed the relation between expression of CD44s and metastasis-free survival rates (MFSR) of patients with soft tissue sarcoma. A few sarcomas expressed CD44v3 (2/47) and v7 (2/47), but none of the sarcomas expressed CD44v10. CD44v4 (5/47), v5 (4/47), v6 (10/47), and v9 (9/47) are relatively common types of variant isoforms in soft tissue sarcomas. Expression of CD44v6 is more frequently detected in high-grade than in low-grade tumors. CD44v6 or CD44v9 expression was correlated with metastasis-free survival of patients with soft tissue sarcomas.

Adolescent↗
PubMed2000

High incidence of silent myocardial ischemia in elderly patients with non insulin-dependent diabetes mellitus.

The present study was designed to reveal the incidence of silent myocardial ischemia in asymptomatic elderly non-insulin-dependent diabetic (NIDDM) patients (aged over 60 years). As a first step screening, maximal treadmill exercise test was performed. Of 140 patients studied, 54 (38.6%) were unable or not expected to achieve diagnostic levels of exercise during treadmill testing. A positive exercise test was noted in 39 of 86 (45.3%) subjects. As a second step examination, dipyridamole thallium scintigraphy was performed for 93 subjects who exhibited a positive exercise test and could not perform a maximal exercise test. Abnormal perfusion pattern was found in 39 of 93 (41.9%), who were finally considered to have a silent myocardial ischemia. Coronary angiography was performed in 18 subjects with diagnosis of silent myocardial ischemia, who gave their consent. Significant coronary artery stenosis was in fact found in 17 of 18 (94.4%) subjects studied, confirming a very high positive predictive value of this diagnostic procedure. In conclusion, elderly NIDDM patients (aged over 60 years) had an extremely high prevalence (estimated 26.3%) of silent myocardial ischemia. This evidence suggests that early and intensive detection may be needed as a part of routine care for this group.

Aged↗
PubMed2000

Optical recording of membrane potential in dissociated mouse vestibular ganglion cells using a voltage-sensitive dye.

We investigated membrane electrophysiological features of dissociated vestibular ganglion neurons, using a voltage-sensitive dye and a multiple site optical imaging system. The neuronal nature of the cultured vestibular ganglion cells was confirmed by positive staining with the anti-neurofilament 200 kDa antibody, using immunocytochemical methods. Optical absorption of the dye which binds to the external surface of neuron membranes increased while the cells were depolarized during perfusion with 150 mM potassium solution. The relative ratio (deltaI/I) of optical absorption change was 0.23 +/- 0.08% (means +/- S.D., n = 16). These optical responses were wavelength dependent, therefore, the optical response apparently originated from the voltage-sensitive dye. Under our experimental conditions, photodynamic damage and pharmacological effects of the dye were either absent or insignificant. We therefore concluded that optical recording is a new, practical and non-invasive method to simultaneously monitor changes in membrane potential from cultured vestibular ganglion cells. Optical recording is expected to provide further insight into mechanisms of information processing by vestibular ganglion neurons.

Absorption↗
PubMed2000

In vivo evaluation of hippocampal anti-oxidant ability of zonisamide in rats.

We evaluated the anti-oxidant property of zonisamide (ZNS) in the rat brain under freely moving conditions by means of in vivo microdialysis of two exogenous nitroxide radicals, 3-carbamoyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (carbamoyl-PROXYL) and 3-methoxy carbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl (PCAM). Time-dependent changes in the signal intensities of these exogenous nitroxide radicals obtained from the hippocampal perfusates were observed using an X-band ESR spectrometer at 20-min intervals. The ESR signal intensities of nitroxide radicals decreased exponentially in all animals, which indicates that their half-life could be used as a parameter to estimate the decay rate of nitroxide radicals. Nitroxide radicals lose their paramagnetism when exposed to reductants in a biological system. Thus, half-life reflects the in vivo reducing ability. Although the half-life of carbamoyl-PROXYL, which could not pass the blood-brain barrier (BBB), was not changed when compared with the controls, pre-treatment with ZNS significantly shortened the half-life of PCAM, which could pass through the BBB. These findings suggest that the ZNS-induced increase in reducing ability did not occur within the extracellular space, but rather mainly at the neural cell membrane. This study is the first in vivo evaluation of the reducing ability of ZNS in freely moving animals.

Animals↗
PubMed2000

Duodenal somatostatinoma: a case report and review of 31 cases with special reference to the relationship between tumor size and metastasis.

Somatostatinomas are rare functioning neoplasms usually arising in the pancreas and duodenum. We report a case of somatostatinoma in a 42-year-old male with neither neurofibromatosis nor somatostatinoma syndrome. A large tumor in the descending duodenum had given rise to multiple lymph node metastases. An additional 31 duodenal somatostatinoma cases were also reviewed. Most originated in the descending part of the duodenum, with the ampulla and peri-ampullary area as the most common sites (60%). Frequent manifestations were abdominal pain (25%), jaundice (25%), or cholelithiasis (19%), the latter two reflecting obstruction of the bile duct by tumors. Only two cases showed a possible somatostatinoma syndrome (6%). The tumors with metastases, lymph nodes (10) and liver (2), were significantly larger than average than those without (2.91 +/- 1.49 cm vs 1.36 +/- 0.71 cm, P < 0.05). With a cut-off point of 2.0 cm, diagnostic accuracy for metastasis was 77.78% with 87.50% specificity and 63.64% sensitivity. The smallest tumor with metastases was 0.8 cm and the largest without metastases was 3.0 cm. These results indicate that duodenal somatostatinomas are malignant by nature and the risk of metastasis significantly increases with tumors larger than 2.0 cm.

Adult↗
PubMed2000

A study of carboplatin-coated tube for the unresectable cholangiocarcinoma.

Most cases of cholangiocarcinoma have reached an unresectable stage by the time they are discovered despite significant progress of diagnostic modalities. Many of these patients with obstructive jaundice are often treated by biliary drainage using stents to relieve the jaundice. However, the stent patency period is as short as 3 to 9 months because of tumor ingrowth or overgrowth, and mean survival is at most 12 months. Therefore, both continuous relief of obstructive jaundice and local control of the tumor are required in the treatment for advanced cholangiocarcinoma. In this investigation, we developed a new percutaneous transhepatic biliary drainage tube coated with carboplatin (carboplatin-coated tube; CCT). CCT continuously released a fixed amount of carboplatin for 4 weeks and showed an antitumor effect on human cholangiocarcinoma cell line HuCC-T1 in vitro. When CCT was embedded in subcutaneous tumor inoculated in nude mice, a significant reduction of tumor size with no apparent damage to normal adjacent tissue was observed. On the basis of these studies, 5 patients with inoperable cholangiocarcinoma were treated with CCT for 4 weeks. Overall efficacy rate of 5 patients with cholangiocarcinoma was 60% (partial response in 3 and no change in 2). No apparent side effect was observed in these patients. Thus, CCT may provide a new treatment modality for this disease. Randomized controlled trials comparing CCT therapy with palliative stenting are required to confirm these results.

Aged↗
PubMed2000

The effects of high magnitude cyclic tensile load on cartilage matrix metabolism in cultured chondrocytes.

Excessive mechanical load is thought to be responsible for the onset of osteoarthrosis (OA), but the mechanisms of cartilage destruction caused by mechanical loads remain unknown. In this study we applied a high magnitude cyclic tensile load to cultured chondrocytes using a Flexercell strain unit, which produces a change in cell morphology from a polygonal to spindle-like shape, and examined the protein level of cartilage matrixes and the gene expression of matrix metalloproteinases (MMPs), tissue inhibitors of matrix metalloproteinases (TIMPs) and proinflammatory cytokines such as IL-1beta and TNF-alpha. Toluidine blue staining, type II collagen immunostaining, and an assay of the incorporation of [35S]sulfate into proteoglycans revealed a decrease in the level of cartilage-specific matrixes in chondrocyte cultures subjected to high magnitude cyclic tensile load. PCR-Southern blot analysis showed that the high magnitude cyclic tensile load increased the mRNA level of MMP-1, MMP-3, MMP-9, IL-1beta, TNF-alpha and TIMP-1 in the cultured chondrocytes, while the mRNA level of MMP-2 and TIMP-2 was unchanged. Moreover, the induction of MMP-1, MMP-3 and MMP-9 mRNA expression was observed in the presence of cycloheximide, an inhibitor of protein synthesis. These findings suggest that excessive mechanical load directly changes the metabolism of cartilage by reducing the matrix components and causing a quantitative imbalance between MMPs and TIMPs.

Animals↗
PubMed2000

A novel cis-acting element regulates HES-1 gene expression in P19 embryonal carcinoma cells treated with retinoic acid.

The regulatory mechanisms of mammalian hairy and Enhancer of split homologue-1 (HES-1) genes were examined in mouse P19 embryonic carcinoma cells (P19 cells). Undifferentiated P19 stem cells expressed a basal level of the HES-1 gene, whereas the expression of this gene was increased upon induction of the cells to a neural cell lineage using retinoic acid (RA). Reporter co-transfection analysis identified an activating region within the upstream promoter region of HES-1 from nucleotides -201 to -172. This activating region, called activating region X (ARX), shows a high GC content and contains both an AP-2 binding motif and a CCAAT box. An electrophoretic mobility shift assay using nuclear proteins extracted from P19 cells showed that ARX forms a specific DNA-protein complex. Importantly, ARX-dependent transcription, as well as ARX-binding activity, was significantly increased in P19 cells treated with RA. These results indicate that ARX transduces signals that up-regulate HES-1 gene expression in response to RA-treatment. Thus, a novel cis-acting element involved in HES-1 gene regulation that plays a role in RA-induced neural differentiation of P19 cells has been identified.

Animals↗
PubMed2000

Roles of the AGE-RAGE system in vascular injury in diabetes.

This study concerns whether advanced glycation endproducts (AGE) are related to microvascular derangement in diabetes, exemplified by pericyte loss and angiogenesis in retinopathy and by mesangial expansion in nephropathy. AGE caused a decrease in viable pericytes cultivated from bovine retina. On the other hand, AGE stimulated the growth and tube formation of human microvascular endothelial cells (EC), this being mediated by autocrine vascular endothelial growth factor. In AGE-exposed rat mesangial cells, type IV collagen synthesis was induced. Those AGE actions were dependent on a cell surface receptor for AGE (RAGE), because they were abolished by RAGE antisense or ribozyme. The AGE-RAGE system may thus participate in the development of diabetic microangiopathy. This proposition was supported by experiments with animal models; several indices characteristic of retinopathy were correlated with circulating AGE levels in OLETF rats. The predisposition to nephropathy was augmented in RAGE transgenic mice when they became diabetic.

Animals↗
PubMed2000

Breast cancer: importance of spiculation in computer-aided detection.

PURPOSE: To determine the prevalence of spiculation in a large series of screening-detected breast cancers appearing as masses on mammograms and to assess the sensitivity of a computer-aided detection (CAD) algorithm that uses spiculation measures in the detection of such lesions. MATERIALS AND METHODS: Six hundred seventy-seven consecutive cases of breast cancers detected as masses on mammograms were independently reviewed by three radiologists who determined if the lesions were spiculated. All cancers were then analyzed by the CAD system. RESULTS: All three radiologists interpreted 375 (55%) of the 677 masses as being spiculated on at least one view. The CAD algorithm correctly marked 322 (86%) of the 375 clearly spiculated masses, with a mean of 0.24 additional mass mark per image. With a looser definition of spiculation, 585 (86%) of the 677 masses were called spiculated by at least one radiologist on one view. The algorithm correctly marked 464 (79%) of the 585 lesions that were spiculated or possibly spiculated. CONCLUSION: Spiculation was clearly present in a majority (55%) of consecutive screening-detected breast cancer masses found on mammograms in a large clinical trial. Incorporation of spiculation measures is, therefore, an important strategy in the detection of breast cancer with CAD. A present-generation CAD algorithm correctly identified a large proportion (86%) of spiculated breast cancers.

Algorithms↗
PubMed2000

Kamegainema cingulum (Linstow, 1902) n. gen., n. comb. (Nematoda: Dracunculidae), a subcutaneous parasite of cryptobranchids (Amphibia: Caudata).

The monotypic Kamegainema n. gen. is proposed for Filaria cingula, a subcutaneous parasite of cryptobranchids. Examination of female specimens recently collected from the Japanese giant salamander, Andrias japonicus, revealed that it belongs to Dracunculidae. Kamegainema is closest to Protenema Petter and Planelles, 1986, the only other dracunculid genus known from Amphibia, but is readily distinguished by having prominent cuticular bosses. Kamegainema cingulum is redescribed.

Animals↗
PubMed2000

[Pulse pressure and common carotid arterial wall thickness assessed by ultrasonography].

This study was conducted on a total of 358 normotensive (mean blood pressure < 107 mmHg) inpatients (182 men and 176 women, mean age: 67.8 years) who had no cardiorenal or nutrition disorders that would affect blood pressure, lipid and glucose metabolism and who had not been given depressors or antilipidemic agents during the four years from September 1995 to August 1999. In addition to the known risk factors for atherosclerosis, the effects of pulse pressure and mean blood pressure on sclerotic changes of the carotid arteries were examined. These sclerotic changes were assessed by measuring the thickness of the combined intima-media of the common carotid artery (carotid arterial wall thickness) by ultrasonography (Hitachi EUB-565) and linear probe (7.5 MHz). When the patients were divided into three groups based on pulse pressure (PP1, lower than 51 mmHg: PP2, 51-65 mmHg; PP3, higher than 65 mmHg), the age of the group with higher pulse pressure was significantly higher (p = 0.0011), women more (p = 0.0315). However there were no differences in background factors such as body mass index, Brinkman index, lipid metabolism, uric acid, and glucose metabolism. There was observed a positive correlation between the mean blood pressure and the pulse pressure for both men and women (r = 0.31, p < 0.001, respectively). As for the relation between the pulse pressures and the blood pressure parameters, the systolic blood pressure, pulse pressure and the mean blood pressure were significantly higher in the group with higher pulse pressure (p < 0.001, respectively), but the diastolic blood pressure was significantly lower (p = 0.0275). As for the relation between the pulse pressure and the carotid wall thickness, the groups of both men and women with higher pulse pressures had significantly greater carotid arterial wall thickness (p < 0.001, p = 0.0042, respectively). Logistic regression analysis of the carotid arterial wall thickness (defined as hypertrophic if greater than 1.0 mm) as the object variable and various risk factors including pulse pressure as the explanatory variables revealed that pulse pressure and LDL-C were significant independent contributing factors for men. The age, Brinkman index, T-Chol and HDL-C were significant independent contributing factors for women. For all subjects men, the age, Brinkman index, pulse pressure, TG and LDL-C were significant independent contributing factors. These facts suggest that pulse pressure is an important risk factor for thickening of the carotid arterial wall.

Adult↗
PubMed2000

[A study of mental health in community-dwelling older persons--influence of cared elderly].

This study aimed to evaluate mental health of elderly persons living in the community and understand the various backgrounds and effects of care giving. The study used a questionnaire from similar to the one used by Matsubayashi et al in the Kahoku-cho study. The Japanese Version of General Health Questionnaire 12 (GHQ-12) was used to evaluate mental health. Responses were received from 2,799 (81.5%) of 3,432 Numura-cho residents (81.5%). After removing inadequate responses, 1,268 (36.9%) (575 men and 693 women) were analyzed. Fifty-five men (9.6%) and 69 women (10.0%) were caring for someone at home. Multiple logistic regression analysis which examined the relation between mental health and the background factors such as having someone to care for, revealed that their mental health was significantly poor compared to those having no one to care for (odds ratio (OR) = 2.01, 95% confidence interval (CI), 1.29-3.15). As for the relation between the degree of care giving and their mental health, the subjective burden was significantly poor at 72-100% (OR = 3.40, 95% CI, 1.71-6.78) and for those with three to eight years of care-giving (OR = 2.22, 95% CI, 1.00-4.90), disabled activity of daily living (almost bed ridden) of the cared for person (OR = 5.53, 95% CI, 2.23-13.7), severely demented state (OR = 5.13, 95% CI, 2.14-12.3), their mental health was significantly poor. However, being able to participate in an event (OR = 0.12, 95% CI, 0.03-0.49) and strong emotional support (OR = 0.12, 95% CI, 0.03-0.49) were negatively associated with caregivers' psychiatric distress. Having someone to care for largely affected mental health of the elderly to subjects living in the community. Services should be devised to serve the needs such as psychological care of care-givers as well as those being cared for.

Activities of Daily Living↗
PubMed1999

Effects of TAK-637, a tachykinin receptor antagonist, on lower urinary tract function in the guinea pig.

The effects of TAK-637 ((aR,9R)-7-[3,5-bis(trifluoromethyl)benzyl]-8, 9,10,11-tetrahydro-9-methyl-5-(4-methylphenyl)-7H-[1,4]diazocino[2 , 1-g][1,7]naphthyridine-6,13-dione), a novel tachykinin NK(1) receptor antagonist, on the micturition reflex in guinea pigs were studied in comparison with those of anti-pollakiuria agents. Cystometry was performed under urethane anesthesia. TAK-637 increased the volume threshold with a minimum effective dose of 0.03 mg/kg, i.v. without affecting voiding pressure. Oxybutynin, tolterodine, propiverine and inaperisone also increased the volume threshold in urethane-anesthetized guinea pigs, but they decreased voiding pressure, although the effect of propiverine was not statistically significant. A structurally unique tachykinin NK(1) receptor antagonist, (+/-)-CP-99,994 ((+/-)-(2S, 3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine), increased the volume threshold with a minimum effective dose of 0.3 mg/kg, i.v. TAK-637 increased the volume threshold with a minimum effective dose of 0.01 mg/kg, p.o. in unanesthetized guinea pigs. These results indicate that TAK-637 may be useful as pharmacotherapy for detrusor overactivity without decreasing voiding pressure or causing voiding difficulties.

Animals↗