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Biomedical subjects

T Nakata

Publications and source records attributed to T Nakata.

At least 217 records · Page 12Linked to original sources

Manidipine inhibits the progression of hypertension and atherosclerosis in endothelium-injured and cholesterol-fed Goldblatt 2K1C rats.

In the present study, arteriosclerotic change of the aorta was induced in rats. The effects of manidipine hydrochloride on the resulting hypertension and arteriosclerotic change were studied. In endothelium-injured cholesterol-fed Goldblatt 2K1C rats, moderate elevation of blood pressure was noted at 3, 4, and 5 weeks. Laboratory studies performed at the end of 6 weeks also showed hypercholesterolemia, accompanied by a reduction of triglycerides and HDL cholesterol. Regular doses of manidipine (200 or 500 mg/kg) resulted in a dose dependent inhibition of the blood pressure elevation and a reduction of HDL cholesterol, but had no effect on cholesterol or triglyceride levels. Morphological studies in endothelium-injured rats afflicted with hypercholesterolemia and hypertension, showed medial thickening and intimal hyperplasia. Hyperplasia of the intima was a result of excessive proliferation of the smooth muscle cells. These cells showed an unusually large number of fat droplets and were considered indicative of atheromatous plaque formation. In rats treated with manidipine, hyperplasia of the media was completely suppressed while hyperplasia of the intima was reduced by a minimum of 50%. This study demonstrated that hypercholesterolemia and hypertension produced arteriosclerotic change in endothelium-injured rats, which was inhibited by manidipine. It is not known whether antiarteriosclerotic action was involved in the antihypertensive effect of manidipine.

Animals↗

Effect of manidipine on cardiac hypertrophy and coronary circulation in DOCA/salt hypertensive rats.

The effect of manidipine on cardiac hypertrophy, coronary circulation, left ventricular weight and maximal coronary flow in hypertension was measured in DOCA/salt treated systolic hypertensive rats with and without manidipine treatment. Normotensive rats were used as controls. After feeding with 0.05% manidipine-containing food, blood pressure was reduced only in DOCA/salt hypertensive rats, but not in control rats. After 3 weeks of treatment, sodium excretion was significantly increased in DOCA/salt-treated rats with or without manidipine treatment. Hearts were removed and perfused with modified Krebs-Henseleit solution with adenosine (5 x 10(-5) M) in a Langendorff apparatus. Maximal coronary flow (MCF) was significantly decreased only in DOCA/salt hypertensive rats without treatment, while manidipine treatment restored MCF. Left ventricular weight/body weight was also markedly greater in DOCA/salt-treated rats not given manidipine. Left ventricular weight in DOCA/salt-treated rats given manidipine was significantly reduced compared with DOCA/salt hypertensive rats without treatment, although it was heavier than in the control animals. Morphological examination showed that the increased wall/lumen ratio in DOCA/salt hypertensive rats was reduced by manidipine treatment. These findings suggest that treatment with manidipine in DOCA/salt hypertensive rats lowered high blood pressure and improved impaired coronary circulation with a reduction in left ventricular and vascular hypertrophy.

Aldosterone↗

[Nd-YAG laser treatment for central airway lesions].

YAG laser treatment was conducted in 55 patients with central airway lesions over the last 8 years. The malignant lesions comprised 1 primary tracheal cancer, 1 chondroma of the trachea, 34 primary lung cancer, and 10 metastatic lung tumor. The benign lesions comprised one each of hamartoma, lipoma, bronchial lithiasis, post-tracheotomy granuloma, and bronchial web, and 3 other cases. Nd-YAG laser treatment was performed in 55 patients with airway lesions, with a success rate of 73%. The success rates in the above patients were 70% for primary lung cancer, 60% for metastatic lung tumor, 100% for primary tracheal cancer and chondroma of trachea, and 89% for benign lesions. In 34 patients with primary lung cancer, palliative widening of the airway was planned with the exception of 2 patients with endoscopically early lung cancer for whom curative vaporization was intended, 6 months-survival rate was 59.3% in patients in whom various combined treatments were performed after the laser treatment. For all patients with hamartoma or lipoma in those with benign lesions, curative vaporization was performed. The severe complication of lethal massive hemoptysis occurred in 3 patients. We consider that Nd-YAG laser treatment is a powerful therapeutic means of performing lifesaving or emergency, curative, and supplemental treatment.

Adult↗

[Role of oxygen radical and superoxide dismutase in ovulation in the rat].

We studied the effect of Cu,Zn-superoxide dismutase (SOD) and Mn-SOD, which are specific scavenging enzymes of the superoxide anion radical, on ovulation and examined the localization of SOD in rat ovaries. The results were as follows. 1) The number of ova in the Cu,Zn-SOD (8 mg x 4) administrated group (27.8 +/- 5.4 : p less than 0.01) was significantly reduced compared to the control group (49.0 +/- 3.3). Similarly, the number of ova in the Mn-SOD (2 mg x 2) administrated group (16.9 +/- 7.6 : p less than 0.01) was significantly reduced compared to the control (52.9 +/- 6.3). 2) In the rat ovary, Cu,Zn-SOD examined by the immunohistological method was found to be localized in the granulosa cells of mature Graafian follicles, growing follicles, primordial follicles and epithelial cells of the fallopian tubes. Mn-SOD was localized in the external theca cells of mature Graafian follicles and the corpus luteum. The activity of SOD estimated by the modified nitroblue tetrazolium method was consistent with the immunohistological localization of both SODs. We considered that oxygen radicals and SODs play an important role in rat ovulation, and Cu,ZN-SOD and Mn-SOD have a different localization and action in the rat ovary.

Animals↗

[Induction of manganese superoxide dismutase in ovarian carcinoma].

A monoclonal antibody against manganese superoxide dismutase (Mn-SOD) was assessed for its use in detecting a marker for epithelial ovarian carcinoma. An enzyme-linked immunosorbent assay has been developed to detect serum Mn-SOD. With this assay, only 1.7% of the 240 healthy females tested had more than 130 ng per milliliter of serum Mn-SOD. In contrast, 39 of 66 patients (59.1%) with epithelial ovarian carcinoma showed high levels of Mn-SOD. The serum Mn-SOD increased according to the clinical stage and declined to reflect the effect of therapy. The determination of Mn-SOD levels proved to be a clinical useful marker for monitoring the response to treatment and to early detection of the recurrence of epithelial ovarian carcinomas.

Adolescent↗

Organization of cortical cytoskeleton of cultured chromaffin cells and involvement in secretion as revealed by quick-freeze, deep-etching, and double-label immunoelectron microscopy.

We have studied the organization of the cytoskeleton in both unstimulated and stimulated cultured chromaffin cells, as well as its relationship with their secretory process by exocytosis. We found the spatial heterogeneity in the intensity of cortical rhodamine-phalloidin staining within a cell. The overall staining pattern or intensity was minimally altered after stimulation, although dopamine-beta-hydroxylase (DBH) antigen, a marker for the chromaffin granule membrane, was exposed preferentially on the plasma membrane areas with lower intensity of rhodamine-phalloidin staining. Using the quick-freeze, deep-etch technique, we found the heterogeneity in the organization of cortical cytoskeletal networks--some regions have actin filament bundles running parallel to the plasma membrane interspersed between granules and the plasma membrane, while others have few actin filaments beneath the plasma membrane before stimulation. Actin filaments were rarely observed in the inner cytoplasm. We did not observe the overall change in its organization after stimulation. Double-label immunogold EM using anti-DBH antibody and anti-actin antibody combined with statistical analysis showed that (1) DBH was exposed on the plasma membrane preferentially where actin was sparse after stimulation (significant at less than 0.1%), although (2) regions having sparse actin were not always the sites for DBH exposure, and (3) the cortical actin zone was sometimes disrupted at the DBH-exposed sites after stimulation. The present data suggested that (1) secretion is related to heterogeneous organization of cortical cytoskeleton after stimulation and (2) massive synchronized reorganization of the cytoskeleton in the whole cell is not necessary for secretion, although small changes of the cytoskeleton might occur under local regulation at each exocytotic site at the moment of the release.

Actins↗

Sympathetic inhibition and attenuation of spontaneous hypertension by PVN lesions in rats.

To determine whether the paraventricular nucleus (PVN) contributes to the development of hypertension in spontaneously hypertensive rats (SHR), we compared cardiovascular responses to ganglionic blockade with hexamethonium or vasopressin antagonism with dPVAVP in sham-operated or PVN lesioned SHR and Wistar-Kyoto rats (WKY). Lesions were produced electrolytically when the rats were 5 weeks old. During the next 3 weeks, tail-cuff measurements showed that the development of hypertension in SHR was inhibited, while systolic pressure in WKY was unaffected. Mean pressures recorded directly from the femoral artery at 8 weeks of age were lower in lesioned than in sham-operated SHR (141 +/- 5 vs 110 +/- 3 mm Hg, P less than 0.05), but did not differ in corresponding WKY groups (110 +/- 4 vs 112 +/- 5 mm Hg). Depressor responses to ganglionic blockade induced by i.v. injection of hexamethonium (25 mg/kg) were significantly larger in sham-operated than in lesioned SHR (-41 +/- 4% vs -28 +/- 3%, P less than 0.05). By contrast, vasopressin antagonism with dPVAVP did not alter blood pressure in all rat groups. In 24-h urine samples, excretion of vasopressin was unaffected, but that of norepinephrine was significantly reduced in lesioned SHR. These findings suggest that the PVN contributes to the development of spontaneous hypertension by sympathetic activation without increasing vasopressin secretion.

Animals↗

Effect of environmental stress on release of norepinephrine in posterior nucleus of the hypothalamus in awake rats: role of sinoaortic nerves.

Norepinephrine(NE) release in posterior nucleus(PH) of the hypothalamus was examined before and during acute shaker (oscillation) stress in sinoaortic denervated(SAD) and sham-operated(SO) rats. NE in PH extracellular fluid of freely moving rats was collected by microdialysis and measured by sensitive radioenzymatic assay. Three days after SAD or SO operation, mean arterial pressure(MAP) and heart rate(HR) were significantly higher in SAD rats than SO rats. Baseline levels of NE in PH dialysate were also significantly elevated in SAD rats. Although five minutes of shaker stress elicited pressor and tachycardic responses coupled with increased NE release in PH of both groups, the increases in MAP and dialysate NE were larger in SAD than SO rats. These findings indicate that noradrenergic neurons in the PH respond to stress-induced stimuli and receive tonic input from baroreflex pathways.

Animals↗

Predominant and developmentally regulated expression of dynamin in neurons.

We have cloned a cDNA for dynamin, a 100 kd microtubule-associated motor protein whose 5' region contains a GTP-binding motif homologous to that of the Mx proteins, from a rat brain library and analyzed its expression. Dynamin mRNA is 3.6 kb and is preferentially expressed in the brain after postnatal day 7, parallel to the developmental increase of the protein. In situ hybridization revealed high levels of dynamin transcripts in neural cells in the cerebellar cortex, hippocampus (particularly in the CA3 area), and cerebral cortex. The transcripts appeared in cerebellar granular cells only after they had ceased dividing and had migrated to the inner granular layer. We show that dynamin is expressed predominantly in neural cells after elongation of their processes, suggesting a role especially in mature neurons.

Adrenal Gland Neoplasms↗

Hypothalamic NE release and cardiovascular response to NaCl in sinoaortic-denervated rats.

We determined the activity of noradrenergic neurons in the nucleus of the posterior hypothalamus (PH) of sinoaortic-denervated (SAD) and sham-operated (SO) rats during cardiovascular responses to intravenous (iv) or local brain dialysis of NaCl. PH extracellular norepinephrine (NE) was collected by microdialysis from freely moving rats, and dialysate NE was measured by radioenzymatic assay. Three days after SAD or SO, mean arterial pressure (MAP) and heart rate (HR) were significantly higher in SAD rats than SO rats. Basal levels of PH dialysate were also significantly elevated in SAD rats. Local dialysis of PH with hypertonic NaCl produced pressor and tachycardiac responses coupled with increased NE release in PH in both groups, but the increases in MAP and dialysate NE were larger in SAD than SO rats. Ganglionic blockade with iv hexamethonium elicited significantly larger depressor and bradycardiac responses in SAD rats, whereas the percent increase of dialysate NE was smaller than that of SO rats. The iv infusion of hypertonic NaCl produced larger pressor responses in SAD than SO rats and a significant increase in dialysate NE from PH of SAD but not SO rats. These findings indicate that 1) PH is an important site of NaCl action and 2) noradrenergic input in PH receives tonic inhibitory input from baroreflex pathways and contributes to cardiovascular hyperactivity and hypertension in SAD rats.

Animals↗

A case of congenital left ventricular diverticulum with pulmonary stenosis and its scintigraphic characteristics.

We encountered a 31-year-old female patient with mild valvular pulmonary stenosis who had no abnormality in the electrocardiogram but pulmonary dilatation in the chest radiograph. Two-dimensional echocardiography and magnetic resonance imaging demonstrated two small protrusions at the interventricular septum indicating diverticula. Large perfusion defects were observed at the anterior wall in the thallium-201 myocardial tomograms. Short axial and vertical long axial images by ECG-gated blood pool tomography revealed an out-pouching best seen during diastole and a good contraction during systole in the corresponding areas. These findings suggested the presence of thin but normal myocardium in the anterior wall, i.e. a muscular type of left ventricular diverticulum. The presence of the muscular type of left ventricular diverticulum at the anterior and septal walls was confirmed by contrast left ventriculography. A congenital diverticulum at the anterior and septal walls with pulmonary stenosis is very rare. Furthermore, its scintigraphic images were quite characteristic and useful for its diagnosis.

Adult↗

Enhanced norepinephrine release in hypothalamus from locus coeruleus in SHR.

The hypothesis that a functional projection from the locus coeruleus (LC) to the posterior hypothalamus contributes to the development of hypertension in SHR, was tested by measuring norepinephrine (NE) in the posterior hypothalamus by brain dialysis after injections of L-glutamate (L-glu) into LC. L-glu elicited a prolonged elevation of blood pressure in both SHR and WKY. Pressor effects were significantly larger in SHR than in WKY. Extracellular NE in the posterior hypothalamus increased after LC stimulation; NE release was significantly higher in SHR than in WKY. Injections of 6-hydroxydopamine (6-OHDA) into posterior hypothalamus lowered the resting blood pressure and attenuated the pressor responses to L-glu injections into the LC in SHR. These findings suggest that the LC projects functionally to the posterior hypothalamus and that the projection can contribute to the development of hypertension in SHR.

Animals↗

Normalized left ventricular filling indexes to detect diastolic dysfunction in hypertension and in hypertrophic cardiomyopathy.

In order to establish a normalizing method for left ventricular filling indexes, peak filling rate (PFR) and time to peak filling rate (TPFR), derived from resting radionuclide ventriculography using Fourier analysis with third-order harmonics, were analyzed in 45 normal subjects, 40 hypertensive patients, and 29 patients with hypertrophic cardiomyopathy. PFR was significantly negatively correlated with age (r = -0.62) and significantly positively correlated with peak ejection rate (PER) (r = 0.58) in normals. TPFR normalized for heart rate (N-TPFR) was correlated positively with age in normals (r = 0.60) and hypertensives (r = 0.49) but not in patients with hypertrophic cardiomyopathy. N-TPFR was not significantly correlated with systolic parameters. A significant relationship between PFR normalized to PER (PFR/PER) and age was observed in normals (r = -0.58) but not in patients with hypertension or hypertrophic cardiomyopathy. To cancel the ageing effect, individual data of PFR/PER and N-TPFR were expressed as a percentage of the predicted regression value in normal subjects (%PFR/PER and %N-TPFR, respectively). Per cent PFR/PER was significantly lower and %N-TPFR was significantly greater in patients with hypertension and hypertrophic cardiomyopathy compared to normals. When normal limits of these indexes were defined as %PFR/PER greater than 80% and %N-TPFR less than 120%, the sensitivity, specificity and diagnostic accuracy of differentiating normals from patients with hypertension or hypertrophic cardiomyopathy were 41 of 45 (91%), 44 of 68 (65%), and 85 of 113 (75%), respectively. These findings indicate that %PFR/PER and %N-TPFR might be more reasonably normalized parameters for describing diastolic filling and its abnormality.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Myocardial accumulation of monoclonal antimyosin Fab in hypertrophic cardiomyopathy and postpartum cardiomyopathy.

Indium-111-antimyosin Fab scan was performed in patients with hypertrophic and postpartum cardiomyopathies to assess whether or not myocardial damage can be delineated. In two patients with hypertrophic cardiomyopathy, intense and diffuse antimyosin uptake was observed, although there was no evidence of acute myocardial damage or wall motion abnormality. A patient with postpartum cardiomyopathy showed a dense and relatively localized accumulation in the left ventricular anterior wall in association with thallium perfusion and wall motion abnormalities. Thus, antimyosin scanning can delineate not only manifested but also subclinical myocardial damage in hypertrophic and postpartum cardiomyopathies which may not be detectable by other techniques.

Adult↗

Myocardial distribution of indium-111-antimyosin Fab in acute inferior and right ventricular infarction: comparison with technetium-99m-pyrophosphate imaging and histologic examination.

In a postmortem study of a 69-yr-old female patient who had suffered 2 yr previously a non-Q-wave anterior infarction and who had sustained just seven days earlier a left inferior and right ventricular infarction, the distribution of 111In-antimyosin Fab was compared to the results of 99mTc-pyrophosphate imaging and histologic examination. Indium-111-antimyosin Fab imaging could not be performed because of cardiogenic shock. However, postmortem gamma scintillation counting revealed increased activities of antimyosin Fab in the inferoapical and right ventricular infarcted regions in which 99mTc-pyrophosphate positive imagings were observed; in contrast, a histologically confirmed old subendocardial anterior infarction had no definite activity. Thus, the myocardial distribution of 111In-antimyosin Fab corresponded well to the results of 99mTc scintigrams and histologic examinations in a human heart, suggesting that this technique could be useful in vivo for detecting several-day-old myocardial infarction of the right ventricle as well as the left ventricle. Tissue from the 2-yr-old infarction was not identified by this technique.

Aged↗

[Scintigraphic diagnosis of postinfarction left ventricular aneurysm and the prediction of the residual left ventricular function after aneurysmectomy using ECG gated blood pool SPECT].

The diagnostic accuracy of ECG gated blood pool SPECT (blood pool SPECT) for detecting and quantify postinfarction left ventricular aneurysm (LVA) was assessed in 49 patients with myocardial infarction and 15 control subjects. LVA, which was detected in 35 of 49 patients, was defined as a regional protrusion through a cardiac cycle in contrast ventriculography and as a non-contracting segment with a markedly delayed phase angle in the tomographic functional images derived from phase analysis. The blood pool SPECT technique showed a high sensitivity (100%), specificity (78.6%) and accuracy (93.3%) for detecting LVA and was very useful for precisely determining LVA location and sizing contractile and non-contractile volume of left ventricle in patients with LVA. Furthermore, left ventricular ejection fraction (LVEF) after the excision of LVA was predicted using preoperative pool SPECT images in 9 patients. The predicted LVEF was closely correlated with the measured LVEF after the operation (y = 1.09x-4.37, r = 0.87, p less than 0.01). Thus, gated blood pool SPECT can be a useful non-invasive technique not only for detecting and quantifying left ventricular aneurysm but also for predicting a residual left ventricular function after aneurysmectomy.

Adult↗