Biomedical subjects

N Ohshima

Publications and source records attributed to N Ohshima.

At least 37 records · Page 2Linked to original sources

PubMed1998

Hepatocyte culture utilizing porous polyvinyl formal resin maintains long-term stable albumin secretion activity.

To investigate the effects of culture conditions on the maintenance of metabolic functions of cultured hepatocytes, long-term hepatocyte culture lasting 20 days was performed under two different culture conditions, i.e. stationary cultures utilizing porous polymer (polyvinyl formal (PVF) resin) as a substratum and conventional monolayer dish cultures without PVF. Metabolic activities specific to hepatocytes were evaluated in terms of ammonia metabolism, urea synthesis, and albumin secretion. Concerning ammonia metabolic and urea synthetic activities, no significant differences in maintenance of these activities were found between the two culture conditions, and these activities rapidly decreased with the elapse of the culture period, especially during the early stage of the experiments. However, after day 10, these activities in the stationary cultures were maintained at a slightly more favorable level than in the monolayer cultures. On the other hand, compared with ammonia metabolism and urea synthesis, stable and well-maintained albumin secretion of hepatocytes (60% of the activity in day 1) was exhibited in the stationary culture experiments, despite that this particular activity under the monolayer culture condition gradually reduced to a very low level (5.7% of that on day 1) at the end of the culture. From the morphological observations, hepatocytes immobilized in the PVF resin revealed individual spherical shapes without forming multicellular aggregation, and it was suggested that this characteristic structure contributed to good albumin secretion of hepatocytes. In conclusion, the advantages of the hepatocyte culture technique utilizing PVF resin over the conventional dish culture in maintaining some representative metabolic function specific to hepatocytes were clarified.

Albumins↗

PubMed1998

The characteristics of endothelin receptor subtypes on muscle contraction and neuro-transmission in rat vas deferens.

We observed endothelin (ET)-induced contractile responses on prostatic and epididymal segments, as well as the facilitation of an electrically stimulated tone on prostatic segments of isolated rat vas deferens. In both segments, the selective ET(B)-receptor agonists, IRL 1620 and sarafotoxin S6c, produced only a small contraction or no contraction at a concentration of 1 microM. The rank order of contraction potencies (pD2 value) was ET-1 = ET-2 > ET-3 >> sarafotoxin S6c = IRL 1620. The maximum responses of ET-induced contractions in the prostatic segments were larger than those in the epididymal segments. The contractile response to ET-3 was antagonized by pretreatment for 30 min with BQ-123 (10 nM), a selective ET(A) receptor antagonist, and BQ-788 (1 microM), a selective ET(B) receptor antagonist. The contractile responses to ET-1 were antagonized by pretreatment with BQ-123 (10 microM), but not with BQ-788 (1 microM). The ET-3-induced facilitation on the twitch response to electrical stimulation in the prostatic segment of the vas deferens was antagonized by BQ-123 (0.1 microM) and BQ-788 (1 microM). The ET-1-induced facilitation was antagonized by pretreatment with BQ-123 (3 microM), but not with BQ-788 (10 microM). These results suggest that in rat vas deferens the ET(A) receptors are divided into BQ-123-sensitive ET(A1) and BQ-123-insensitive ET(A2) subtypes, and the production of a contractile response of smooth muscle as well as the facilitation of neurotransmission are accomplished through mediation by ET(A1)- and ET(A2)-subtypes.

Animals↗

PubMed1998

[A case of progressive right coronary ostial stenosis after Carrel patch method using gelatin-resorcin-formalin glue].

A 31-year-old man with type A chronic aortic dissection associated with annuloaortic ectasia underwent the concomitant graft replacement of the total aortic root and the transverse aortic arch. The two coronary arteries were reconstructed using the Carrel patch method. The false lumen of right coronary artery was closed by injection of GRF glue into the dissected space and compressing the dissected layers. Postoperative course was uneventful, and the patient has returned to normal daily life 2 months after surgery. Remarkable progression of the right coronary artery ostial stenosis was observed by coronary angiography 6 months after surgery. The remarkable progression of stenosis may occur in association with injection of GRF glue into the dissected space, although the exact etiology of the progressive stenosis remains obscure.

Adult↗

PubMed1998

[Autologous blood donation with recombinant human erythropoietin prior to elective cardiac surgery in anemic patients].

Despite the reducing exposure to allogeneic blood in cardiac surgery, most of patients with anemia still require allogeneic blood. In this study, we have attempted to harvest the blood from cardiac patients with baseline hemoglobin levels below 11.0 g/dl using recombinant human erythropoietin (rHuEPO). 29 anemic patients undergoing cardiac surgery at our hospital between January 1994 and March 1997 were divided into two groups: 3 weeks' treatment with recombinant human erythropoietin (rHuEPO) and blood donation (group 1, n = 15) and iron supplementation alone (group 2, n = 14). There were no statistically significant differences among the two groups in patients characteristic and surgical data. No serious adverse events after phlebotomy were apparent in patients donating autologous blood. Patients in group 1 had significantly higher hemoglobin levels than patients in group 2 at 7 days before operation. The number of reticulocytes were increased at just before operation in group 1, whereas group 2 showed no significant increase. The estimated hemoglobin increase in group 1 were higher at 7 days and just before operation. In 75% of group 1, allogeneic blood transfusion could be avoided, while all patients in group 2 received allogeneic blood transfusion. This study suggests that the combination of rHuEPO administration and autologous blood donation would be beneficial for anemic patients in elective cardiac surgery. The use of rHuEPO should not be restricted to anemic patients.

Aged↗

PubMed1997

Dietary effect of a symmetrical triacylglycerol, 1,3-biseicosapentaenoyl-2-gamma-linolenoyl glycerol, on fatty acid composition of guinea pigs.

The dietary effect of 1,3-biseicosapentaenoyl-2-gamma-linolenoyl glycerol (STG) on the fatty acid composition of guinea pigs was examined and compared with that of an eicosapentaenoic acid ethyl ester (EPA-E) and of a soybean oil (SBO) diet. In terms of content of plasma lipid, EPA-E had a greater hypolipidemic effect than STG. On the other hand, in terms of EPA incorporation, contents of EPA in liver lipid were almost the same in the STG and EPA-E groups. Considering that the amount of EPA administered in the EPA-E group was almost 1.5 times that of the STG group, EPA may be absorbed more effectively as the glycerol ester than as the ethyl ester in guinea pigs. In all the tissue lipids, the STG group had a higher unsaturation index (UI) than the EPA-E group even though there is a lower UI in the STG diet than the EPA-E diet. These results suggest that greater amounts of desaturase products as a whole were synthesized in the STG group than in the other two groups. The dihomo-gamma-linolenic acid/arachidonic acid (DGLA/AA) ratio in plasma total lipids in the STG group was 3.5 times that of SBO group, and the DGLA/AA ratio in the EPA-E group was half that of the SBO group. In liver lipid, the ratios of DGLA/AA and EPA/AA in the STG group were 0.687 and 0.488 (phosphatidylcholine fraction) and 0.237 and 0.752 (phosphatidylethanolamine fraction), respectively. The ratio of DGLA/AA as well as the high EPA/AA ratio obtained in the present study with the STG diet may lead to physiological alterations, including enhanced synthesis of 1- and 3-series eicosanoids.

8,11,14-Eicosatrienoic Acid↗

PubMed1997

Packed-bed type reactor to attain high density culture of hepatocytes for use as a bioartificial liver.

In an attempt to develop a bioartificial liver using cultured hepatocytes, we investigated the short-term and long-term viability and metabolic functions of hepatocytes cultured in a new type of packed-bed type reactor using reticulated polyvinyl formal (PVF) resin as a supporting material. Perfusion culture experiments using this reactor, as well as monolayer cultures using conventional collagen-coated Petri dishes as control experiments, were performed. It was found that the highest density of immobilized hepatocytes attained with PVF resin was on the order of 10(7) cells/cm3 PVF and that hepatocytes cultured in this type of module for up to a week showed a sufficient level of liver-specific metabolic functions, such as ammonium metabolism, urea-N synthesis, and albumin secretion, to be comparable to those in the monolayer culture. It is concluded that the packed-bed reactor system utilizing PVF resin is a promising means to develop a bioartificial organ using hepatocytes.

Alanine Transaminase↗

PubMed1997

[The comparison of tepid and moderate hypothermic cardiopulmonary bypass in cardiac surgery].

Normothermic cardiopulmonary bypass (CPB) is being increasingly used at some institutions. Patients undergoing normothermic CPB have a higher systemic oxygen demand and may be at higher risk for ischemic injury. This study was designed to confirm the clinical efficacy and safety of tepid hypothermic CPB. Thirty-six patients undergoing open heart surgery between June 1993 and August 1994 were divided into two groups: tepid (n = 18, 32 degrees C) and moderate (n = 18, 26 degrees C) hypothermic CPB. There were no significant differences in preoperative and perioperative patients characteristics between the two groups. The mean aortic cross-clamp time did not differ between two groups, but the mean CPB time was significantly shorter in tepid hypothermic patients. Serum lactate after CPB and lactate/pyrvate ratio during CPB in tepid hypothermic patients were significantly lower than in moderate hypothermic patients. The mixed venous oxygen saturation in tepid hypothermic patients was significantly lower however, it was maintained at levels more than 70% during CPB. This study suggests that tepid hypothermic CPB is a safe and effective alternative to moderate hypothermic CPB for patients undergoing open heart surgery. Previous reports have documented that patients undergoing normothermic CPB are at greater risk for cerebral desaturation. We should evaluate cerebral venous oxygen saturation during tepid hypothermic CPB before the induction of normothermic CPB.

Cardiac Surgical Procedures↗

PubMed1996

Synergistic effect of aurintricarboxylic acid and triflavin in a photochemically induced thrombosis model in rats.

We report here the synergistic antithrombotic effect of aurintricarboxylic acid in combination with a snake venom-derived disintegrin, triflavin, in a photochemically induced thrombosis model in rats. The time to initiation of thrombus was prolonged by i.v. bolus injection of aurintricarboxylic acid at 10 mg/kg. In contrast, time to occlusion was dose-dependently prolonged by both agents, this prolongation being significant with aurintricarboxylic acid at 10 mg/kg i.v. and with triflavin at more than 3 mg/kg i.v. Interestingly, the combination of aurintricarboxylic acid at 3 mg/kg i.v. and triflavin at 1 mg/kg i.v. prolonged not only the initiation of thrombus, but also the time to occlusion.

Animals↗

PubMed1996

Angiogenic vascular growth in the rat peritoneal disseminated tumor model.

The objective of this study was to provide the first quantitative measurements of the process of vascular growth in the rat peritoneal disseminated tumor model in both arteriolar and venular systems. Male Fischer 344 rats were injected intraperitoneally with 1 x 10(7) cells of colon carcinoma cell line (RCN-9). Three to eleven days after tumor cell inoculation, the rats were subjected to intravital microscopic observation of the mesenteric microcirculation. Accompanying tumor growth, mesenteric windows showed a marked neovascularization. The branching pattern of the vascular network was analyzed based on Horton's law of bifurcation. Arterioles and venules were given an order of branching separately according to the Strahler's nomenclature, and the number of vessel segments (N) having the same order number was counted. A vascular density index (VDI) and a bifurcation ratio (BR) were calculated from a semilogarithmic plot of the vessel density (dividing N by the vascularized area) against vessel order. Values of the VDI in venules (3.1 +/- 0.3 in the tumor-free rats, mean +/- SEM, n = 6) were found to be larger than those in arterioles (1.8 +/- 0.2). These values in both arterioles and venules showed a significant increase with time after the tumor cell inoculation (in venules, 12.3 +/- 1.1 at 9-11 days after the tumor cell inoculation; in arterioles, 5.7 +/- 0.7). Moreover, the rate of increase in the venular VDI was larger than that of the arteriolar VDI. The arteriolar BR remained almost constant (3.8 +/- 0.2 for the tumor-free rats and 4.1 +/- 0.1 for 9-11 days after tumor cell inoculation), whereas the venular BR showed an increase with time (3.0 +/- 0.1 and 3.8 +/- 0.2, respectively). In conclusion, a marked angiogenesis was observed in the mesentery of the rats bearing peritoneal tumors. Neovascularization was found to occur predominantly in the venular system.

Adenocarcinoma↗

PubMed1996

Viscoelastic properties of cultured porcine aortic endothelial cells exposed to shear stress.

The viscoelastic properties of cultured endothelial cells exposed to shear stress were measured by the micropipette technique and analyzed using a standard linear viscoelastic model. Cells from porcine aorta were cultured on glass coverslips. A shear stress of 2 Pa was applied using a parallel-plate flow chamber. After flow exposure, the cells were detached from the coverslips and suspended in culture medium. The micropipette experiment was performed on single cells under an inverted microscope. The desired negative pressure was applied stepwise to the tip of the micropipette by opening a solenoid valve. The deformation process of cells in the micropipette was observed through a TV camera and recorded on a videotape. To obtain the viscoelastic parameters, a half-space model of an endothelial cell was used. The cell was assumed to be a homogeneous and incompressible material, and a standard linear viscoelastic model was employed to account for the viscoelastic response. Cells exposed to shear stress for 6 h became spherical in shape after detachment from the substrate. In the case of a 24 h exposure, about half of the detached cells retained an elongated shape upon detachment, with the others taking on a spherical shape. The elastic constants, as determined based on the model, were approximately two times higher for the elongated cells than for control cells from static culture, no-flow conditions, indicating that the elongated cells became stiffer. Enhanced viscous properties also were observed for the elongated cells. These viscoelastic properties are considered to be closely related to cytoskeletal structure. Spherical cells upon detachment, even those that had been exposed to shear stress for 24 h, did not show such significant changes in viscoelastic mechanical properties.

Animals↗

PubMed1996

Long-term performance of albumin secretion of hepatocytes cultured in a packed-bed reactor utilizing porous resin.

A packed-bed reactor utilizing the porous polymer, polyvinyl formal (PVF) resin, as a supporting material was applied for the long-term culture of rat hepatocytes. Perfusion cultures using this reactor, as well as monolayer cultures, were performed for up to 1 week under 3 different media conditions. When serum-free or epidermal growth factor-containing medium was used, albumin secretion rates showed constant decreases in both the perfusion and the monolayer cultures, and approximately 10% of the activity exhibited on Day 1 was preserved at the end of the cultures. In contrast, the hepatocytes supplemented with serum-containing medium exhibited stable ability of albumin secretion throughout the culture period under the perfusion culture condition using PVF resin. From the microscopic observation, the immobilized hepatocytes in this medium revealed round shapes, and a cluster of cell aggregates was scarcely seen.

Albumins↗

PubMed1996

Antiplatelet and antithrombotic effects of YM337, the Fab fragment of a humanized anti-GPIIb/IIIa monoclonal antibody in monkeys.

The antiplatelet and antithrombotic effects of the Fab fragment of the humanized antiplatelet glycoprotein (GP) IIb/IIIa monoclonal antibody C4G1 (YM337) were investigated in monkeys. First, the relationship between the inhibition of platelet aggregation and the prolongation of bleeding time was studied in rhesus monkeys. YM337 dose-dependently inhibited ex vivo platelet aggregation, with complete inhibition at doses higher than 0.25 mg/kg intravenous injection or 1.5 micrograms/kg/min infusion. At 0.25 mg/kg bolus injection followed by 1.5 micrograms/kg/min infusion, YM337 immediately and continuously inhibited platelet aggregation during the 6-h infusion period with platelet aggregation rapidly returning to over 50% of baseline within 1 h after the cessation of infusion. Template-bleeding time was significantly prolonged during the period of complete inhibition of platelet aggregation. Second, the antithrombotic effects of YM337 were investigated in a photochemically-induced thrombosis model in squirrel monkeys. YM337 at a dose of 1 mg/kg intravenous injection followed by 6 micrograms/kg/min infusion for 60 min prevented occlusive thrombus formation in all 4 monkeys. In contrast, time to occlusive thrombus formation did not change on intravenous bolus injection of aspirin 17 mg/kg (11.3 +/- 5.2 min) or sodium ozagrel (9.4 +/- 3.0 min) compared with saline (13.3 +/- 4.0 min). YM337 but not aspirin or sodium ozagrel significantly inhibited ex vivo ADP-induced platelet aggregation, while all drugs completely inhibited arachidonic acid-induced platelet aggregation. However, while aspirin and sodium ozagrel inhibited the thromboxane B2 generation accompanying arachidonic acid-induced platelet aggregation, YM337 had no effect on this variable. Platelet counts and bleeding time showed no significant change in any group in this squirrel monkey model. These results indicate that YM337, with a short half-life, may be a useful therapeutic agent in patients with thrombotic disorders.

Animals↗

PubMed1996

[Application of extracorporeal membrane oxygenation for respiratory failure following septic pulmonary emboli].

A 23-year-old man, diagnosed as ventricular septal defect in childhood, was hospitalized with right-sided infective endocarditis. He developed acute respiratory failure following septic pulmonary emboli and underwent urgent surgical treatment, because vigorous medical treatment was ineffective. Extracorporeal membrane oxygenation was performed to maintain arterial blood oxygen tension after cardiopulmonary bypass and the patient was weaned from ECMO after 36 hours. Postoperatively, mechanical ventilation for respiratory failure was needed continuously and pleural leaks due to lung injuries were increased. The reduction of pleural leaks by surgical closure of fistula and plication of the cyst decreased gas exchange impairment. To our knowledge, application of extracorporeal membrane oxygenation for septic pulmonary emboli is unprecedented.

Adult↗

PubMed1996

Flow visualization of microcirculation in solid tumor tissues: intravital microscopic observation of blood circulation by use of a confocal laser scanning microscope.

To visualize the blood flow in the neovasculature of a solid tumor tissue, we utilized an intravital microscope system equipped with real-time confocal laser scanning optics. Fluorescent labeling of the blood cells and blood plasma enabled quantitative measurements of microhemodynamic parameters such as flow velocity, blood cell flux and vessel diameter in both the normal and tumor microvasculature.

Animals↗

PubMed1996

[A case of primary anterior mediastinal liposarcoma with a heterotopic mass in the pericardium of the same histology].

We experienced a case of primary anterior mediastinal liposarcoma with a heterotopic mass in the pericardium of same histology. Twenty reported cases in Japan were also studied. The patient was a 50-year-old male who visited the hospital because of an abnormal shadow on a chest X-ray. The diagnosis of anterior mediastinal tumor was confirmed by a chest CT. The patient underwent a complete resection of the mediastinal and intrapericardial masses. The histologic diagnosis was a well differentiated liposarcoma of Enzinger's classification. No evidence of recurrence or metastasis was detected in the third postoperative year. Liposarcoma is rarely seen in the mediastinum. Since radiotherapy and chemotherapy are ineffective therapeutic modalities, surgery would be the treatment of choice and complete surgical resection is mandatory.

Heart Neoplasms↗

PubMed1995

Antithrombotic activity of a symmetrical triglyceride with eicosapentaenoic acid and gamma-linolenic acid in guinea pig mesenteric microvasculature.

The antithrombotic effect of a synthetic symmetrical triglyceride having eicosapentaenoic acid (EPA) at positions 1 and 3, and gamma-linolenic acid (GLA) at position 2 was investigated. Administration of the triglyceride significantly increased thrombus formation time and thrombotic occlusion time induced by light irradiation and a fluorescent dye in guinea pigs after 14 days administration compared to that of soybean oil. The antithrombotic effect of the triglyceride was similar to that of EPA ethyl ester. Administration of the triglyceride increased GLA, dihomo-gamma-linolenic acid (DGLA) and EPA contents in plasma and the liver, and the ratio of DGLA to arachidonic acid. These results might be responsible for this antithrombotic effect.

8,11,14-Eicosatrienoic Acid↗

PubMed1995

The relationship between the pharmacological effect of amitriptyline based on an improved forced-swimming test and plasma concentration in rats.

The relationship between the plasma concentration of amitriptyline (AMI) and its pharmacological effect was investigated in rats. The plasma concentration of AMI was maintained constantly from 5 h to 7 d after intraperitoneal infusion by the implantation of an osmotic minipump with an adjusted release rate of 20 mg/kg/d of AMI. Neither the plasma or brain concentrations of AMI in a 24-h infusion group were significantly different as compared with those in the 7-d group. The pharmacological effect of AMI was measured by our improved forced-swimming test. When AMI (dose of 20 and 50 mg/kg/d) was infused, the pharmacological effect in both infusion groups of rats was increased significantly at each dose in comparison to that of the control rats (p < 0.05). With 10 mg/kg/d infusion, the effect in the 7-d group increased significantly as compared with that of the control (p < 0.05), although the effect in the 24-h group did not change. The effect was increased in both groups with an increase of dose. When the effect was plotted to the area under the plasma concentration-time curve (AUC), the effect approached a limiting value (12 micrograms/ml.h). Therefore, it was suggested that 12 micrograms.ml/h as the AUC for AMI was enough to obtain a maximum AMI pharmacological effect in rats. From these results, we concluded that the AUC for AMI may be a useful index to evaluate its pharmacological effect, rather than the plasma concentration.

Amitriptyline↗

PubMed1995

Subpressor dose of angiotensin II increases susceptibility to the haemodynamic injury of blood pressure in Dahl salt-sensitive rats.

OBJECTIVE: To investigate the effects of subpressor doses of angiotensin II (Ang II) on the progression of renal injuries in Dahl salt-sensitive (Dahl-S) rats with hypertension. METHODS: Rats were fed a high-salt (4% NaCl) diet and given an Ang II infusion (10 or 50 ng/kg per min, subcutaneously) for 4 weeks. RESULTS: The plasma Ang II concentration achieved in the high-dose Ang II infusion was lower than that in low-salt (0.3% NaCl) normotensive rats. The Ang II infusion did not affect systolic blood pressure, cardiac hypertrophy or weight of thoracic aorta. However, the high-dose Ang II infusion increased proteinuria by 58%, enhanced the urinary N-acetyl-beta-D-glucosaminase index by 77% and reduced the glomerular filtration rate by 37%. The impaired renal function was associated with a progression of glomerulosclerotic lesions. Neither tubular nor arterial lesions were exacerbated. The infusion did not influence prostacyclin production or urinary cyclic GMP excretion. CONCLUSION: A subpressor dose of Ang II infusion impairs renal function with progression of glomerulosclerosis, and these alterations may be due to increased susceptibility of the glomerulus in Dahl-S rats to Ang II-induced injuries. Such a mechanism might underlie a predisposition to hypertension-induced organ damage seen in Dahl-S rats with salt-induced hypertension.

Angiotensin II↗