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Biomedical subjects

T Nagata

Publications and source records attributed to T Nagata.

At least 433 records · Page 24Linked to original sources
PubMed1991

Possible role of prostacyclin synthase in altered prostacyclin generation in DOCA-salt hypertensive rats.

Prostacyclin (PGI2) synthase is one of the key enzymes for vasodepressor PGI2 biosynthesis in the vascular wall. In this study, we attempted to define the alterations in PGI2 synthase and its role in the PGI2 generation in the vascular wall of deoxycorticosterone acetate (DOCA)-salt rats. The PGI2-generating capacity was enhanced significantly when DOCA-salt rats established hypertension, whereas the generation of other arachidonate metabolites, eg, PGE2, PGF2 alpha, and thromboxane, was unaltered. Moreover, the increase in PGI2 generation was associated with an increase in PGI2 synthase activity in the vascular wall. Indeed, the averaged PGI2 generating capacity was closely correlated to the averaged PGI2 synthase activity in DOCA-salt hypertensive rats and three lines of control rats. Incontrast, phospholipase C and phospholipase A2, both of which liberate arachidonate for PGI2 synthesis, were rather lowered in DOCA-salt hypertensive rats. These data clearly indicate that vascular PGI2 generation is increased in the development of DOCA-salt hypertension and that PGI2 synthase is mainly responsible for this enhancement. The increased PGI2 synthase may be relevant to the blood pressure elevation and is expected to have beneficial effects on the vascular protection in hypertension.

Animals↗
PubMed1991

Evidence for medial-mass regression in the vascular wall of Dahl hypertensive rats by cicletanine treatment.

We designed experiments to investigate the effects of cicletanine, a novel antihypertensive drug, on medial hypertrophy in Dahl rats susceptible to salt-induced hypertension (Dahl S rats). Cicletanine treatment (500 mg of cicletanine/kg of chow) for 6 weeks lowered blood pressure by 19% in Dahl S rats challenged with a high-salt (4%) diet. The blood pressure reduction was associated with a significant decrease in weight of the aortic vessels. Morphological examination revealed that this treatment decreased medial hypertrophy and expansion of intimal tissue, in concert with resolution of the periarteritis in the intrarenal arteries. In fact, the content of actin in the aortic wall, analyzed by SDS-PAGE, was decreased significantly with this treatment and myosin content was reduced to the same extent as well. Moreover, cicletanine per se lowered protein synthesis in randomly cycling cultured vascular smooth muscle cells (VSMCs) from Sprague-Dawley rats. Actin formation by VSMCs was decreased with cicletanine. Thus, these data indicate that chronic cicletanine treatment produces regression of the medial hypertrophy in Dahl S rats. Direct inhibitory effects on cytoskeleton protein synthesis, as well as its antihypertensive action, are partly responsible for this regression in vivo.

Animals↗
PubMed1991

Antiproliferative effects of the serotonin type 2 receptor antagonist, ketanserin, on smooth muscle cell growth in rats.

We defined the role of a serotonin type 2 receptor antagonist, ketanserin, in the growth of aortic vascular smooth muscle cells (VSMCs) from Wistar rats, using cell culture and cell synchrony methods. Deoxyribonucleic acid (DNA) replication in the G0/G1- or G1/S-synchronized VSMCs was assessed by [3H]thymidine uptake into DNA. Ketanserin at 2 x 10(-5) M significantly decreased the thymidine uptake by 48% in the proliferating VSMCs, whereas methysergide, a nonspecific serotonin inhibitor, unaffected the thymidine uptake. Ketanserin at 10(-5) M did not influence the duration of the G1 resting period. However, this dose of ketanserin significantly lowered DNA replication in the DNA synthetic (S) period in a dose-dependent manner. Neither methysergide nor the alpha 1-adrenoceptor antagonist, prazosin, affected DNA synthesis in the S period. Ketanserin exhibits antiproliferative effects on rat VSMC growth probably through the suppression of DNA replication in the S phase. This property would also contribute to the vascular protective effects of ketanserin with its well-documented antihypertensive action.

Animals↗
PubMed1991

Immunoelectron microscopic study of a new D-amino acid oxidase-immunoreactive subcompartment in rat liver peroxisomes.

We report the presence of a new subcompartment in rat liver peroxisomal matrix in which only D-amino acid oxidase is localized and other matrix enzymes are absent. By electron microscopic observation, the rat liver peroxisome has generally been considered to consist of a single limiting membrane, an electron-dense crystalline core, and a homogeneous matrix. Immunohistochemical staining for D-amino acid oxidase by the protein A-gold technique revealed the presence of a small area in the matrix that was immunoreactive for the enzyme and was less electron-dense than the surrounding matrix. The localization of D-amino acid oxidase in this small area of the peroxisomal matrix was confirmed by immunoelectron microscopy on freeze-substituted tissues processed without chemical fixation. To analyze the characteristics of the electron-lucent area, immunoreactivity for various peroxisomal enzymes, including catalase, acyl-CoA oxidase, enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase bifunctional protein, 3-ketoacyl-CoA thiolase, L-alpha-hydroxy acid oxidase (isozyme B), and glycolate oxidase (isozyme A), was assayed. The electron-lucent area was negative for all of these. By double staining for D-amino acid oxidase and catalase, using colloidal gold particles of different sizes, these enzymes were shown to be located in separate areas in the matrix.

Animals↗
PubMed1991

Immunoelectron microscopic evidence for organ differences in the composition of peroxisome-specific membrane polypeptides among three rat organs: liver, kidney, and small intestine.

We examined the distribution of peroxisome-specific membrane polypeptides (PMPs) among peroxisomes of the liver, renal cortex, and jejunal mucosa, using antibodies for 70 KD, 26 KD and 22 KD PMPs. Immunoblot analysis showed signals for 70 KD polypeptide in all three kinds of tissue, but for the other two only in the liver and renal cortex, with neither being detected in jejunal mucosa. The total amounts of PMPs increased in all three organs with DEHP (di-(2-ethylhexyl)phthalate) administration. By immunoelectron microscopic analysis using protein A-gold, the three PMPs were localized along the peroxisomal membrane. Quantitation of the gold particles associated with the peroxisomal membrane showed an increase in the density of 70 KD and 26 KD PMPs but a decrease in 22 KD PMP with the administration of DEHP. The presence of tissue-specific localizations of PMPs suggest the 70 KD PMP is a common constituent of peroxisomes of these three tissues, whereas 26 KD and 22 KD PMPs are absent in microperoxisomes of jejunal mucosal epithelium.

ATP-Binding Cassette Transporters↗
PubMed1991

Nifedipine-induced gingival hyperplasia: a clinical and in vitro study.

Two cases of gingival hyperplasia associated with long-term administration of nifedipine, a drug that dilates coronary arteries, are reported. The clinical and histopathological features of the gingival hyperplasia induced by nifedipine were similar to those induced by phenytoin, an anticonvulsant drug. In the present cases, gingival inflammation had developed before drug administration. In one case, extensive dental plaque control in addition to surgical removal of the overgrown gingival tissues resulted in satisfactory progress without the need to discontinue drug administration, suggesting that the preexisting gingival inflammation was involved in the development of this periodontal disease. In the other case, change from nifedipine to another drug resulted in spontaneous recovery, strongly suggesting that the drug had induced the gingival hyperplasia. Nifedipine had no direct effects in vitro on proliferation or collagen synthesis of gingival fibroblastic cells from one of the patients. Study of these two cases suggests that both local inflammatory factors and long-term administration of nifedipine were responsible for the gingival hyperplastic changes observed.

Cell Division↗
PubMed1991

Protective effect of taurine against acute paraquat intoxication in rats.

The effect of taurine (TA) on acute paraquat (PQ) intoxication was investigated in rats. Treatment with TA was begun 10 min after rats received a s. c. injection of PQ 40 mg/kg. Saline (0.9%) or 5% TA solution were infused i.v. for 5-6 min (short-interval infusion study). One hour after TA infusion, PQ concentration in the blood was increased and that in the urine was lowered, as compared with those in the saline-infused group. Significant increases of the PQ concentration was observed in kidney at 3 hours after TA administration. Excreted urine volume was significantly higher in the TA group during the time-period of 0-1 and 0-5 hours after the 5% TA administration compared with that of the saline group. However, there were no significant differences in total urinary PQ excretion between the two groups. Saline or 2.5% and 5% TA was infused continuously during the time-period of 0-1, 0-3 or 0-5 hours (long-interval infusion study). A marked increase in PQ concentration in blood and a reduction of PQ concentration in kidney were noticed during the time-period of 1-5 hours after the 5%TA infusion. Urinary excretion was remarkably accelerated by 5% TA infusion and the total urine volume increased to 20 times during the time-period 0-1 hour and 1.7 times during the time-period of 3-5 hours as compared with the saline control. In addition, urinary volume during the time-period of 0-5 hours almost reached that of 5% TA volume which infused to animals. The mortality rate of the groups that received either single or double short-time infusion of 5% TA was 100%. Thus, these results suggest that a long continuous infusion of 5% TA increased urine output and inhibits of PQ accumulation in renal tissue despite a rise in blood PQ concentration.

Acute Disease↗
PubMed1991

A lectin from the mushroom Pholiota aurivella.

A lectin was isolated from the fruiting bodies of Pholiota aurivella by preparative PAGE and named PAA (Pholiota aurivella agglutinin). PAA was a polymeric protein of more than several hundred kDa consisting of 18-kDa subunits. The amino acids were sequenced from the N-terminus of the lectin; they were YSVTTPNSVKGGTNQG. PAA agglutinated human erythrocytes regardless of blood type equally and Pronase treatment of erythrocytes increased the sensitivity to agglutination by the lectin. In a hemaggluting inhibition assay, none of the mono-and oligosaccharides used affected agglutination by the lectin. Among glycoproteins, asialofetuin was the best inhibitor. This is first isolated and characterized lectin from the family Strophariaceae.

Amino Acid Sequence↗
PubMed1991

Protein synthesis in the livers of aging mice studied by electron microscopic radioautography.

The application of 3H-leucine results in labeling of the liver cells of mice in which protein is synthesized at various ages of the animals. Quantitative changes of protein synthesis in the hepatocytes of aging mice were studied by electron microscopic radioautography. The silver grains in the hepatocytes were mainly located over the rough surfaced endoplasmic reticulum, mitochondria, Golgi apparatus, cytoplasmic matrix, and a few over the nuclei. The number of silver grains in the cytoplasm and nuclei of the hepatocytes gradually increased after birth, reached the maximum at 1 month after birth, thereafter it continued to decrease with aging until the 24th month. The number of silver grains in the hepatocyte cytoplasm was more than that in nuclei at various ages. The number of silver grains in the rough surfaced endoplasmic reticulum and mitochondria gradually increased from embryo to 1 month after birth, thereafter it continued to decrease with aging until the 24th month. The number of silver grains in the Golgi apparatus showed almost no change from fetal stage to 6 months after birth, thereafter it continued to decrease with aging until the 24th month. The number of silver grains in the cytoplasmic matrix gradually increased from fetal stage to 2 months after birth, then decreased with aging until the 24th month. These changes reflect the quantity of protein synthesized in each cell organelle at various ages of animals.

Aging↗
PubMed1991

Three-dimensional structure of the sarcoplasmic reticulum of skeletal myofibers in chicken and frog.

The three-dimensional structure of the sarcoplasmic reticulum (SR) of the twitch and slow tonic fibers in the skeletal muscles of the chicken and frog was examined using a modified Golgi method combined with stereoscopy employing high-voltage electron microscopy. In both types of fibers the SR network was classified into two categories, intermyofibrillar SR and subsarcolemmal SR. The intermyofibrillar SR in twitch fibers was basically similar and consisting of three or four typical structural regions. The configuration of the intermyofibrillar SR in twitch fibers was divided into two main groups which represented the SR in the fast twitch and the slow twitch fibers. The form of intermyofibrillar SR in slow tonic fibers is entirely different from that in twitch fibers in chicken, whereas it was rather similar in frogs. Regarding their function, the most striking feature of the SR structure was the paucity of the junctional SR in slow tonic fibers. The structure of subsarcolemmal SR in slow tonic fibers of the chicken and frogs was almost the same as in twitch fibers, forming polygonal mesh at the center of A-band and a loose tubular network including distended cisternae.

Animals↗
PubMed1991

Quantitative assessment of lysosomal size, number and enzyme activity in mouse kidney during maturational development.

Image and cytochemical analyses were undertaken to determine possible correlation between the number and size of acid phosphatase-positive granules (lysosomes), and variation in acid phosphatase (AcP) activity in the proximal tubule cells of mouse-kidney during growth and development. Eighteen ddY strain mice ages: 1 day, 1 and 2 weeks, and 1, 2 and 10 months were used. The lanthanide-based method for the ultrastructural localization of AcP-activity was employed. The number and size of AcP positive granules were quantitatively analyzed by image analysis, and AcP activity by X-ray microanalysis. Significance was evaluated by 2-tailed-Student's t-test for the difference between means. AcP activity was observed in the lysosomes and the reaction product appeared dense and heterogeneous. In some cells, it appeared apparently homogeneous. The results showed that the number and size of AcP Positive granules (lysosomes) increased significantly from the first day after birth, recorded a peak in one week time and thereafter, it gradually declined until the 10th month. The result of X-ray microanalysis demonstrated a variation in accordance with the degree of AcP activity at different ages of the animals studied. The AcP activity decreased significantly from day one and progressively until the 10th month. From the results of the present work, it could be inferred that the changes in size and number of AcP positive granules, at least, at the early stage, and/or the variation in AcP activity are related to the growth and development of the animal.

Acid Phosphatase↗
PubMed1991

[Follow-up study in a case of traumatic epilepsy with increased accumulation of 123I-N-isopropyl-p-iodoamphetamine].

Recent studies suggested the potential use of 123I-N-isopropyl-p-iodoamphetamine (IMP) for the assessment of pathophysiology of epilepsy. We studied a case of epilepsy with increased accumulation of IMP. Brain SPECT scan of IMP was performed in a case of 31-year-old male with traumatic epilepsy. Increased accumulation of IMP was observed in the left temporal area on both early (20 min after injection) and delayed (3 hr) images of studied 6 weeks after the head trauma. X-CT did not show any abnormalities. The accumulation of IMP decreased as the symptom of the patient improved. The SPECT study performed 3 months after the accident showed slightly decreased uptake in the left temporal area on the early image with homogeneous uptake in the delayed image. These findings suggested the altered retention mechanism of IMP in this case.

Adult↗
PubMed1991

Immunohistochemical evidence for the overexpression of protein kinase C in proliferative diseases of human thyroid.

We report immunohistochemical evidence for the overexpression of protein kinase C in various proliferative diseases of human thyroid. Immunohistochemical characterization of various surgically removed thyroid tissues, viz., cancer tissues: papillary carcinoma and follicular carcinoma; adenoma tissues: tubular, trabecular and colloid adenomas; adenomatous goiter; and normal thyroid was done using the monospecific monoclonal antibodies MC-1a, MC-2a and MC-3a, each of which is specific for types I, II and III isozymes of protein kinase C, respectively. For protein kinase C type II, a remarkable difference in staining intensity was noted between the cancerous and normal tissues. The cytoplasm of papillary and follicular carcinoma cells stained more intensely than that of normal thyroid cells. In the benign tumor and adenomatous goiter tissues, stronger staining was noted in the papilliform-proliferating portion and cubic epithelial cells. In the normal thyroid tissues, epithelial cells of greater height were more strongly stained than simple squamous epithelial cells. These results indicated that protein kinase C type II isozyme is expressed in larger amounts in cancerous and proliferative tissues of the human thyroid.

Adenocarcinoma↗
PubMed1991

[A case of central retinal vein occlusion accompanied by central retinal artery occlusion].

A 81-year-old woman developed central retinal vein occlusion (CRVO) in her left eye subsequent to central retinal artery occlusion (CRAO). She noticed sudden visual loss in the left eye. At initial examination, her left visual acuity was 0.03, and only a small visual field was preserved at temporal area. The left fundus showed findings of mild non-ischemic CRVO. In addition white clouded retina was recognized at the left posterior pole which indicated CRAO. FAG showed remarkably prolonged arterial circulation, but no retinal capillary obliteration. Then retinal hemorrhage increased rapidly and her left eye developed hemorrhagic retinopathy. Two weeks after initial examination, FAG showed extensive retinal capillary obliteration. In this case it was supposed that central retinal artery occlusion due to arteriosclerosis produced ischemic capillaropathy and venous thrombosis, after which restoration of arterial circulation caused hemorrhagic retinopathy.

Aged↗
PubMed1991

X-ray microanalysis of cerium in mouse spleen cells demonstrating acid phosphatase activity using high voltage electron microscope.

An X-ray microanalytical study was carried out on mouse spleen cells demonstrating acid phosphatase (AcP-A) activity, using cerium (Ce) as the capture agent at different accelerating voltages. The enzyme reaction products were localized in the lysosomes and appeared dense and homogeneous. The presence of cerium was confirmed by X-ray microanalysis. The main spectral line of cerium was present at La = 4.84 keV. The result showed that the X-ray count of Ce and the background (B) decreased significantly with increasing accelerating voltage between 100 and 400 kV. The change was more pronounced between 100 and 200 kV and thereafter, minimal change was noted. Consequently, the computed P/B ratio increased appreciably with increasing accelerating voltage. Thus, significant P/B ratio in X-ray microanalysis of biological specimens could be achieved by using a medium voltage transmission analytical electron microscope at accelerating voltage between 300 and 400 kV.

Acid Phosphatase↗
PubMed1991

[Coplanar PCBs, PCDFs and PCDDs in the subcutaneous adipose tissue of Yusho patients and normal controls].

3,4,3',4'-tetrachlorobiphenyl (T4CB), 3,4,5,3',4'-pentachlorobiphenyl (P5CB) and 3,4,5,3',4',5'-hexachlorobiphenyl (H6CB) [Co-PCBs] in the subcutaneous adipose tissue of seven Yusho patients and eight normal controls were determined to assess the contribution in the risk caused by the Yusho causual agents (PCBs, PCDFs, PCDDs and Co-PCBs) by using high resolution gas chromatography/high resolution mass spectrometry in selected ion monitoring mode. 3,4,3',4'-T4CB, 3,4,5,3',4'-P5CB and 3,4,5,3',4',5'-H6CB were detected in the subcutaneous adipose tissue of the Yusho patients at the levels, of 6 to 29 ppt, of 32 to 130 ppt and of 160 to 1,140 ppt, respectively. The TCDD-Eq (Equivalents) value calculated by TCDD-TEfs (Toxic Equivalent factors) was from 8 to 30 ppt. On the other hand, 3,4,3',4'-T4CB, 3,4,5,3',4'-P5CB and 3,4,5,3',4',5'-H6CB were detected in the subcutaneous adipose tissue of normal controls at the levels, of 3 to 9 ppt, of 41 to 280 ppt and of 47 to 200 ppt, respectively. The TCDD-Eq value calculated by TCDD-TEfs was from 9 to 57 ppt. In the Yusho patients, the average TCDD-Eq value calculated by TCDD-TEfs of the residual Co-PCBs, PCDFs and PCDDs was 17, 491 and 24 ppt, respectively. Therefore, we concluded that the typical symptoms for the Yusho patients are caused mostly by PCDFs.

Adipose Tissue↗
PubMed1991

Postmortem changes of ingested thinner components in tissues.

Postmortem changes of thinner components in body tissues were examined in rats, orally given 1 ml of standard thinner solution, which was prepared by mixing toluene, ethyl acetate and isobutanol in the proportion of 8:1:1. Analysis was made by gas chromatography combined with the head space method. Three thinner components and ethanol, a metabolite of ethyl acetate, were detected in the gastric contents of all rats up until 48 hours after death. An increase in the concentration of toluene was found in the blood, lung, kidney, liver, brain and abdominal muscle with the lapse of time. On the other hand, no changes were observed in the thigh muscle throughout the 48-hour period. Isobutanol showed a similar increasing pattern to toluene, with little or no changes in the brain or in the thigh muscle. Ethyl acetate was not detected in any tissues throughout the study but it was found in the gastric contents. The results indicate that every thinner component ingested, gradually diffuses into the surrounding tissues through the stomach wall after death, and that only muscle tissue remote from the abdominal cavity, together with the gastric contents, should be analyzed for a correct diagnosis of thinner ingestion.

Administration, Oral↗