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Biomedical subjects

M Yanai

Publications and source records attributed to M Yanai.

At least 73 records · Page 4Linked to original sources

[Treatment results in childhood acute myeloblastic leukemia--a report of clinical trials of a past decade from the Japanese children's Cancer and Leukemia Study Group (CCLSG)].

Treatment results were evaluated in 167 children with acute myeloblastic leukemia (AML) treated on four protocols (ANLL 861, 8912, 9205, APL-ATRA) of the Children's Cancer Leukemia Study Group. In the ANLL 9205 protocol, anthracycline was used with a continuous infusion of cytosine arabinoside, followed by an intensive sequential post remission chemotherapy of short duration, 42/46 patients (91.3%) achieved complete remission, and 58.8% of these patients projected a 3-year disease free survival. These results were apparently superior to those obtained with the ANLL 861 & 8912 protocols, which used conventional doses of multi drugs followed by a moderate post remission chemotherapy of long duration. This favorable response with the ANLL 9205 protocol was attributed mainly to the high induction rate of patients with the M4 and M5 FAB subtypes, as compared to those in the previous two protocols (91.3% in ANLL 9205 vs 57.9% in ANLL 861 + 8912; p < 0.05). No significant difference in the patients outcome was found between the chemotherapy group and allogenic bone marrow transplantation group in the ANLL 9205 study. The patients with the M3 FAB subtype treated with the APL-ATRA protocol which consisted of an alternative use of all-trans retinoic acid and chemotherapy significantly prolonged event free survival as compared with the patients treated with ANLL 861/8912 protocols without all-trans retinoic acid.

Anthracyclines↗

Intracellular pressure is a motive force for cell motion in Amoeba proteus.

The cortical filament layer of free-living amoebae contains concentrated actomyosin, suggesting that it can contract and produce an internal hydrostatic pressure. We report here on direct and dynamic intracellular pressure (P(ic)) measurements in Amoeba proteus made using the servo-null technique. In resting apolar A. proteus, P(ic) increased while the cells remained immobile and at apparently constant volume. P(ic) then decreased approximately coincident with pseudopod formation. There was a positive correlation between P(ic) at the onset of movement and the rate of pseudopod formation. These results are the first direct evidence that hydrostatic pressure may be a motive force for cell motion. We postulate that contractile elements in the amoeba's cortical layer contract and increase P(ic) and that this P(ic) is utilized to overcome the viscous flow resistance of the intracellular contents during pseudopod formation.

Amoeba↗

Prostaglandin production via induction of cyclooxygenase-2 by human gingival fibroblasts stimulated with lipopolysaccharides.

The purpose of the present study was to investigate the involvement of cyclooxygenase-1(COX-1) and cyclooxygenase-2 (COX-2) in PGE2 production by human gingival fibroblasts stimulated with lipopolysaccharides (LPS) from periodondopathogenic bacteria. LPS were isolated from Porphyromonas gingivalis (P. gingivalis), Actinobacillus actinomycetemcomitans (A. actinomycetemcomitans) and Eschericia coli (E coli) by the phenol-water procedure. The three LPS preparations produced PCE2 up to 48 h in a time-dependent manner in human gingival fibroblasts. P. gingivalis-LPS was the most potent stimulator of PGE2 production and, to a lesser extent, A actinomycetemcomitans- and E coli-LPS. Treatment of the cells with indomethacin, a non selective COX-1/COX-2 inhibitor and NS-398, a selective COX-2 inhibitor, completely depressed PGE2 production. Treatment of dexamethasone, known to inhibit COX-2 expression, also significantly prevented PGE2 production. Immunohistochemical staining of COX-2 protein demonstrated that expression of COX-2 protein was increased at 24 h after P gingivalis-LPS stimulation, while expression of COX-1 protein was not affected by P. gingivalis-LPS. In order to investigate the regulation of PGE2 production. P. gingivalis-LPS-stimulated cells were treated with herbimycin A and genistein, both inhibitors of tyrosine kinases. Both the inhibitors significantly inhibited PGE2 production. Herbimycin A treatment depressed expression of COX-2 protein. These data suggest that human gingival fibroblasts stimulated with LPS from periodontopathogenic bacteria mainly produce PGE2 not by COX-1, but by COX-2, induction of which may be regulated by tyrosine kinase and that the produced PGE2 may be involved in the pathogenesis of periodontal diseases.

Aggregatibacter actinomycetemcomitans↗

Blood density monitoring during dialysis.

Continuous monitoring of blood density (BD) was preformed in 4 stable dialysis patients in 20 sessions using a density meter based on a mechanical oscillator technique. Mean predialysis and postdialysis BDs were 1.0427 +/- 0.0031 g/cm3 and 1.0502 +/- 0.0055 g/cm3, respectively. For similar predialysis to postdialysis total body water reduction, significant difference in the mean BD increase was found between hypotensive and nonhypotensive groups (1.29 +/- 0.07%, 0.47 +/- 0.12%, respectively; p < 0.001). Eight hypotensive episodes occurred during 6 sessions. The mean value of the blood density changes slope (dBD/dr) during the 5 min preceding a hypotensive episode increased about 2.5 times more than did the mean of the predialysis to postdialysis blood density slope (27.6 +/- 2.2 g/cm3.min.10(-5), 10.5 +/- 0.4 g/cm3.min.10(-5), respectively; p < 0.001) under the condition of a constant ultrafiltration rate of 18.9 +/- 0.6 ml/min. Continuous monitoring of blood density allows abrupt change in plasma volume to be identified and seems to have a potential utility to the prevention of symptomatic hypotension episodes in patients receiving hemodialysis.

Adult↗

Dependence of collateral and small airway resistances of CO2 and volume in dog lobes.

We examined the hypothesis that collateral channels were identical within small airways and ducts, therefore both should respond similarly to chemical and mechanical stresses. A double lumen catheter was wedged into a segmental bronchus of the dog and humidified air or 10% CO2 in air (Vs) flowed at a segmental bronchial pressure (Pb) of 2 cm H2O. A small circular area about 1 cm diameter was peeled from the wedged segment and covered with a capsule glued to the surrounding pleura for measuring either a small airway flow (Vsaw) or capsule pressure (Pcap). Collateral resistance (Rcoll) and small airway resistance (Rsaw) were calculated as Rcoll = Pb/(Vs-Vsaw), Rsaw = (Pb-Pcap)/Vsaw, respectively. Hypocapnia (air) resulted in increases in Rcoll and Rsaw, while hypercapnia (10% CO2) generally had the opposite effect. Gcoll and Gsaw both increased linearly with lung volume (VL). The pattern of the responses of Rsaw closely paralleled those of Rcoll to local hypercapnia and hypocapnia, and to changing VL, implying that the major sites of resistance along collateral channels and along the airways are functionally and structurally similar.

Airway Obstruction↗

Conditioned enhancement of cough response in awake guinea pigs.

To determine whether psychological factors affect the cough response, we employed a classical conditioning procedure in which capsaicin challenge was paired with the presentation of an odor in awake guinea pigs. On days 1-4, animals received combined administrations of the unconditioning stimulus, capsaicin aerosols, and the conditioning stimulus, camphor aerosols (group 1), capsaicin and saline aerosols (group 2), and camphor and saline aerosols (group 3), and the number of coughs was counted. On day 5, all groups received camphor and saline aerosols. A significant number of coughs (p < 0.01) was observed only in group 1 when the animals were exposed to the odor alone on day 5. This suggests that associative learning enhances the cough response.

Aerosols↗

Beneficial effects of enteral fat administration on liver dysfunction, liver lipid accumulation, and protein metabolism in septic rats.

The purpose of this study was to examine the effect of different amounts of fat in enteral diets on liver function, liver lipid accumulation, and protein metabolism in septic rats. Sepsis was induced in Wistar rats by cecal ligation and puncture. The rats were divided into four groups and were fed enterally 0% (FO, n = 7), 10% (F10, n = 7), 20% (F20, n = 8), or 30% (F30, n = 9) of total calories as fat. The liquid diet consisted of medium-chain and long-chain triglyceride mixtures as the fat sources, casein oligopeptide, and dextrin (100 kcal/100 ml). Intraduodenum feeding was ended on the 6th day. Serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activities, indices of liver dysfunction, were highest in the FO group, and triglycerides accumulated in the livers of that group, possibly because of the large proportion of carbohydrate in the diet. Value of nitrogen balance was highest in the F 10 group, and serum total protein and albumin concentration were higher in the F10 and F20 groups than in the FO and F30 groups. The liver protein content in the F10 and F20 groups was higher than in the FO and F30 groups. Serum triglyceride in the F30 group was about 2 times higher than in the F10 and F20 groups. These results indicate that enteral fat administration in septic rats as 30% of total calories reduced liver dysfunction and liver triglyceride accumulation, but might have been excessive for optimal protein metabolism. Therefore, the preferable amount may range from 10% to 20% of total calories.

Alanine Transaminase↗

Recombinant human erythropoietin has no direct or strong vasoconstrictor effects in vivo and in vitro.

An elevation of blood pressure is observed in approximately 30% of dialysis patients treated with recombinant human erythropoietin (rHuEPO). Various studies have been performed in order to elucidate possible underlying mechanisms, but it is not yet well understood whether there is one major mechanism involved. In this present study, samples were obtained from male normotensive Wistar-Kyoto rats (WKY) and genetically hypertensive rats (SHR) at the age of 5 and 20 weeks. Thoracic aorta rings, with or without endothelium, isolated from WKY and SHR were used to evaluate the direct effect of rHuEPO on vascular smooth muscle by measuring the tension of vascular smooth muscle induced by various concentrations (1-100 IU/ml) of rHuEPO. Also, rHuEPO (10, 100, 1000 and 10,000 IU/kg) was intravenously administrated and the changes in mean blood pressure were recorded for 5-10 min. rHuEPO produced no significant contraction in the rat aortae in any of the preparation studies, in the presence or the absence of endothelium. The intravenous administration of rHuEPO had no immediate effect on mean blood pressure in 5- and 20-week-old WKY and SHR. These results suggest that the elevation of blood pressure observed in the clinical setting following the administration of rHuEPO is not due to a direct pressor effect on vascular smooth muscle.

Animals↗

Effects of diet high in medium-chain triglyceride on plasma ketone, glucose, and insulin concentrations in enterectomized and normal rats.

The effects of dietary medium-chain triglyceride (MCT) on the concentration of plasma ketone bodies in enterectomized and normal rats were examined, together with the effects on plasma glucose, plasma immuno-reactive insulin, and liver function. Four groups of enterectomized rats and four groups of normal rats were fed experimental diets containing 0, 6, 11, or 21% of MCT by weight for 6 days. All animals including normal rats received meal-feeding for 3 h once a day. On day 3, concentration of plasma ketone bodies in enterectomized rats increased dose-dependently with dietary MCT and the level was higher than that in normal rats. However, all the values in enterectomized rats never exceeded 2 mM, the maximum physiological concentration. In contrast, plasma glucose in the enterectomized rats showed a tendency to decrease more clearly and dose-dependently with dietary MCT, followed by a marked increase of insulin secretion compared with those in normal rats. On the final day, no significant differences in the results of liver function tests were observed among these groups. These results indicate that the MCT-induced ketosis was within an acceptable range, and dietary MCT is useful for the suppression of increase in plasma glucose following a surgical operation without any disadvantageous effects on liver function.

Animals↗

Magnesium and parathyroid hormone changes to magnesium-free dialysate in continuous ambulatory peritoneal dialysis patients.

OBJECTIVE: For the normalization of serum magnesium (Mg) concentration, dialysate Mg concentration tends to be reduced in continuous ambulatory peritoneal dialysis (CAPD) patients. The aim of this study was to evaluate the influence of Mg on parathyroid hormone (PTH). DESIGN: Prospective study of the utilization of Mg-free dialysate for 8 weeks. SETTING: Dialysis service, Itabashi Hospital, Nihon University School of Medicine. PATIENTS: Five stable CAPD patients (1 male; 4 female; age 49.7 +/- 1.3 years; duration of CAPD 27 +/- 9 months). MAIN OUTCOME MEASURES: Serum Mg, serum high sensitive PTH, and Mg content in mononuclear cells were measured at 4-week intervals. RESULTS: In comparison to baseline, serum Mg concentration was significantly reduced at week 4 (p < 0.01) and week 8 (p < 0.01), and serum PTH was significantly increased at week 4 (p < 0.05) and at week 8 (p < 0.05). However, the PTH level at week 8 was lower than that at week 4. Furthermore, the Mg content in mononuclear cells was significantly decreased at week 4 (p < 0.01) and at week 8 (p < 0.01). Serum-ionized calcium and phosphate concentrations did not change. CONCLUSIONS: The removal of Mg by Mg-free dialysate leads to Mg depletion in CAPD patients. In addition, Mg depletion stimulates PTH synthesis or secretion at 4 weeks, but at 8 weeks PTH synthesis or secretion is also influenced by other factors.

Blood Urea Nitrogen↗

Acute promyelocytic leukemia with t(15;17) abnormality after chemotherapy containing etoposide for Langerhans cell histiocytosis.

BACKGROUND: Epipodophyllotoxins, etoposide and teniposide, have been shown to be implicated in the development, of acute myelogenous leukemia in patients treated for solid tumors or acute lymphoblastic leukemia. Etoposide has been shown to be an effective agent against Langerhans cell histiocytosis (LCH) and has gained wider use recently for first-line and salvage chemotherapy in cases of systemic LCH. METHODS: The authors report two patients with secondary acute promyelocytic leukemia (APL) with a t(15;17) abnormality after chemotherapy that included etoposide for the treatment of LCH. RESULTS: Patient 1, a 6-year-old girl, had APL develop 11 months after cessation of therapy that included vinblastine, prednisolone, and etoposide (9600 mg/m2 in total dose) for LCH. Patient 2, a 3-year-old girl, had APL develop 9 months after cessation of therapy that included vincristine, methotrexate, prednisolone, cyclophosphamide (10,800 mg/m2), and etoposide (4800 mg/m2) for LCH. CONCLUSIONS: The authors have experience with four patients treated with etoposide for LCH and suggest that there is a predisposition to secondary APL with t(15;17) for patients with LCH treated with etoposide. The authors warn against the imprudent use of etoposide as a first-line therapy for LCH.

Child, Preschool↗

Endopeptidase activity of cathepsin C, dipeptidyl aminopeptidase I, from bovine spleen.

By employing various synthetic substrates, as well as soluble denatured protein substrate (TAP-lysozyme) and its derivatives, endopeptidase activity of cathepsin C, dipeptidyl aminopeptidase I [EC 3.4.14.1], from bovine spleen was investigated. Cathepsin C efficiently degraded Z-Phe-Arg-MCA, Pro-Phe-Arg-MCA, and Suc-Leu-Leu-Val-Tyr-MCA. This endopeptidase activity required sulfhydryl reagents and halide ions, as in the case of the dipeptidyl aminopeptidase (DAP) activity. We confirmed that this endopeptidase activity is due to cathepsin C itself based on the results on gel-filtration and anion-exchange chromatographies, comparative studies of the inhibitory effects of leupeptin and E-64 on this activity and those of cathepsins B and L, and further the competitive inhibitions by mutual substrates for the DAP and endopeptidase activities of cathepsin C. We also found that cathepsin C endopeptidase activity towards TAP-lysozyme and its N-alpha-acetylated tryptic peptides showed marked dependence on sulfhydryl reagents and chloride ion. Thus, we concluded that cathepsin C has endopeptidase activity as well as DAP activity. The binding energy between the enzyme and the amino acid side chains of the substrate may be as important for the endopeptidase activity as is the electrostatic interaction between the enzyme and the free alpha-amino group of the substrate for the DAP activity.

Animals↗