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Biomedical subjects

M Kanno

Publications and source records attributed to M Kanno.

At least 199 records · Page 11Linked to original sources

Argyrophilic nucleolar organizer region counts in exocrine pancreatic tumors.

We enumerated the number of Ag-NORs in normal pancreatic ducts and exocrine pancreatic tumors to assess their cellular activity. Our results indicate that the mean number of Ag-NOR counts increased stepwise in the following order: normal pancreatic duct (1.26), serous cystadenoma (1.27), mucinous cystadenoma (1.65), mucinous cystadenocarcinoma (2.29), noninvasive intraductal variant of mucin-producing papillary adenocarcinoma (3.16), and a common type of invasive duct cell adenocarcinoma (3.78). These results suggest that cellular proliferative activity is low in normal pancreatic ducts and serous cystadenoma, intermediate in mucinous cystadenoma, and high in mucinous cystadenocarcinoma and duct cell adenocarcinoma. In addition, mucinous cystadenocarcinoma has significantly lower Ag-NOR counts than duct cell adenocarcinoma. We conclude that a clear quantitative difference between the Ag-NOR content of tumor cells of serous cystadenoma, mucinous cystadenoma, mucinous cystadenocarcinoma, and duct cell adenocarcinoma reflects the underlying different biologic behavior (chiefly, grade of malignancy) of these lesions.

Carcinoma, Intraductal, Noninfiltrating↗

Mechanism of the membrane depolarization induced by oxidative stress in guinea-pig ventricular cells.

Mechanism of the membrane depolarization induced by oxidative stress was examined using ion-selective microelectrode and patch clamp techniques. In guinea-pig papillary muscles stimulated at 0.5 Hz, cumene hydroperoxide (CH) at a concentration of 300 microM decreased the resting membrane potential and shortened the action potential, concomitantly with muscle contracture. The membrane depolarization was not associated with a significant decrease in intracellular potassium ion activity, indicating that the depolarization is not due to a decrease in potassium equilibrium potential resulting from leak of intracellular K+. In isolated guinea-pig ventricular cells. CH (10-30 microM) consistently decreased the inward rectifier potassium current and slightly decreased the calcium current. In cell-attached patches CH inhibited the opening of the inward rectifier K+ channel without affecting the unit amplitude of the single channel current. Thus, the depolarization of the resting membrane induced by oxidative stress is, at least in part, due to the inhibition of the inward rectifier K+ channel activity, and may play an important role in the genesis of reperfusion-induced arrhythmias.

Animals↗

DNA polymerase alpha positive-cell rate in colorectal cancer and its relationship to prognosis.

A total of 63 patients with colorectal cancer were studied for proliferative activity by an immunohistochemical technique using a monoclonal antibody against DNA polymerase alpha. The DNA polymerase alpha positive cell rates ranged from 24.0% to 74.6%. There was a correlation between the DNA polymerase alpha positive cell rates of biopsies and resected specimens. There was no significant correlation between DNA polymerase alpha positive cell rates and histological type, tumour size, invasion of bowel wall, lymphatic invasion, venous invasion, lymph node metastasis or peritoneal metastasis. Tumours with a high growth fraction (a DNA polymerase alpha positive cell rate greater than or equal to 42%) were more frequently associated with liver metastasis than those with a low growth fraction (a DNA polymerase alpha positive cell rate less than 42%). Patients with high growth fraction tumours had significantly poorer prognoses than those with low growth fraction tumours. The results of multivariate analysis using the proportional hazard model of Cox indicated that the DNA polymerase alpha positive cell rates, liver metastasis, and peritoneal metastasis were independent prognostic factors. The results indicate that the DNA polymerase alpha positive cell rate may be a useful prognostic marker of colorectal cancers.

Antibodies, Monoclonal↗

Voltage-dependent modification of Vmax recovery from use-dependent block by pirmenol in guinea pig papillary muscles: comparison with other class I drugs.

Voltage-dependent modification of Vmax (the maximum upstroke velocity of the action potential) recovery from use-dependent block (UDB) by pirmenol was examined and compared with those observed with other Class I drugs using standard microelectrode techniques. A partial depolarization of the resting membrane by increasing extracellular potassium concentration ([K+]o) from 4 to 8 mM potentiated UDB at 2 Hz stimulation by any of the following drugs: pirmenol (10 microM), disopyramide (20 microM), pentisomide (50 microM), quinidine (20 microM), mexiletine (30 microM), and flecainide (5 microM). The recovery time constants from UDB of quinidine and mexiletine were prolonged and that of flecainide was unchanged in 8 mM [K+]o. However, the recovery time constant from UDB of pirmenol was shortened in high K+ solution, as observed with disopyramide and pentisomide. Thus, disopyramide and its analogues, including pirmenol, show a voltage dependency of recovery process, which is different from those of other class Ia, Ib, and Ic drugs. The main unblocking pathway of disopyramide and its analogues from sodium channels during diastolic interval may be different from that of other Class I drugs.

Action Potentials↗

Immunohistochemical study of carcinoembryonic antigen in mucinous cystic neoplasm of the pancreas.

Pathologic and immunohistochemical studies of 13 patients with mucinous cystic neoplasm of the pancreas were performed in order to determine whether these lesions represent overt or latent malignancy. In 9 patients with mucinous cystadenoma, the foci of mucus-rich columnar epithelia formed the usual pattern of stratifications and papillary projections with a benign appearance and did not stain with mouse monoclonal antibody to CEA (CM-010, Mochida, Japan). In contrast, the foci of mucus-poor columnar epithelia which were in a focal distribution showed moderate to severe atypical hyperplasia and reacted strongly with anti-CEA in 6 of the 9 patients. In addition, areas of both noninvasive and invasive mucinous cystadenocarcinomas in 4 patients, which were composed primarily of mucus-poor columnar epithelia, showed diffuse cytoplasmic and/or apical reactivity with anti-CEA. Based on these results, we conclude that severe atypical epithelial hyperplasia composed primarily of mucus-poor columnar epithelia represents a precursor to mucinous cystadenocarcinoma, and, therefore, mucus-poor atypical epithelia may undergo malignant transformation.

Adult↗

Argyrophilic proteins of the nucleolar organizer region in acute leukemias and its relation to the S-phase fraction of leukemic cells.

Nucleolar organizer regions (NORs) are loops of DNA which transcribes to ribosomal RNA. The NOR-related protein becomes visible in nucleus by a silver-staining technique under a light microscope, and it has been named argyrophilic protein of NOR (Ag-NOR). In various malignancies, the correlation between the proliferation potential of tumor cells or histological grade and the number of Ag-NORs has been reported. In this study, we investigated the Ag-NOR of acute leukemic cells and its relation to the in vivo proportion of bone marrow leukemic cells in DNA synthetic phase. The number of Ag-NORs in bone marrow leukemic cells was more than that in peripheral blood (means values 2.78 and 2.48, respectively, p less than 0.01). This result shows that the number of Ag-NORs reflects the vigorous proliferative potential of bone marrow leukemic cells. However, no significant correlation was obtained between the number of Ag-NORs and the bromodeoxyuridine-labeling indices (r = 0.2064). These results suggest that Ag-NOR might be one of the markers for cellular proliferation in leukemia, while DNA synthesis of leukemic cells do not seem to be directly related to Ag-NOR. In order to clarify the role of Ag-NOR in leukemia, further studies are needed.

Adolescent↗

Immunohistochemical detection of c-myc products in colorectal cancer and proliferative cell rate.

Expression of c-myc protein was studied immunohistochemically in colorectal cancers using a monoclonal antibody, MYC-1. Immunoblotting assays with cellular lysates demonstrated a band of the gene products at the level of 60 kDa. c-myc-protein-positive tumor cells were observed in 43 (43.4%) of 99 specimens of colorectal cancers. There was no significant correlation between the incidence of MYC-1-positive tumors and clinicopathological findings. The rate of MYC-1 proteins occurring in patients with liver metastasis was significantly higher than that in patients without the metastasis. The rate of occurrence of DNA polymerase-alpha-positive cells in MYC-1 protein-positive tumors was significantly higher than in MYC-1 negative ones. The results suggested that MYC-1 immunoreactivity might possibly be a useful prognostic marker of colorectal cancers.

Adenocarcinoma↗

Bilateral metastatic sclerochoroidal calcification in a patient with hyperparathyroidism.

We present the case of a 39-year-old man with bilateral sclerochoroidal calcification with primary hyperparathyroidism. Both the calcium and parathyroid hormone levels were elevated. Funduscopic examination revealed slightly elevated, multiple yellow lesions in both eyes. Fluorescein angiography showed filling defects of the choroid. Ultrasonography showed elevated, highly reflective lesions, and a computed tomography scan of the globe disclosed sclerochoroidal lesions with high density. We discuss the mechanism of sclerochoroidal calcification.

Adult↗

Alpha 1-adrenoceptor stimulation enhances the delayed rectifier K+ current of guinea pig ventricular cells through the activation of protein kinase C.

The effect of alpha 1-adrenoceptor stimulation on the delayed rectifier K+ current (IK) was examined in isolated guinea pig ventricular cells by use of the patch-clamp method. IK was evoked by a 3-second depolarizing pulse from a holding potential of -30 mV in a Na(+)- and K(+)-free solution containing 3 microM nifedipine. Phenylephrine (30 microM) in the presence of propranolol (1 microM) produced an increase in IK. In five cells, phenylephrine increased the tail current of IK by 23 +/- 5%. This effect of phenylephrine was blocked by prazosin (0.3 microM), a selective alpha 1-blocker. Phenylephrine produced only a small effect on the voltage and time dependence of IK. Pretreatment with 1-(5-isoquinolinylsulfonyl)-2-methylpiperazine (H-7, 10 microM) abolished the phenylephrine-induced increase in IK. In addition, pretreatment with a maximally effective concentration of 12-O-tetradecanoylphorbol 13-acetate (100 nM) abolished the phenylephrine-induced increase in IK. In conclusion, alpha 1-adrenoceptor stimulation increases IK in guinea pig cardiomyocytes. This alpha 1-adrenoceptor-mediated response may be related to an activation of protein kinase C. The increase in IK may explain a shortening of action potential duration observed after alpha 1-adrenoceptor stimulation in guinea pig cells.

Action Potentials↗

Differential sensitivity of diabetic rat papillary muscles to negative inotropic effects of oxybarbiturates versus thiobarbiturates.

The negative inotropic effects of oxybarbiturates and thiobarbiturates were examined in papillary muscles isolated from streptozotocin-induced diabetic rats and in papillary muscles from age-matched control rats. The muscles from diabetic rats exhibited less negative inotropic responses to pentobarbital and secobarbital than the muscles from control rats. Conversely, the negative inotropic responses to thiopental and thiamylal were significantly enhanced in diabetic muscles. Differences in sensitivity to pentobarbital between control and diabetic muscles became less marked by treatment with ouabain or by lowering [Na+]o. Enhancement of the negative inotropic effect of thiamylal observed in diabetic muscles remained unchanged with these treatments. In both control and diabetic muscles, the negative inotropic effect of pentobarbital was completely reversed by increasing [Ca2+]o, but the effect of thiamylal was only partially reversed. These results suggest a difference in mechanism of action involved in establishment of the negative inotropic effects of oxybarbiturates vs thiobarbiturates. Oxybarbiturates appear to exclusively reduce the influx of extracellular Ca2+, whereas thiobarbiturates appear to affect Ca2+ movements at the Ca2+ storage sites in addition to the Ca2+ influx inhibition.

Animals↗

Influence of aminoglycoside antibiotics, streptomycin and kanamycin on histamine secretion in mast cells.

Effects of kanamycin and streptomycin on histamine release from rat mast cells were examined in response of the cells to concanavalin A(Con A) plus phosphatidylserine (PS), phytohemagglutinin (PHA) plus PS or a mixture of low-molecular-weight polymers of P-methoxy-N-methylphenethylamine (compound 48/80). In the response to each of the above stimuli, kanamycin (20 mM) or streptomycin (20 mM) caused a decrease in the histamine release elicited in the presence of extracellular Ca2+ (1 mM), although streptomycin showed the much higher inhibitory potency than kanamycin. Similarly, streptomycin was much more effective in suppressing compound 48/80-triggered histamine release in the absence of external Ca2+. Histamine release in the absence of external Ca2+ in the response to the lectin plus PS diminished with increasing concentration of kanamycin, and in this respect streptomycin was much less effective. In the response to the lectin plus PS, external Ca2+ possessed potency to antagonize kanamycin (10 mM)- or streptomycin (10 mM)-caused inhibition of the histamine release, although more markedly the kanamycin-caused one. Streptomycin and kanamycin inhibit histamine release from mast cells challenged with IgE-directed secretagogue or compound 48/80, and the responsible mechanisms seem to implicate the Ca(2+)-antagonistic action on the stimulus-provoked influx of Ca2+ and impairment of the cellular events linked to exocytosis.

Animals↗

[Application of bromodeoxyuridine (BrdU) and anti-BrdU monoclonal antibody for the analysis of tumor cell kinetics by flow cytometry].

Bromodeoxyuridine (BrdU) is a thymidine analogue which is incorporated into the cells of DNA synthetic phase. BrdU-labeling index (BrdU-LI) of tumor cells can be estimated with an anti-BrdU antibody. Bivariate distributions of BrdU and DNA content are simultaneously obtained by flow cytometric two parameter analysis with a double staining method. The exact DNA synthetic cells are determined using this method by removal of the cells having S phase DNA content without DNA synthesis; quiescent (S0) cells. Once the BrdU-LIs are obtained, DNA synthesis time (Ts) and other time parameters of tumor cell kinetics can be calculated by mathematical methods. BrdU and anti-BrdU monoclonal antibody makes it possible to easily and rapidly recognize the tumor cell kinetics with high accuracy.

Antibodies, Monoclonal↗

Inhibition by 5-hydroxytryptamine of the beta adrenoceptor-mediated positive inotropic responses to catecholamines in rabbit papillary muscles: direct interaction with beta adrenoceptors.

The effects of 5-hydroxytryptamine (5-HT) on the positive inotropic responses to catecholamines were investigated in isolated rabbit papillary muscles. 5-HT produced a concentration-dependent positive inotropic effect, an effect which was antagonized by prazosin, but not by propranolol. The positive inotropic effect of 5-HT diminished greatly in muscles from rabbits pretreated with 6-hydroxydopamine. Thus, it is likely that 5-HT causes a release of norepinephrine and increases force of contraction indirectly through alpha-1 adrenoceptors. In the presence of prazosin, 5-HT exerted a concentration-dependent inhibition of the positive inotropic response to isoproterenol. The positive inotropic responses to tyramine and a beta-1 adrenoceptor agonist T-1583 were also inhibited by the addition of 5-HT. The inhibitory effect of 5-HT on the beta adrenoceptor-mediated responses was unaffected by methysergide, ketanserin, ICS 205-930 or atropine. Pretreatment with pertussis toxin did not block the inhibitory effect of 5-HT on the inotropic response to isoproterenol, while abolishing the cholinergic interaction against the isoproterenol response. In contrast to its antagonizing effect on the inotropic response to isoproterenol, 5-HT produced an additive effect on the positive inotropic response to norepinephrine. However, when neuronal amine uptake was blocked by cocaine, the positive intropic response to norepinephrine was suppressed by the addition of 5-HT. 5-HT inhibited (-)-[125I]iodocyanopindolol binding to the membranes from rabbit ventricles with a monophasic displacement curve.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Selectivity of class I antiarrhythmic agents, disopyramide, pirmenol, and pentisomide for peripheral muscarinic M2 and M3 receptors.

The interactions of the class I antiarrhythmic agents, disopyramide, pirmenol, and pentisomide with peripheral muscarinic receptors were investigated by binding assay with [3H]N-methylscopolamine ([3H]NMS) as a ligand. All the agents inhibited the specific [3H]NMS binding to membrane preparations obtained from guinea pig submandibular gland (SG) and urinary bladder (UB) smooth muscle. The competition curves of these agents for [3H]NMS binding to SG membranes were monophasic, indicating competition with [3H]NMS at a single site. Comparison of results with those of our previous binding experiments using guinea pig left atrial (LA) membranes, showed that pirmenol had sevenfold lower affinity for glandular-type muscarinic receptors (M3) than for cardiac-type muscarinic receptors (M2). On the other hand, the dissociation constants (Ki) for disopyramide and pentisomide in SG were comparable to the high-affinity Ki values for these agents at M2 receptors. The competition curves of the three agents for [3H]NMS binding to UB membranes were biphasic and showed high- and low-affinity states of binding. The high- and low-affinity Ki values for pirmenol in UB were similar to its Ki values at M2 and M3 receptors obtained in LA and SG, respectively. The high-affinity Ki values for disopyramide and pentisomide were consistent with the respective Ki values determined in SG, whereas the low-affinity binding sites for these agents were presumably the result of their allosteric interactions with the receptors. All agents at higher concentrations slowed the dissociation of [3H]NMS elicited by an excess of atropine in both UB and SG, thus indicating allosteric interactions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

[A case of traumatic aortic valve rupture].

A case of aortic valve rupture as a result of blunt trauma by motorcycle accident is presented. A previously healthy 18-year-old male developed severe congestive heart failure 46 days after the initial trauma. There were crescentic tears in the right and non-coronary cusps parallel to and along the whole length of the cusps. The valve was excised and replaced with a 21 mm St. Jude Medical prosthesis. Following the procedure he made an relatively uneventful recovery and was discharged on the 83rd postoperative day. The possibility of damage to the heart valves in traffic accidents must be borne in mind since rapid deterioration can occur and early surgical therapy is essential.

Accidents, Traffic↗

Effects of macrolides on ultrastructure of Staphylococcus aureus during postantibiotic phase.

The postantibiotic effects (PAEs) of macrolide antibiotics, such as midecamycin acetate (Miocamycin, MOM), erythromycin (EM), josamycin (JM) and clarithromycin (CAM), on Staphylococcus aureus and the ultrastructure of the pathogen during the postantibiotic phase were investigated. After exposure to 2 x MIC for 2 h, MOM showed the longest PAE of 3.9 h, while EM, JM and CAM showed PAE durations 1.2, 2.5 and 1.9 h, respectively. On examining the serum levels of these agents in man, the longest PAE of 2.4 h was induced by exposure to MOM. JM and CAM induced PAEs for durations of 1.4 and 1.3 h, but EM hardly induced the PAE. The ultrastructure was examined by transmission electron microscopy, and thick cell walls with an undulating outer layer and a multiple thick cross-section were observed for 4 h after exposure to 2 x MIC of MOM for 2 h. After exposure to 2 x MIC of EM, JM and CAM for 2 h, ultrastructural changes were observed for 1, 2 and 2 h, respectively. The size of these cells was about 1.5 to 2 times larger than the normal cells. Ultrastructural changes in S. aureus were observed during the PAE phase of each macrolide.

Anti-Bacterial Agents↗

[Immunohistochemical detection of p53 in colorectal cancer and its relationship to prognosis].

The expression of p53 in colorectal tumors was studied immunohistochemically by monoclonal antibody (PAb1801). No nuclear staining was evident in the tumor cells of colorectal adenomas. p53 immunoreactivity was found in 59 (61.5%) of 96 colorectal cancers. There was no significant correlation between the p53 immunoreactivity and histologic type, tumor size, invasion of bowel wall, lymphatic invasion, venous invasion, lymph node metastasis, peritoneal dissemination, or liver metastasis. However, the p53 negative tumors showed a recurrence rate of 3.3%, while for the p53 positive tumors a recurrence rate of 20.9%. p53 negative tumors were associated with favorable prognosis, whereas those with p53 positive tumors were related to poor prognosis. DNA polymerase alpha positive cells rate in p53 positive tumors was significantly higher than in p53 negative tumors. The results suggested that p53 immunoreactivity might possibly be a useful prognostic marker of colorectal cancers.

Biomarkers, Tumor↗