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Biomedical subjects

M Takeuchi

Publications and source records attributed to M Takeuchi.

At least 109 records · Page 6Linked to original sources
PubMed1990

[Three-month oral subacute toxicity study of mofezolac (N-22) in rats].

A three-month oral subacute toxicity study of mofezolac (N-22), a non-steroidal anti-inflammatory agent, was performed using dose levels of 6, 20, 60 and 200 mg/kg in rats, and recovery was also assessed one month after withdrawal. 1. Toxic signs caused by N-22 administration, observed only in the 200 mg/kg group, were as follows: soiling around the mouth and/or nose, piloerection, anemia, diarrhea, emaciation and decreased spontaneous locomotor activity. Nine males and thirteen females in the 200 mg/kg group excreted bloody diarrhea and died of general exhaustion between weeks four and thirteen of study. 2. In the 200 mg/kg group, decrease in food consumption and suppression of body weight gain were noted in males from about week four and in females from about week six after initiation of administration, and increase in water consumption was noted in males from about week seven. 3. Urinary examination revealed a decline in urinary pH in males of the 20 mg/kg and above groups and elevation of urobilinogen levels in males of the 60 and 200 mg/kg groups. 4. Hematological examination showed decreases in erythrocyte count (RBC), hematocrit value (Ht) and hemoglobin concentration (Hb) and increase in reticulocyte rate in both sexes of the 200 mg/kg group and an increase in neutrophil rate in males of the 200 mg/kg group. 5. Biochemical examination demonstrated a decrease in chloride (Cl-) in males receiving the 20 mg/kg or above doses and a decrease in calcium (Ca++) in males of the 60 and 200 mg/kg groups. Moreover, there were decreases in cholinesterase (ChE) activity, total protein (TP) and albumin (Alb) values, as well as increases in blood urea nitrogen (BUN), uric acid (UA) and potassium (K+) in both sexes of the 200 mg/kg group, along with elevations in GOT and lactate dehydrogenase (LDH) activities in females of the 200 mg/kg group. 6. The absolute and/or relative organ weights for liver, kidneys, spleen and adrenals were increased in the 200 mg/kg group. 7. On pathological examination, perforating ulceration in the jejunum and ileum, turbid ascites, adhesion and inflammatory changes in capsules of the abdominal organs, splenomegaly, mesenteric lymph node hyperplasia and inflammatory changes in the thoracic cavity were observed in dead animals of the 200 mg/kg group. Similar pathological changes were observed in a few survival cases of the 200 mg/kg group. 8. After a one month recovery period, the above-mentioned changes had mostly recovered, indicating that they were reversible.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1990

[Three-month subacute oral toxicity study of mofezolac (N-22) in dogs].

Mofezolac (N-22) is a new developed analgesic and anti-inflammatory agent. A subacute oral toxicity test of N-22 was carried out at dose-levels of 0, 2, 6 and 20 mg/kg/day using male and female beagle dogs. Treatment for 3 months was followed by 1 month recovery period except in the case of both sexes receiving 20 mg/kg/day. The results obtained from the present study were as follows. 1. Observation of general conditions revealed vomiting, sporadic bloody feces, anemia, recumbency and hyposthenia in both sexes receiving 20 mg/kg/day. Anemia or erosion of tongue was observed in each female receiving 6 mg/kg/day. 2. Respectively 3 dogs of both sexes receiving 20 mg/kg/day died during dosing period. In these animals, perforating ulcers were observed in the pars pylorica ventriculi or duodenum, and loss of blood, peritonitis and aggravation of general exhaustion were considered as causes of death. 3. Body weight tended to decrease in both sexes receiving 20 mg/kg/day, and food and water consumption levels decreased in males receiving 2 mg/kg/day or above and females receiving 2 mg/kg/day. 4. Urinalysis demonstrated an increasing tendency for specific gravity of urine and a decreasing tendency for urine volume in males receiving 2 mg/kg/day or above. 5. Hematological examination showed decreases in red blood cell count and Hb concentration in males receiving 2 mg/kg/day or above, and in Ht values in males receiving 6 mg/kg/day or above. 6. Serum biochemical examination revealed decreases in total protein and albumin in both sexes receiving 20 mg/kg/day. 7. There were no remarkable changes in hepatic and renal function, ophthalmological findings or electrocardiogram. 8. In the organ weights, significant decrease in thymus weights was observed in the dead animals receiving 20 mg/kg/day. 9. Pathologically, the dead animals receiving 20 mg/kg/day were found to exhibit peritonitis with perforating ulcers in the pars pylorica ventriculi or duodenum. In the surviving animals of this group, scar ulcers in the pars pylorica ventriculi and small intestine were evident on necropsy, and histopathology revealed neutrophils infiltration and thrombosis in blood vessels in the thickened submucosal stomach tissues. Moreover, localized hepatocyte necrosis and intrasinusoidal cellular infiltration in liver, as well as interstitial cellular infiltration, degeneration and dilatation of the renal tubules in the kidney were observed. In females receiving 6 mg/kg/day, the changes in kidney were similar to those in surviving animals receiving 20 mg/kg/day, and male of the group showed atrophy of thymus.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗
PubMed1990

Croconazole metabolism in rats.

1. Following subcutaneous administration of 1-(2-(3-chlorobenzyloxy)phenyl)vinyl)-1H-imidazole (croconazole) to rats, four metabolites were identified by comparison of their mass and n.m.r. spectra, g.l.c., and t.l.c. with those of synthetic compounds and enzyme hydrolysis. These compounds are o-hydroxyacetophenone sulphate (M1S), 1-(1-(2-hydroxyphenacyl)vinyl)-1H-imidazole sulphate (M12S), 2-(3-chlorobenzyloxy)phenacyl alcohol (M2), and 2-(3-chlorobenzyloxy)benzoic acid (M9-1). 2. At 10 mg/kg dosing of croconazole the elimination rate of the unchanged drug from plasma was faster in male than in female rats. 3. The percentage of excretion of M12S in 24 h urine was 17% for males and 7.5% for females, and that of M1S was 6.6% for males and 6.5% for females. The percentage of excretion of M2 in 24 h bile was 14% for males and 22% for females, and that of M9-1 was 3.7% for males and 1.6% for females.

Animals↗
PubMed1990

Active and passive cutaneous anaphylaxis in WBB6F1 mouse, a mast cell-deficient strain.

WBB6F1 mouse, a mast cell-deficient strain, was tested for active and passive cutaneous anaphylactic reactions. Active cutaneous anaphylaxis was not produced in mice which had been immunized for 1 to 2 weeks by an intraperitoneal injection of bovine serum albumin with either adjuvant, Freund's complete adjuvant or Bordetella pertussis organisms, even though circulatory IgE and IgG1 antibodies were raised. Passive cutaneous anaphylaxis (PCA) was also absent, when the mice had been sensitized with allogeneic IgE or IgG1 monoclonal antibodies. However, obvious PCA was produced when allogeneic or xenogeneic hyperimmune serum was employed. These findings indicate that mast cells are not necessarily needed for the production of PCA. Some mechanism quite different from the well-elucidated mechanism, i.e., IgE- or IgG1 antibody-triggered histamine release from mast cells, seems to be operative.

Animals↗
PubMed1990

[The mechanism of speech perception using multichannel cochlear implant].

The mechanism of speech perception in patients with Australian multi-channel cochlear implant was investigated. 1) Vowel recognition abilities of patients were sufficient with this implant, whereas, consonant recognition abilities were insufficient. 2) Although the cochlear hair cells were functionally damaged, cochlear nerves had the ability to characterize frequency. 3) The signals from the implanted material were very simple compared to those from normal cochlea, however these patients could understand speech well, perhaps due to aid from the central nervous system.

Adult↗
PubMed1990

[Study of a monoclonal antibody against new epithelial membrane antigens of transitional cell carcinoma].

Immunizing mice with a transitional cell cancer (TCC) tissue in the renal pelvis, we produced a monoclonal antibody (EH14) against new epithelial antigens. After the mice were immunized repeatedly, their splenic cells were harvested and fused with NS/1 myeloma cells. The normal kidney tissue of the same patient was used on Dot blots to select the hybridoma. A a result, one hybridoma whose antibody (EH14) reacted very strongly with TCC but only faintly with normal kidney tissue or normal bladder mucosa was obtained. On immunohistochemistry, EH14 stained all of the 29 TCC tissues. EH14 also stained uterus cancer (7/7) and gastric cancer (6/6) as well as the normal squamous cell and many types of the normal epithelium. All of the lymphnodes containing metastatic bladder cancer were strongly stained with EH14. EH14, however, did not stain interstitial tissues, muscles and sarcomas. The molecular weight of the antigen recognized by EH14 was 14KD and 28 KD on Western blot analysis, and the antigen was stable with formalin or ethanol. The antigen was not the same as that reported previously, and may be useful as a histological marker of TCC.

Animals↗
PubMed1990

[Inhibitory factors of calcium oxalate crystal growth in urinary macromolecules].

We studied the inhibitory effect of urinary glycosaminoglycans (GAGs), in the natural form, on calcium oxalate crystals. Control urine was collected from five healthy subjects and filtered by 5 microns and 0.22 micron membranes. The urine was cut off by a membrane of 30,000 M.W. and the remaining urine was fractionated into three groups by anion-exchange chromatography on DEAE-cellulose: peak A contained only protein, peak B both protein and GAGs and peak C only GAGs. Peak A and peak B were fractionated again through a Sephacryl S-200 gel column. Each fractionated sample was examined for the inhibitory effect on calcium oxalate crystal growth using the 14C-oxalate seeded crystal growth assay in a metastable solution developed by Koide et al. GAGs were determined by two-dimensional electrophoresis on cellulose acetate membrane. SDS-polyacrylamide electrophoresis was used to determine the molecular weights of proteins. Peak A was found to have many kinds of proteins which had low inhibitory effects. Peak B had three kinds of proteins such as those with molecular weights of 130,000, 45,000 and 35,000 as well as uronic acid. These proteins and uronic acid had high inhibitory effect and the highest inhibitory effect was found in the fraction of around 50,000 M.W. where protein and uronic acid were contained. The molecular weight of this protein was 42,000 by SDS electrophoresis. Uronic acid was a keratan sulphate by a two-dimensional electrophoresis. In peak C there were mainly chondroitin sulphate and a small amount of heparan sulfate which had high inhibitory effect.(ABSTRACT TRUNCATED AT 250 WORDS)

Calcium Oxalate↗
PubMed1990

Studies on inhibitors of rat mast cell degranulation produced by microorganisms. I. Screening of microorganisms, and isolation and physico-chemical properties of eurocidins C, D and E.

Microorganisms producing anti-inflammatory substances were screened by the inhibitory effect on mast cell degranulation. Three new compounds related to pentaene macrolide eurocidins, eurocidins C, D and E, have been isolated from the culture broth of Streptoverticillium eurocidicum IFO 13491 as the inhibitors. Their molecular weights and molecular formulae were estimated as 781.89 and C39H59NO15 for eurocidin C, 795.92 and C40H61NO15 for eurocidin D, and 779.92 and C40H61NO14 for eurocidin E, respectively.

Animals↗
PubMed1990

Trehalase inhibitors, validoxylamine A and related compounds as insecticides.

Validoxylamine A showed a potent inhibitory activity against insect trehalase in a competitive manner with a Ki value of 4.3 x 10(-10) M. The other validoxylamines and validamycins also exhibited the activity in vitro. Injection of these compounds to young last instar larvae of the tobacco cutworm, Spodoptera litura, elicited the morphological abnormality followed by death after the cessation of feeding. Validoxylamine A showed 100% mortality at a dose of 10 micrograms/ last instar larva.

Animals↗
PubMed1990

[Retinal degeneration after intravitreal injection of ornithine. 1. Early change after administration].

Retinal damage 1 to 7 days after intravitreal injection of 1-ornithine hydrochloride solution into monkey eyes was investigated. Clinically the retinal pigment epithelium (RPE) showed edema, and hyperfluorescence on fluoroangiograms, predominantly in the equatorial region at 3 to 7 days. No retinal changes were seen at the posterior pole. Histopathologically, RPE in the equatorial region showed severe damage 24 hours after injection, becoming liquefactively necrotic and degenerated at 3 to 7 days. Early changes in RPE consisted of an increase in the number of secondary lysosomes, disappearance of basal infolding, destruction of most of the smooth endoplasmic reticulum, shortening of microvilli, and marked swelling of mitochondria. These RPE changes were seen slightly in the posterior pole. There were slight changes in the inner retina including photoreceptors. In eyes injected intravitreally by hi-osmosis of 3.5% NaCl solution, with equivalent osmolarity to ornithine solution, mild changes of microvilli and mitochondria were seen, but not necrotic changes. Our experiment showed that intravitreal injection of a small amount of 1-ornithine hydrochloride induced severe RPE damage. Selective toxicity of ornithine to RPE appeared mainly in the equatorial region.

Animals↗
PubMed1990

[A case of membranous lipodystrophy (Nasu) with diffuse cerebral white matter involvement and cerebellar atrophy on brain CT and MRI].

A 37-year-old female was admitted to our hospital because of progressive dementia and gait disturbance. She was healthy until 34 years of age when she had difficulty in walking and memory disturbance with personality changes. At age 36, she developed urinary incontinence and dementia. The neurological examination demonstrated euphoric mental state, emotional incontinence, severe dementia, paraplegia, dysmetria, choreic movements in both arms and urinary incontinence. Diffuse hyperreflexia and bilateral Babinski signs were observed. Routine laboratory examination showed slightly increased erythrocyte sedimentation rate and alkaline phosphatase. Electroencephalogram revealed diffuse irregular slow waves. X-ray film of the ulnar bone revealed osteoporotic and cystic lesions. The biopsy of the left tibial bone showed a specific membranous cystic structure. Computerized tomography (CT) of the brain showed symmetric, diffuse low density areas in the cerebral white matter and severe atrophy of the cerebellum. T2-weighted magnetic resonance imaging (MRI) revealed diffuse high intensity areas in the cerebral white matter. The present case is characterized by diffuse changes in cerebral white matter and cerebellar atrophy, which have been never reported in Nasu-Hakola disease. The diffuse cerebral white matter changes shown by CT and MRI appear to indicate that this patient is the first case of leukodystrophy of sudanophilic type since the original case reported by Nasu et al.

Adult↗
PubMed1990

[Purification and characterization of alkaline phosphatase obtained from bovine periodontal ligament].

Alkaline phosphatase (ALP) activity has been demonstrated in periodontal ligament (PDL). On the basis of electron microscopic study, distribution of the enzyme in PDL tissue has also been indicated not only as a cell associated activity but also as an extracellular matrix associated activity. This study is concerned with the purification and characterization of the enzyme obtained from bovine PDL tissue. Purification of ALP extracted from the tissue included solubilization with 10 mM Tris-HCl buffer, pH 7.4, containing 0.2 mM MgCl2 and 0.1% Nonidet P-40 and fractionation by sequential chromatography utilizing DEAE-sephacel, Sepharose CL-6B and concanavalin A Sepharose 4B. Purity was established by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). This was followed by staining for ALP activity first with 2 mM beta-naphthyl acid phosphate and 1 mM Fast Blue BB Salt and then the protein with Coomassie Brilliant Blue. SDS-PAGE of the crude enzyme preparations gave a broad band with apparent molecular weight of 110,000-130,000 dalton. ALP activities were separated into two major peaks using Sepharose CL-6B chromatography. The void volume peak showed a purified form of 110,000 dalton ALP (110K ALP) while the second peak contained 120,000-130,000 dalton ALP (120-130K ALP) and other proteins. Sequentially, 120-130K ALP was purified by chromatography on concanavalin A Sepharose 4B. A polyclonal antibody was raised against purified bovine PDL 110K ALP in a rabbit. Immunodiffusion analysis showed that a polyclonal antibody against 110K ALP recognized 120-130K ALP. Analytical affinity chromatography on concanavalin A Sepharose 4B indicated that 110K ALP and 120-130K ALP had distinct affinity to the column which may depend upon the sugar chain structure. Digestion of 110K ALP with phosphatidylinositol-specific phospholipase C affected electrophoretic mobility but 120-130K ALP had no effect. It is suggested that 110K ALP is attached to a cell membrane anchored by a phosphatidylinositol glycan. In conclusion, bovine PDL contains two types of alkaline phosphatase i.e. 110K ALP and 120-130K ALP. Both ALPs are immunologically related although they have different sugar chain moieties. Furthermore, 110K ALP has a membrane anchoring domain. These results suggest that 110K ALP would be localized on the surface of the cell membrane and 120-130K ALP may associated with the extracellular matrix.

Alkaline Phosphatase↗
PubMed1990

An acoustically investigated case of phonetic change in higher vertical dimension.

This report presents the phonetic changes of a patient whose occlusal vertical dimension is extended. His chief complaint is esthetic restoration of his anterior teeth, but his occlusal vertical dimension is abnormally shortened by long-time attrition. Therefore we extended his occlusal vertical dimension, and reconstructed his occlusion, and carried out acoustic observations.

Aged↗
PubMed1990

Fibronectin on prosthetic denture fabrication.

It is well known that fibronectin adheres to various oral bacteria and shows affinity to various components. Thus the existence fibronectin which is present in the salivary flow, acquired pellicle and dental plaque, was investigated in used acrylic resin dentures with a direct immunohistochemical fluorescent technique using antihuman fibronectin goat serum which was labeled with fluorescein isothiocyanate (FITC). It was found that fibronectin frequently was present on the surface of acrylic resin dentures.

Acrylic Resins↗
PubMed1990

[A case of inorganic germanium poisoning with peripheral and cranial neuropathy, myopathy and autonomic dysfunction].

A 51-year-old man, taking beverage containing inorganic germanium (Ge), (90-100 mg/day, total 70 g) for two years, developed body weight loss, anemia, renal dysfunction, peripheral neuropathy, myopathy, autonomic dysfunctions and multiple cranial nerve palsies. Serum CK, GOT, LDH, BUN, and creatinine levels were elevated. The cerebrospinal fluid showed albumino-cytologic dissociation. Sural nerve biopsy showed axonal degeneration, and peroneal muscle biopsy showed neurogenic changes including type 2 fiber atrophy and ragged red fibers. High level of Ge content was detected from the hair and nail by inductively coupled plasma atomic emission spectrometry. Despite discontinuation of Ge taking, the peripheral neuropathy and autonomic dysfunction progressed. The symptoms remained unchanged even in the treatment with prednisolone. These findings suggest that inorganic Ge has a serious irreversible multiple system toxicity.

Autonomic Nervous System Diseases↗
PubMed1990

[Increased oxidant production by peripheral blood granulocytes in patients with idiopathic pulmonary fibrosis].

Oxidant production by peripheral granulocytes stimulated with phorbol myristate acetate (PMA) was investigated in 11 patients with idiopathic pulmonary fibrosis (IPF), 6 with interstitial pneumonia associated with collagen vascular disease (IP-CVD), 8 with sarcoidosis and 12 healthy subjects. Oxidant production was examined by flow cytometry using dichlorofluorescein diacetate. The reactivity of granulocytes to PMA was assessed according to the ratio between mean fluorescent intensity of granulocytes stimulated maximally with PMA and that without PMA, (stimulation index: S.I.). The concentration of PMA that induced half maximal fluorescent intensity of granulocytes (PC 1/2 max) was used as the index of sensitivity. The S.I. was 7.2 +/- 0.45 in IPF, 6.3 +/- 0.6 in IP-CVD, 6.0 +/- 0.71 in sarcoidosis, and 5.8 +/- 0.2 in healthy subjects. However differences between groups were not significant. PC 1/2 max was 7.3 +/- 2.1 ng/ml in IPF, 9.1 +/- 3.0 ng/ml in IP-CVD, 12 +/- 6.9 ng/ml in sarcoidosis and 16.1 +/- 5.8 ng/ml in healthy subjects. There was significant difference between IPF and healthy subjects (p less than 0.05) indicating that peripheral granulocytes in patients with IPF are more highly sensitive to PMA than healthy subjects.

Adult↗