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Biomedical subjects

T Inoue

Publications and source records attributed to T Inoue.

At least 127 records · Page 7Linked to original sources
PubMed2000

[Antiarrhythmic effects of pilsicainide hydrochloride and effects on cardiac function and ECG in dogs: comparison with disopyramide].

Antiarrhythmic effects and cardiovascular effects of pilsicainide hydrochloride were compared with those of disopyramide in a canine model of coronary ligation-induced ventricular arrhythmias and anesthetized dogs. Pilsicainide (1.25, 2.5 and 5 mg/kg) and disopyramide (2.5 and 5 mg/kg) decreased the arrhythmic ratio ¿(ventricular arrhythmias/total heart rate) x 100¿ dose-dependently. Pilsicainide at 2.5 and 5 mg/kg and disopyramide at 5 mg/kg suppressed ventricular arrhythmias more than 50%. The effective dose of pilsicainide was lower than that of disopyramide, but the effective plasma concentration of pilsicainide was between 3 and 8 micrograms/ml, which was almost the same as that of disopyramide. In anesthetized dogs, both drugs decreased LV dP/dt max in almost the same concentration-dependent manner. PQ-interval was prolonged by pilsicainide, but not by disopyramide. QRS and QTc were prolonged by both drugs in a concentration-dependent manner. However, the prolongation of QTc by disopyramide was provoked at lower plasma concentrations than by pilsicainide. Because the excessive prolongation of QTc lead to the lethal arrhythmias such as torsades de pointes, pilsicainide may be useful as an injectable antiarrhythmic agent superior to disopyramide.

Anesthesia↗
PubMed2000

Cloning and characterization of a gene complementing the mutation of an ethanol-sensitive mutant of sake yeast.

Ethanol-sensitive mutants (esl to es10) were isolated from sake yeast, Saccharomyces cerevisiae SY-32. These mutants were unable to grow at 7% ethanol at which the wild type strain SY-32 does grow. The mutants had a variety of fermentation rates and viabilities in the presence of ethanol. The gene ERG6, complementing the ethanol-sensitive mutation of es5, was cloned from an SY-32 gene library. ERG6 encodes S-adenosylmethionine: delta 24-sterol-C-methyltransferase (EC 2.1.1.41) in the ergosterol synthetic pathway. Mutant es5 had a reduced ability to synthesize ergosterol. An erg6 disruptant was also ethanol-sensitive. These results suggested that ERG6 plays an important role in the ethanol tolerance of S. cerevisiae.

Cloning, Molecular↗
PubMed2000

Monoclonal antibody against bovine alpha1-acid glycoprotein.

Monoclonal antibodies (Mabs) against bovine alpha1-acid glycoprotein (alpha1AGP) were prepared from mouse hybridoma cell line. Bovine alpha1AGP as antigen was purified by using ion exchange column chromatography and the yield from 500 ml serum was about 10 mg. Immunoglobulin isotypes of 3 Mabs obtained were IgM and light chain types were kappa. The Mabs reacted with bovine alpha1AGP on immunoblot analysis, but not with alpha1AGP digested with N-glycosidase, suggesting that an epitope recognized by these Mabs may be associated with a glycan side chain of bovine alpha1AGP.

Amidohydrolases↗
PubMed2000

Expression of porcine interleukin-2 in Escherichia coli.

A mature form of porcine interleukin-2 (IL-2) protein without signal peptides was expressed as glutathione S-transferase (GST) fusion proteins in Escherichia coli using pGEX vector. Since most of GST-IL-2 fusion protein was detected in an insoluble fraction on SDS-PAGE analysis, the insoluble fusion protein was solubilized by refolding procedure using urea. The recombinant IL-2 (rIL-2) was purified by a batch method using Glutathione Sepharose 4B and factor Xa digestion and used for preparation of antisera in mice. The antisera reacted with rIL-2 expressed in baculovirus system on immunoblot analysis. In addition, the purified rIL-2 showed a high biological activity on CTLL-2 proliferative response.

Animals↗
PubMed2000

Cloning and expression of the M5 RNA segment encoding outer capsid VP5 of epizootic hemorrhagic disease virus Japan serotype 2, Ibaraki virus.

The complete nucleotide sequence of a cDNA clone representing the M5 RNA segment of epizootic hemorrhagic disease virus Japan serotype 2 (EHDV-2), Ibaraki virus, was determined. The M5 segment is 1641 base pairs long with the single open reading frame which predicts a polypeptide of 527 amino acids. The comparison of the amino acid sequence of the VP5 with those of EHDV-1, bluetongue virus serotype 10, and African horse sickness virus serotype 4 revealed that the protein shared 67%, 57% and 42% homologies, respectively. In addition, the VP5 protein was expressed in insect cells by recombinant baculovirus, which could be recognized by the mouse anti-EHDV-2 sera at a position of the expected 59 kDa on immunoblot analysis.

Amino Acid Sequence↗
PubMed2000

The complete nucleotide sequence of segment L2 of Ibaraki virus encoding for the antigen recognized by neutralizing antibodies.

The complete nucleotide sequence of cDNA clones representing the L2 dsRNA from Japan isolate of epizootic hemorrhagic disease serotype 2 (EHDV-2JPN) was determined. The EHDV-2JPN L2 gene is 3002 base pairs long with a single open reading frame of 2949 bp which predicts a polypeptide of 982 amino acid residues. Comparison of VP2 sequence between Japan and North American Isolates of EHDV-2 showed a 72% homology in spite of the same serotype, although those among the North American isolates showed a high genetic identity (>97%).

Animals↗
PubMed2000

Glucose metabolic analysis of musculoskeletal tumours using 18fluorine-FDG PET as an aid to preoperative planning.

We performed positron emission tomography (PET) with 18 fluorine-fluoro-2-deoxy-D-glucose (FDG) on 55 patients with tumours involving the musculoskeletal system in order to evaluate its role in operative planning. The standardised uptake value (SUV) of FDG was calculated and, to distinguish malignancies from benign lesions, the cases were divided into high (> or =1.9) and low (< 1.9) SUV groups. The sensitivity of PET for correctly diagnosing malignancy was 100% with a specificity of 76.9% and an overall accuracy of 83.0%. The mean SUV for metastatic lesions was twice that for primary sarcomas (p < 0.0015). Our results suggest that the SUV may be useful in differentiating malignant tumours from benign lesions. However, some of the latter, such as schwannomas, had high SUVs so that biopsy or wide resection was selected as the first operation. Thus, some other quantitative analysis may be required for preoperative planning in cases of high-SUV neurogenic benign tumours. The reverse transcription-polymerase chain reaction revealed that the RNA message of a key enzyme in glucose metabolism, phosphohexose isomerase (PHI)/autocrine motility factor, was augmented in only high FDG-uptake lesions, suggesting that a high expression of the PHI message may be associated with accumulation of FDG in musculoskeletal tumours.

Adolescent↗
PubMed2000

Prediction of functional recovery after revascularization in coronary artery disease using (18)F-FDG and (123)I-BMIPP SPECT.

STUDY OBJECTIVES: Clinical studies comparing fatty acid and glucose metabolism in relation to functional recovery of ischemic myocardium after coronary revascularization are scarce. This study evaluated the recovery of regional and global left ventricular function after coronary revascularization in relation to uptake patterns of beta-methyl-iodophenyl-pentadecanoic acid (BMIPP) and fluorodeoxyglucose (FDG) in patients with ischemic myocardial dysfunction. METHODS: Patients with ischemic regional wall motion abnormality underwent baseline viability imaging with (18)F-FDG, (123)I-BMIPP, and (99m)Tc- methoxyisobutylisonitrile, and the regions with evidence for maintained tissue viability were revascularized. Mismatch of uptake score between two different single-photon emission CT (SPECT) images in the same myocardial region was graded as low or high mismatch. Regional and global left ventricular functional changes after revascularization were analyzed in relation to mismatch severity and difference of total uptake score in each SPECT image pair. A total of 33 vessels in 30 patients related to the asynergic regions were revascularized, and a total of 100 myocardial segments perfused by the revascularized vessels were analyzed. RESULTS: Segments showing high metabolic mismatch (FDG/BMIPP) had lowest regional wall motion score at baseline, representing the most severely impaired ischemic myocardium, and had highest improvement in regional wall motion score after revascularization. Difference of total uptake score between FDG and BMIPP showed a significant positive correlation with difference of ejection fraction between pre- and postrevascularization (r = 0.774, p < 0.0001). CONCLUSIONS: Combined metabolic SPECT imaging with FDG and BMIPP has the potential to identify severely impaired ischemic myocardium leading to more efficient therapeutic management of patients with coronary artery disease.

Aged↗
PubMed2000

Extended activity in cynomolgus monkeys of a granulocyte colony-stimulating factor mutein conjugated with high molecular weight polyethylene glycol.

The activity of a granulocyte colony-stimulating factor (G-CSF) mutein (nartograstim; [NTG]) conjugated with an average of two polyethylene glycol (PEG) chains per protein molecule was examined in cynomolgus monkeys following a single s.c. injection. Groups of monkeys were given 10 microg/kg, 30 microg/kg, or 100 microg/kg. For comparison, one group of monkeys was given 5 microg/kg of recombinant human G-CSF (rHuG-CSF) daily for six days. In monkeys given 100 microg/kg of PEG-NTG, neutrophil levels reached a peak one day after injection approximately 20-fold higher than baseline levels. Neutrophil numbers in these animals were still significantly elevated six days after injection. In contrast, peak neutrophil levels in monkeys given six injections of rHuG-CSF reached a peak only on day 6 and were approximately the same as that in monkeys given a single dose of PEG-NTG six days before. Pharmacokinetics of PEG-NTG in these monkeys indicated that the area under the plasma concentration time curve (AUC) increased with increasing the dose from 497 ng x h/ml at 10 microg/kg, 6,140 ng x h/ml at 30 microg/kg to 27,900 ng x h/ml at 100 microg/kg. In a separate study, the effects of single doses of 100 microg/kg of PEG-NTG, rHuG-CSF, and unmodified NTG were compared. In this experiment, peak numbers of neutrophils were reached two days after injection in animals receiving PEG-NTG and one day after in animals given unmodified proteins. The pharmacokinetic parameters demonstrated increased exposure for PEG-NTG relative to the unmodified proteins with an AUC0. of 21,012 ng x h/ml compared with 5,492 ng x h/ml for rHuG-CSF and 5,153 ng x h/ml for NTG. These results demonstrate that conjugation of a G-CSF mutein with high molecular weight PEG results in a preparation that can induce prolonged elevation of neutrophils in normal nonhuman primates following a single injection.

Animals↗
PubMed2000

Ultrastructural and immunoelectron microscopic studies of the peri-implant epithelium-implant (Ti-6Al-4V) interface of rat maxilla.

BACKGROUND: The role played by the internal basal lamina (IBL) and hemidesmosomes between an implant and the peri-implant epithelium (PIE) in the adherence of the epithelium to the implant is controversial. This study used rat maxilla implantation models to clarify the ultrastructure of the PIE-implant interface. METHODS: Ti-6Al-4V implants were inserted either immediately or 2 weeks after the extraction of the upper left first molar of 6- or 4-week-old rats, respectively. The junctional epithelium (JE) of the upper right molars in the same animals was used as a control. Four weeks after implantation, the animals were sacrificed to prepare specimens for light and immunoelectron microscopy. RESULTS: Under light microscopy, the PIE appeared to attach to the implant surface. Ultrastructurally, IBL, consisting of the lamina densa and lamina lucida, and hemidesmosomes were formed only in the lower region, and rarely in the middle region, of the PIE-implant interface. In control teeth, the IBL and hemidesmosomes formed throughout the dento-JE interface. Laminin-1 was found in the IBL and also in the vesicles and vacuoles of the PIE and JE cells. Statistical analysis showed that there was also a significant difference in the amount of IBL between the PIE-implant and dento-JE interfaces. CONCLUSIONS: PIE attached to the implant via hemidesmosomes and IBL in the lower region of the PIE-implant interface. Although PIE cells may secrete laminin-1, which contributes to epidermal cell adhesion, the PIE which attaches to implants only in the lower region of the interface is considered to be the poorly adhered epithelium.

Alloys↗
PubMed2000

Effects of an agent inducing dominant lethals on rat sperm--examination with ethyl methanesulfonate.

Ethyl methanesulfonate (EMS), an alkylating agent which induces dominant lethals, was administered in oral doses of 100 mg/kg to Crj:CD(SD)IGS male rats for 5 consecutive days. At the termination of treatment and after a 28-day withdrawal, mating with untreated females and sperm analysis (motion, number, and morphology) were performed. The copulated females were sacrificed at 20 days of gestation. At the termination of treatment, no clinical signs related to EMS were observed except for a decrease in body weight. Gross pathology and sperm analysis revealed no abnormalities in treated males. However, females mated at the termination of treatment had a clearly higher fetal mortality. Females mated after the 28-day withdrawal exhibited lower fetal mortality than females mated at the termination of treatment. On the other hand, females mated after the 28-day withdrawal exhibited a lower implantation rate that was not observed in females mated at the termination of treatment. For males after a 28-day withdrawal, sperm analysis revealed both a decrease in sperm motion and number and an increase in morphological change. These findings indicate that two types of male reproductive toxicity induced by EMS can be distinguished. One induces a low implantation rate that can be detected by sperm analysis, while the other induces fetal lethals that could not be detected by sperm analysis in this study.

Animals↗
PubMed2000

Aromatic retinoid Ro 40-8757 reduces immunotoxicities of cyclophosphamide as revealed by immunohistochemical staining of lymphoid tissues and general pathologic examinations.

The aromatic retinoid (arotinoid) Ro 40-8757 (4-[2-[p-(E)-2-(5,6,7,8-Tetrahydro-5,5,8,8-tetramethyl-2-naphthyl) propenyl]phenoxy]ethyl]-morpholine), a compound with antitumor activities, has been studied in a combination therapy with the cytostatic antitumor drug cyclophosphamide (CPA), and was found to protect bone marrow from the toxic effects of CPA. To evaluate its protective effects against CPA toxicities on lymphoid systems, we treated BDF1 mice with Ro 40-8757 orally for 1 to 5 weeks in combination with CPA intraperitoneally. After the combination treatment, mice were subjected to immunohistochemical analysis with antibodies against cell surface markers (Thy 1.2, Lyt-2, L3T4, Kappa chain, and Ia) and, in addition, general pathologic examinations were done. The protective effects of Ro 40-8757 on CPA toxicities were observed. The lymphocyte reductions (both in T cells and B cells) in lymphoid organs by CPA were apparently less severe. In particular, recovery of immature T cells in the thymic cortex was greater in combination treatment with Ro 40-8757 and CPA than in treatment with CPA alone. From these results, it can be concluded that Ro 40-8757 protects the lymphoid organs (thymus, spleen, and lymph node) from the immunotoxicity of CPA, and the protective effect is evident, especially in the thymic cortical lymphocytes.

Animals↗
PubMed2000

Primary thumb sensory cortex located at the lateral shoulder of the inverted omega-shape on the axial images of the central sulcus.

Useful landmarks on magnetic resonance (MR) images were identified for preoperative prediction of the relationship of a tumor to the primary sensory cortex of the thumb. Functional MR (fMR) imaging and magnetoencephalography were used to retrospectively localize the hand-digit sensorimotor area in four patients who underwent tumor resection around the central sulcus with intraoperative neurophysiological mapping. fMR imaging revealed the hand-digit motor cortex in the so-called "precentral knob" inside the characteristic inverted-omega on axial MR images. Equivalent current dipoles of the N20 m response in somatosensory evoked fields (SEFs) of the thumb, median nerve, and ulnar nerve stimuli were localized at the lateral portion of the inverted omega-shape from the lateral to medial directions. The SEF-based thumb sensory cortex was verified by intraoperative functional mapping with a neuronavigation system. The hand-digit somatosensory cortices were localized at the lateral shoulder of the inverted-omega, in the lateral anterior inferior position to the hand-digit motor cortices in the precentral knob. Axial MR imaging can provide useful preoperative planning information for the surgical treatment of tumors within or adjacent to the motor-somatosensory cortex.

Adult↗
PubMed2000

Brain-derived neurotrophic factor regulates glucose metabolism by modulating energy balance in diabetic mice.

We previously reported that brain-derived neurotrophic factor (BDNF) regulates both food intake and blood glucose metabolism in rodent obese diabetic models such as C57BL/KsJ-lepr(db)/lepr(db) (db/db) mice. To elucidate the effect of BDNF on glucose metabolism, we designed a novel pellet pair-feeding apparatus to eliminate the effect of appetite alteration on glucose metabolism. The apparatus was used to synchronize food intake precisely between BDNF-treated and vehicle-treated db/db mice. It was shown using this pellet pair-feeding apparatus that BDNF administered daily (20 mg x kg(-1) x day(-1)) to db/db mice significantly lowered blood glucose compared with pellet pair-fed db/db mice. To evaluate the effect of BDNF on insulin action, we used streptozotocin-induced type 1 diabetic mice. In this case, BDNF did not lower blood glucose concentration but rather enhanced the hypoglycemic action of insulin. In hyperglycemic db/db mice, pancreatic insulin content was reduced and glucagon content was increased compared with normoglycemic db/m mice. BDNF administered to db/db mice significantly restored both pancreatic insulin and glucagon content. Histological observations of aldehyde-fuchsin staining and immunostaining with anti-insulin indicated that insulin-positive pancreatic beta-cells were extensively regranulated by BDNF administration. We also studied the effect of BDNF on KK mice, normoglycemic animals with impaired glucose tolerance. In these mice, BDNF administration improved insulin resistance in the oral glucose tolerance test. To elucidate how blood glucose was metabolized in BDNF-treated animals, we investigated the effect of BDNF on the energy metabolism of db/db mice. Body temperature and oxygen consumption of the pellet pair-fed vehicle-treated mice were remarkably lower than the ad libitum-fed vehicle-treated mice. Daily BDNF administration for 3 weeks completely ameliorated both of the reductions. Finally, to clarify its action mechanism, the effect of intracerebroventricular administration of BDNF on db/db mice was examined. Here, a small dose of BDNF was found to be effective in lowering blood glucose concentration. This indicates that BDNF regulates glucose metabolism by acting directly on the brain.

Animals↗
PubMed2000

Two cases of tinea corporis by infection from a rabbit with Arthroderma benhamiae.

The first cases of tinea corporis with Arthroderma benhamiae in Japan are reported. A 7-year-old girl and a 30-year-old mother in Shimane prefecture suffered from dermatophyte infections on the neck, shoulder, arms and leg. Three isolates from the two patients and a rabbit by which they supposedly were infected, were identified as Trichophyton mentagrophytes. On the bases of mating tests using the tester strains of both the African race and the Americano-European race of A. benhamiae, they were identified as A. benhamiae African race mating type (-). Our results are the first to indicate that both races of A. benhamiae exist in Japan.

Adult↗
PubMed2000

Increased expression of alpha2beta1-integrin in the peritoneal dissemination of human gastric carcinoma.

The prognosis of advanced gastric cancer remains poor, given the frequent incidence of peritoneal metastasis. beta1-integrin is known to be associated with metastasis, though few reports have addressed the expression of beta1-integrin subunits in gastric cancer at primary and peritoneal lesions from the perspective of individual cases. We studied specimens from primary tumors from 50 patients and from metastatic peritoneal lesions from 27 patients with gastric carcinoma, including specimens from 22 metastatic lesions taken from the same patients whose primary tumors were sampled. Expression of beta1-integrin subunits, alpha2-alpha6beta1 integrins, was studied using an immunohistochemical method. alpha2beta1-integrin was significantly expressed on a larger proportion of tumor cells in peritoneal metastasis (70.4%) than in primary tumors (48%) (p<0.05), though alpha3beta1, alpha4beta1, alpha5beta1 and alpha6beta1-integrins did not demonstrate significant discrepancy. The expression of alpha2beta1-integrin in peritoneal lesions was significantly increased compared with its expression in the primary lesion in the same individual. In contrast, no relationship was found between the expression level of beta1 integrins and clinicopathological parameters. Peritoneal implantation of gastric carcinoma might be closely associated with alpha2beta1-integrin.

Adult↗
PubMed2000

TGF-beta1 secreted by gastric fibroblasts up-regulates CD44H expression and stimulates the peritoneal metastatic ability of scirrhous gastric cancer cells.

Gastric fibroblast-derived conditioned medium and TGF-beta1 stimulated the adhesion ability of scirrhous gastric cancer cells to mesothelial cells, but not that of well-differentiated gastric cancer cells. The CD44H expression of scirrhous gastric cancer cells was significantly up-regulated by gastric fibroblast-derived CM and TGF-beta1. The stimulated adhesion ability and CD44H expression was significantly inhibited by anti TGF-beta1 neutralizing antibody. These findings suggested that TGF-beta1 secreted by gastric fibroblasts up-regulated the CD44H expression of scirrhous gastric cancer cells, which resulted in the stimulation of the adhesion ability of scirrhous gastric cancer cells to the mesothelium, and increased the peritoneal dissemination potential. These results might explain one of the reasons why scirrhous gastric carcinomas develop frequent peritoneal dissemination.

Adenocarcinoma, Scirrhous↗