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Biomedical subjects

T Murakami

Publications and source records attributed to T Murakami.

At least 901 records · Page 50Linked to original sources

Close correlation between the dephosphorylation of p53 and growth suppression by transforming growth factor-beta 1 in nasopharyngeal carcinoma cells transduced with adenovirus early region genes.

The mechanism of growth inhibition by transforming growth factor (TGF)-beta 1 was investigated. We examined the growth inhibitory effects of TGF-beta 1 on human nasopharyngeal carcinoma (KB) cells which constitutively expressed p53. TGF-beta 1 suppressed the DNA synthesis of KB cells in a dose-dependent manner. It had minimal effect on adenovirus-2-transduced KB cells expressing either adenovirus early region 1B (E1B) or 1A (E1A) product, which respectively binds to p53 or Rb product and inhibits its function, and no growth inhibition at all was observed with KB cells expressing both E1B and E1A products. Dephosphorylation of the p53 was promoted by TGF-beta 1 stimulation in KB cells, but not in E1B-producing KB cells, which sequestrate the function of p53. The growth inhibition of KB cells by TGF-beta 1 was significantly reduced by treatment with okadaic acid. These results suggest that p53 transduces the antiproliferative signal of TGF-beta 1 possibly through its dephosphorylation.

Adenovirus E1A Proteins↗

The vascular tissue angiotensin I-converting enzyme activity and aortic elastin content in stroke-prone spontaneously hypertensive rats fed fish diet.

1. Stroke-prone spontaneously hypertensive rats (SHRSP) were fed a diet with fish meal as the protein source (fish diet) during the progressive stage of hypertension, and its effects on the activity of angiotensin I-converting enzyme (ACE) in serum and vascular tissues and on the aortic elastin content were studied. The effects of the antihypertensive drugs captopril and hydralazine were also studied. 2. Stroke-prone spontaneously hypertensive rats fed the fish diet showed a distinctly lower level (P < 0.05) of serum ACE activity than the control group fed a commercial stock chow. 3. ACE activity was enhanced in the SHRSP which was administered with captopril. 4. Serum ACE activity was similar in the SHRSP receiving the hydralazine treatment and the control group. 5. The thoracic aorta ACE activity was lowered more (P < 0.05) in the fish diet group and the captopril-treated group than in the control group. In the hydralazine-treated group however, the activity was similar to the control group. 6. The ratio of aorta weight to bodyweight was significantly lower (P < 0.05) in the fish diet group and the captopril-treated group than in the control group, but there was no difference in the hydralazine group. Higher levels of aortic elastin were observed in the drug-treated groups (P < 0.05). 7. No differences were seen between the fish diet and captopril-treated groups by electron-microscopy. 8. The results suggest that suppression of hypertrophy and ameliorations of reduction in elasticity of the vascular wall in the SHRSP fed a fish diet were due to inhibition of vascular tissue ACE activity.

Animals↗

Anti-obesity and anti-diabetic effects of carteolol in non-insulin-dependent diabetic mice.

1. When carteolol, a beta-adrenergic blocker, was administered to KK-Ay/Ta Jc1 mice that are obese and develop spontaneously non-insulin dependent diabetes, their increase in bodyweight was arrested from the age of 16 weeks. Since their intake of food and water was not influenced by carteolol treatment, compared with the control KK-Ay/Ta Jc1 mice, abolition of the weight gain might be attributed to increased energy metabolism. 2. Non-fasting serum glucose levels in carteolol-treated mice at the age of 17 weeks were within normal range (118 +/- 4 vs 186 +/- 12 mg/dL). An intraperitoneal glucose-tolerance test revealed that the carteolol treatment markedly restored glucose metabolism; fasting plasma glucose (88 +/- 6 mg/dL) was within normal range, and immunoreactive insulin (IRI; 5.8 +/- 0.8 vs 33.3 +/- 10.5 ng/mL) and plasma glucose levels at 60 min post glucose (361 +/- 44 vs 541 +/- 32 mg/dL) were significantly lower in carteolol-treated mice than those in the control group at the age of 20 weeks. 3. From these findings, carteolol is considered to have little effect on the growth of mice but to correct the obesity that develops after age 16 weeks, when their growth terminates. In addition, the normalization of blood glucose and marked decrease in IRI levels suggests that carteolol improves glucose tolerance by increasing the insulin sensitivity. 4. Since brown adipose tissue (BAT) is closely associated with thermogenesis and energy consumption, we tested whether carteolol may affect BAT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue, Brown↗

Inflammatory pseudotumor of the urinary bladder with an aberrant expression of cytokeratin.

A case of inflammatory pseudotumor of the urinary bladder in a 47 year old Japanese male patient is presented. Inflammatory pseudotumor of the urinary bladder is a benign but rare proliferative lesion of the submucosal stroma, easily mistaken for a malignant neoplasm. Based on the clinical diagnosis of bladder cancer by cystoscopy and magnetic resonance imaging (MRI), urologists started chemotherapy before results of the histological report were available which described inflammatory pseudotumor on the biopsy. Biopsied materials showed marked proliferation of irregularly bundled spindle cells, varied in size and shape and separated in severe loose myxoid stroma with moderate infiltration of the inflammatory cells and capillary proliferations. At a glance, these findings resemble the sarcomatous pattern. However neither severe nuclear atypism nor atypical mitoses were present. Immunohistochemically, these spindle cells, which were positive for vimentin and alpha-smooth muscle actin, showed a diffuse aberrant expression of cytokeratin. Some of them were positive for phosphotungstic acid hematoxylin. Electron microscopy revealed only the fibroblasts. No recurrence has been observed for 10 months. These findings indicate that inflammatory pseudotumor is a benign mesenchymal lesion that must be discriminated from true sarcoma to avoid subjecting the patient to unnecessary therapy. Only careful histological examination can enable a successful diagnosis.

Granuloma, Plasma Cell↗

Results of circulatory support for postoperative cardiogenic shock.

Over the last 5 years, 15 patients received ventricular assist devices (VADs) (Group 1) and 5 received percutaneous cardiopulmonary support (CPS) (Group 2) while in postoperative cardiogenic shock. Group 1 consisted of 8 men and 7 women ranging in age from 22 to 73 years (average age, 55 years). Nine of these patients underwent surgery for valve replacement, 5 for coronary artery bypass grafting, and 1 for closure of a ventricular septal rupture. The duration of VAD support ranged from 6 h to 9 days (mean, 3.9 days). Group 2 consisted of 4 men and 1 woman ranging in age from 49 to 68 years (average age, 57 years). One of these patients underwent surgery for valve replacement, 1 for coronary artery bypass grafting, 2 for replacement of a thoracic aneurysm, and 1 for left ventricular aneurysmectomy. The duration of CPS ranged from 4 h to 8 days (mean, 2.8 days). In Group 1, 13 patients were weaned from the VADs and 8 survived. Bleeding occurred in 5 patients, renal failure in 4, infection in 3, cardiac failure in 4, cerebral infarction in 1, perioperative myocardial infarction in 1, arrhythmia in 1, and ileus in 1. In Group 2, 4 patients were weaned from the CPS and 3 survived. Bleeding occurred in 3 patients, renal failure in 2, CNS injury in 2, and cardiopulmonary failure in 1. The 8 survivors in Group 1 have been followed for 2 to 56 months (mean, 28.7 months). Five patients were in NYHA class I, 2 were in class II and 1 was in class III.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Extraserosal invasion in advanced gastric cancer: evaluation with MR imaging.

PURPOSE: To evaluate the usefulness of magnetic resonance (MR) imaging in the diagnosis of extraserosal invasion in advanced gastric cancer. MATERIALS AND METHODS: MR imaging was performed in 48 patients with advanced gastric cancer, and the results were correlated with the histopathologic findings. Images perpendicular to the gastric wall with cancer were obtained with spoiled gradient-recalled acquisition in the steady state (GRASS). The degree of serosal invasion was classified on the basis of the appearance of a low-signal-intensity band around the lesion. RESULTS: Advanced gastric cancer appeared as a thickened wall of high signal intensity after the administration of contrast material. A low-signal-intensity band disappeared or showed irregularity in the area of extraserosal invasion by the gastric cancer. The MR imaging-determined grade correlated with the histopathologic findings for 11 of 14 (79%) pT2 tumors, 23 of 24 (96%) pT3 tumors, and eight of 10 (80%) pT4 tumors. The overall accuracy was 88%. CONCLUSION: Presence of a low-signal-intensity band at MR imaging is useful for the preoperative evaluation of serosal invasion.

Adult↗

Enzymatic and genetic adaptation of soleus muscle mitochondria to physical training in rats.

To evaluate the effects of physical training on mitochondrial gene expression and mitochondrial biogenesis in slow-twitch muscle, adult female Sprague-Dawley rats were trained for 3, 6, and 12 wk by running on a motor-driven treadmill (speed of 25 m/min and duration of 90 min/day, 5 days/wk), and the activities of citrate synthase, ubiquinol-cytochrome-c oxidoreductase, cytochrome oxidase, mitochondrial cytochrome b mRNA (by Northern blot analysis), and mitochondrial DNA (by slot-blot and Southern blot analyses) were measured in rat soleus muscle. A DNA probe for detection of mitochondrial mRNA and DNA was prepared from a 1,500-bp fragment of human mitochondrial DNA that included the coding region of the cytochrome b gene. Training for 3, 6, and 12 wk significantly increased the activities of citrate synthase (31, 28, and 47%, respectively), ubiquinol-cytochrome-c oxidoreductase (61, 63, and 77%, respectively), and cytochrome oxidase (25, 26, and 32%, respectively) in muscle. The concentration of cytochrome b mRNA in the muscle was proportionally elevated with the enzyme activities. On the other hand, the mitochondrial DNA concentration in the muscle was not altered by training for 3 or 6 wk but increased significantly after training for 12 wk (35% in the slot-blot analysis and 31% in the Southern blot analysis). These results suggest that an increase in the oxidative capacity of slow-twitch muscle by the relatively short-term training is regulated at the pretranslational step in mitochondrial protein synthesis but that the increase by the long-term training involves mitochondrial replication.

Adaptation, Physiological↗

Pravastatin effectively lowers LDL cholesterol in familial combined hyperlipidemia without changing LDL subclass pattern.

Familial combined hyperlipidemia (FCHL) is the most common genetic lipid disorder among young survivors of myocardial infarction. Elevations of plasma total and low-density lipoprotein (LDL) cholesterol and the prevalence of small, dense LDL particles are both involved in the high coronary risk of FCHL patients. We investigated the ability of pravastatin to favorably correct plasma lipid and lipoprotein levels and LDL structure in FCHL patients. Twelve patients with FCHL, documented by studies of first-degree relatives, received pravastatin (40 mg/d) for 12 weeks. Pravastatin significantly lowered plasma total and LDL cholesterol levels by 21% and 32%, respectively. Triglyceride levels did not change, and apolipoprotein B (apoB) concentrations decreased by 9% (P = NS). High-density lipoprotein (HDL) cholesterol increased by 6% because of a significant 73% rise of HDL2 cholesterol. LDL were smaller (diameter, 24.5 +/- 0.5 nm), less buoyant, and apoB-rich (cholesteryl ester-apoB ratio, 1.64 +/- 0.46) in the selected patients compared with patients with familial hypercholesterolemia or healthy control subjects. LDL became even smaller (23.8 +/- 0.6 nm) and richer in apoB (cholesteryl ester-apoB ratio, 1.27 +/- 0.52) after pravastatin treatment. Although pravastatin favorably altered plasma lipid and lipoprotein levels in FCHL patients, the abnormal LDL particle distribution and composition were not affected. Because of the apparent resistance of the small, dense LDL to drug-induced modifications, a maximal lipid-lowering effect is needed to reduce coronary risk in FCHL patients.

Adult↗

Chronic dynamic exercise improves a functional abnormality of the G stimulatory protein in cardiomyopathic BIO 53.58 Syrian hamsters.

BACKGROUND: The effects of chronic exercise training on myocardial contractility and beta-adrenergic signal transduction in hearts with left ventricular dysfunction have not been determined. METHODS AND RESULTS: Fourteen-week-old cardiomyopathic BIO 53.58 and normal F1B Syrian hamsters underwent 10 weeks of treadmill training and were compared with 24-week-old BIO 53.58 and F1B untrained controls. Left ventricular isovolumic maximum positive dP/dt and peak developed pressure were significantly lower in BIO 53.58 than in F1B controls. Exercise training improved left ventricular contractile indices in BIO 53.58 but not F1B hamsters. The left ventricular beta-adrenergic receptor number (Bmax) was similar in BIO 53.58 and F1B controls. Basal adenylate cyclase activity (ACA) and ACAs stimulated by isoproterenol, 5'-guanylylimidodiphosphate (GppNHp), sodium fluoride, and forskolin were significantly lower in BIO 53.58 than in F1B controls. The functional activity of stimulatory guanine nucleotide-binding protein (Gs), as determined by reconstitution with S49 lymphoma cyc- cell membranes, was significantly lower in BIO 53.58 controls. After 10 weeks of exercise training, Bmax and basal and isoproterenol-stimulated ACAs were unchanged in either BIO 53.58 or F1B hamsters compared with controls. However, in F1B hamsters, training decreased ACAs stimulated by GppNHp, sodium fluoride, and forskolin, with a reduced functional activity of Gs. In contrast, these ACAs increased significantly in association with an enhanced Gs activity in cardiomyopathic BIO 53.58 hamsters after training. CONCLUSIONS: Chronic exercise training does not change receptor-mediated beta-adrenergic responsiveness in either F1B or BIO 53.58 hamsters. However, exercise training reduces Gs activity in normal F1B hamsters and improves the functional abnormality of Gs in cardiomyopathic BIO 53.58 hamsters. This improvement may potentially contribute to augmented left ventricular contractility in BIO 53.58 after training.

Adenylyl Cyclases↗

Familial carpal tunnel syndrome due to amyloidogenic transthyretin His 114 variant.

We studied two patients from a Japanese family with carpal tunnel syndrome (CTS). The biopsy samples obtained during CTS surgical release revealed deposits of amyloid that stained with antihuman transthyretin (TTR) antiserum. Single-strand conformation polymorphism analysis and sequence analysis of polymerase chain reaction (PCR)-amplified exons of the proband's TTR gene revealed a point mutation resulting in a substitution of histidine for tyrosine at position 114. The mutation was confirmed by PCR-primer-induced restriction analysis. Our findings account for clinical heterogeneity of TTR-derived amyloidosis, and suggest the importance of substitution itself for deposits of amyloid in CTS.

Aged↗

Molecular parameters for the anti-human immunodeficiency virus activity of T22 ([Tyr5,12, Lys7]-polyphemusin II).

T22 ([Tyr5,12, Lys7]-polyphemusin II) was found to exhibit strong anti-human immunodeficiency virus (HIV) activity and exert its effects on a virus-cell fusion process. In the present study, the all-D enantiomer of T22 and its related compounds were synthesized to examine the molecular parameters required for the interaction of T22 with membrane components of cells or viruses in order to exert this anti-HIV activity. The anti-HIV activity of these analogs was investigated in comparison with their membrane permeability with aspect to large unilamellar vesicles (LUVs). The all-D enantiomer of T22 exhibited a 20-fold lower anti-HIV activity compared with T22, whereas they both showed the same membrane permeability. No positive correlation between anti-HIV activity and membrane permeability was observed. These results suggest that the anti-HIV activity of T22 is mediated through the interaction with chiral component(s) of the cell or virus.

Amino Acid Sequence↗

Elatoside E, a new hypoglycemic principle from the root cortex of Aralia elata Seem.: structure-related hypoglycemic activity of oleanolic acid glycosides.

A new inhibitor named elatosides E (which was shown to affect the elevation of plasma glucose level by oral sugar tolerance test in rats) was isolated from the root cortex of Aralia elata Seem. together with elatoside F. The structures of elatosides E and F were elucidated on the basis of chemical and physicochemical evidence. The hypoglycemic activities of oleanolic acid and nine oleanolic acid glycosides obtained from the root cortex of Aralia elata have been examined, and some structure-activity relationships have been found.

Animals↗

Escins-Ia, Ib, IIa, IIb, and IIIa, bioactive triterpene oligoglycosides from the seeds of Aesculus hippocastanum L.: their inhibitory effects on ethanol absorption and hypoglycemic activity on glucose tolerance test.

Five triterpene oligoglycosides named escins-Ia, Ib, IIa, IIb, and IIIa were isolated from the seeds of Aesculus hippocastanum L. and their chemical structures were determined on the basis of chemical and physicochemical evidence. Escins-Ia, Ib, IIa, and IIb were found to exhibit inhibitory effect on ethanol absorption and hypoglycemic activity on oral glucose tolerance test in rats. Among them, escins-IIa and IIb showed the higher activities for both bioassays, while desacylescins-I and II had no activity.

Animals↗

Camelliasaponins B1, B2, C1 and C2, new type inhibitors of ethanol absorption in rats from the seeds of Camellia japonica L.

New type inhibitors of ethanol absorption, camelliasaponins B1, B2, C1 and C2, were isolated from the seeds of Camellia japonica L. The structures of camelliasaponins were elucidated on the basis of chemical and physicochemical evidence. The inhibitory effect of camelliasaponins and related saponins on ethanol absorption have been examined, and it was found that the triterpene oligoglycoside structure having an acyl group was essential to exerting the activity.

Animals↗

Amino acids and peptides. XX. Preparation of beta-cyclododecyl aspartate and its application to synthesis of fibronectin- and laminin-related peptides.

beta-Cyclododecyl aspartate was prepared and its application to peptide synthesis was examined. Derivatives of beta-cyclododecyl aspartate are more likely to crystallize and should be useful for peptide synthesis. The cyclododecyl ester was much stable to bases than the benzyl ester and rather more stable than the cyclohexyl ester. It was removable by HF treatment and trifluoromethanesulfonic acid treatment. beta-Cyclododecyl aspartate was used for synthesis of laminin- and fibronectin-related peptides by solid phase and liquid phase methods.

Amino Acid Sequence↗

Amino acids and peptides. XXI. Laminin-related peptide analogs including poly(ethylene glycol) hybrids and their inhibitory effect on experimental metastasis.

Laminin-related peptides, Tyr-Ile-Gly-Ser-Arg analogs, were prepared and their inhibitory effects on experimental metastasis were examined. Of the amino acids in the Tyr-Ile-Gly-Ser-Arg sequence, L-Arg was very important and Ile was not essential for the inhibitory effect. To obtain a potent inhibitor of metastasis, hybrids of Tyr-Ile-Gly-Ser-Arg-Gly and 2 types of poly(ethylene glycol) were prepared. The inhibitory effects of the hybrids were more potent than that of Tyr-Ile-Gly-Ser-Arg-Gly.

Amino Acid Sequence↗

[Chemical and chemotaxonomical studies of ferns. LXXXV. Constituent variation of Microlepia marginata (2)].

A new chemotype of Microlepia marginata, P-type strain, was found in the Central districts of Japan. The two main constituents were characterized to be 2 beta,15(R),16-trihydroxy-ent-pimar-7-en-3-one (fumotoshidin A) and 3 alpha-alpha-L-arabinofuranosyloxy-15(R),16-dihydroxy-ent-pimar+ ++-7-ene (fumotoshidin arabinoside). The young fronds of this strain have reddish stripes, which is a common feature to Y-type strains also containing ent-pimarane-type glycosides.

Arabinose↗

Anionic sites on the free surface of the peritoneal mesothelium: light and electron microscopic detection using cationic colloidal iron.

To examine charged sites on the peritoneal free surface, cationic and anionic colloidal iron methods were applied. Light microscopy of the human and mouse specimens using cationic colloidal iron staining at pH 1.5-7.3 and successive ferrocyanide treatment resulted in a distinct Prussian blue reaction on the free surface of the parietal, mesenteric and visceral peritonea at all the examined pH values. In transmission electron microscopy of specimens stained with cationic colloidal iron at pH 1.5, colloidal particles accumulated in a dotted fashion on the free surface of the mesothelial cells. At pH 7.3, colloidal particles were deposited as numerous fine strands (100-300 nm in length), whose ends often attached to the luminal aspect of the mesothelial cell membrane. Anionic colloidal iron stain at pH 7.2 gave no deposition of colloidal particles on the mesothelial free surface. Priorly methylated samples lost stainability of the peritoneal free surface to cationic colloidal iron staining at pH 1.5 or 2.5, while methylated-saponified sections recovered it. Pretreatment with neuraminidase inhibited the cationic colloidal iron staining at pH 1.5 on the mesothelial free surface. These results indicate that the mesothelial surface anionic sites ionizing at pH 1.5 are mostly due to the carboxyl group of sialic acid. It is suggested that the peritoneal free surface substance stained with the cationic colloidal iron may be membrane-associated sialomucin, whose rich negative-charged sites may repulse each other to prevent peritoneal adhesion or to maintain peritoneal cavity.

Adolescent↗