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Biomedical subjects

M Kanno

Publications and source records attributed to M Kanno.

At least 55 records · Page 3Linked to original sources

Altered in vitro apoptosis of cultured mast cells prepared from an inbred strain of mice, NC/Kuj.

BACKGROUND: An inbred strain of mice, NC, develops dermatitis associated with highly elevated serum IgE and dermal mast cell hyperplasia. OBJECTIVES AND METHODS: To clarify the mechanisms for the dermal mast cell hyperplasia in NC, we prepared bone marrow-derived mast cells (BMMCs) from three strains of mice, NC/Kuj, C57BL/6 and BALB/c, and compare histamine contents, histamine release abilities, adhesive properties and apoptosis of the BMMCs. RESULTS: Compared with BMMCs obtained from C57BL/6 and BALB/c, NC/Kuj BMMC possessed higher histamine content and higher adhesive ability to plastic plates, although histamine release from BMMCs was found to be similar in the three strains. The most intriguing finding is the lack of apoptosis in the BMMCs from NC/Kuj upon growth factor deprivation as determined by DNA ladder formation and loss of membrane phospholipid asymmetry. CONCLUSION: The altered in vitro properties of mast cells in NC/Kuj partially account for an increase of dermal mast cells, which might be involved in the development of skin lesions in NC.

Animals↗

Compound A concentrations during low-flow sevoflurane anesthesia correlate directly with the concentration of monovalent bases in carbon dioxide absorbents.

UNLABELLED: Sevoflurane degrades to Compound A, which is nephrotoxic in rats. Potassium hydroxide (KOH) and sodium hydroxide (NaOH) are primary determinants of this degradation reaction. To address this, new carbon dioxide absorbents, such as Amsorb((R)) (A; Armstrong Medical, Coleraine, Northern Ireland), which contains neither KOH nor NaOH, Drägersorb 800 Plus((R)) (D; Dräger, Luebeck, Germany), and Medisorb((R)) (M; Datex-Ohmeda, Bromma, Sweden), which contain some NaOH (1% to 2%) and only trace amounts of KOH (0.003%), were recently developed. We compared Compound A concentrations using these three CO(2) absorbents during low-flow (1 L/min) sevoflurane anesthesia in surgical patients, with those using a conventional CO(2) absorbent, Drägersorb 800 (C). The mean Compound A concentrations +/- SD using C, A, D, and M were 18.7 +/- 2.5, 1.8 +/- 0.7, 13.3 +/- 3.5, and 11.2 +/- 2.6 ppm, respectively, with significant differences (P < 0.001; A versus C, A versus D, A versus M, C versus D, C versus M). Amsorb prevented the degradation of sevoflurane to Compound A, whereas Drägersorb 800 Plus and Medisorb decreased the degradation to Compound A. IMPLICATIONS: Sevoflurane degradation to Compound A is decreased by lowering the concentration of monovalent bases in the carbon dioxide absorbent (Drägersorb 800 Plus) [Dräger, Luebeck, Germany] and Medisorb) [Datex-Ohmeda, Bromma, Sweden]) and is virtually eliminated in the absence of these bases (Amsorb) [Armstrong Medical, Coleraine, Northern Ireland]).

Absorption↗

Agonist-dependent difference in the mechanisms involved in Ca2+ sensitization of smooth muscle of porcine coronary artery.

This study was undertaken to explore possible signal-transduction mechanisms involved in the Ca2+-sensitizing effects of carbachol and endothelin-1 (ET-1) by using beta-escin-skinned smooth muscle of porcine coronary artery. Pretreatment with C3 exoenzyme of Clostridium botulinum, which selectively inactivates rho p21 by adenosine diphosphate (ADP) ribosylation, resulted in a significant inhibition of ET-1-induced Ca2+ sensitization, but had no effect on carbachol-induced Ca2+ sensitization. Whereas the protein kinase C (PKC) inhibitors calphostin C and staurosporine did not affect the Ca2+-sensitizing effect of carbachol, the tyrosine kinase inhibitors genistein and tyrphostin 25 greatly but incompletely suppressed it. In contrast, the Ca2+-sensitizing effect of ET-1 was significantly inhibited by either calphostin C or genistein. Although the inhibitory effect of calphostin C on ET-1-induced Ca2+ sensitization was less than that of genistein, the effects of calphostin C and genistein were additive. The genistein-sensitive component of ET-1-induced Ca2+ sensitization appeared to include the C3-sensitive one. However, a substantial enhancement by ET-1 of the Ca2+-induced contraction was observed even in the presence of the two inhibitors. In beta-escin-skinned smooth muscle of rabbit mesenteric artery, ET-1-induced Ca2+ sensitization was marginally affected by C3 pretreatment, calphostin C, and genistein. We conclude that, although PKC activation and rho p21 protein-dependent and -independent tyrosine phosphorylation each plays an important role in an increase in myofilament Ca2+ sensitivity, the contributions of these signaling pathways to Ca2+ sensitization are different depending on receptor agonists and tissues used. Furthermore, these data suggest the existence of an as yet undefined signal-transduction mechanism involved in Ca2+ sensitization caused by receptor agonists.

Animals↗

Effects of topical nipradilol, a beta blocking agent with alpha blocking and nitroglycerin-like activities, on intraocular pressure and aqueous dynamics in humans.

AIMS: To study the effects of topical nipradilol, a non-selective beta blocker with alpha blocking and nitroglycerin-like activities, on intraocular pressure (IOP) and aqueous humour dynamics in normal humans and in patients with ocular hypertension. METHODS: Nipradilol (0.06%, 0.125%, 0.25%, 0.5%) was applied to normal volunteers (n = 12) to test for IOP lowering effects. In a second group of normal volunteers (n = 11), nipradilol (0.125% and 0.25%) and timolol (0. 5%) were compared for IOP lowering effects. After a single administration of 0.25% nipradilol, IOP, flare intensity in the anterior chamber, aqueous flow, uveoscleral outflow, tonographic outflow facility, and episcleral venous pressure were either directly measured or mathematically calculated. Topical nipradilol (0.25%) was administered to 24 patients with ocular hypertension twice daily for 8 weeks. RESULTS: Administration of 0.25% nipradilol decreased IOP with a maximum reduction of 4.2 mm Hg lasting 12 hours. A single instillation of both 0.25% nipradilol and 0.5% timolol reduced the IOP in normotensive human subjects to the same degree. A single instillation of 0.25% nipradilol decreased the aqueous flow rate in the treated eye by 20%. Nipradilol produced no significant effect in tonographic outflow facility or episcleral venous pressure, but uveoscleral outflow was increased. In patients with ocular hypertension, twice daily instillation of 0.25% nipradilol decreased IOP without tachyphylaxis for the 8 week test period. CONCLUSION: Topical nipradilol (0.25%) reduced IOP by decreasing the aqueous flow rate and probably also by increasing uveoscleral outflow. Nipradilol should be further investigated as a new antiglaucoma drug.

Administration, Topical↗

Prognosis of node-positive breast cancer patients who underwent parasternal lymph node biopsy during surgery followed by doxorubicin- or mitoxantrone-containing adjuvant chemotherapy.

The authors examined the survival rates of 60 patients with breast cancer who underwent parasternal lymph node biopsy during surgery with axillary lymph node dissection and had histologically confirmed axillary node metastasis followed by adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy to ascertain whether administration of anthracycline or its analogue improved the prognosis of both axillary and parasternal node-positive patients. The overall survival rate (OS) for the parasternal node-positive patients (n=13, 21.7%) was 30.6%, and relapse-free survival rate (RFS) fell to 0% at the 104-month follow-up. Although the survival rate for all axillary node-positive patients was similar to those in previous reports, the OS and RFS for both axillary and parasternal node-positive patients were significantly worse than that for axillary node-positive and parasternal node-negative patients, despite treatment with adjuvant doxorubicin- or mitoxantrone-containing combination chemotherapy. Other intensive adjuvant treatment strategies are needed to reduce distant metastases for high-risk breast cancer patients having both axillary and parasternal nodes positive.

Adult↗

[Cardiac tamponade due to ruptured intramural hematoma of the ascending aorta: a case report].

A 72-year-old man with a history of hypertension for 20 years was admitted with symptoms of acute aortic dissection. Computed tomography showed a crescentic thickening of the ascending aortic wall, suggesting an intramural hematoma. Sixteen hours after admission, he underwent urgent repair of the ascending aorta because of cardiac tamponade. We inspected the inside of the aorta from the aortic valve to the arch. Subadventitial hematoma due to hemorrhage from the outer media was confirmed. Rupture of the vasa vasorum was thought to be an initiating mechanism. The affected aortic wall was simply resutured and was not replaced with a graft because the intima was intact and the media was not dissected and the aortic wall was considered to be tolerable to normal blood pressure. The patient continues to do well 18 months following operation. An intramural hematoma of the ascending aorta should be regarded as a precursor of imminent rupture or classic dissection.

Aged↗

Predominant contribution of the G protein-mediated mechanism to NaF-induced vascular contractions in diabetic rats: association with an increased level of G(qalpha) expression.

The purpose of this study was to determine the mechanism responsible for alterations in NaF-induced contractions of blood vessels from streptozotocin-induced diabetic rats. In the presence of AlCl(3), NaF (>/=7.5 mM) produced significantly greater contractions in diabetic aorta and mesenteric artery compared with age-matched controls. Pretreatment with 1 microM nifedipine eliminated the enhanced contractile responses of diabetic vessels to NaF, resulting in no difference in the magnitude of NaF-induced contractions between control and diabetic vessels. In the presence of 100 microM deferoxamine, an Al(3+) chelator, NaF-induced contractions of diabetic vessels were markedly attenuated, whereas only the responses to lower concentrations of NaF were reduced in control vessels. No significant difference was found in the peak amplitude of transient contractions induced by 10 microM cyclopiazonic acid between control and diabetic vessels. The addition of 10 microM okadaic acid produced attenuated contractions in diabetic vessels. These findings indicate no involvement of the inhibitory effects of NaF on endoplasmic reticular Ca(2+)-pump ATPase and protein phosphatases in the genesis of the enhanced responsiveness of diabetic vessels to NaF. Western blot analysis showed a 2.5-fold increase in the expression of G(qalpha) in diabetic aortic membranes. In contrast, the G(ialpha) level was modestly decreased and the G(salpha) and G(betagamma) levels were unchanged in diabetes. The present results suggest that enhanced vascular contractions to NaF in diabetes is attributed predominantly to a G protein-mediated Ca(2+) channel activation that results from markedly increased G(qalpha) expression in vascular tissues under this pathological state.

Aluminum Chloride↗

Measurement of bacterial growth potential in a reclaimed water.

The objectives of this paper are to show a bio-assay method using direct total microbial count (DTMC) and to demonstrate the applicability of this method to reclaimed water for evaluating its potential of bacterial growth. We have applied our method to four types of reclaimed water, measuring the time course of DTMC and dissolved organic carbon in a bio-assay process. The experimental findings are summarised as follows: 1) By regulating organic carbon, bacteria growth could be controlled. 2) Reduction of the initial concentration of bacteria was effective to delay their growth, but this operation could not control their maximum level. This implies that the retention time of the storage and distribution system of reclaimed water should be considered in design and operation of the disinfection process. 3) Ozonation increased the growth potential. Carbon adsorption process reduced it, but the ozone plus carbon adsorption process could not improve the biological stability. 4) A linear relationship between DTMC and biodegradable organic carbon has been observed, the gradient of this linear correlation, however, depended on the source of reclaimed water.

Colony Count, Microbial↗

[Biweekly low-dose cisplatin and 5-fluorouracil combination chemotherapy for advanced gastrointestinal carcinoma].

Biweekly intravenous infusions of low-dose cisplatin (CDDP) and 5-fluorouracil (5-FU) were evaluated in 80 patients with advanced or recurrent gastric, colorectal, pancreatic or gallbladder adenocarcinoma. CDDP was given biweekly at a dose of 15 mg/m2 infused for 30 minutes, and 5-FU 375 mg/m2 was infused for 2 hours as many times as possible. The response rate among patients with gastric cancer was 26%, colorectal cancer 10%, pancreatic cancer 7.7%, and gallbladder cancer 42.9%. The response rates were not so high, but the median survival time of patients with recurrent gastric cancer was 17.3 months, pancreatic cancer 6.7 months, and gallbladder cancer 10.7 months. A patient with unresected advanced pancreatic head cancer with liver and para-aortic lymph node metastases received this therapy 38 times, and lived for 54 months. No severe side effects occurred in any of these cases. Thus, this chemotherapy could well be effective for the outcome of cases of advanced gastrointestinal carcinoma.

Adenocarcinoma↗

[Non-Hodgkin's lymphoma in two married couples].

Couple 1: A 74-year-old woman was diagnosed as having diffuse large B-cell lymphoma (DLBL) by left axillary lymph node biopsy. About 6 months later, DLBL was also diagnosed in her 79-year-old husband by right submandibular lymph node biopsy. Although the wife achieved partial remission with chemotherapy, she died due to disease progression. The husband's disease was chemotherapy-resistant, and he died of renal failure. Couple 2: An 86-year-old man was diagnosed as having DLBL by left axillary lymph node biopsy. About 4 years later, DLBL was also diagnosed in his 86-year-old wife by left axillary lymph node biopsy. Both the husband and the wife received chemotherapy. The husband is currently alive in complete remission, and although the wife achieved partial remission, she died due to disease progression. In both of these couples, it was considered unlikely that Epstein-Barr virus or human T-cell lymphotropic virus type I was related to the development of non-Hodgkin's lymphoma, and no environmental factors were confirmed to be involved. It is postulated that other unknown factors or agents may be associated with the development of lymphoma in married couples.

Aged↗

Diabetes-induced down-regulation of beta1-adrenoceptor mRNA expression in rat heart.

The present study addressed the question of whether the number of myocardial beta-adrenoceptors in rats with 4- to 6-week streptozotocin-induced diabetes is regulated in a transcriptional or translational manner. Radioligand binding experiments with [3H]CGP 12177 {4-(3-t-butylamino-2-hydroxypropoxy)-[5,7-3H]benzimidazol-2-one} showed that the density of beta-adrenoceptors fell by 50% with no change in affinity in diabetic rat ventricular myocardium compared with age-matched control myocardium. The relative content of beta1-adrenoceptor mRNA in diabetic myocardium also was reduced from the control level by 57%, as determined by northern blot analysis. The reductions in myocardial beta-adrenoceptor number and beta1-adrenoceptor mRNA observed in diabetes were prevented by insulin therapy. These data indicate that the diminished density of myocardial beta-adrenoceptors in diabetes occurred, at least in part, at the mRNA level.

Animals↗

Preferential impairment of nitric oxide-mediated endothelium-dependent relaxation in human cervical arteries after irradiation.

BACKGROUND: Vascular abnormalities are a major cause of postoperative complications in irradiated tissues. Endothelial cell dysfunction characterized by diminished endothelium-dependent relaxation may be involved. We examined the endothelium-dependent relaxation and morphology of the endothelium in irradiated human cervical arteries. METHODS AND RESULTS: Irradiated arteries were taken from the neck region of patients who had radiation therapy. Arteries from patients who did not receive radiation therapy were used as controls. Endothelium-dependent relaxation to acetylcholine and A23187 was impaired in irradiated arteries. Norepinephrine-induced contraction and sodium nitroprusside-induced relaxation were unchanged. In control arteries, N(omega)-nitro-L-arginine and indomethacin each caused a partial inhibition of endothelium-dependent relaxation. In irradiated arteries, the impaired endothelium-dependent relaxation was unaffected by these agents, but it was abolished by high K(+). Acetylcholine produced similar degrees of hyperpolarization in control and irradiated arteries. Immunohistochemical examination for endothelial nitric oxide synthase indicated no expression in the endothelium of irradiated arteries. Electron scanning microscopy showed morphologically intact endothelial cells in irradiated arteries. CONCLUSIONS: In irradiated human cervical arteries, the nitric oxide- and prostacyclin-mediated endothelium-dependent relaxation, but not endothelium-derived hyperpolarizing factor-mediated relaxation, are specifically impaired, without significant morphological damage of the endothelium. The impaired nitric oxide-mediated relaxation was associated with a lack of endothelial nitric oxide synthase expression. Our results suggest the importance of impaired endothelial function in irradiated human blood vessels, which may partly explain the development of vascular stenosis and poor surgical wound healing in irradiated tissues.

Acetylcholine↗

Prognostic Relevance of Tn Expression in Breast Cancer.

BACKGROUND: Abnormal glycosylation patterns have been recognized as a featureof carcinomaassociated mucins. The expression of the Tn antigen in breast cancer tissue was investigated to assess its prognostic relevance. METHODS: Formalin-fixed, paraffin-embedded materials from 219 patients with breast cancer were used. Immunohistochemical staining of the Tn antigen was retrospectively investigated and a lesion staining 10% or more was considered positive RESULTS: Tn antigen expression was present in 99 (45%) of 219 lesions. There were no correlations between Tn antigen expression and mean patient age, nodal status, estrogen receptor status, or menopausal status, but there was a slightly significant association between Tn and tumor size. Patients negative for the Tn antigen had a significantly better survival rate than those who were positive. Multivariate analysis also indicated that Tn expression correlated significantly with overall survival in addition to nodal status and tumor size. CONCLUSION: Tn expression was a significant prognostic factor in breast cancer, but the significance was lost on multivariate analysis. The biological implication of Tn expression in breast cancer needs further investigation.

Journal Article↗

Rat retinal ganglion cells culture enriched with the magnetic cell sorter.

The magnetic cell sorter (MACS) technique was applied to isolate retinal ganglion cells (RGCs) for culture. RGCs were labeled retrogradely with 1.1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (Dil). Subsequently retinal cell suspensions were incubated with biotinylated anti-rat Thy-1 antibody and MACS Streptavidin MicroBeads, and then applied onto the column in the magnetic fields. Cells attached on the column were flashed out without magnetism and plated on glass cover slips. RGCs were enriched to 31.0% of all cells with MACS from 0.55% before applying onto the magnetic column. Mean diameters of Dil-labeled cells were significantly larger than those of unlabeled cells. All cells with soma diameter over 11 microm were labeled. The number of viable RGCs were counted in the 10 fields of six cultures at a magnification of x200; the mean numbers on the 2nd, 7th and 14th culture-day were 53+/-3, 24+/-2 and 21+/-3, respectively (mean +/- SEM, n = 6). Thus, the MACS technique was confirmed to be useful for enrichment of RGCs and long-term study of cultured RGCs.

Animals↗

Prognostic impact of cyclin-dependent kinase inhibitor p27kip1 in node-positive breast cancer.

BACKGROUND AND OBJECTIVES: p27kip1 (p27) plays an important role as a negative regulator of cell cycle-dependent kinase activity during progression of the cell cycle. The most important prognosticator of breast cancer is nodal status, and the aim of this study was to determine the prognostic implication of p27 in breast cancer patients with lymph node metastases. METHODS: Immunohistochemical staining for p27 was performed on tissues from 102 patients with node-positive breast cancer. RESULTS: A nuclear staining over 50% was defined as high expression. High expression of p27 was shown in 59 patients (57.8%). A significant correlation was found between high p27 and positive estrogen receptor status, but there was no correlation between p27 staining and age, menopausal status, nodal status, or tumor size. Low expression of p27 was significantly associated with shorter survival. A multivariate analysis also showed that the only independent variable was p27. CONCLUSIONS: The results indicated that low expression of p27 was an independent factor associated with poor prognosis. Therefore, p27 can be an important tool in making therapeutic decisions.

Adult↗

Cardiac profile of EGIS-9377, a novel cardiotonic agent as a Ca2+ sensitizer with bradycardiac activity.

The cardiac profile of EGIS-9377 ¿2-(1-methylthio)-5-(2-morpholinoethylamino)-8,9-dihydro-7H-thi opyrano[3,2-d][1,2,4]triazolo[1,5-a]pyrimidine dihydrochloride¿, a newly synthesized cardiotonic agent, was compared with those of pimobendan and isoprenaline in cardiac preparations isolated from guinea pigs. The positive inotropic potency and efficacy of EGIS-9377 were equal to those of pimobendan in electrically paced papillary muscles, with each agent maximally increasing force of contraction by 30-35% of the maximum effect of isoprenaline. The positive inotropic effects of EGIS-9377 and pimobendan were accompanied by an increase in the relaxation time of the isometric contraction curve, whereas that of isoprenaline was associated with an abbreviation of this parameter. Pimobendan significantly increased the spontaneously beating frequency of right atria, and its positive chronotropic effect amounted to 40% of the maximum effect of isoprenaline. In contrast, EGIS-9377 exerted a significant negative chronotropic action, which resulted in a 30% decrease in the basal frequency. In beta-escin-skinned trabecular muscles, both EGIS-9377 and pimobendan substantially enhanced contractions induced by Ca2+. EGIS-9377 at concentrations to cause a significant negative chronotropic action produced a marked prolongation of action potential duration (APD) in guinea pig papillary muscle and greatly inhibited the delayed rectifier potassium current (I(K)) in guinea pig ventricular single cells. This suggests that the negative chronotropic effect of EGIS-9377 may, at least in part, be due to the prolongation of APD as a result of the I(K) inhibition. The present results indicate that EGIS-9377 efficiently increases myocardial contractile force possibly due to its Ca2+ -sensitizing activity, and yet produces a substantial negative chronotropic action. This cardiac profile of EGIS-9377 is suggested to be a clinically favorable feature compared with the inotropic agents having cyclic AMP generation or phosphodiesterase inhibition as their action mechanisms.

Animals↗