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Biomedical subjects

M Masuda

Publications and source records attributed to M Masuda.

At least 325 records · Page 18Linked to original sources

Coronary reserve and contractile reserve in crystalloid- and blood-perfused rabbit hearts.

Coronary reserve and contractile reserve were compared between crystalloid-perfused and blood-perfused rabbit hearts at various perfusion pressures (40-110 mmHg). Contractile function of the crystalloid-perfused hearts was dependent on the perfusion pressure, according to Gregg's phenomenon. Developed left ventricular pressure (LVP) increased from 67 +/- 6 mmHg to 121 +/- 5 mmHg and positive dP/dt maximum (dP/dt max) from 1,083 +/- 75 to 2,233 +/- 126 mmHg/s at perfusion pressures between the lowest and highest perfusion pressure. In the blood-perfused hearts, the perfusion pressure-induced changes were less pronounced: developed LVP changed from 107 +/- 11 mmHg to 138 +/- 8 mmHg and dP/dt max from 1,517 +/- 181 to 2,008 +/- 187 mmHg/s. The blood-perfused hearts showed better cardiac function, especially negative dP/dt minimum (dP/dt min), compared to the crystalloid-perfused hearts. Contractile reserve estimated by paired pacing technique was quite independent of the perfusion pressure in the blood-perfused hearts but not in the crystalloid-perfused hearts, and was significantly better in the blood-perfused hearts (e.g., 81% increase of developed LVP with blood perfusion, and 26% increase with crystalloid perfusion at a perfusion pressure of 80 mmHg). Coronary reserve, estimated by reactive hyperemia, was independent of the perfusion pressure in both groups. Coronary reserve was small in the crystalloid-perfused hearts (< 23%) and more than double the control value in the blood-perfused hearts. It is proposed that blood-perfused hearts are more suitable for physiological and pathophysiological studies.

Animals↗

Nucleolar organizer regions in bladder cancer: application to urinary cytology.

OBJECTIVES: We investigated the relationship between the numbers of nucleolar organizer regions (NORs) in nonmalignant reactive cells and those in transitional cell carcinomas using urinary exfoliated cell specimens. Another aim of this study was to determine whether higher numbers of NORs are correlated with tumors with higher pathologic grade. METHODS: Nucleolar organizer regions, which are important for regulating protein synthesis, were counted by means of a silver staining technique in urinary exfoliated cells from 34 patients with transitional cell carcinoma (TCC) and in 30 patients with other urologic diseases (controls). RESULTS: The number of argyrophilic proteins of the nucleolar organizer region (Ag-NORs) per cell (mean +/- SD) was 2.9 +/- 0.5 in the control group and 5.5 +/- 1.9 in patients with TCC, which was significantly higher than that in the controls (p < 0.001). It was 4.0 +/- 1.0 in patients with grade 1 TCC, 5.4 +/- 2.0 in those with grade 2 TCC, and 6.5 +/- 1.2 in those with grade 3 TCC. Although no statistically significant difference was observed between the groups, the patients with grade 2 TCCs with higher numbers of Ag-NORs showed a tendency to have more diffuse and/or invasive lesions. CONCLUSIONS: This method is simple and quick, and can identify low-grade malignancy. It could be used as a tool for further grading of grade 2 TCCs and for determining prognosis.

Adult↗

Do astral microtubules play a role in metaphase chromosome positioning?

From several recent studies on monopolar spindles, it is now clear that a phase analogous to metaphase in bipolar spindles exists in the monopolar spindle, denying the validity of the favored model for metaphase which is based on the balance between two oppositely directed poleward forces acting on the unsplit kinetochores. Faced with this new fact, several investigators have proposed new models for metaphase plate formation which work for both the monopolar and the bipolar spindles. Since astral microtubules are thought to play important roles in certain models, we have investigated the role of astral microtubules in maintaining chromosomes at the metaphase position by using monopolar spindles induced in sea urchin embryo cells. When monopolar spindles were exposed to 1 microM nocodazole, a microtubule depolymerizing agent, most of the astral microtubules were rapidly depolymerized while the kinetochore fibers appeared to be little affected. Chromosomes were locked into the metaphase position for as long as 2 min, indicating that the metaphase chromosome position in sea urchin monopolar spindles can be maintained with little or no astral microtubules. By the effect of the antimitotic drug, kinetochore fibers slowly shortened and chromosomes which were attached to the far end of kinetochore fibers moved toward the pole. On the other hand, the chromosome position rapidly shifted farther away from the pole when monopolar spindles were treated with taxol or D2O. These results indicate that the metaphase chromosome position can be altered by affecting microtubule dynamics, particularly that of the kinetochore fiber microtubules as suggested by the results of the nocodazole experiments.

Animals↗

Sialosylcholesterol effects on reconstitution of microfilament and glia filament.

The effects of alpha-sialosylcholesterol (alpha-SC) on formation of either microfilament or glia filament of rat astrocytes were investigated using a reconstitution system. Polymerization of the depolymerized microfilament preparation that had been extracted from a crude cytoskeletal fraction of rat astrocytes, in the presence of 100 mM KCl and 10 mM MgCl2, was suppressed in a dose-dependent manner by alpha-SC. alpha-SC inhibited polymerization of G-actin in a similar manner. The intensity of alpha-SC inhibition of G-actin polymerization was as great as that of microfilament polymerization, suggesting that the inhibition of microfilament polymerization by alpha-SC was due to the direct action of alpha-SC on actin, the main component of microfilament. alpha-SC depolymerized partly the polymerized microfilament preparation, which resembled F-actin (microfilament-like filaments). alpha-SC suppressed, in a dose-dependent manner, polymerization of a glia filament preparation that had been extracted from astrocyte cytoskeletons in the presence of phalloidin. An increase in the amount of added alpha-SC (up to 15 microM) decreased the amount of the larger glia filament-like filaments, which were 10 nm thick and centrifuged down at 16,000 g for 30 min, and increased that of smaller ones precipitated only after centrifugation at 100,000 g for 1 h. The lower the concentration of the depolymerized glia filament extract, the greater was the inhibition by alpha-SC of the polymerization. alpha-SC repressed polymerization of vimentin, the dominant component of glia filament. Vimentin polymerization was more strongly inhibited by alpha-SC than polymerization of glia filament was.(ABSTRACT TRUNCATED AT 250 WORDS)

Actin Cytoskeleton↗

Centrally induced vasopressor and sympathetic responses to a novel endogenous peptide, adrenomedullin, in anesthetized rats.

Possible central actions of adrenomedullin were explored and compared with the peripheral effects by injecting it into the lateral ventricle, cisterna magna, and femoral vein in urethane-anesthetized rats. Adrenomedullin, 1.0 to 3.0 nmol/kg, injected intravenously (i.v.), caused a transient vasodepression of about 10 to 30 mm Hg, dose dependently, which lasted for < 15 min. On the other hand, intracerebroventricular (ICV) and intracisternal (IC) injections of adrenomedullin elicited sustained elevations of arterial pressure of gradual onset, dose dependently; the arterial pressure started to rise at about 3 min after the injection, and gained peak response after > 20 min. The pressor response lasted for > 2 h. Heart rate was not significantly influenced by these doses of adrenomedullin. The abdominal sympathetic outflow was markedly increased in relation to the blood pressure elevation. The time-course of the responses was quite similar with both ICV and IC injections. Hypotensive effects of i.v. injected adrenomedullin was partially attenuated, and the centrally induced vasopressor responses were abolished by the pretreatment with human calcitonin gene-related peptide (hCGRP)-receptor antagonist, hCGRP(8-37). These findings indicate that the receptors for adrenomedullin exist in the brain, and that the receptor site may be anatomically far from the surface of the brain and the ventricular system because the onset of the pressor response was delayed. Or, CGRP and adrenomedullin may share the same receptors, particularly in the brain.

Adrenomedullin↗

Binding and aggregation of human gamma-globulin by cis-diamminedichloroplatinum(II) through disulfide bond.

The incubation of gamma-globulin with cis-diamminedichloroplatinum (II) (cis-DDP) resulted in gradual formation of insoluble aggregates. Since the precipitates, composed of polymerized gamma-globulin and cis-DDP, were completely solubilized with urea, the reaction mixture containing precipitate was examined in terms of the binding of cis-DDP and the effect on disulfide (S-S) bonds in the gamma-globulin. When gamma-globulin was incubated with 30 molar excess cis-DDP at pH 7.4 and 37 degrees C, cis-DDP gradually bound to as much as 12 mol per mol of gamma-globulin in 14 d. Concurrently, about four disulfide bonds were cleaved without reaching a certain plateau. An sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) of the aggregated gamma-globulin induced by cis-DDP was significantly different from that of the heat-denaturated aggregate form or the reduced form by sulfitolysis. The aquated complexes of cis-DDP also produced an insoluble precipitate and affected the S-S bond to a greater extent than the parent drug.

Cisplatin↗

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↗

[Studies on the inhibitory action of leminoprazole against rabbit gastric H+,K(+)-ATPase].

Inhibitory action of leminoprazole ((+/-)-2-[[2-(isobutylmethylamino)benzyl]sulfinyl]-1H-benzimidazol e, NC-1300-O-3, LEM) against the H+,K(+)-ATPase activity in rabbit gastric vesicles was investigated. LEM inhibited the H+,K(+)-ATPase activity in leaky vesicles in a concentration- and time-dependent manner. When preincubated with gastric vesicles (20 micrograms protein/ml) for 30 min at 37 degrees C in medium (pH 6.1 or 7.4), the IC50 values were 5.3 microM and 19 microM, respectively. The inhibitory action of LEM was not competitive with respect to K+ and was not reversed by dilution, suggesting that the inhibitory action is irreversible. Inhibition of the enzyme activity by LEM was not found when beta-mercaptoethanol (0.1 mM) was premixed with enzyme before addition of LEM, and it was partially recovered by addition of beta-mercaptoethanol or dithiothreitol (50 mM) after LEM treatment. These results suggest that LEM reacts with essential SH groups of H+,K(+)-ATPase and inactivates the enzyme by forming a covalent disulfide bond. The inhibitory activity of LEM was more potent at pH 6.1 than at pH 7.4, and the rate of the reaction of LEM with GSH was enhanced by lowering the pH of the medium. The inhibition of proton transport by LEM (30 microM) was found after the intact vesicles were fully acidified. LEM also strongly inhibited the valinomycin-stimulated H+,K(+)-ATPase activity. Therefore, it is considered that LEM inhibits H+,K(+)-ATPase activity by an unknown activated reaction under the acidic condition. Alternatively, the possibility was also suggested that an acidic condition is not always necessary for the inhibition of H+,K(+)-ATPase activity by LEM, since LEM, at higher concentration, inhibited the initial rate of acidification and inhibited nigericin-stimulated H+,K(+)-ATPase activity in intact vesicles.

Animals↗

[Effect of a new antiulcer drug, leminoprazole, on the gastric mucosal H+,K(+)-ATPase activity in rats].

The inhibitory action of leminoprazole on the activity of rat gastric mucosal H+,K(+)-ATPase was investigated in vitro and ex vivo. Leminoprazole and omeprazole concentration-dependently inhibited the H+,K(+)-ATPase activity, and their IC50 values were 31 microM and 24 microM, respectively, at pH7.4. Leminoprazole dose-dependently inhibited the H+,K(+)-ATPase activity at 3 and 6 hr after the administration at 10-100 mg/kg, p.o. Leminoprazole (60 mg/kg, p.o.) inhibited the H+,K(+)-ATPase activity persistently, and the duration of its inhibitory action was much longer than that of omeprazole (30 mg/kg, p.o.). In pylorus-ligated rats, good correlations between the respective inhibitory rates against gastric acid output and H+,K(+)-ATPase activity was found after the administration of leminoprazole. These results suggest that leminoprazole inhibits the gastric acid secretion by its ability to inhibit the H+,K(+)-ATPase activity in rats; its inhibitory activity was comparable to that of omeprazole. In addition, leminoprazole (100 mg/kg) inhibited the H+,K(+)-ATPase activity even when administered intragastrically after pylorus-ligation, suggesting that this drug can inhibit H+,K(+)-ATPase activity directly from the gastric lumen. Moreover, leminoprazole (100 mg/kg, p.o.) when administered repeatedly for 2 or 4 weeks inhibited the H+,K(+)-ATPase activity to the same degree as the single administration.

Animals↗

Effects of NC-1300-O-3 on gastric mucus secretion and prostaglandin release in rats.

We investigated the effect of NC-1300-O-3 on gastric mucus secretion and prostaglandin release into the gastric lumen in rats. NC-1300-O-3 following single or repeated administration for up to 4 weeks significantly increased the hexose content in the gastric lumen at 10 to 100 mg/kg, p.o. Omeprazole and cimetidine at doses that strongly inhibited gastric acid secretion had no effect on the hexose content following single or repeated administration for 8 days. When administered repeatedly for 8 days, NC-1300-O-3, omeprazole and cimetidine significantly decreased the hexosamine content in gastric surface mucosa, but significantly increased gastric mucus secretion was observed at the same time only with NC-1300-O-3, indicating that this agent has a profile of action on gastric mucus metabolism different from those of omeprazole and cimetidine. NC-1300-O-3 at 10 and 30 mg/kg, p.o. and omeprazole at 30 mg/kg, p.o. increased the release of prostaglandins into the gastric lumen, and this was markedly inhibited by pretreatment with indomethacin, suggesting that these agents may enhance prostaglandin biosynthesis in the gastric mucosa. From these results, it seems that the enhancement of NC-1300-O-3 on gastric mucus secretion and prostaglandin biosynthesis in the gastric mucosa contribute to the antiulcer effect of NC-1300-O-3.

Animals↗

Cytoprotective effect of NC-1300-O-3 against gastric lesions induced by necrotizing agents in rats.

The cytoprotective effect of NC-1300-O-3 and its mechanism of action were investigated. NC-1300-O-3 at doses of 3 and 10 mg/kg, p.o. significantly prevented the formation of gastric lesions by HCl.ethanol in rats, and its efficacy was not influenced by repeated administration for up to 4 weeks. The interaction between NC-1300-O-3 and necrotizing agents in the stomach, which is considered to be related to the development of cytoprotection, was not observed. A preventive effect of NC-1300-O-3 against gastric lesions was observed at the same dose even when gastric secretion was completely inhibited by pretreatment with omeprazole. This suggests that the cytoprotective effect of NC-1300-O-3 is an action on the gastric mucosa independent of its antisecretory effect. The cytoprotective effect of NC-1300-O-3 was not affected by pretreatment with indomethacin but was partly decreased by N-ethylmaleimide pretreatment, suggesting the participation of endogenous sulfhydryl compounds in the action of NC-1300-O-3. This compound dose-dependently increased the hexosamine content in the gastric lumen in rats at a dose range of 3-30 mg/kg, p.o. and slightly inhibited a reduction in surface mucus and mucosal hexosamine content caused by necrotizing agents. Moreover, NC-1300-O-3 at doses of 10 and 30 mg/kg, p.o. significantly inhibited the increased gastric vascular permeability caused by alcohol treatment; and at 30 mg/kg, p.o., it inhibited the reduction in potential difference caused by aspirin in rats. These actions were suggested to contribute to the cytoprotective effect of NC-1300-O-3.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Clinical characteristics in non-insulin-dependent diabetic patients with long duration in Japan--relation to risk factors for vascular complications.

In this study, we evaluated the control state of body weight, blood pressure, and blood glucose during the recent 10 years in 82 patients of non-insulin-dependent diabetes mellitus (NIDDM) who had long duration of diabetes for 20-25 years without ischemic heart disease (IHD) and diabetic nephropathy (Neph). The patients without either IHD or Neph showed significantly lower incidences of obese (11 vs. 40%, p < 0.05), hypertensive (0 vs. 20%, p < 0.05) and poor glycemic control state (7 vs. 27%, p < 0.05) for 10 years than the patients with IHD alone, and showed significantly lower incidences of hypertensive (0 vs. 20%, p < 0.05) and poor glycemic control state (7 vs. 33%, p < 0.01) than the patients with Neph alone. The control state of body weight was similar between the patients without either IHD or Neph and with Neph alone. In addition, the patients without either IHD or Neph showed significantly lower incidences of obese (11 vs. 56%, p < 0.01) and hypertensive control state (0 vs. 40%, p < 0.01) for 10 years than the patients with both IHD and Neph. The control state of blood glucose was similar between the two groups. These results suggest that for long survival of NIDDM patients without development or progression of IHD and Neph, non-obese and non-hypertensive state as well as good glycemic control should be maintained for long time.

Aged↗

Evidence of partial involvement of P-450 2D in mutagenic activation of benzo(a)pyrene in liver S-9 fraction from untreated rats.

In order to clarify which species of cytochrome P-450 is involved in activation of benzo(a)pyrene (BP) in untreated rat liver, strain and sex differences in the ability of rat liver 9000 g supernatant (S-9) to mutagenically activate BP was investigated using Ames test. The numbers of histidine revertants in Ames test after pre-incubation of TA 98 strain of Salmonella typhimurium and BP with liver S-9 from male rats were markedly higher than those obtained using female rats. In addition, a marked strain difference (Wistar > DA) in the ability of liver S-9 from Wistar and DA rats to activate BP was observed. Antibody against cytochrome P-450 2D inhibited up to 50% of the revertant formation by the activation of BP with liver S-9 from male Wistar rats. These results indicate the partial involvement of cytochrome P-450 2D subfamily as well as cytochrome P-450 species specific to male rats in activation of BP to ultimate mutagen in untreated rat liver.

Animals↗

Secretory capacity of pancreatic protein during luminal feedback regulation in conscious rats.

Pancreatic exocrine secretion in conscious rats is regulated by bile and pancreatic juice in the proximal intestine (luminal feedback regulation), and bile-pancreatic juice diversion from the intestine results in cholecystokinin (CCK) release and pancreatic hypersecretion. Pancreatic protein secretion increases to a maximum 60-90 min after bile-pancreatic juice diversion, and then decreases slightly to a steady level of two times the basal level. Change in plasma CCK concentration parallels protein secretion. In this study, the mechanism of the decreases of protein secretion and CCK concentration was examined by stimulation with various species of peptides having different stimulatory mechanisms. Cannulae for draining bile and pancreatic juice separately and a duodenal cannula and extrajugular vein cannula were inserted into male Wistar rats. Four days later, basal levels in a 90-min period were determined, bile and pancreatic juice were diverted for 90 min, and then either secretin (1.2 nmol/kg/h), CCK-8 (25 and 100 pmol/kg/h), neuromedin C (350 pmol/kg/h and 3.5 nmol/kg/h), or CCK-JMV-180 (200 nmol/kg/h) was infused intravenously for 60 min. Infusion of secretin significantly increased protein secretion and prevented its decrease after its maximum induced by bile-pancreatic juice diversion. The plasma CCK concentrations were not increased further by neuromedin C. In conclusion, pancreatic exocrine secretion and CCK release in conscious rats are maximally stimulated by luminal feedback regulation that the decrease after maximal protein output may be due to limitation of secretory capacity and/or desensitization of acinar cells.

Animals↗

[Adrenal cyst with an immunohistochemical evidence of mesothelial origin. Report of a case].

A case of adrenal cyst with an immunohistochemical evidence of mesothelial origin is presented. A 73-year-old Japanese woman was referred to our hospital with a complaint of left flank pain. The diagnosis of left adrenal cyst was made based on the radiographic and hormonal examinations. The adrenal cyst was removed surgically. Histological examination revealed that the cyst was lined with either a single layer of squamous or cuboidal cells. In immunohistochemistry testing, the cells were positive for keratin and carbohydrate antigen 125, while they were negative for epithelial membrane antigen, vimentin, desmin, and factor VIII related antigen. Thus, the present case was classified as epithelial cyst of mesothelial origin.

Adrenal Gland Diseases↗

[Proliferation of pulmonary fibroblasts obtained from rats with bleomycin-induced pulmonary fibrosis and effects of rat rIL-1 alpha on this proliferation].

To clarify the mechanism of pulmonary fibrosis, the growth rate of fibroblasts obtained from bleomycin (BLM)-treated rats was compared with that of fibroblasts obtained from control rats. Proliferation of fibroblasts obtained from rats at 4 days after BLM instillation (BRF) was significantly more rapid than that of fibroblasts obtained from rats at 4 days after saline instillation (CRF), as assessed by cell counting and 3H-TdR incorporation. CRF and BRF were separated by the method of discontinuous Percoll gradients. Three fibroblast fractions of specific gravity (S.G.), S.G. < 1.036, 1.036 < or = S.G. < 1.050, 1.050 < or = S.G. < 1.062, were obtained. Percentages of the densest fibroblast fraction were 46.2 +/- 5.2 in BRF and 6.4 +/- 2.8 in CRF. The densest fibroblasts in BRF proliferated more rapidly than the least dense fibroblasts. Rat rIL-1 alpha suppressed the proliferation of CRF and BRF, dose dependently. These results suggest that an increase in the densest fibroblasts in the lung might correlate with BLM-induced pulmonary fibrosis and that IL-1 alpha suppresses the proliferation of pulmonary fibroblasts.

Animals↗

[A case of malignant pheochromocytoma with high levels of serum neuron-specific enolase (NSE) and calcitonin].

A 71-year-old woman was admitted with the chief complaint of headache, lumbago and slight fever. Computerized tomographic (CT) scan demonstrated a large soft tissue mass with multiple cystic necrosis in the right adrenal region. The plasma norepinephrine concentration was excessive and serum levels of neuron-specific enolase (NSE), calcitonin and parathormone were elevated. MIBG scintigraphy showed a high uptake in the same region. Under the diagnosis of pheochromocytoma without distant metastasis, right adrenalectomy was performed. The tumor was removed en bloc with right kidney and a part of the liver because of inflammatory adhesion. The histological examination revealed benign pheochromocytoma. After the operation, norepinephrine and calcitonin decreased to normal but the levels of NSE and PTH remained high. One year after operation, chest X-ray revealed multiple lung metastases and after 1.5 years she died of respiratory failure. Autopsy revealed multiple lung and bone metastases and a liver metastasis, parathyroid glands showed hyperplasia but the thyroid gland showed no abnormal change. This clinical course suggests that serum NSE might be a useful tumor marker for differentiating malignant pheochromocytoma from benign one, and this tumor producing calcitonin caused secondary hyperparathyroidism.

Adrenal Gland Neoplasms↗