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Biomedical subjects

A Sakai

Publications and source records attributed to A Sakai.

At least 127 records · Page 7Linked to original sources
PubMed1997

Orthovanadate, an inhibitor of protein tyrosine phosphatases, acts more potently as a promoter than as an initiator in the BALB/3T3 cell transformation.

The phosphorylation and dephosphorylation of proteins are critical in cellular signal transduction. Phorbol esters and okadaic acid, which affect protein phosphorylation, are potent promoters in mouse skin carcinogenesis and cell transformation in vitro. Orthovanadate inhibits protein tyrosine phosphatases and causes hyperphosphorylation of cellular proteins. We have performed two-stage transformation assays using BALB/3T3 cells to determine the major activity of orthovanadate (1-10 microM) for transformation. This chemical acted as a weak initiator because its initiating treatment produced a significant, though small, number of transformed foci in the presence of promoting treatment by 12-O-tetradecanoylphorbol-13-acetate (TPA) but not in the absence of TPA. Promoting treatment by orthovanadate markedly enhanced the transformation of the cells pretreated by a subthreshold dose of 3-methylcholanthrene (MCA) but not of non-pretreated cells. Superiority of promoting over initiating activity of orthovanadate was confirmed by an assay carried out in the reversed treatment sequence (orthovanadate and then MCA), where the transformation frequency was conspicuously decreased compared with the regular treatment sequence. The transformed foci in the cultures treated by orthovanadate, following MCA treatment, continued to grow in normal medium, showing cell proliferation independent of orthovanadate. Orthovanadate, in addition to TPA and okadaic acid, will be a useful reagent for studying the signaling cascades responsible for tumor promotion.

3T3 Cells↗
PubMed1997

Hemosiderin deposition in portal endothelial cells is a histologic marker predicting poor response to interferon-alpha therapy in chronic hepatitis C.

Interferon (IFN)-alpha is regarded as an efficient therapy for chronic hepatitis C, despite the fact that less than 50% of patients receiving IFN-alpha are known to show an initial biochemical response, and several adverse reactions related to this therapy are becoming a serious clinical problem. For a more efficient and safer treatment of IFN-alpha, several pretreatment factors to predict a favorable or unfavorable response to IFN-alpha therapy are now being evaluated, such as hepatitis C virus (HCV)-RNA levels in serum and the genotypes of HCV. Recently, the hepatic iron concentration has been reported to influence the outcome of IFN-alpha therapy for chronic viral hepatitis. In the present study, whether hemosiderin deposition in liver is a histologic predictor of response to IFN-alpha therapy was evaluated, as well as which anatomical location showing the hemosiderin deposition was more closely related to the response to this therapy. Two factors, high titer of HCV-RNA in serum and hemosiderin deposition in portal endothelial cells, were found to be predictable factors of poor response to IFN-alpha therapy, and these two factors were found to be related to each other. Results showed that the hemosiderin deposition in portal endothelial vessels is an easily evaluable histologic finding, and clinicians and histopathologists are encouraged to use this finding when selecting patients with chronic hepatitis C suitable for IFN-alpha therapy.

Adult↗
PubMed1997

Cerebral infarction in incontinentia pigmenti: the first report of a case evaluated by single photon emission computed tomography.

A 2-month-old girl with incontinentia pigmenti presented with acute-onset right-handed focalized seizures and subsequent seizure generalization. Computed tomography, magnetic resonance imaging and single photon emission computed tomography results indicated that she had multiple cerebral infarctions. These findings suggest that incontinentia pigmenti should be included among the neurocutaneous syndromes associated with ischemic strokes in childhood. This is the first report of a case with incontinentia pigmenti associated with cerebral infarction evaluated by single photon emission computed tomography.

Brain↗
PubMed1997

[Suppressive effect of clarithromycin on the production of verotoxin by E. coli O157].

Effects of low concentration of clarithromycin (CAM) on the production of Verotoxin (VT) by Escherichia coli O157 was investigated in vitro. The production of VT1 was suppressed up to 10 hours when bacteria was incubated with 0.64 micrograms/ml (equivalent to the 1/100th of MIC) or higher concentrations. However, the production of VT1 reached to the control level after 22 hours even with 6.4 micrograms/ml of CAM. On the other hand, production of VT2 by 22 hours was partially suppressed with 0.64 micrograms/ml of CAM and completely with 6.4 micrograms/ml of CAM. When the eight clinical isolates were incubated with 0.64 or 6.4 micrograms/ml of CAM, VT1 and VT2 were suppressed in two and eight strains, respectively. In these strains, similar but less efficient suppression of the toxin production was also observed with erythromycin. In contrast to the macrorides, ampicillin did not inhibit or rather stimulated the production of VT1 and VT2 in some strains.

Ampicillin↗
PubMed1997

P-selectin and vascular cell adhesion molecule-1 are focally expressed in aortas of hypercholesterolemic rabbits before intimal accumulation of macrophages and T lymphocytes.

The accumulation of monocyte/macrophages and T lymphocytes in arterial intima is a hallmark of early atherogenesis. To investigate the temporal relationships between endothelial expression of adhesion molecules (eg, P-selectin and vascular cell adhesion molecule-1 [VCAM-1]) and intimal accumulation of macrophages and T lymphocytes, immunostaining was performed by using serial frozen sections from intercostal branch points of thoracic aortas of New Zealand White rabbits that had been fed a 0.3% cholesterol diet. After 1 week of cholesterol feeding, neither macrophages nor T lymphocytes were detected, although endothelial expression of P-selectin and VCAM-1 was observed. After 3 weeks, macrophages were detectable in 75% and T lymphocytes were present in 25% of the rabbits. Expression of P-selectin and VCAM-1 was sustained until 10 weeks. Infiltration of T lymphocytes was restricted in areas in which macrophages were accumulated and did not appear to precede macrophage infiltration. E-selectin expression was not detectable before accumulation of mononuclear leukocytes; however, very few endothelial cells covering foam cell lesions expressed E-selectin after 6 weeks. Similar results were obtained in Watanabe heritable hyperlipidemic rabbits aged 1, 2, and 3 months. Taken together, localized expression of P-selectin and VCAM-1 may play a key role in the initial recruitment of macrophages and T lymphocytes in early atherogenesis.

Animals↗
PubMed1997

Increased oxidative metabolism in cow tracheal epithelial cells cultured at air-liquid interface.

Airway epithelial cells cultured at the air-liquid interface possess highly differentiated functions and structures compared with the cells cultured under immersion. We examined the oxidative metabolism and glycolysis in cow tracheal epithelial cells on Days 3, 6, 10, and 13, cultured under three different conditions: (1) immersion culture on porous filters with apical and basolateral feeding (IM), (2) air-exposed culture on porous filters with basolateral feeding, i.e., air-liquid interface culture (AI), and (3) conventional immersion culture in plastic dishes with apical feeding (DI). Lactate production was less in AI than in IM and DI on Day 3 through Day 13, whereas cellular adenosine triphosphate content and basal O2 consumption were greater. Ouabain-sensitive and ouabain-insensitive O2 consumption, and the uncoupled O2 consumption were also greater in AI. Cytosolic lactate dehydrogenase activities on Day 10 were lower in AI, whereas alpha-ketoglutarate dehydrogenase activities were higher. The increased oxidative metabolism in AI was more pronounced at the late phase of culture (Days 10 and 13). In contrast, glycolysis remained elevated during the experiment in IM and DI. These data suggest that (I) AI begins to promote oxidative metabolism from growth phase by the provision of adequate oxygenation, and then further shifts to oxidative metabolism with differentiation; and (2) apical feeding may be responsible for the disturbance of the development of the oxidative metabolism.

Adenosine Triphosphate↗
PubMed1997

Effect of intraluminal pressure on the intimal thickening in injured rabbit carotid arteries in an organ-culture system.

We developed an organ culture system in order to examine the effect of intraluminal pressure on intimal thickening in injured arteries. After endothelial denudation, an excised rabbit common carotid artery was incubated at 37 degrees C in a glass bottle perfused with Dulbecco's modified Eagle medium containing 10% fetal calf serum at a constant flow rate of 6 ml/h at various static pressure of 60, 95, 130, 165, or 200 cmH2O. Intimal thickening, which consisted of smooth muscle cells and extracellular matrix, increased in a time- and pressure-dependent manner up to 130 cmH2O. Excessive pressured (165 and 200 cmH2O), however, caused necrosis in the media. These results suggest that a rise in intraluminal pressure accelerates intimal thickening in injured arteries.

Animals↗
PubMed1997

[Anti-allergic activity of betotastine besilate (TAU-284), a new anti-allergic drug].

The anti-allergic activity of betotastine besilate (betotastine), a new anti-allergic drug, was investigated in several allergy models of rats in comparison with other anti-allergic drugs.1) Orally administered betotastine (0.1-30 mg/kg) inhibited homologous passive cutaneous anaphylaxis (PCA) in rats in a dose-dependent manner (ID30-value: 0.38 mg/kg). The inhibitory activity of betotastine was significant at 1 mg/kg and was more potent than that of ketotifen, terfenadine, cetirizine and epinastine. The PCA-inhibitory activity of betotastine lasted more than 8 hr after administration, and the repeated administration of betotastine lasted more than not induce drug-tolerance. 2) Orally administered betotastine inhibited the histamine-induced skin reaction in rats in a dose-dependent manner (ID30:0.10 mg/kg), and the inhibitory activity lasted more than 4 hr after the administration. Its inhibitory activity was significant at 0.1 and 1 mg/kg and was more potent than those of ketotifen, terfenadine, cetirizine and epinastine. 3) Betotastine suppressed histamine release from rat peritoneal mast cells at a high concentration (10(3)(10(-3)M). These results suggest that betotastine has a potent and long acting anti-allergic activity, and these effects are mainly due to histamine antagonistic activity.

Administration, Oral↗
PubMed1997

Dibutyryl cAMP inhibits endotoxin-induced increases in pulmonary vascular resistance and fluid filtration coefficient in the perfused rat lung.

We investigated the effects of pre-treatment with dibutyryl cAMP (db-cAMP) or cGMP on endotoxin-induced hemodynamic changes and pulmonary vascular permeability in isolated perfused rat lungs. Intraperitoneal injection of Salmonella enteritidis endotoxin (2 mg/kg) caused increases in pulmonary arterial resistance (Ra) after venous reservoir elevation, in pulmonary filtration coefficient (Kf) and in lung wet-to-dry (W/D) weight ratio. Pre-treatment with db-cAMP blocked endotoxin-induced increases in Ra, Kf and W/D weight ratio. Pre-treatment with cGMP attenuated only the increase in Ra caused by endotoxin. Moreover, administration of db-cAMP 2 hours after endotoxin injection attenuated the increase in Ra induced by endotoxin treatment. The increases in Kf and W/D weight ratio caused by endotoxin were not affected by post-treatment with db-cAMP. Since the increases in Ra, Kf and W/D weight ratio caused by endotoxin were blocked by pre-treatment with db-cAMP, agents that increase intracellular cAMP level may be useful to prevent acute pulmonary vascular injury.

Animals↗
PubMed1997

[Reoperation for malfunction of Ionescu-Shiley bovine pericardial bioprosthetic valves in the mitral position--special consideration with emergency operation].

Sixty-eight patients have had mitral valve replacement with Ionescu-Shiley bovine pericardial bioprosthesis from 1981 to 1984. Thirty five patients were required reoperation due to primary tissue failure of the bioprosthesis, 10 (28.6%) were on emergency basis and 25 (71.4%) were on elective. Hospital deaths were two (20.0%) on emergency and four (16.0%) on elective. Clinical features of emergency cases were as follows: progressive congestive heart failure in eight, severe hemolysis with massive hemoglobinuria in eight and acute renal failure in four. Cusp tears were observed in all valves, 8.1 +/- 1.5 mm in emergency group and 4.2 +/- 3.6 mm in elective group. Neointimal ingrowth over Dacron cloth of the inner surface of the stent was absent in 29 valves (89.2%). Calcification was observed in seven valves, however these were not dominant causes of primary tissue failure. Clinical symptoms were correlated with structural deterioration of explanted valves. Structural deterioration of the bioprosthesis may occur suddenly and progressively. Our experience demonstrated that life-threatening prosthetic valve failure may occur with a relatively high incidence and that careful follow-up is needed for Ionescu-Shiley bovine pericardial bioprosthesis.

Bioprosthesis↗
PubMed1997

Distribution of fiber types determined by in situ hybridization of myosin heavy chain mRNA and enzyme histochemistry in rat skeletal muscles.

We analyzed fiber types in rat skeletal muscles using a novel combination of in situ hybridization of myosin heavy chain (MyHC) mRNA, and enzyme histochemistry for succinate dehydrogenase (SD), which displayed metabolic properties. The fiber types were classified into the four major subtypes of I(beta/slow), IIA, IIX and IIB, and their intermediate types coexpressed two MyHC mRNAs: I and IIA, IIA and IIX, or IIX and IIB. The distribution of fiber types differed markedly in each skeletal muscle. The superficial region of limb muscles was composed mainly of fast-twitch fibers with oxidative-glycolytic and glycolytic activities, such as type IIX and type IIB. In contrast, the deep region was composed almost exclusively of type I and type IIA fibers both with oxidative activity. In this region, type IIA/IIX hybrid fibers were noted more frequently than type I/IIA and IIX/IIB hybrid fibers. In axial muscles, slow-twitch fibers and fast-twitch fibers composed predominantly of type IIB were distributed dispersively. The diaphragm and masseter showed a high proportion of type IIX and type IIB, respectively, to adapt to tissue-specific functional requirements and more frequently contained type IIX/IIB hybrid fibers than other observed muscles.

Animals↗
PubMed1997

Inhibitory effect of betotastine besilate on antigen-induced airway eosinophil infiltration and peripheral blood eosinophilia in mice.

Eosinophilic inflammations has been recognized as a characteristic of allergic diseases. The effect of betotastine besilate (betotastine, CAS 125602-71-3, TAU-284), a new potent antihistamine drug, on the model of eosinophilic inflammation which shows eosinophil infiltration into the airway and peripheral blood eosinophilia was examined. The mice sensitized with ovalbumin (OVA) were challenged with aerosolized OVA 12 days after the first sensitization. One day after the challenge, the numbers of leukocytes and eosinophils in bronchoalveolar lavage fluid (BALF) were increased and the increase lasted up to 10 days after the challenge. Additionally, peripheral blood eosinophilia was also observed and the change peaked on the third day after the challenge. Betotastine (10 mg/kg, b.i.d., p.o.) inhibited the increase of eosinophil number in BALF on the third day after the challenge and that in peripheral blood from 1 to 3 days after the challenge. These results suggest that betotastine is an effective drug against eosinophilic inflammation of allergic diseases.

Animals↗
PubMed1997

[Effects of milrinone in patients undergoing cardiac surgery].

We investigated effects of milrinone in twenty consecutive patients (6 adults, 1 child, and 3 early infants) during cardiac surgery requiring cardiopulmonary bypass (CPB). The operations were: CABG 5, CABG+mitral valve repair 2, MVR 2, redo-MVR 4, aortic surgery 3 (total arch replacement 2), VSD+pulmonary hypertension 2 (infants), Tetralogy of Fallot 1, and PDA aneurysm 1 (infant). Ten minutes after release of aortic cross-clamp, all patients received milrinone by loading dose (50 micrograms/kg, bolus), followed by a continuous infusion of 0.5 or 0.75 microgram/kg/min. All of patients weaned from CPB with milrinone and low-dose of dopamine. The 75% of patients did not require any other drugs except for milrinone during post operative ICU stay. At the same time, we evaluated the effect of milrinone on platelet number in the patients before and after CPB. Milrinone administration did not cause significant changes in platelet number after CPB. No adverse effects attributable to this drug were found. Milrinone appears to be effective and safe in patients undergoing cardiac surgery of all kinds.

Adult↗
PubMed1997

[A report of two cases of Carpentier-Edwards pericardial mitral valve malfunction due to neointimal overgrowth expanding to valve cusps].

Two cases of Carpentier-Edwards pericardial mitral valve malfunction due to neointimal overgrowth were reported. Case one was a 51-year-old female undergone redo mitral valve replacement at nine years after first operation. Removed valve showed remarkable overgrowth of neointima expanding to the valve cusps. Case two was a 67-year-old male. A valve removed at nine years after first operation and at 1.5 years after recovery of prosthetic valve endocarditis. Removed valve also showed neointimal overgrowth expanding to the valve cusps. Although we experienced only two cases of neointimal overgrowth, these findings were considered being important in durability of Carpentier-Edwards pericardial valve.

Aged↗
PubMed1997

[Stenosis of Carpentier-Edwards pericardial bioprosthesis in the tricuspid position caused by adhesion of native valve cusps to the bioprosthesis].

We experienced a case of dysfunction of Carpentier-Edwards pericardial bioprosthesis in the tricuspid position. Explanted bioprosthesis showed overgrowth of neointima from ring to cusps and adhesion to remnants of native cusps. This restricted the motion of the pericardial leaflets resulting in orifice stenosis. Care must be taken in such valve replacement by this prosthesis leaving native valve tissue.

Aged↗
PubMed1997

[A case report of chronic dissecting aortic aneurysm (Stanford type A) with circumferential detachment of the intima].

A 57-year-old man underwent Bentall's procedure (Piehler's modification) and partial aortic arch replacement for Stanford type A chronic aortic dissection. Circumferential detachment of intima with intimal intussusception into the aortic arch was found at the time of operation. Preoperative findings did not show the intimal tear involving entire circumference of the ascending aorta. He was asymptomatic but coughing before consulting our hospital. He was discharged from the hospital 26 days after operation.

Aortic Dissection↗
PubMed1996

Diclofenac inhibits endothelial cell adhesion molecule expression induced with lipopolysaccharide.

Stimulation of cultured human umbilical vein endothelial cells (HUVEC) with lipopolysaccharide (LPS) induces adherence for human promyelocytic cell line HL60. Adherence of HL60 cells to HUVEC stimulated with LPS for 4 hr and for 24 hr were completely inhibited by pretreatment with diclofenac. While some other nonsteroidal antiinflammatory drugs (NSAIDs), such as ketoprofen, phenylbutazone, indomethacin, ibuprofen and acetylsaticylic acid, did not inhibit. The mechanism whereby diclofenac inhibits the adhesiveness of HUVEC was investigated. Pretreatment of diclofenac inhibited LPS-induced expression of E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in HUVEC, determined by flow cytometry and a cellular enzyme-linked immunosorbent assay (cell-ELISA). The inhibitory activity was concentration dependent between 15.6 and 250 micrograms/ml. Diclofenac also inhibited LPS-induced increases in E-selectin, ICAM-1 and VCAM-1 mRNAs, indicating that the action of diclofenac is to inhibit synthesis of these molecules. These data demonstrate that diclofenac is capable of inhibiting the expression of E-selectin, ICAM-1 and VCAM-1 in HUVEC.

Animals↗