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Biomedical subjects

A Takeuchi

Publications and source records attributed to A Takeuchi.

At least 145 records · Page 8Linked to original sources

Effect of KRN2391 on canine ventricular arrhythmia models.

1. KRN2391 (3-30 micrograms/kg, i.v.) produced a decrease in mean blood pressure (MBP) with concomitant increase in heart rate (HR) and change in electrocardiogram (ECG) such as the shortening of PP and PQ intervals and the prolongation of QTc and these changes in HR and ECG were attenuated by pretreatment with propranolol (1 mg/kg) in normal dogs. 2. KRN2391 at 30 micrograms/kg induces neither suppression nor aggravation of ventricular arrhythmias caused by adrenaline and digitalis. 3. In two-stage coronary ligation-induced arrhythmia, KRN2391 inhibited arrhythmia at 48 hr. 4. These results suggest that KRN2391 may be effective on arrhythmia related to ischemia. In addition, it is considered that arrhythmia is not induced even by a high dose of KRN2391 in the normal condition.

Animals↗

Vasospasmolytic effect of KRN2391 on 3,4-diaminopyridine-induced rhythmic contraction of porcine coronary artery.

1. In the present study, we examined the vasospasmolytic effect of KRN2391 on rhythmic contractions of porcine coronary artery caused by 3,4-diaminopyridine (3,4-DAP) compared with cromakalim and nitroglycerin. 2. KRN2391 at 10(-7) showed a tendency to prolong the cycle length and at 10(-6) M completely eliminated rhythmic contractions in all preparations. The elimination by 10(-6) M KRN2391 was antagonized by either oxyhemoglobin (10(-5) M) or glibenclamide (3 x 10(-6)) although not completely. 3. Cromakalim at 10(-5) M and nitroglycerin at 10(-7) M completely eliminated 3,4-DAP-induced rythmic contractions in all preparations. The elimination by cromakalim and nitroglycerin was completely antagonized by glibenclamide and oxyhemoglobin, respectively. 4. The present study suggests that the vasospasmolytic effect of KRN2391 on 3,4-DAP-induced rhythmic contractions is based on its nitrate action and K channel opening action.

4-Aminopyridine↗

The enzymatic formation of 1 alpha,25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3 in the liver of fetal rats.

We have confirmed the existence of 25-hydroxyvitamin D3 (25-OH-D3)-1 alpha-hydroxylase in the liver of fetal rats, in addition to that in the kidney, by in vitro experiments. The findings are similar to those in the fish liver as reported previously (Takeuchi et al., Life Sci. 32, 275-282, 1991). When [3H]-25-OH-D3 was incubated with liver homogenates of vitamin D-deficient fetal rats, a peak corresponding to [3H]-1 alpha,25-dihydroxyvitamin D3 (1,25-(OH)2D3) was observed in the profile of high-performance liquid chromatography (HPLC). The formation of the metabolite was confirmed by thermal isomerization into the pre-isomer, binding affinity to the receptor and mass fragmentography. Lineweaver-Burk plot analysis of mitochondrial 25-OH-D3-1 alpha-hydroxylase in the liver gave an apparent Km value of approximately 2 microM of 25-OH-D3 and a Vmax value of 0.2 pmol of 1,25(OH)2D3/30 min/mg protein. These findings suggest that the enzyme in the liver disappeared with the growth of the fetus and became predominant in the kidney of mature rats.

Aging↗

The binding properties, with blood proteins, and tissue distribution of 22-oxa-1 alpha,25-dihydroxyvitamin D3, a noncalcemic analogue of 1 alpha, 25-dihydroxyvitamin D3, in rats.

The binding properties, with blood proteins, and tissue distribution of 22-oxa-1 alpha,25-dihydroxyvitamin (22-oxacalcitriol; OCT), a noncalcemic analogue of 1 alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], in rats were investigated. The binding affinity of OCT to plasma vitamin D binding protein (DBP) is extremely low and OCT mainly circulates in the blood as an intact form nonspecifically bound to lipoproteins especially to chylomicrons and low density lipoprotein (LDL). OCT intravenously injected into normal rats rats rapidly disappeared from the blood, and rapidly appeared in the bile as glucuronides of intact OCT and 1 alpha, 3 beta,20(S)-trihydroxy-9,10-secopregna-5,7,10(19)-triene (23,24,25,26, 27-pentanorOCT; pentanorOCT) as an OCT metabolite. When OCT or 1,25(OH)2D3 was injected into normal rats, significant amounts of OCT and 1,25(OH)2D3 were quickly detected in the thyroid and parathyroid glands, thymus, adrenals, liver, plasma, small intestine, kidneys, and calvaria. The detected amounts of OCT in the parathyroid glands, thymus, adrenals, liver, small intestine, and kidneys were significantly higher than the respective values for 1,25(OH)2D3 2 and/or 10 min after injection, while those of OCT in the plasma and calvaria were significantly lower than those of 1,25(OH)2D3. The in vivo rapid turn-over, nonspecific transportation, and incorporation of detectable amounts into the tissues are typical characteristics of OCT which may account for its specific activities.

Animals↗

Evaluation of regional cerebral blood flow changes on perifocal brain tissue SPECT before and after removal of arteriovenous malformations.

In fifteen cases of arteriovenous malformation (AVM), serial examinations of regional cerebral blood flow (rCBF) using single photon emission computed tomography (SPECT) and N-isopropyl-(123I)p-iodoamphetamine were performed. On SPECT images, the nidus was visualized as a focal rCBF defect in all cases preoperatively and seven of these cases had abnormal decreased perfusion areas in the tissues adjacent to the nidus. In five cases, the postoperative SPECT images on the day after surgery revealed an abnormal increased perfusion area adjacent to the nidus and in one case the increased perfusion was accompanied by a massive intracerebral haemorrhage detected by brain computed tomography (CT). In seven cases, postoperative SPECT images showed widespread abnormal decreased perfusion areas in the surrounding tissues and brain CT revealed either intracerebral haemorrhage or significant cerebral oedema. In the other three cases, no remarkable rCBF changes were found in comparison with the pre-operative study. There was a tendency for the preoperative abnormal decreased perfusion area adjacent to the nidus to correlate with the postoperative hyperperfusion and for the postoperative abnormal decreased perfusion area to reflect brain damage.

Adolescent↗

Idiopathic infantile hypercalcemia discovered in the newborn period.

We report a male newborn with typical clinical signs of idiopathic infantile hypercalcemia (IIH); that is, hypercalcemia, hypercalciuria, an elfin face and nephrocalcinosis without giving Vitamin D3 supplementation to the patient. He had been treated with a vitamin D-free, low calcium milk and rectal administration of exogenous calcitonin (elcatonin). The latter seemed to be more effective as a treatment for IIH. The serum calcium level came within the normal range and the serum 1,25-dihydroxyvitamin D3 (1,25[OH]2D3) level decreased from 101.5 to 75.6 pg/mL with the treatments mentioned above. These results suggest that a high serum concentration of 1,25(OH)2D3 is part of the pathogenesis of IIH. However, we were not able to clarify the pathogenesis of the high serum concentration of 1,25(OH)2D3.

Administration, Rectal↗

New monoclonal antibodies directed against mouse follicular dendritic cells.

The follicular dendritic cells (FDC) in B-lymphoid follicles are unique reticular cells that retain immune complexes on their surfaces. We developed new monoclonal antibodies (MAb), SKY01, 28, 41, and 49, against mouse FDC without useful cell markers. Immunohistochemical study of spleen and lymph node tissues from Balb/c, C3H, and C57BL/6 mice revealed that SKY01 and 49 were highly specific for FDC, whereas SKY28 and 41 reacted with other stromal components as well as FDC. On immunoelectron microscopy (IEM), reaction products for all MAb were localized on the surfaces of FDC. In ontogenetic study of Balb/c spleen, FDC precursors were not immunodetected with any of the MAb at 1 week after birth. The FDC that first appeared as immune complex-retaining cells at 2 weeks were a subpopulation of SKY01-, 49-, 28+, and 41+ reticular cells. At 3 weeks, FDC were positive for all MAb, like adult spleen. These results indicate that our MAb recognize differentiation antigens of FDC. Comparative immunohistochemical studies of spleen from athymic nude and severe combined immunodeficiency mice suggested that B-cells may be required for the differentiation of FDC. Consequently, these MAb are considered useful tools for research on FDC.

Animals↗

Antagonistic effects of antipamezole on medetomidine-midazolam induced sedation in dogs.

Antagonistic effect of atipamezole (80 micrograms/kg) on medetomidine (20 micrograms/kg)-midazolam (0.3 mg/kg) induced sedation was evaluated in dogs. Atipamezole effectively reversed sedation and significantly shortened arousal time and total recovery time without apparent side effects. Atipamezole also effectively reversed changes in heart rate, respiratory rate and body temperature produced by medetomidine-midazolam. The possible use of atipamezole as a reversal agent might enhance the value and availability of medetomidine-midazolam for a chemical restraint agent in dogs.

Adrenergic alpha-Agonists↗

Histopathological findings of the digits in dairy cows in Japan.

Two hundred and thirty-nine digits of 45 Holstein dairy cows, which were raised in typical Japanese dairy farms and received poor hoof management, were randomly obtained in the slaughterhouses and examined histopathologically. The findings were classified into 5 grades on the basis of the severity of circulatory disturbances and of keratogenesis. The lesions from Grade 1 to 5 were considered as manifestations of serial lesions indicating that subclinical laminitis advanced to other hoof lesions. The incidence of Grade 2, regarded as subclinical laminitis, reached approximately 50% of digits examined. The lesions classified as Grades 3 (23.9%) and 4 (5.4%) were mainly characterized by circulatory disturbances, which were similar to those of chronic laminitis in the previous reports. The incidence of Grade 5, characterized by sole ulcer, was 5.4%. It is suggested that a considerable number of daily cows in Japan suffered from subclinical laminitis, which may be the cause of recent high incidence of hoof diseases in dairy cows.

Animals↗

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↗

Establishment and characterization of a new cell line from a canine osteosarcoma.

A new cell line has been established directly from a spontaneous osteosarcoma on the femur of a 1.5-year-old male mongrel dog and named POS. Doubling time of the cells was approximately 33 hr. Morphologically, spherical cells, fibroblast-like cells, large or small polygonal cells and multinucleated giant cells seemed to be the major component of this cell line. The transmission electron microscopic feature of most of the cells was abundant dilated rough endoplasmic reticulum. Alkaline phosphatase activity as one of the osteoblastic properties was high in this cell line. The tumor tissue produced by the inoculation of the cells into nude mice was histologically identical to the original osteosarcoma.

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↗

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↗