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Biomedical subjects

T Shibata

Publications and source records attributed to T Shibata.

At least 325 records · Page 18Linked to original sources

Identification of human cadherin-14, a novel neurally specific type II cadherin, by protein interaction cloning.

Cadherins, a family of Ca2+-dependent cell-cell adhesion molecules, mediate neural cell-cell interactions and may play important roles in neural development. By searching for molecules that interact with beta-catenin, a cytoplasmic regulator of cadherins, we have identified a new member of the cadherin family, which we named human cadherin-14. Cadherin-14 had high amino acid sequence homology with the type II subgroup of cadherins and was broadly expressed in the central nervous system. Cadherin-14 is a novel neurally specific cell-cell adhesion molecule and may regulate neural morphogenesis.

Amino Acid Sequence↗

Differences in behavior among the chlorides of seven rare earth elements administered intravenously to rats.

Differences in behavior among the chlorides of seven rare earth elements (REEs)-yttrium (Y), cerium (Ce), and praseodymium (Pr) (light REEs); europium (Eu) and dysprosium (Dy) (medium REEs); ytterbium (Yb) and lutetium (Lu) (heavy REEs)-were investigated through intravenous administration of the REEs to rats. (1) Distributions of REEs and mineral concentrations in the organs on Day 1 were investigated at low and high doses (9-10 and 18-20 mg REE/kg, or 56-66 and 112-132 mumol REE/kg). More than 78% of the REEs administered was distributed into liver, bone, and spleen. High doses of Y, Eu, and Dy markedly increased the accumulation of REEs in spleen and lungs as well as the concentration of Ca in liver, spleen, and lungs. (2) The distribution patterns of REEs and changes in Ca concentrations in major organs over time were investigated by the administration of Pr, Eu, Dy, Yb (low dose), and Y (high dose). REEs disappeared from the blood within 1 day but were retained in the organs for a long time. The percentages of the doses of Y, Eu, Dy, and Yb found in the liver were highest at 8 hr to 2 days, then decreased gradually; hepatic Pr levels, however, remained high. Changes in Ca concentrations in liver, spleen, and lungs were in accordance with those of REEs. (3) Severe hepatotoxicity was observed after administration of Ce and Pr; fatty liver, jaundice, and elevated serum GOT and GPT levels were most prominent on Day 3. Therefore, we hypothesized that REE chlorides might be categorized into three groups according to their ionic radii (light REEs, Y and medium REEs, and heavy REEs) and from their behavior, i.e., distribution pattern, Ca-accumulating action, and hepatotoxicity.

Alanine Transaminase↗

Visual evoked potentials relating to imagery: words for concrete objects versus absolute concepts.

We recorded visual evoked potentials (VEPs) elicited with high or low imaginable Chinese characters (HIC or LIC), representing concrete objects or absolute concepts, respectively. A closed circle (CC) acts as control stimulus. These were displayed (at 1.6 degrees visual angle) for 35 ms on a TV monitor. Twenty-one channel VEPs (band-pas filter: 0.05-60 Hz), using balanced non-cephalic electrodes, were recorded from -100 to 924 ms for 11 right-handed male volunteers. The VEPs were analyzed by multivariate analysis of variance (MANOVA) and comparison of topographies at four remarkable peaks (P110, N160, P230 and N320). MANOVA showed significant differences (p < 0.001) for both conditions of channel and stimuli (HIC, LIC or CC). P100 for the CC-VEPs, N160 for the HIC- and LIC-VEPs, P230 for the CC-VEPs, and N320 for the HIC-VEPs were remarkable in the posterior scalp regions. Topographies at P100 and N160 showed no difference between the HIC- and LIC-stimuli. However, those at N320 showed difference between the HIC- and LIC-stimuli over the occipital and posterior temporal areas. Those results suggest that the responses at P100 and N160 might segregate Chinese characters from non Chinese characters. N320 suggested certain processes in imagery on recognizing Chinese characters over the occipital and posterior temporal areas.

Adult↗

A randomized study comparing VMCP and MMPP in the treatment of multiple myeloma.

PURPOSE: To compare VMCP, a multidrug combination chemotherapy comprising vincristine (VCR), melphalan (MPH), cyclophosphamide (CPM) and prednisolone (PSL), with MMPP comprising MPH, ranimustine (MCNU), procarbazine, and PSL as induction, to elucidate the value of alternating combination chemotherapy, and to search for an appropriate maintenance therapy in multiple myeloma. METHODS: At 16 institutions in the Nagoya City area, we carried out a randomized trial of VMCP versus MMPP as the initial treatment. Patients who were refractory or resistant to the initial therapy were crossed over into the other arm (crossover trial). For patients who achieved a partial response (PR) or a minor response (MR) and in whom the paraprotein level ceased to decrease, the maintenance therapy was randomized either to an MPH/PSL combination (MP) or to alternating combination therapy (AT) with VMCP and MMPP. RESULTS: In the 94 evaluable patients of the 111 enrolled, the response rate (PR rate) was 27.7% (13/47) in the VMCP arm and 44.7% (21/47) in the MMPP arm (P = 0.0859). The crossover trial resulted in a PR rate of 15.8% (3/19) for the VMCP-->MMPP crossover and 14.3% (2/14) for the MMPP-->VMCP crossover. The median survival time was 23.4 months for those initially begun in the VMCP arm and 24.9 months for those in the MMPP arm, showing a tendency for better survival during a follow-up of 2-6 years with MMPP treatment, but without statistical significance. The survival time of patients with progressive disease was significantly shorter than that of patients with PR, MR or no change (NC). However, there was no significant difference in the survival rate among those who achieved PR, MR, or NC. As to the maintenance therapy, there was no significant difference in survival between MP therapy and AT. Patients who reached a plateau phase survived significantly longer than those who did not. Except for six cases of grade 3 or 4 neurotoxicity in the VMCP arm, there was no significant difference in the hematologic or gastrointestinal toxicity between the two arms. CONCLUSIONS: We conclude that VMCP is less effective for myeloma than MMPP as the induction treatment, that alternating noncrossresistant chemotherapeutic combinations do not offer an advantage in multiple myeloma, and that patients who reach a plateau phase have a significantly longer survival time.

Adult↗

An experimental study of the removal of cemented dowel-retained cast cores by ultrasonic vibration.

A technique for the removal of cemented post-cores by means of ultrasonic vibration was studied clinically and histologically. The removal time was measured for 80 extracted human teeth, including 40 single-rooted teeth and 40 multiple rooted ones and then statistically analyzed. The periapical tissue reaction to the ultrasonic vibration was also examined histologically in dogs. The best result was achieved when lateral vibration was simultaneously given by 2 removal tips using 2 ultrasonic generators. There was little harmful influence on the periodontal tissue, excluding a transient reversible reaction.

Animals↗

Structure and functional expression of the cloned mouse neuronal high-affinity glutamate transporter.

A cDNA encoding a neuron-specific glutamate transporter was isolated from mouse cerebellum and characterized. Expression of this cDNA in HEK293 cells induced high-affinity uptake of L-glutamate that was dependent on external Na+. The deduced amino-acid sequence of the cDNA shares 96% identity with its human homologue. Northern blot analysis of mouse tissues revealed that the mRNA of this transporter is specific to the brain. In situ hybridization in mouse brain sections showed that the mRNA is expressed densely and selectively in cell bodies of Purkinje cells.

ATP-Binding Cassette Transporters↗

In staphylococcus enterotoxin B (SEB)-stimulated human PBMC, the LAK activity of non-T cells might have a major role in the mechanism of glomerular endothelial cells' injury.

In this study the SEB-activated LAK cytotoxicity was identified and characterized in human peripheral blood lymphocytes (PBMC). After 3 days of SEB stimulation, the PBMC acquired a cytotoxicity against traditional LAK targets, K-562 and Daudi, beside that human glomerular endothelial cells (HGEC) were effectively lysed. The magnetic separation of SEB-stimulated CD5+ T cells revealed that the dominant LAK cytotoxicity remained in the CD5- lymphocyte fraction. The major part of the SEB-generated cytotoxicity of CD5- cells could be blocked with specific antibodies to IL-2 and IFN-gamma. The IFN-gamma pretreatment of HGEC reduced the target sensitivity, but because of the upregulation of MHC class II on HGEC surface, these cells were able to present SEB to CD5+ cells. These results suggested that in bacterial superantigen-mediated infection, the non-T (NK cells-derived) LAK cells might have a primary pathogenic role, and the adverse effect of IFN-gamma, that was massively secreted from superantigen-stimulated cells, requires greater consideration.

Antibodies↗

Interleukin 1 beta and stromelysin (MMP3) activity of synovial fluid as possible markers of osteoarthritis in the temporomandibular joint.

PURPOSE: This study investigated the early signs of synovitis and cartilage degradation by means of synovial fluid analysis in temporomandibular joints (TMJs) with internal derangement (closed lock) or osteoarthritis (OA). PATIENTS AND METHODS: Synovial fluid was obtained from 25 TMJs in 22 patients diagnosed with closed lock and from 15 asymptomatic TMJs of 12 normal controls. IL-1 beta concentrations were measured using enzyme-linked immunosorbent assay (ELISA), and proteinase activity was detected by means of gelatin enzymography. RESULTS: Nine of the 25 TMJs with closed lock (CL group) exhibited osteolytic changes on the surface of the condyle. TMJs in the normal control group did not show any bony changes. Mean IL-1 beta concentration in the synovial fluid (SF) protein in the CL group was 330.1 +/- 347.7 pg per 100 micrograms protein, which was significantly higher than in the normal control (76.7 +/- 95.3 pg/100 micrograms SF-protein). Synovial fluid from the TMJs with osteolytic changes contained higher levels of IL-1 beta (531.8 +/- 379.6 pg/100 micrograms SF-protein) than those without bony changes (216.7 +/- 280.1 pg/100 micrograms SF-protein). Matrix metalloproteinase (MMP) activity with a molecular weight of 50 kd (stromelysin or MMP3) was detected in a highly augmented form in two synovial fluid samples of seven closed lock patients. CONCLUSION: The results suggest that IL-1 beta levels in synovial fluid of the TMJ have a positive correlation with OA change. The MMP3 activity detected was greatly increased in patients with cartilage degradation. These findings suggest that both changes may be important markers of early bone deterioration in TMJs that are undetectable by radiograph imaging.

Adolescent↗

Protection by diphenyliodonium against glutamate neurotoxicity due to blocking of N-methyl-D-aspartate receptors.

The protective effect of diphenyliodonium, known as an inhibitor of flavin enzymes including nitric oxide synthases, was examined against the neurotoxicity of excitatory amino acids on cultured spinal neurons of the rat. Diphenyliodonium reduced the neuronal damage induced by 15-min exposure to glutamate or N-methyl-D-aspartate in a dose-dependent manner; half effective concentrations (EC50) were about 3 microM for both. Protection was only observed when diphenyliodonium was added into the exposure medium. Diphenyliodonium showed no effect on the toxicity induced by 24 h exposure to non-N-methyl-D-aspartate receptor agonists. Using a microfluorometry technique with Fura 2, we observed that diphenyliodonium reversibly inhibited the N-methyl-D-aspartate-evoked intracellular Ca2+ elevation. The amount of 45Ca2+ influx induced by N-methyl-D-aspartate was also inhibited by diphenyliodonium in a dose-dependent manner; EC50 was about 3 microM. Furthermore, we examined the effect of diphenyliodonium on an opening activity of the N-methyl-D-aspartate receptors estimated by binding of dizocilpine maleate to membrane fractions from whole brain of adult rat and from cultured spinal neurons. Diphenyliodonium inhibited the binding of dizocilpine maleate dose-dependently; EC50 was 5-8 microM. These results suggest that diphenyliodonium is a new antagonist to the N-methyl-D-aspartate receptors and that diphenyliodonium protects neurons against glutamate toxicity due to a direct blocking of the Ca2+ influx. This conclusion is supported by the similarity of the stereochemical structures predicted by computer between diphenyliodonium and dizocilpine maleate.

Animals↗

Unexpected nerve gas exposure in the city of Matsumoto: report of rescue activity in the first sarin gas terrorism.

This report describes the rescue activities and the exposure of rescue and hospital personnel from the first unexpected nerve gas terrorist attack using sarin (isopropyl methylphophonofluoridate) in the city of Matsumoto at midnight on June 27, 1994. The details of the emergency activities in the disaster were studied based on the records from emergency departments of the affiliated hospitals and records from the firehouse. About 600 people, including residents and rescue staff, were exposed to sarin gas. Fifty-eight residents were admitted to hospitals, and 7 died. Among 95 rescuers and the duty doctor from the doctor car, 8 had mild symptoms of poisoning. All the rescue activity took place without gas masks or decontamination procedures. In this case of unexpected mass exposure to sarin gas, the emergency rescue system for a large disaster in Matsumoto city, which had been established for a conflagration or a local earthquake, was effective.

Humans↗

Detection of Helicobacter pylori in biopsy of patients with gastric carcinoma.

Superficial chronic gastritis caused by Helicobacter pylori may lead potentially to the development of atrophic gastritis, a precursor of gastric carcinoma. Based on histological studies, the prevalence of Helicobacter pylori infection in gastric cancer patients, has been reported to vary widely from 38% to 100%. This positivity rate tends to be higher in patients with gastric cancer in early stage than in those with advanced malignant disease, probably, due to the relative mild atrophic and intestinal metaplastic changes of the surrounding gastric mucosa that occur in the former group. The prevalence of Helicobacter pylori infection is not related to the anatomical localization of cancer in the stomach. The inclusion of cases in advanced stages of disease and the examination of a few small-sized number of gastric specimens may explain the discrepant findings reported so far regarding the prevalence of Helicobacter pylori infection in patients with gastric cancer. We found a strong association between Helicobacter pylori infection and the occurrence of gastric carcinoma. Therefore, Helicobacter pylori may be an important carcinogenetic factor for the occurrence of malignant disease in the stomach. Cure of Helicobacter pylori infection may potentially reduce the incidence of gastric cancer.

Biopsy↗

Magnesium lithospermate B ameliorates cephaloridine-induced renal injury.

To determine whether magnesium lithospermate B ameliorates renal injury induced by cephaloridine, the effect of cephaloridine was investigated in rats given magnesium lithospermate B for 20 days preceding cephaloridine administration and in control rats given no magnesium lithospermate B. In the control rats, blood and urinary parameters and the activity of radical-eliminating enzymes in the renal tissue deviated from the normal range, indicating damage to the kidneys. In contrast, rats given magnesium lithospermate B showed decreased urine volume, increased urinary osmotic pressure, and decreased urinary levels of glucose, protein, sodium and potassium, denoting less damage to the kidney. In this group, the urinary nitrite/nitrate ratio, and the activities of superoxide dismutase and catalase in the renal tissue were increased, while the malondialdehyde levels were decreased, suggesting the involvement of radicals in the normalizing of kidney function. The increased levels of urea nitrogen in the blood of rats with induced renal failure were also lowered by administering magnesium lithospermate B.

Animals↗

Effects of protease inhibitors on postischemic recovery of the heart.

It is well known that activation of proteases in the lysosomes and cytosol is one of the mechanisms of ischemic injury. It might thus be beneficial to determine whether the addition of several clinically available protease inhibitors to a cardioplegic solution can improve its protective ability. Using an isolated working rat heart preparation, the effects of several protease inhibitors (serine protease inhibitors; nafamostat mesilate and gabexate mesilate, a thiol-protease inhibitor; NCO-700; and a urinary trypsin inhibitor, urinastatin) on the postischemic recovery of function and enzyme leakage were investigated in this study. These protease inhibitors were added to either the cardioplegic solution or reperfusion solution. The addition of each of the protease inhibitors, except urinastatin, to the cardioplegic solution improved the postischemic recovery of function and reduced enzyme leakage. The dose-response characteristics of these three protease inhibitors were bell shaped, and the optimal concentrations of nafamostat mesilate, gabexate mesilate, and NCO-700 were 5 microM, 100 microM, and 20 microM, respectively. In contrast to the results of the preischemic treatment study, the addition of any of the protease inhibitors to the perfusion medium during Langendorff reperfusion failed to improve the postischemic recovery of function and to reduce enzyme leakage. Surprisingly, the addition of NCO-700 to the reperfusion solution at a concentration of 5 microM or higher had rather harmful effects on both functional recovery and enzyme leakage. These findings suggest that serine and thiol proteases may play an important role in myocardial injury during ischemia, but not necessarily during reperfusion.

Animals↗

Conditioning with cyclophosphamide/antithymocyte globulin for allogeneic bone marrow transplantation from HLA-matched siblings in children with severe aplastic anemia.

Graft rejection has been a problem after bone marrow transplantation for patients with severe aplastic anemia (SAA). Ten children with SAA were conditioned for bone marrow transplantation from HLA-identical siblings, using cyclophosphamide (CY, 50 mg/kg) plus antithymocyte globulin (ATG, 15 mg/kg) for 4 successive days. Marrow was infused 36 h after the last dose of CY. Cyclosporin A and methotrexate were administered as graft-versus-host disease (GVHD) prophylaxis. All patients achieved durable engraftment at follow-up of 7-41+ months (mean, 25) without significant GVHD. Since investigators have used different sources, doses, and time schedules of ATG, we compared our results with other published reports. We conclude that CY/ATG conditioning is well tolerated and effective in children with SAA.

Adolescent↗

Immunohistochemical analysis of heme oxygenase-I in rat liver after ischemia.

Total hepatic ischemia was induced by clamping the hepatic artery, portal vein, and bile duct. After 15 min hepatic ischemia, we examined a time course of the changes in the steady-state levels of heme oxygenase-1 (HO-1) mRNA and protein in the livers. The levels of HO-1 mRNA was transiently induced and peaked at 4 h after the start of reperfusion. In addition, a pattern of the time course of HO-1 protein levels was similar to that of HO-1 mRNA levels. Immunohistochemical analysis clearly showed that the localization of HO-1 protein induced by hepatic ischemia was restricted to the hepatocytes in the pericentral vein.

Animals↗

Topographic comparison of subneural apparatuses at neuromuscular junctions in normal and dystrophic (mdx) mice: a scanning electron microscope study.

The differences in the morphodifferentiation of subneural apparatuses (SNAs) at neuromuscular junctions (NMJs) in the extensor digitorum longus muscle of normal and dystrophic (mdx) mice were examined by scanning electron microscopy. In normal mice, primitive shallow cup-like synaptic troughs present at birth had developed to anastomosing grooves containing both pit-like and slit-like junctional folds (JFs) during the 2nd postnatal week. At the 35th day, the SNAs had developed to almost the adult forms, consisting of labyrinthine synaptic grooves with exclusively slit-like JFs. In the mdx mice, the SNAs showed transformation similar to those in the normal mice until the 35th postnatal day. After this period, SNAs with a number of cup-like depressions occurred and increased in number. These morphological changes seemed to be found on regenerating muscle fibers after necrosis, probably indicating the remodelling of their NMJs.

Animals↗