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Biomedical subjects

R Nishimura

Publications and source records attributed to R Nishimura.

At least 55 records · Page 3Linked to original sources

Morphological analysis of cervical vertebrae in ataxic foals.

Morphological differences between cervical vertebrae were statistically analyzed in ataxic foals to clarify abnormal structural factors in the pathogenesis of this problem. At first, multiple regression analysis and cluster analysis were performed with 28 variables in C3-C7 of 39 control foals without lameness. As a result, there were no sex differences in the growth of all cervical vertebral sites, and the most suitable categorization of the age of the foals was 3 clusters of 8 months old or younger, 9-12 months old and 13 months old or older in any sites in the cervical vertebrae. Twenty-eight ataxic and 19 control foals at the age of 13 months or older were then used for discriminant analysis with 20 variables. As a result, 1-7 variables on C3-C7 were selected for sufficient discrimination, in which the heights of the cranial and caudal orifices of the spinal canal, longitudinal length of the vertebral head and height of the vertebral fossa strongly contributed to the discrimination of all the cervical vertebrae. In addition, the widths and longitudinal diameters of the articular processes on articular surfaces strongly contributed to the discrimination of the caudal region of the neck. In conclusion, it was suggested that the lesion in the cervical spinal cord observed in ataxic foals was caused by morphological abnormalities including osteochondrosis and subsequent degenerative joint disease in the cervical vertebrae.

Animals

Efficacy of the new radiographic measurement method for cervical vertebral instability in wobbling foals.

Cervical myelography and survey radiography was performed on 12 light breed wobbling foals and a new radiographic measurement method was applied for more accurate diagnosis of cervical vertebral instability. Ratios of stenosis of the spinal canal on survey radiography and myelography using relative values in an individual foal were defined on radiograms of lateral flexed position of mid-cervical region, and coincidence between the ratios and histopathological lesions in the cervical spinal cord was investigated. Five of 6 foals had ratios of stenosis on myelography more than 40% at the intervertebral sites where the most severe histopathological lesions were observed. Four of 6 foals had ratios of stenosis on survey radiography more than 40% at the intervertebral sites where the most severe histopathological lesions were observed. Four of 6 foals had ratios of stenosis on survey radiography more than 40% at the intervertebral sites where the most severe histopathological lesions were observed. False-positive diagnosis of CVI was observed in 1 out of 6 foals without histopathological lesion when both ratios of stenosis on myelography and survey radiography were applied. Although the standard value of 40% should be further investigated, the new radiographic measurement method in this study is very useful in clinical diagnosis of cervical vertebral instability in wobbling foals, and the presence of lesions in the cervical spinal cord and their sites by survey radiography may be estimated more accurately.

Animals

Relationships between radiography of cervical vertebrae and histopathology of the cervical cord in wobbling 19 foals.

Nineteen wobbling foals (17 males and 2 females) showing lameness of hindlimbs at 6 to 21 months of age were investigated radiographically and histopathologically. Minimum sagittal diameter (MSD), minimum flexion diameter (MFD) and minimum dural sagittal diameter (MDD) were measured on plain radiograms or myelograms taken at neutral and flexed positions as indicators of narrowed vertebral canal. After necropsy, the cervical spines and the spinal cord were examined macroscopically and respectively the relationships between radiographic findings and the corresponding morphological lesions were evaluated. Radiographically, lower values than each minimum reference limits were recorded in 14 foals in MSD, 5 foals in MFD and 6 foals in MDD, respectively. According to the histopathologic examination, the disappearance of axons and myelin sheaths, vacuolated spongy degeneration and appearance of macrophages were recognized symmetrically in the white matter of the cervical cord. These lesions were centrally located at the spinal cord radiographically demonstrated as compressed sites in 12 out of 17 foals examined. Macroscopically, asymmetrical overgrowth of one side of the process, encroachment of articular processes into the intervertebral foramina and proliferation of bone around articular facets were observed in the articular processes of bone specimens in the caudal neck of 6 foals. In conclusion, the equine incoordination might mainly be caused by the cervical stenotic myelopathy resulting from cervical vertebral malformation, and therefore the cervical vertebral radiography, especially myelography, is quite very important and effective for the diagnosis of wobbling foals.

Animals

Cardiopulmonary effects of medetomidine-midazolam and medetomidine-midazolam- atipamezole in laboratory pigs.

The cardiopulmonary effects of medetomidine (40 micrograms/kg)-midazolam (0.2 mg/kg) and medetomidine (40 micrograms/kg)-midazolam (0.2 mg/kg)-atipamezole (160 micrograms/kg) were evaluated in laboratory pigs. The intramuscular administration of medetomidine-midazolam caused a pressor response, characterized by a rapid increase in arterial and pulmonary arterial pressure mediated mainly through systemic and pulmonary vasoconstriction. These pressures decreased after reaching a peak 5 to 10 min after the administration of sedatives, but maintained higher values than the base-line. However, all these changes caused by medetomidine-midazolam were within the physiological fluctuation. In addition, this combination did not induce bradycardia, subsequent hypotension or a significant decrease in cardiac output, which were generally observed with alpha 2-adrenoceptor agonists, and caused fewer changes in the respiratory system. The administration of atipamezole resulted in a marked transient decrease in vascular resistance, and caused a decrease in blood pressure and increases in cardiac output and heart rate. However, these changes were relatively small and sustained for a short time. Thus the combination of medetomidine-midazolam and atipamezole have minimal cardiopulmonary effects and might be used safely in laboratory pigs.

Adrenergic alpha-Agonists

Plasma concentrations of substances suspected as uremic toxins in experimentally induced and spontaneous uremic dogs.

Plasma concentrations of four substances, a pyridine derivative (S7a), uric acid (UA), hippuric acid (HA) and kynurenic acid (KA), suspected as uremic toxins in dogs were determined in dogs with experimentally induced uremia by the ligations of renal arteries, spontaneous uremic dog patients and normal dogs. In experimentally induced uremic dogs, plasma concentrations of S7a, HA and KA showed continuous increase after the ligation of renal arteries together with a significant correlation to plasma creatinine concentration (Cre). Plasma UA concentration increased rapidly, but it showed a varying fluctuation without showing any correlation to Cre. Plasma concentrations of S7a, UA, HA and KA in spontaneous uremic dogs were almost within the ranges of those of experimentally induced uremic dogs.

Animals

Effects of medetomidine-midazolam on plasma glucose and insulin concentrations in laboratory pigs.

Effects of medetomidine (40 micrograms/kg)-midazolam (0.2 mg/kg) on plasma glucose and insulin concentrations were evaluated in laboratory pigs. Intramuscular injection of medetomidine-midazolam induced a gradual hyperglycemic response associated with hypoinsulinemia which was much smaller than that by 80 micrograms/kg of medetomidine alone and was almost within a physiological fluctuation. These mild responses induced by medetomidine-midazolam were antagonized by use of an alpha 2-adrenoreceptor antagonist atipamezole (160 micrograms/kg), therefore those changes were thought to be mainly attributed to the effect of medetomidine on alpha 2-adrenoreceptors. A combination of medetomidine at a low dose and midazolam reduces undesirable effects, while providing more profound sedation than medetomidine alone in laboratory pigs.

Adrenergic alpha-Agonists

20 alpha-hydroxysteroid dehydrogenase activity in canine spontaneous neoplasms.

20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD) activities in 57 neoplastic tissues surgically removed from dogs were measured. Forty-eight of 57 tumor samples were shown to possess 20 alpha-HSD activity. These tissues were histopathologically classified into 22 benign and 26 malignant tumors. Among these tumors, mixed tumor types demonstrated the higher 20 alpha-HSD activity than epithelial and non-epithelial types, and malignant tumors of each tissue type showed slightly but not significantly higher 20 alpha-HSD activities comparing with the corresponding benign ones. Comparing with the activity of normal tissues examined, the corresponding tumor tissues showed significantly higher 20 alpha-HSD activities. Thus, 20 alpha-HSD activity was found in neoplastic tissues at a considerable high rate and the activity seemed to be higher in pathologically malignant tumors.

20-Hydroxysteroid Dehydrogenases

Computed tomography on renal masses in dogs and cats.

Computed tomography (CT) was performed on renal tumors (Wilms' tumor and renal cell carcinoma) and renal cysts in dogs and cats. CT images in renal tumors were well correlated with macroscopic findings, and contrast CT images were quite useful in differentiating tumoral regions from non-tumoral ones. On renal cysts, intravenous pyelography and ultrasonography were as effective as CT images in morphological diagnosis, but CT was considered to be superior for evaluating three-dimensional (3-D) relationships in complicated lesions.

Animals

Comparison of sedative effects induced by medetomidine, medetomidine-midazolam and medetomidine-butorphanol in dogs.

Sedative effects of combinations of medetomidine at 20 micrograms/kg--midazolam at 0.3 mg/kg (Me-Mi) and medetomidine at 20 micrograms/kg--butorphanol at 0.1 mg/kg (Me-B) were evaluated comparing with those of medetomidine alone (20, 40 and 80 mu/kg). All dogs given Me-Mi or Me-B were smoothly and rapidly induced to more profound and longer sedation than those by medetomidine alone. Especially, Me-Mi produced desirable sedation with moderate reflex depression, analgesia, excellent muscle relaxation and immobilization without further side effects. This potent effect of this combination seemed to be induced by a synergistic interaction between medetomidine and midazolam. This combination is available and valuable as a chemical restraint agent in dogs for various diagnostic or therapeutic procedures accompanied by light pain.

Animals

Nck associates with the SH2 domain-docking protein IRS-1 in insulin-stimulated cells.

Nck, an oncogenic protein composed of one SH2 and three SH3 domains, is a common target for various cell surface receptors. Nck is thought to function as an adaptor protein to couple cell surface receptors to downstream effector molecules that regulate cellular responses induced by receptor activation. In this report, we show that Nck forms a stable complex in vivo with IRS-1 in insulin-stimulated cells. The interaction between IRS-1 and Nck is mediated by the binding of the SH2 domain of Nck to tyrosine-phosphorylated IRS-1. Although Nck associates with IRS-1, Nck phosphorylation is not affected by insulin stimulation. Furthermore, in vitro and in vivo studies show that the SH2 domains of Nck, GRB2, and p85 bind distinct phosphotyrosine residues in IRS-1. After insulin stimulation all three signaling molecules can be found complexed to a single IRS-1 molecule. These findings provide further evidence that, in response to insulin stimulation, IRS-1 acts as an SH2 docking protein that coordinates the regulation of various different signaling pathways activated by the insulin receptor.

Adaptor Proteins, Signal Transducing

Charge isomers of urinary bikunin (trypsin inhibitor).

It was observed that the purified urinary bikunin (trypsin inhibitor) consisted of four major isomers with different electric charges which could be separated by HPLC using a Mono Q column. These isomers revealed the same antitrypsin activity and did not show any differences in the apparent molecular weight by SDS-PAGE, amino-acid composition, N-terminal amino-acid sequence (1-40) and C-terminal amino acid (Leu). The contents of sialic acid and uronic acid were also identical among these isomers. However, analysis of chondroitin sulfate revealed all the glycosaminoglycan chains of these isomers were undersulfated, comprising nonsulfated and 4-sulfated disaccharide units, and 4-sulfated disaccharide unit ratio varied among these isomers. After the chondroitin ABC lyase digestion, all the isomers were eluted at the same position on a Mono Q column chromatography. These results indicated that charge isomers of urinary bikunin was attributed to the difference on sulfation ratio in a glycosaminoglycan chain.

Amino Acids

Liquid chromatography-mass spectrometry for the determination of medetomidine and other anaesthetics in plasma.

A liquid chromatographic-atmospheric pressure chemical ionization mass spectrometric method is presented for the simultaneous determination of medetomidine and other anaesthetic drugs in solutions and dog plasma. The drugs examined were flumazenil, butorphanol, atropine, ketamine, xylazine, medetomidine, atipamezole and midazolam. The separation was carried out on a reversed-phase column using methanol-0.1 M ammonium acetate (3:2) as eluent.

Anesthetics

Thoracic vertebral bone metastasis from uterine leiomyosarcoma.

We report a patient with solitary thoracic vertebral bone metastasis (Th 8) from uterine leiomyosarcoma. The vertebral metastatic lesion was treated surgically, and vertebral body replacement with ceramic prosthesis and anterior spinal stabilization were performed. Such aggressive surgical intervention for solitary vertebral bone metastasis may contribute to the improvement of prognosis and maintenance of general quality of life in the patient.

Female

Correlation of sequential magnetic resonance imaging of experimental brain ischemia with histologic changes in gerbils.

RATIONAL AND OBJECTIVES: To characterize Gd-DTPA-enhanced T1-weighted images (Gd-T1WI) in the acute phase of cerebral ischemia, sequential magnetic resonance images of 84 Mongolian gerbils with occlusion of the left common carotid artery were evaluated. METHODS: Twelve gerbils were used for each group, among which the occlusion time (5-180 minutes, permanent) varied. Histopathologic changes developing within the first 2 weeks were compared with patterns on T2-weighted images and Gd-T1WI on a 7.05-Tesla system. RESULTS: Although T2-weighted images and Gd-T1WI both demonstrated abnormal findings as early as 3 hours after occlusion, Gd-T1WI demonstrated more definite abnormalities with shorter occlusion than T2-weighted images (especially when there were only mild histologic changes). The earliest changes were an abnormal enhancement around and within the lateral ventricles in temporary occlusions; this was not demonstrated in permanent occlusions. CONCLUSIONS: Magnetic resonance images using Gd-DTPA demonstrated abnormal permeability within 3 hours after occlusion, and the pattern is correlated with intensity of ischemia.

Animals

Establishment of a leukaemic cell line from a patient with acquisition of chromosomal abnormalities during disease progression in myelodysplastic syndrome.

A cell line designated SKM-1 was newly established from leukaemic cells of a 76-year-old Japanese male patient with monoblastic leukaemia following myelodysplastic syndrome (MDS). The cells were obtained from peripheral blood of the patient when he lost multiple point mutations of ras genes with acquisition of chromosomal abnormalities during disease progression in MDS. The cells grew as a single floating cell, and have been continuously growing with the morphological characteristics of immature monoblasts by serial passages during the past 42 months with a doubling time of about 48 h. By cytochemical analysis, the cloned cells were positive for butyrate esterase, but negative for the Epstein-Barr virus associated nuclear antigen. Phenotypic analysis revealed the expression of myelomonocyte specific antigens such as CD4, CD13, CD33 and HLA-DR. Cells from the primary peripheral blood and those from 50 passages of the SKM-1 cell line both possessed no activated ras genes but showed karyotype abnormalities with 46,XY, del(9)(q13;q22), der(17) t(17;?)(p13;?). The SKM-1 cells have two mutations in p53 gene and overexpress the p53 products. This cell line may contribute to a better understanding of molecular mechanisms in the progression from MDS to myelogenous leukaemia.

Aged

Two signaling molecules share a phosphotyrosine-containing binding site in the platelet-derived growth factor receptor.

Autophosphorylation sites of growth factor receptors with tyrosine kinase activity function as specific binding sites for Src homology 2 (SH2) domains of signaling molecules. This interaction appears to be a crucial step in a mechanism by which receptor tyrosine kinases relay signals to downstream signaling pathways. Nck is a widely expressed protein consisting exclusively of SH2 and SH3 domains, the overexpression of which causes cell transformation. It has been shown that various growth factors stimulate the phosphorylation of Nck and its association with autophosphorylated growth factor receptors. A panel of platelet-derived growth factor (PDGF) receptor mutations at tyrosine residues has been used to identify the Nck binding site. Here we show that mutation at Tyr-751 of the PDGF beta-receptor eliminates Nck binding both in vitro and in living cells. Moreover, the Y751F PDGF receptor mutant failed to mediate PDGF-stimulated phosphorylation of Nck in intact cells. A phosphorylated Tyr-751 is also required for binding of phosphatidylinositol-3 kinase to the PDGF receptor. Hence, the SH2 domains of p85 and Nck share a binding site in the PDGF receptor. Competition experiments with different phosphopeptides derived from the PDGF receptor suggest that binding of Nck and p85 is influenced by different residues around Tyr-751. Thus, a single tyrosine autophosphorylation site is able to link the PDGF receptor to two distinct SH2 domain-containing signaling molecules.

Amino Acid Sequence

Isolation and identification of canine plasma components suspected as uremic toxins.

Suspected uremic substances contained in four fractions, which had been selected as the suspected canine uremic peaks in the previous study, were isolated by two stages of preparative liquid chromatography (PLC) from plasma of uremic dogs treated with the ligation of the ureter, and then their physicochemical properties were examined. The primary separation of the suspected uremic peaks were performed with the same anion exchange resin as used in the analytical HPLC in the previous study. Analytical reverse phase HPLC showed that three of 4 suspected uremic peaks almost consisted of single substances, but the other contained several substances. Main subfractions of these peaks were successfully isolated by the secondary stage reverse phase PLC. By means of thin layer chromatography, ultraviolet absorption spectrometry and proton-nuclear magnetic resonance spectroscopy, components of 4 main peaks were confirmed to be small molecules such as a pyridine derivative, uric acid, hippuric acid and kynurenic acid, respectively.

Animals

Cardiopulmonary effects of a combination of medetomidine and butorphanol in atropinized pigs.

Cardiopulmonary effects of a combination of medetomidine and butorphanol were evaluated in atropinized pigs. This combination unchanged the cardiac output and significantly lowered the oxygen consumption compared with base-line values. Although some statistically significant changes were recorded, both medetomidine and butorphanol did not have a marked effect on the cardiopulmonary parameters in atropinized pigs. It was indicated that the administration of the combination of medetomidine and butorphanol is relatively safe in atropinized pigs.

Adrenergic alpha-Agonists