Biomedical subjects

M Kanno

Publications and source records attributed to M Kanno.

At least 235 records · Page 13Linked to original sources

PubMed1991

Application of bromodeoxyuridine (BrdU) and anti-BrdU monoclonal antibody for the in vivo analysis of proliferative characteristics of human leukemia cells in bone marrows.

To investigate the proliferative characteristics of human bone marrow leukemic cells in vivo, we developed a new method using bromodeoxyuridine (BrdU) and its monoclonal antibody. Thirty minutes after a bolus BrdU infusion, a lst bone marrow aspiration (BMP) was performed to calculate the BrdU labeling index (BrdU-LI). Then, a 150-min continuous infusion of BrdU was started. Immediately after the infusion, a 2nd BMP was done to analyze the increasing rate of the BrdU-LI for 3 h. Each smear was stained by an immunohistochemical method. The BrdU-LI, the duration of S phase (Ts) and the cell cycle time (Tc) of leukemic cells from 13 previously untreated patients with acute leukemias were estimated. A mean value of 7.2% for BrdU-LI was obtained. Furthermore, mean values of 9.7 h and 152.5 h for Ts and Tc respectively were calculated. This method may prove to be useful in the in vivo cell cycle analysis of leukemias and other malignancies.

Antibodies, Monoclonal↗

PubMed1991

Binding profiles of class I antiarrhythmic agents to cardiac muscarinic receptors: competitive and allosteric interactions with the receptors and their pharmacological significance.

The binding profiles of the class I antiarrhythmic agents disopyramide, pirmenol and pentisomide (CM7857) to cardiac muscarinic receptors were characterized by the binding assay using [3H]-N-methyl scopolamine ([3H]NMS) as a ligand and their anti-muscarinic actions were investigated functionally in left atrial preparations. All the agents displaced the specific binding of 200 pM [3H]NMS from guinea pig left atrial membranes. Computer-assisted analysis indicated that pirmenol interacted with a single class of binding sites, but the displacement curves of disopyramide and pentisomide were shallow and best fitted to a two-site model. When the concentration of [3H]NMS was increased to 1 nM, the displacement curve of pirmenol was best fitted to a two-site model. In higher concentrations, these agents inhibited the dissociation of [3H]NMS initiated by 1 microM atropine in a concentration-dependent manner, thus revealing allosteric interactions. Two enantiomers of pirmenol possessed qualitatively the same binding properties as the racemate. In guinea pig left atria, disopyramide, pirmenol and pentisomide shifted the concentration-response curves for the negative inotropic effect of carbachol in a parallel manner. The slopes of Schild plot were not significantly different from unity, indicating that they act as a competitive antagonist of cardiac muscarinic receptors. Excellent correlation between the high affinity pKi values and the pA2 values was established for the antiarrhythmic agents. These findings suggest that disopyramide, pirmenol and pentisomide all interact with cardiac muscarinic receptors in both a competitive fashion and an allosteric one. The dual mode of the interaction with cardiac muscarinic receptors seems to be independent of their chiralities.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

[A case of acute postinfarction mitral insufficiency and cardiogenic shock caused by total rupture of a papillary muscle].

A 61-year-old male in cardiogenic shock was transferred to our hospital with an intra-aortic balloon pumping (IABP). He had had acute posterior myocardial infarction previous day. He had developed progressively increasing dyspnea and physical signs of severe congestive failure. On admission, his blood pressure was 60 mmHg even with IABP. He was anuric with a high blood urea nitrogen and serum creatinine level. An echocardiogram demonstrated a rupture of a posterior papillary muscle and massive mitral insufficiency. His deteriorating condition did not allow us to perform cardiac catheterization. He underwent an emergency operation. Total rupture of a posterior papillary muscle was confirmed. Mitral valve replacement with a SJM prosthetic valve was performed. A postoperative course was uneventful.

Humans↗

PubMed1990

Effect of granulocyte colony-stimulating factor on neutropenia due to chemotherapy for non-Hodgkin's lymphoma.

The authors administered recombinant human granulocyte colony-stimulating factor (rhG-CSF) to 16 patients with advanced non-Hodgkin's lymphoma treated with combination chemotherapy. Groups of three to five patients were treated with 50, 100, 200, and 400 micrograms/m2 per day of rhG-CSF by intravenous infusion for 14 days, beginning 3 days after chemotherapy. There was a strong linear relationship between the dose and the area under the curve over this dose range. The rhG-CSF was rapidly cleared from serum, with a mean half-life of 5.97 hours for the second phase (t1/2). In patients treated with a dose of more than 100 micrograms/m2 per day, the duration of neutropenia (P less than 0.01) and the duration of fever (P less than 0.05) were significantly decreased. The rhG-CSF was well tolerated and the only clinical observation that appeared relating to rhG-CSF administration was slight bone pain. This study strongly suggests that an optimum dose of rhG-CSF in patients after chemotherapy is 100 to 200 micrograms/m2. Our study shows that rhG-CSF is a clinically useful drug for patients treated with myelosuppressive chemotherapy.

Adult↗

PubMed1990

Effects of N-acetylprocainamide and sotalol on ion currents in isolated guinea-pig ventricular myocytes.

The effects of N-acetylprocainamide (NAPA) and sotalol on membrane current systems of guinea-pig ventricular myocytes were examined and compared with those of quinidine using patch-clamp techniques. All of the drugs prolonged the action potential duration (i.e. Class III effect) in isolated guinea-pig papillary muscles. In isolated ventricular cells. NAPA (300 microM) and sotalol (100 microM) produced a decrease in the delayed outward potassium current (IK) concomitantly with a slight decrease in the calcium current (ICa), which was similar to quinidine (10 microM). NAPA also slightly depressed the inward rectifier potassium current (IKrect). Thus, NAPA and sotalol both inhibited IK, and this action appears to be mainly responsible for their Class III effect.

Acecainide↗

PubMed1990

Beta-adrenoceptor-mediated depolarization of the resting membrane in guinea-pig papillary muscles: changes in intracellular Na+, K+ and Cl- activities.

Effects of beta-adrenergic stimulation on the membrane potential and intracellular Na+, K+ and Cl- activities were examined in isolated guinea-pig ventricular muscles using conventional and ion-selective electrodes. Isoproterenol in concentrations of 30 nM - 1 microM produced a transient depolarization followed by a slight hyperpolarization in electrically stimulated or quiescent papillary muscles. The negative logarithm of the concentration producing 50% maximum effect (pD2) for the membrane-depolarizing effect of isoproterenol was smaller than that for the positive inotropic effect, suggesting that a higher level of cAMP accumulation is required to produce the transient depolarization. Whereas the isoproterenol(1 microM)-induced depolarization was not blocked by tetrodotoxin (10 microM), nifedipine (10 microM), Cs+ (5 mM), Ba2+ (0.3 mM), amiloride (1 mM) or ouabain (10 microM), it was significantly attenuated by anthracene-9-carboxylic acid (1 mM), a Cl(-)-channel blocker. Intracellular K+ activity increased, whereas intracellular Na+ activity slightly decreased during the transient depolarization. Intracellular Cl- activity significantly decreased during the isoproterenol-induced depolarization of the resting membrane. These results suggest that an inward current resulting from outward Cl- movement, rather than inward Na+ movement, may be involved in the beta-adrenoceptor-mediated membrane depolarization.

Adrenergic beta-Agonists↗

PubMed1990

Clinical experience of biliary tract carcinoma associated with anomalous union of the pancreaticobiliary ductal system.

Between 1978 and 1988, 15 patients with gallbladder cancer and 2 patients with bile duct cancer were seen among 49 patients with anomalous union of the pancreaticobiliary ductal system. Radiographic findings revealed two types of this anomalous condition: one in which the pancreatic duct entered the common bile duct (type 1) and one in which the common bile duct entered the pancreatic duct (type 2). In gallbladder cancer, the common bile duct presented no dilatation, or in some patients, mild dilatation, and type-1 anomalous union was frequently found among these patients. In contrast, the two patients with bile duct cancer had cystic dilatation of the common bile duct and type-2 anomalous union. The bile amylase level, which was determined in seven patients, was extremely high in all the patients. Histopathologically, the tumors in most patients showed papillary to papillo-tubular proliferation in the mucosal layer while atypical epithelial hyperplasia was noted in the vicinity of the tumor area. These findings suggest that this congenital anomaly in both ducts results in a loss of the normal sphincteric mechanism of the duodenal papilla, and that chronic relapsing cholecystitis or cholangitis, caused by the reflux of pancreatic juice into the biliary tract, can induced progressive changes to atypical epithelial hyperplasia which may develop into carcinoma.

Adult↗

PubMed1990

A clinicopathological study on intrahepatic cholesterol gallstones.

In order to clarify the pathogenesis and process of the formation of intrahepatic cholesterol gallstones, we examined the clinical features, cholangiograms and pathological findings of eight patients with intrahepatic cholesterol gallstones. When examining the clinical features, one patient was found to have developed intrahepatic cholesterol gallstones 3 years after a complete lithotomy. The cholangiograms of two patients revealed small gallstones in the peripheral bile ducts of the lateral segment of the liver, and these bile ducts showed localized cystic dilatation and were tightly filled with gallstones. Conversely, their other bile ducts which contained no gallstones showed an entirely normal cholangiogram. Pathologically, these two cases showed mild chronic cholangitis, and cholesterol crystals in the peripheral bile ducts. The other six cases showed moderate or severe dilatation of the bile duct and severe chronic proliferative cholangitis. From the above results, we proposed the following theory to explain the pathogenesis and process of the formation of intrahepatic cholesterol stones: The cholesterol crystals in the peripheral intrahepatic bile ducts may be a primitive form of intrahepatic cholesterol gallstones, and the formation of intrahepatic cholesterol gallstones may precede and cause such deformities of the bile ducts as strictures or dilatations.

Adult↗

PubMed1990

Inhibitory effect mediated by alpha 1-adrenoceptors on transient outward current in isolated rat ventricular cells.

In order to clarify the underlying ionic mechanism(s) by which alpha 1-adrenoceptor stimulation prolongs the action potential duration (APD), single rat ventricular cells were voltage-clamped under a Na(+)-free condition using patch pipettes. Depolarizing pulses from a holding potential of -77 mV induced a 4-aminopyridine-sensitive transient outward current (Ito). Phenylephrine, in the presence of the beta-blocker propranolol (1 microM), inhibited Ito in a concentration-dependent fashion and the maximum inhibition of Ito (42.5 +/- 10.0%, n = 5) was produced by 30 microM phenylephrine. The inhibitory effect of phenylephrine on Ito was almost abolished by 1 microM prazosin, a selective alpha 1-blocker, indicating that the Ito inhibition is mediated by alpha 1-adrenoceptors. On the other hand, phenylephrine had little influence on the Ca2+ current in the presence of 4-aminopyridine. In isolated rat papillary muscles, both the alpha 1-adrenoceptor-mediated APD prolongation and positive inotropic response were markedly attenuated by pretreatment with 1.5 mM 4-aminopyridine. These results suggest that the inhibition of Ito is a primary cause of the prolongation of APD produced by alpha 1-adrenoceptor stimulation and that the Ito inhibition may be causally related to the positive inotropic effect mediated by alpha 1-adrenoceptors.

4-Aminopyridine↗

PubMed1990

Protein kinase C activation enhances the delayed rectifier potassium current in guinea-pig heart cells.

The possible involvement of protein kinase C in modulating membrane currents was investigated in isolated guinea-pig ventricular cells. In a Na(+)-and K(+)-free external solution, the delayed rectifier K+ current (IK) was increased by the activator of protein kinase C (PKC), 12-O-tetradecanoylphorbol-13-acetate (TPA). The amplitude of the IK tail elicited by a return from a depolarizing pulse for 3 s at + 50 mV to a holding potential of -30 mV was increased by 32 +/- 4% (mean +/- S.E., (n = 6) after the external application of 1 nM TPA, and by 60 +/- 17% (n = 5) after 10 nM. The increase in IK produced by 1 nM TPA was abolished by the inhibitor of PKC, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H-7, 10 microM). In addition, the synthetic diacylglycerol 1-oleoyl-2-acetylglycerol (OAG, 125 microM) also increased IK (58 +/- 9%, n = 3). PKC purified from bovine brain remarkably increased IK (151 +/- 101%, n = 5) in the presence of 1 nM TPA when it was internally applied using the cell dialysis method. The concentration-response curve of IK for the intracellular concentration of Ca2+ was shifted to the left by 1 nM TPA, suggesting a Ca2(+)-dependent action of PKC and/or altered Ca2(+)-sensitivity of IK channels by phosphorylation. On the other hand, 1 nM TPA had no substantial influence on the Ca2+ current (decreased by 7 +/- 4%, n = 5) or the inward-rectifier K+ current (decreased by 5 +/- 5% in outward component, and 3 +/- 8% in inward component, n = 6). Therefore, the action of PKC was to specifically increase IK without affecting the other two currents.

Animals↗

PubMed1990

Detection of the growth fraction in colorectal tumours by a monoclonal antibody against DNA polymerase alpha.

The cell kinetics of 54 colorectal tumours were examined by immunohistochemical methods, using the monoclonal antibody DNA polymerase alpha which reacts with an antigen found only in proliferating cells. The rate of DNA polymerase alpha positive cells in colorectal cancer was 44.8%, a figure that was significantly higher than the 21.9% found in colorectal adenomas. The rate of DNA polymerase alpha positive cells tended to rise as the degree of differentiation decreased according to the standard histological grading criteria for colorectal cancer. Positive cells were detected in much greater numbers in tumours with liver metastasis (55.4%) than in those without metastasis (41.7%). The rate of DNA polymerase alpha positive cells for aneuploid lesions was higher than that for lesions with a diploid pattern. The determination of growth fractions with a monoclonal antibody (DNA polymerase alpha) may be a biological marker of great prognostic significance.

Adenocarcinoma↗

PubMed1990

Inability of endothelin to increase Ca2+ current in guinea-pig heart cells.

Effects of endothelin, a novel vasoconstrictor peptide derived from vascular endothelial cells, on cardiac contractility and membrane currents, were examined in guinea-pig cardiac preparations. Endothelin (3-1000 nM) produced a positive inotropic effect in papillary muscles in a concentration-dependent manner. In whole-cell voltage clamp recording, endothelin (250 nM) decreased the amplitude of Ca2+ current (ICa, 25.0 +/- 6.6%) in ventricular myocytes. The endothelin-induced decrease in ICa was abolished by pretreatment with ryanodine (1 microM). These results suggest that endothelin does not activate cardiac sarcolemmal Ca2+ channels. The enhancement of the sarcoplasmic reticulum function may play an important role in the positive inotropic effect of endothelin.

Animals↗

PubMed1990

Flow-cytometric analysis of colorectal cancer with hepatic metastases and its relationship to metastatic characteristics and prognosis.

Studying the DNA ploidy patterns of 52 primary tumors, diploid tumors accounted for 48.1% and aneuploid tumors for 51.9%. Out of 31 patients with liver metastases, 35.5% had diploid tumors and 64.5%, aneuploid tumors. Heterogeneity (difference in DNA ploidy pattern between the primary lesion and liver metastases) was found in 20% of the patients examined. In 28 of the patients, the liver metastases were unresectable, and their prognoses were such that the 1- and 2-year survival rates from the diploid tumors were 42.9 and 14.3%, respectively, while 1-year survivors from aneuploid tumors died within 2 years. In resected cases of hepatic metastases, the DNA ploidy pattern of the metastatic lesions did not correlate with the metastasis period, extent of spread or number of lesions. The recurrence rate of aneuploid tumors in the residual livers was 50%, which was slightly higher than the rate of 36.4% for diploid tumors. The prognoses in patients with diploid tumors were significantly better than those in patients with aneuploid tumors: 5-year survival was 71.1% in diploid tumor patients, compared with 21% in aneuploid tumor patients.

Colorectal Neoplasms↗

PubMed1990

Effects of isoflurane on conduction velocity and maximum rate of rise of action potential upstroke in guinea pig papillary muscles.

This study was undertaken to determine whether isoflurane, a volatile anesthetic that is reported to possess a wide margin of cardiovascular safety, exerts electrophysiological effects on cardiac tissue. By use of standard microelectrode techniques, effects of isoflurane on the maximum rate of rise of action potential upstroke (Vmax) and conduction velocity were examined in guinea pig papillary muscles. Isoflurane decreased action potential amplitude and action potential duration in a concentration-dependent fashion. Isoflurane at 1.5 and 2.0 MAC decreased conduction velocity with as little influence on the maximum rate of rise of action potential upstroke as that exerted by halothane and enflurane. However, the effect of isoflurane in slowing intraventricular conduction was less than that of halothane and enflurane when compared at equi-MAC concentrations. Thus, isoflurane may be a safer anesthetic for the patients with intraventricular conduction abnormalities.

Action Potentials↗

PubMed1990

[Application of nucleolar organizer region staining technique to air-dried blood smears].

Silver staining of nucleolar organizer regions (NOR) was applied to air-dried peripheral and bone marrow smears of normal subjects and leukemic patients. Specimens were fixed in buffered acetone formalin. Even in smears kept for 2 years at room temperature, the stainability of Ag-NOR was well preserved. By dipping Giemsa-stained smears in 5% trichloracetic acid and then placing them in methanol for 5 minutes, the stain was leached out. After the dye had been removed, the smears were clearly stained by a Ag-NOR staining technique. The mean number of Ag-NOR per nucleus of mature granulocytes and mononuclear cells in normal peripheral bloods was 0.59 and 1.43 respectively. The mean number of Ag-NOR per nucleus of peripheral and bone marrow leukemic cells from patients with acute leukemia and chronic myelocytic leukemia in blastic crisis was 2.32 and 2.66 respectively. On the other hand, the mean number of Ag-NOR per nucleus of peripheral leukemic cells from patients with chronic lymphocytic leukemia was 1.48. These results suggest that acute leukemia cells possess a more active proliferating potential. The Ag-NOR staining technique is very simple and might be useful for investigation of hematologic cells.

Adolescent↗

PubMed1990

[A flow cytometric cell cycle analysis of familial polyposis coli].

The cell cycle of Familial Polyposis Coli (FPC) has been determined by a flow cytometric (FCM) DNA/bromodeoxyuridine (BrdUrd) bivariate analysis. Specimens were obtained from one FPC cancer patient and, for our controls, from 8 single colon cancer patients and from 8 gastric cancer patients who underwent a colectomy. Procedurally, 1 g i.v. injection of BrdUrd was administered 5 to 7 hours before the resection. Later, the BrdUrd-labeling index (BULI) and the potential doubling time (Tpot) were measured by FCM. No significant differences were uncovered between the BULI of the cancer in the FPC patient and that of our controls, or between the BULI of the unaffected mucosa of the FPC patient and that of the controls. Further, with regard to the FPC patient, the mean BULI of the cancer was significantly higher than that of the adenoma and than that of the unaffected mucosa. Also, the mean Tpot of the cancer was significantly shorter than that of the unaffected mucosa. These results suggest that the BULI and the Tpot may change when an adenoma is generated from the unaffected mucosa in FPC patients.

Adenoma↗

PubMed1990

Inotropic, electrophysiological and biochemical responses to histamine in rabbit papillary muscles: evidence for coexistence of H1- and H2-receptors.

This study was performed to determine the subtypes of histamine receptors that are involved in the electrophysiological, inotropic and biochemical responses to histamine in isolated rabbit papillary muscles. Histamine increased force of contraction and shortened action potential duration (APD) in a concentration-dependent manner. The former was antagonized by chlorpheniramine, a H1-antagonist, whereas the latter was blocked by cimetidine, a H2-antagonist. However, even when H1-receptors were blocked entirely by chlorpheniramine, histamine still produced a positive inotropic effect, an effect which was antagonized by cimetidine. On the other hand, when H2-receptors were eliminated by cimetidine, histamine caused a H1-receptor mediated APD prolongation. Carbachol attenuated the decrease in APD but not the increase in force of contraction caused by histamine. Cyclic AMP and cyclic GMP levels both were elevated significantly by histamine. The increase in cyclic AMP level induced by histamine was abolished by cimetidine, but not altered by chlorpheniramine, whereas the converse was true for the increase in cyclic GMP level. Additionally, histamine produced a significant stimulation of phosphoinositide hydrolysis as measured by [3H]inositol monophosphate accumulation, although its extent was far less than that produced by carbachol. The phosphoinositide response to histamine was blocked by chlorpheniramine. These data suggest that H1- and H2-receptors coexist in rabbit ventricles. Stimulation of H1- and H2-receptors with histamine independently sets off the biochemical responses linked specifically to the respective subtypes of histamine receptors. On the other hand, the inotropic and electrophysiological responses to histamine are governed predominantly by H1- and H2-receptors, respectively, and this results in an apparent restriction of the expression of the responses mediated by another subtype.

Action Potentials↗

PubMed1990

[Flow cytometric analysis in colorectal cancer with hepatic metastases and its relationship to metastatic characteristics and prognosis].

Nuclear DNA ploidy studies were performed by flow cytometry on extracted nuclei from 65 heptic metastases from colorectal cancer. In 25 patients, both primary and metastatic lesions were available for analysis. Primary carcinomas were DNA diploid pattern in 48.1%, DNA aneuploid in 51.9%. Of 31 hepatic metastases, 11 (35.5%) metastases showed a DNA diploid pattern, and 25 (64.5%) showed a DNA aneuploid pattern. Ploidy pattern was constant between primary and metastases in 80% of tumors. No significant relationship between metastatic characteristics and DNA ploidy pattern was found. The DNA aneuploid cancers had a relatively poorer prognosis in patients with unresectable hepatic metastasis. In resected hepatic metastases from colorectal cancer, rate of hepatic recurrence with DNA diploid pattern was lower than that with DNA aneuploid pattern. Survival of patients with DNA diploid metastases (71% alive at 5 years) was significantly better than that of patients with DNA aneuploid metastases (21% alive at 5 years) (p less than 0.05). These results demonstrated that flow cytometric DNA ploidy measurements may have prognostic value for patients with hepatic metastases from colorectal cancer.

Aneuploidy↗