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Biomedical subjects

N Takeda

Publications and source records attributed to N Takeda.

At least 343 records · Page 19Linked to original sources
PubMed1994

Effects of delapril hydrochloride on the myocardium of spontaneously hypertensive rats.

OBJECTIVE: To investigate the effects of long term treatment with delapril hydrochloride (an angiotensin-converting enzyme inhibitor) on myocardial contractility and ventricular myosin isoenzymes in spontaneously hypertensive rats (SHR). DESIGN: Delapril hydrochloride (10 mg/kg/day by mouth) was administered to 22- to 24-week-old male SHR for eight to 10 weeks. The isometric contractions of isolated left ventricular papillary muscles were observed while being perfused with Tyrode's solution (32 degrees C, pH 7.4, bubbled with 95% oxygen: 5% carbon dioxide, stimulation frequency 0.2 Hz). The left ventricular myosin isoenzymes were separated using pyrophosphate-gel electrophoresis. MAIN RESULTS: The mean systolic blood pressure of the delapril-treated group was significantly lower than that of the untreated control group. The mean ventricular weight was also lower in the delapril-treated than control group (mean +/- SD, untreated: 211 +/- 11 mmHg, n = 6; delapril-treated: 183 +/- 14 mmHg, n = 8, P < 0.01). The mean isometric developed tension (T) and +/-dT/dtmax of isolated left ventricular papillary muscles from the delapril-treated and untreated SHR did not differ significantly. The left ventricular myosin isoenzyme pattern obtained by pyrophosphate-gel electrophoresis, however, showed a significant shift towards VM-1 after long term delapril treatment. CONCLUSIONS: Long term treatment of SHR with delapril hydrochloride reduced blood pressure, which was associated with regression of cardiac hypertrophy, and changed the ventricular myosin isoenzyme pattern without significantly affecting myocardial contractility.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1994

1H-NMR analysis of nerve edema in the streptozotocin-induced diabetic rat.

To define the existence of intracellular hydration caused by metabolic derangements in the excised sciatic nerves of diabetic rats quantitatively, relaxation times (T1, T2) and fraction of intracellular water content were measured with 1H-nuclear magnetic resonance (NMR) spectroscopy in normal rats (control group, n = 10), streptozotocin (STZ)-induced (50 mg/kg, i.v.) diabetic rats (DM group, n = 10), STZ-induced diabetic rats treated with an aldose reductase inhibitor (ARI, Epalrestat, 100 mg/kg) (ARI group, n = 8), and STZ-induced diabetic rats treated with insulin (insulin group, n = 4). For selective measurement of intracellular relaxation times, the inversion recovery (IR) method for conventional T1 and Carr-Purcell-Meiboom-Gill method for T2 were used with an aqueous chemical shift reagent, 10 mmol/L dysprosium triethylenetetramine-N,N,N',N",N"',N"'-hexaacetic acid, resulting in distinct separation of intracellular (Schwann cell, axon, endothelial cell, and pericyte) and extracellular waters under the isotonic condition of the rat sciatic nerves. Furthermore, a new method of driven-equilibrium single-pulse observation of T1 (DESPOT) was used for rapid measurement of T1 for the purpose of clinical application on magnetic resonance imaging (MRI). T1 values measured by the DESPOT and IR methods were significantly correlated (p < 0.001). Total and intracellular water contents, sorbitol contents, and relaxation times of the sciatic nerve taken from the DM group were significantly elevated (p < 0.01), while myoinositol (p < 0.01) and extracellular water (p < 0.05) contents were significantly decreased as compared with the control group. Both insulin and ARI treatments significantly improved relaxation times as compared with those in the DM group (p < 0.05-0.01). Relaxation times correlated positively with total water (T1, p < 0.05-0.01; T2, p < 0.01), intracellular water (T1, p < 0.001; T2, p < 0.001), and sorbitol (T1, p < 0.001; T2, p < 0.001) contents of the excised nerve. Sorbitol content correlated positively with total and intracellular water contents (p < 0.01) but negatively with extracellular water content (p < 0.05). These findings indicated that sorbitol itself and/or secondary sodium accumulation caused by an increase in sorbitol may be a major contributor to the increase in intracellular hydration and prolonged relaxation times associated with hyperglycemia, which are reversible with insulin or ARI treatment. It was also suggested that rapid T1 measurement would provide new insights into the pathogenesis of human diabetic neuropathy as a non-invasive evaluation method on MRI.

Aldehyde Reductase↗
PubMed1994

[The effects of transcorneal administration of prostaglandin E2 on rabbit eyes].

The pharmacologic effects of prostaglandin E2 (PGE2) on the anterior ocular segment were investigated. PGE2 was administered with a glass cylinder attached to the cornea in concentrations ranging from 0.05 to 500 micrograms/ml. The intraocular inflammatory reaction was assessed according to the changes in the anterior chamber flare, ocular tension, and components of the aqueous humor. We also performed experiments designed to inhibit the reactions induced by PGE2 using anti-inflammatory agents. The PGE2 elicited a single peak reaction in the anterior chamber flare, which recovered after several hours, and a transient elevation in the ocular tension in the early stage after PGE2 administration. Quantitative analysis of these two reactions revealed that both were dependent on the dose of PGE2 administered. The concentrations of ascorbic acid and glutathione, particularly that of the reduced form of the latter, were transiently reduced in the aqueous humor. The anterior chamber flares were suppressed by agents that inhibit arachdonic acid metabolism. These findings suggest that the metabolism of arachdonic acid becomes newly activated as a result of stimulation by PGE2 of extrinsic origin.

Animals↗
PubMed1993

Myocardial contractility and energetics in cardiac hypertrophy and its regression.

The changes in myocardial contractility and ventricular myosin isoenzymes were investigated in rats with pressure-overload cardiac hypertrophy as well as during its regression. Hypertrophic myocardium was obtained from rats with renovascular hypertension (Goldblatt rats), rats with abdominal aortic constriction (AC), and spontaneously hypertensive rats (SHR). Regression of cardiac hypertrophy was induced by lowering the blood pressure through nephrectomy on the affected side in Goldblatt rats, by opening the clip which constricted the abdominal aorta in AC rats, and by the administration of antihypertensive agents to SHR. The isometric developed tension of isolated left ventricular papillary muscles and the maximum rate of increase in the tension (dT/dtmax) were measured. Left ventricular myosin isoenzymes were separated by pyrophosphate gel electrophoresis. Isometric developed tension remained unchanged, but dT/dtmax was decreased in hypertrophic myocardium, although it recovered along with the regression of cardiac hypertrophy. The left ventricular myosin isoenzyme pattern was shifted towards V3 in hypertrophic myocardium, and shifted back again towards V1 with the regression of cardiac hypertrophy. These results indicate that relief of hemodynamic overload is one of the most important elements in the regression of cardiac hypertrophy and the associated physiological or biochemical alterations. However, other factors such as neurohumoral influences must also be taken into consideration.

Animals↗
PubMed1993

Beneficial effect of ACE inhibitor in congestive heart failure.

The effects of captopril, an angiotensin-converting enzyme inhibitor, on congestive heart failure (CHF) were investigated in animal and clinical studies. Congestive heart failure was induced in rats by a combination of pressure and volume overload. Cardiac pressure overload was induced by constricting one renal artery (Goldblatt rat) and volume overload was induced by aorto-caval fistula. Captopril (100 mg/kg/day) was then administered for 14 weeks. Isometric contraction was assessed using isolated left ventricular papillary muscles. The maximum developed tension and the maximum rate of increase in tension (dT/dtmax) were decreased in untreated rats with CHF and improved in captopril-treated rats. The left ventricular myosin isoenzyme pattern was shifted towards V3 in untreated rats with CHF, and was shifted back towards V1 in the captopril-treated rats. In the clinical study, captopril (37.5-75 mg/day) was administered to patients with cardiomyopathy for 12 months. There was no effect on left ventricular mass in hypertrophic cardiomyopathy, although systolic anterior motion of the mitral valve disappeared in one patient. In dilated cardiomyopathy, however, left ventricular mass tended to decrease. These results indicate that captopril has a beneficial effect in congestive heart failure.

Animals↗
PubMed1993

Presence of 3-deoxyglucosone, a potent protein crosslinking intermediate of Maillard reaction, in diabetic serum.

3-Deoxyglucosone, a potent protein crosslinking intermediate of the Maillard reaction, was first detected in diabetic serum using gas chromatography/mass spectrometry. Serum concentration of 3-deoxyglucosone was elevated in diabetic patients as compared with healthy subjects. More notably, diabetic patients with nephropathy showed higher serum concentration of 3-deoxyglucosone than those without nephropathy. The increased serum concentration of 3-deoxyglucosone in the diabetic patients suggests that 3-deoxyglucosone may be responsible for the development of diabetic complications such as diabetic nephropathy by promoting the formation of advanced glycation end products.

Adult↗
PubMed1993

Presence of N-methyldopamine in parkinsonian and normal human brains.

N-Methyldopamine (epinine) has been identified for the first time in parkinsonian and normal human brains by gas chromatography-mass spectrometry. N-Methylsalsolinol and N-methylnorsalsolinol, which are analogues of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine, which produces parkinsonism in humans, may be synthesized from N-methyldopamine by the Pictet-Spengler condensation reaction as an alternative metabolic pathway.

Brain↗
PubMed1993

Abnormalities of ADP/ATP carrier protein in J-2-N cardiomyopathic hamsters.

ADP/ATP carrier protein (AAC) is located in the mitochondrial inner membrane and has an important function in mitochondrial energy supply. This protein transports ATP to the cytoplasm and counter transports ADP into the mitochondria. J-2-N cardiomyopathic hamsters were investigated to determine the AAC content in cardiac mitochondria. After recording an electrocardiogram and collecting blood, the cardiac mitochondria were isolated. The mitochondrial membranes were labelled with eosin-5-maleimide (EMA) and separated on SDS polyacrylamide gels. The position of the AAC component was identified by exposing the gel under UV light, and the AAC content was determined by densitometry after staining with Coomassie blue. The AAC content ratio was significantly decreased in both 10-week-old and 1-year survived J-2-N hamsters when compared to control Golden hamster. Among 10-week-old J-2-N hamsters, the decrease in the AAC content ratio was more marked for the animals with more severe myocardial damage. The H(+)-ATPase activities of mitochondrial membrane were higher in 10-week-old J-2-N hamsters than in control hamsters. These results suggest that the decrease of AAC in J-2-N hamster plays an important role in the pathogenesis of cardiomyopathy in J-2-N hamsters.

Animals↗
PubMed1993

Mitochondrial DNA deletion in human myocardium.

Mutation of myocardial mitochondrial DNA was investigated in human left ventricles obtained at autopsy using the polymerase chain reaction (PCR). Seventeen autopsy cases were examined, including patients with diabetes mellitus, myocardial infarction, cardiomyopathy, cancer, and other diseases. Two cases of diabetes mellitus, 2 of myocardial infarction, and 1 of pulmonary fibrosis showed a 7.4 kb deletion of myocardial mitochondrial DNA. Primer shift PCR confirmed that an amplified DNA fragment had not been obtained by misannealing of the primers. It is unclear how much these findings are related to the severity or prognosis of the various diseases, but they indicate that mutation of myocardial mitochondrial DNA can occur in other diseases besides cardiomyopathy, although the influence of aging could not be excluded.

Aging↗
PubMed1993

A novel ES cell line, TT2, with high germline-differentiating potency.

In producing mutant mice by gene-targeting and gene-trapping in embryonic stem (ES) cells, the efficient colonization of the mutant ES cells into germline is still a critical matter. We have established a new line of ES cells, TT2, from an F1 embryo between a C57BL/6 female and a CBA male. When the TT2 cells were injected into blastocysts, the colonization into each tissue was very low. However, when injected into eight-cell embryos, the cells segregated inside the blastomeres, localized in an inner cell mass of blastocysts developed 1 day later, and colonized efficiently in each tissue of the pups. The pups were disproportionately male, about half of which were composed of TT2-derived cells primarily; in more than 70% of the males, TT2-derived cells were dominant, accounting for over half of the total cells. When these males were mated, they exclusively yielded TT2-derived offspring. The germline-differentiating potency was stable during 3 weeks of culture. Twenty-one of 24 mutant clones independently isolated yielded germline chimeras, and 19 clones yielded them in a rate comparable to that of the parent cells. Thus, TT2 cells can serve as a valuable vehicle for the production of mutant mice.

Animals↗
PubMed1993

Correlation of MRI and clinical features in meningeal carcinomatosis.

Ten patients with meningeal carcinomatosis associated with nonhaematological neoplasms were examined: six with breast, two with gastrointestinal and one with lung cancer, plus one with a tumour of unknown origin. Cytology was positive in all but one. The patients were classified into four groups according to the gadolinium-enhanced MRI (Gd-MRI) appearances: group 1 had pure leptomeningeal carcinomatosis, group 2 dural carcinomatosis, group 3 spinal leptomeningeal carcinomatosis, and group 4 had normal Gd-MRI except for hydrocephalus. In group 1, Gd-MRI showed diffuse enhancement of the subarachnoid space, including the cisterns around the midbrain, the sylvian fissures, or cerebellar and cerebral sulci. In group 2, Gd-MRI showed diffuse, thick, partially nodular enhancement of the dura mater. No leptomeningeal or subependymal enhancement was evident. In group 3, nodular masses were seen only in the spinal canal. In group 4, no definite evidence of meningeal carcinomatosis was demonstrated on contrast-enhanced CT (CE-CT) or Gd-MRI. The median survival time was 2.0 months in group 1, 1.0 month in group 3, and 4.5 months in group 4, but the two patients in group 2 were alive 10 and 15 months after a definite diagnosis of meningeal carcinomatosis was made. In all patients examined by both CE-CT and Gd-MRI, the latter was superior for identification of meningeal carcinomatosis. Hydrocephalus in an important indirect sign of leptomeningeal carcinomatosis, but was not seen in patients with dural carcinomatosis despite the presence of increased intracranial pressure.

Aged↗
PubMed1993

Three-dimensional distribution of myocardial fibrosis in the new J-2-N cardiomyopathic hamster: comparison with electrocardiographic findings.

Using the new J-2-N strain of cardiomyopathic hamster obtained by cross-breeding Bio 14.6 and Golden hamsters, we investigated the three-dimensional distribution of ventricular myocardial fibrosis and compared it with electrocardiographic (ECG) changes. Twelve-lead ECG recordings were made by our own method. The hearts were cut into serial sections and subjected to light microscopic examination. The distribution, density, and volume of myocardial interstitial fibrosis and replacement fibrosis due to myocardial degeneration (F%) were visualized three-dimensionally using the TRI system (TRI; Three-Dimensional Reconstruction Image; Ratoc System Engineering, Tokyo, Japan). Thirty-two J-2-N hamsters were divided into two groups; one group comprised 17 animals with normal hearts and normal ECG findings similar to those of Golden hamsters, and the other group of 15 hamsters had dilated hearts and abnormal ECG findings. In the normal hearts, the F% values for the right ventricle, left ventricle, and ventricular septum were 6.4 +/- 0.94, 6.5 +/- 0.95, and 6.5 +/- 0.98 (mean +/- SD), respectively. The dilated hearts showed marked fibrosis, which was distributed mainly in the middle layer of the left ventricle and the ventricular septum. The corresponding F% values for the hamsters with cardiac enlargement were 19 +/- 2.6, 19 +/- 1.8, and 22 +/- 3.2 (mean +/- SD), respectively. Replacement of myocytes by fibrosis seemed to correspond to abnormal Q waves in the anterior chest leads and left axis deviation of the QRS complex.

Animals↗
PubMed1993

Pica in rats is analogous to emesis: an animal model in emesis research.

Mitchell et al. (1976, 1977) suggested that pica, eating of nonnutritive substances such as kaolin, is an illness-response behavior in rats. In the present study, we first confirmed their suggestion and then examined the effects of antiemetics on emetic-induced pica in rats. Intraperitoneal injection of apomorphine induced dose-dependent kaolin consumption. Pretreatment with domperidone inhibited apomorphine-induced kaolin intake. Oral administration of copper sulfate and intraperitoneal injection of cisplatin also induced dose-dependent kaolin consumption. Pretreatment with ondansetron inhibited cisplatin-induced kaolin intake. These findings suggest that pica in rats was induced through 1) dopamine D2 receptors in the chemoreceptor trigger zone, and 2) the stomach, partly via 5-HT3 receptors in the visceral afferents in the stomach wall. The present findings support the conclusion that pica in rats is analogous to vomiting in other species and suggest that pica in rats is mediated by the same mechanisms as vomiting in humans. Accordingly, we extended the utility of the animal model to pharmacological research of emesis with pica as an analogue to emesis.

Animals↗
PubMed1993

Immunological analysis of the rats with anterior hypothalamic lesions.

We have previously identified the suppression of lymphocyte blastogenesis and the acceleration of growth of subcutaneous tumors by bilateral anterior hypothalamic lesions in rats. The present study was performed to clarify the changes in lymphocyte subsets and natural killer (NK) activity after making the lesions. The influence on immunological memory was also studied. The CD4/CD8 ratio of peripheral blood lymphocytes and spleen cells, T cell receptor alpha beta-positive cells of the thymocytes and NK activity of the spleen cells decreased significantly. Major histocompatibility complex (MHC) antigen expression on RBL-1 cells injected intraperitoneally into pre-immunized rats was also suppressed. These results suggest that the anterior hypothalamus has some influences on the control of the cellular immunological functions at the peripheral level, on the maturation of T cells at the level of thymus and on the antigen recognition by T cell receptors and MHC antigens.

Animals↗
PubMed1993

Changes in preproenkephalin mRNA after unilateral and bilateral labyrinthectomy in the rat medial vestibular nucleus.

We examined the expression of preproenkephalin (PPE) mRNA in the vestibular nuclei in rats using in situ hybridization histochemistry. In normal rats, PPE mRNA-positive cells were observed in the medial and spinal vestibular nuclei. After unilateral labyrinthectomy, PPE mRNA was increased in the medial vestibular nucleus on the operated side from the 1st through the 3rd day after the surgery. It is suggested that the changes in PPE mRNA level after labyrinthectomy are involved in vestibular compensation.

Animals↗
PubMed1993

Synaptic contact between vestibular afferent nerve and cholinergic efferent terminal: its putative mediation by nicotinic receptors.

The topography and fine structure of cholinergic efferent fibers were examined in the rat vestibular labyrinth using choline acetyltransferase (ChAT) immunohistochemistry. Fiber plexus of cholinergic fibers were observed beneath the sensory cell layer in all vestibular end-organs. Electron microscopic examination revealed that cholinergic fibers make synaptic contacts with chalices of vestibular nerve branches that surround type I hair cells. In situ hybridization histochemistry of nicotinic acetylcholine receptor subunit mRNAs showed that rat vestibular ganglion cells express both alpha 4 and beta 2 subunit mRNAs. These findings suggest that cholinergic efferents modulate vestibular information from type I hair cells by nicotinic receptors at the level of nerve chalices.

Acetylcholine↗
PubMed1993

Simultaneous analyses of monoamines and their metabolites in urine specimens of patients with neuroblastoma.

1. Tyrosine and tryptophan, as well as 26 metabolites of these amino acids, were analyzed simultaneously in urine specimens from patients with neuroblastoma and control infants by a three-dimensional HPLC system to develop an early diagnosis. 2. Levels of detected compounds in urine from patients with neuroblastoma were generally higher in the case of catecholamines and lower in the case of indolalkylamines than those in controls. 3. The pathways of Dopamine-3,4-Dihydroxyphenylacetic acid-Vanillylmandelic acid, Dopamine-3-Methoxy-4-hydroxyphenylethylene glycol-Vanillylmandelic acid and Tyrosine-4-Hydroxyphenylacetic acid-4 were, in particular, found to be active in patients with neuroblastoma.

Biogenic Monoamines↗