Search PubMed⌕ Search

Biomedical subjects

M Kanno

Publications and source records attributed to M Kanno.

At least 217 records · Page 12Linked to original sources

[Flow cytometric analysis of proliferative characteristics of human leukemic cells in bone marrows in vivo using bromodeoxyuridine (BrdU) and its monoclonal antibody].

We developed a new method for analyzing the proliferative characteristics of human acute leukemic cells in bone marrows in vivo using BrdU and its monoclonal antibody. The thirty minutes after a bolus BrdU infusion, a 1st bone marrow aspiration (BMP) was performed to calculate BrdU-LI. Then, a 150-minute continuous infusion of BrdU was started. After the infusion, a 2nd BMP was done to calculate the increasing rate of the BrdU-LI for 3 hours. Each of the bone marrow cells was analyzed by FCM. A mean value of 10.4% for BrdU-LI in 22 previously untreated patients was obtained. In 3 of the patients, Ts and Tpot ranged from 13.5 to 33.9 hours and 6.8 to 10.7 days respectively.

Acute Disease↗

Electrophysiologic mechanisms responsible for inotropic responses to ketamine in guinea pig and rat myocardium.

Inotropic and electrophysiologic effects of ketamine were investigated in cardiac preparations isolated from guinea pigs and rats. Ketamine produced a concentration-dependent negative inotropic effect in electrically driven guinea pig papillary muscles, an effect that was accompanied by a decrease in action potential duration at the 0-mV level (APD0). In contrast, ketamine produced a concentration-dependent positive inotropic effect in rat left atria in the presence of 10(-6) M propranolol. The increase in force of contraction was accompanied by an increase in APD0. Experiments using patch clamp techniques revealed that ketamine reduced the transsarcolemmal Ca2+ current (ICa) as well as the inward rectifier K+ current and delayed outward K+ current in guinea pig single ventricular cells. These results indicate that the shortening of APD0 observed in guinea pig papillary muscles might result from the suppression of ICa. In rat single ventricular cells ketamine reduced the Ca(2+)-insensitive transient outward current (Ito) and did not enhance ICa, suggesting that the ketamine-induced prolongation of APD0 observed in rat left atria is due to a decrease in Ito rather than an increase in ICa. Treatment of rat left atria with the specific Ca(2+)-insensitive Ito inhibitor 4-aminopyridine (2 mM) produced a positive inotropic effect and prolongation of APD0, and these effects were equivalent to those caused by the highest concentration of ketamine. In the presence of 4-aminopyridine, ketamine failed to induce a positive inotropic effect and instead caused a negative inotropic one. In conclusion, the negative and positive inotropic effects of ketamine may result from the suppression of ICa and Ito, respectively. The inhibitory action on these membrane currents may at least in part explain the species and tissue differences in inotropic responses to ketamine.

Action Potentials↗

[Serum sialyl-Tn antigen in colorectal cancer and its relationship to prognosis].

Serum sialyl-Tn antigen level was studied in 117 cases of colorectal cancer. The positive rates for serum sialyl-Tn antigen were 23.1% in primary colorectal cancer. There is a significant correlation between the positive rates of serum sialyl-Tn antigen and liver metastases, peritoneal dissemination, or lymph node metastases. The survival rate for patients with sialyl-Tn antigen positive sera was lower than those with sialyl-Tn antigen negative. Among patients who underwent curative operation, patients with sialyl-Tn positive sera gave a recurrence rate of 35.7%, while those with sialyl-Tn negative sera recorded a recurrence rate of 14.7%. There is no correlation between the positive rates of serum sialyl-Tn antigen and DNA ploidy pattern. Serum sialyl-Tn antigen levels may be a useful indicator in projecting the prognosis of colorectal cancer.

Antigens, Neoplasm↗

[Study on correlation of hematogenous metastasis in advanced colorectal cancer with the morphological mode of tumor invasion in the pm layer].

We studied the influence of the morphological mode of tumor invasion in muscularis propria (pm) layer, in 177 patients who received resection for colorectal carcinoma that invaded beyond the pm layer. Tapering Index (TI = A/B) defined from the ratio between the length of tumor invasion on upper pm layer (A) and that on lower pm layer (B), TI value was significantly lower in cases with hematogenous metastasis than that in cases without hematogenous metastasis. Cases in which TI values were under 1.3 in colon cancer and 1.9 in rectal cancer had higher possibility of synchronous or metachronous hematogenous metastasis and poorer prognosis. Therefore, we suspected that TI value would be an important factor in prediction of hematogenous metastasis.

Adult↗

Characterization of histamine receptors modulating inotropic and biochemical activities in rabbit left atria.

The experiments were performed to identify histamine H1- and H2-receptors in rabbit left atrium and to characterize the pharmacological properties mediated by the respective subtypes of histamine receptors. High-affinity saturable binding to the left atrial membranes was obtained for [3H]mepyramine, yielding a maximum binding capacity (Bmax) of 96 fmol/mg of protein and an equilibrium dissociation constant (KD) of 3.8 nM and also for [3H]tiotidine, yielding a Bmax of 126 fmol/mg of protein and a KD of 14.7 nM. In isolated left atrium, histamine produced a concentration-dependent positive inotropic effect, an effect which was competitively antagonized by cimetidine but not altered by chlorpheniramine. Schild analysis showed that the pA2 value for cimetidine was 6.55 and the slope was not significantly different from unity. An excellent correlation was found between the increase in force of contraction and cyclic AMP in the presence of histamine, suggesting that the positive inotropic effect of histamine in rabbit left atrium is dependent on an increased level of intracellular cyclic AMP through stimulation of histamine H2-receptors. Histamine also produced concentration-dependent stimulation of phosphoinositide hydrolysis as measured by [3H]inositol monophosphate accumulation. The phosphoinositide response to histamine was blocked by chlorpheniramine and mepyramine but not by cimetidine. The data indicate that histamine H1-receptors, in addition to histamine H2-receptors, are present in the rabbit left atrium. Although this tissue lacks an inotropic response to histamine H1-receptor stimulation, the histamine H1-receptors interact with histamine to mediate the stimulation of phosphoinositide hydrolysis.

Animals↗

Clinical significance of tumor marker NCC-ST 439 in large bowel cancers.

We examined serum NCC-ST 439 for its significance as a tumor marker of large bowel cancer in 121 patients with primary and 36 with recurrent large bowel cancer. Serum NCC-ST 439 was positive in 27.3 percent of the former and 66.7 percent of the latter. It was false-positive in only 5.6 percent of patients with benign diseases. Positive serum NCC-ST 439 correlated with lymph node and liver metastases. The combination assay for NCC-ST 439, CEA, and CA19-9 was positive in 49.6 percent of the patients with primary tumors and 88.9 percent of those with recurrent tumors; in other words, the diagnostic accuracy improved. The results demonstrated that the determination of serum NCC-ST 439 in large bowel cancer might be useful in cancer staging and that NCC-ST 439, if used in combination with CEA, is particularly useful in diagnosing recurrences because of its improved diagnostic accuracy.

Antibodies, Monoclonal↗

Detection by CT during arterial portography of colorectal cancer metastases to liver.

A prospective evaluation of the accuracy of real-time ultrasonography (US), computed tomography (CT), infusion hepatic angiography (IHA), and computed tomography during arterial portography (CT-AP) was performed on 65 resected liver metastases of colorectal cancers. The total detection rate was 58.5 percent for US, 56.3 percent for CT, 55.4 percent for IHA, and 86.2 percent for CT-AP. The sensitivity of 29 lesions with diameters of smaller than 1 cm was 65.5 percent for CT-AP, CT found only two, and both US and IHA localized no more than three. The smallest lesions detectable by CT-AP were as small as 0.4 cm in diameter. CT-AP proved most useful in detecting the liver metastases, and the use of this technique is recommended for preoperative planning of hepatectomy on patients with liver metastases.

Angiography↗

The results and problems of extensive radical surgery for carcinoma of the head of the pancreas.

Since 1973, 152 patients with pancreatic carcinoma have undergone surgery in our clinic, including 110 with carcinoma of the head of the pancreas. Of these 110 patients, resections were performed on 43 (39.1 per cent), 33 (30 per cent) of whom underwent a curative resection based on macroscopic evidence. Six of the patients who underwent macroscopic curative resection survived for five years, giving a five-year survival rate of 36.5 per cent by the Kaplan-Meier method after excepting 6 operative deaths. We compared the extent of pancreatic cancer by constructing survival curves according to the General Rules published by the Japan Pancreas Society. There was no statistical difference in survival based on tumor size or stage, however, there was a significant difference in the survival curves of so and se, being the absence or presence of the anterior capsule of the pancreas, rpo and rpe, being the absence or presence of invasion of the retroperitoneal tissue; ew(-) and ew(+) being the absence or presence of invasion at the surgical margin of resection, or n0 and n1 being the extent of lymph node metastasis. The results of this comparison suggest that extended radical pancreatectomy may be indicated for the treatment of pancreatic cancer as the standard radical operation for pancreatic cancer may miss tumors which have spread to the retroperitoneum and extrapancreatic nerve plexus.

Carcinoma↗

Multiple simian virus 40 enhancer elements mediate the trans-activating function of the X protein of hepatitis B virus.

Transient transfections of tissue culture cells with plasmids encoding the X protein of hepatitis B virus result in a transcriptional trans-activation of certain target genes. Our experiments reveal that several individual simian virus 40 enhancer elements and a control element present in the mouse major histocompatibility class I gene H-2Kb are able to mediate the trans-activating function of the X protein. The data suggest that known cellular transcription factors that bind specifically to the multiple enhancer elements participate in trans-activation.

Base Sequence↗

Lateral asymmetry of eye movements in temporal lobe epileptic patients with unilateral foci.

Eye movements in response to visual stimuli (Benton Visual Retention Test) were examined in 22 temporal lobe epileptics (TLEs), 10 primary generalized epileptics (PGEs), and 20 normal controls. In the normal controls, the percent fixation time on the left peripheral figure was higher than that on the right peripheral figure, a tendency also found in the PGEs. In TLEs with right-sided foci, the percent fixation time on the left peripheral figure was higher than that on the right peripheral figure, the direction of asymmetry found in the normal controls and PGEs. However, when calculated as laterality indices (the degree of asymmetry) TLEs with right-sided foci were significantly more negative than those of both the normal controls and PGEs. In TLEs with left sided foci, the percent fixation time on the right peripheral figure tended to be higher than that on the left peripheral figure, an asymmetry which differed significantly from the normal controls, PGEs and the TLEs with right-sided foci. The results here showed that TLEs with unilateral foci had distinct eye movements which varied with the laterality of the lesion in the direction of functional overactivation of the epileptogenic hemisphere.

Epilepsy, Generalized↗

Acute pancreatitis associated with anomalous union of the pancreaticobiliary ductal system.

Between 1978 and 1989, 13 of 48 patients with anomalous union of the pancreaticobiliary ductal system (AUPBD) were diagnosed as having acute pancreatitis. We have studied the clinical, radiologic, and surgical features of these 13 patients. A transient rise in the intraductal pressure of the pancreatic duct during an episode of abdominal pain is responsible for pancreatitis in patients with AUPBD. This rise in the intraductal pressure must be due to bile reflux into the pancreatic duct when an abnormally long common channel is blocked by cholelithiasis, protein plug, or dysfunction of the sphincter of Oddi. The pancreatitis resolves when the common channel obstruction is removed, and bile and pancreatic juice flow easily into the duodenum. We believe that this phenomenon is responsible for acute relapsing pancreatitis. It is our belief that the pancreas appears almost normal during symptom-free intervals.

Acute Disease↗

Pharmacological analysis of the positive inotropic effect of endothelin-1 in guinea pig left atria.

Endothelin-1 (ET-1) increased the force of contraction and stimulated phosphoinositide hydrolysis in guinea pig left atria. ET-1 at 20 nM produced a dual-component positive inotropic effect composed of an initial increasing phase (early component) and a second and late developing, greater positive inotropic phase (late component). The late component was preferentially and markedly inhibited by nifedipine and the protein kinase C inhibitors H-7 and staurosporine. In guinea pig left atria, the activation of protein kinase C might contribute to the establishment of the positive inotropic effect of ET-1 mediated by modulation of voltage-dependent Ca2+ channels.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Identification and characterization of histamine H1- and H2-receptors in guinea-pig left atrial membranes by [3H]-mepyramine and [3H]-tiotidine binding.

1. Histamine receptors in the membranes prepared from guinea-pig left atria were characterized with [3H]-mepyramine and [3H]-tiotidine binding. 2. The binding of the H1-antagonist, [3H]-mepyramine, was saturable and of high affinity with a maximum binding capacity of 307 +/- 27 fmol mg-1 protein (n = 14) and with an equilibrium dissociation constant (KD) of 1.5 +/- 0.2 nM (n = 14). The binding was rapid and readily reversible. 3. The competition curve for [3H]-mepyramine binding by histamine was biphasic and revealed high and low affinity states of binding. The addition of 5'-guanylylimidodiphosphate (GppNHp) (100 microM) converted this heterogeneous binding into homogeneous binding of low affinity. 4. The competition curves of H1-antagonists with [3H]-mepyramine had Hill coefficients not significantly different from unity, consistent with competition with [3H]-mepyramine at a single site. GppNHp did not shift the competition curves. 5. Dissociation constants for H1-antagonists determined from inhibition of [3H]-mepyramine binding correlated well with the constants derived from inhibition of the positive inotropic response of guinea-pig left atria to histamine. 6. The H2-antagonist, [3H]-tiotidine, labelled an apparently homogeneous population of recognition sites with a maximum binding capacity of 41 +/- 8 fmol mg-1 protein (n = 6) and a KD of 10.8 +/- 1.2 nM (n = 6). 7. Although histamine competed for [3H]-tiotidine binding in a concentration-dependent manner, the curve was monophasic and was not shifted by GppNHp. 8. It is concluded that both H1- and H2-receptors exist in guinea-pig left atria. H1-receptors probably couple to intracellular effector(s) through a guanine nucleotide-dependent transducing mechanism. On the other hand, H2-receptors seem unlikely to be linked to guanine nucleotide regulatory proteins in guineapig left atria, which may explain the failure of histamine to cause an increase in cyclic AMP in spite of the presence of H2-receptors.

Animals↗

Effects of ATP-sensitive K+ channel blockers on the action potential shortening in hypoxic and ischaemic myocardium.

1. In order to determine whether activation of adenosine triphosphate (ATP)-sensitive K+ channels exclusively explains the hypoxia- and ischaemia-induced action potential shortening, effects of tolbutamide and glibenclamide on changes in action potential duration (APD) during hypoxia, metabolic blockade or experimental ischaemia were examined in guinea-pig and canine isolated myocardium by standard microelectrode techniques. 2. With use of patch clamp techniques, activity of ATP-sensitive K+ channels was recorded from open cell-attached patches of guinea-pig isolated ventricular myocytes. The probability of opening of the K+ channels was decreased by 2 mM tolbutamide and 20 microM glibenclamide to almost the same extent, whereas it was increased by 100 microM pinacidil. 3. In guinea-pig papillary muscles a marked shortening of the action potential produced by 100 microM pinacidil was completely antagonized by 2 mM tolbutamide or 20 microM glibenclamide. 4. In guinea-pig papillary muscles exposed to hypoxic, glucose-free solution or dinitrophenol (10 microM)-containing, glucose-free solution, APD declined gradually and twitch tension decreased. Pretreatment with glibenclamide partially but significantly inhibited the action potential shortening, whereas tolbutamide failed to improve it during hypoxia or metabolic blockade. 5. When in canine isolated myocardium, experimental ischaemia was produced by the cessation of coronary perfusion, APD was gradually shortened. The action potential shortening was partially but not completely inhibited by pretreatment with 20 microM glibenclamide. 6. These results suggest that changes in membrane current(s) other than the outward current through ATP-sensitive K+ channels also contribute to the action potential shortening in hypoxic or ischaemic myocardium.

Action Potentials↗

Protein kinase C is not involved in alpha 1-adrenoceptor-mediated positive inotropic effect.

This study was performed to determine whether activation of protein kinase C is responsible for the positive inotropic effect of alpha 1-adrenoceptor stimulation in rat papillary muscle. In the presence of 1 microM propranolol, phenylephrine (10 microM) produced triphasic inotropic response that was accompanied by prolongation of action potential duration (APD) and hyperpolarization of membrane potential. Phorbol 12,13-dibutyrate (PDBu, 0.1 microM) abolished the negative inotropic effect of phenylephrine and apparently resulted in enhancement of the positive inotropic effect. PDBu also attenuated the phenylephrine-induced hyperpolarization without affecting the APD prolongation. However, such changes were not observed with 12-O-tetradecanoylphorbol-13-acetate (TPA, 0.1 microM). Neither PDBu nor TPA increased the force of contraction or prolonged APD similar to phenylephrine. The protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methyl-piperazine (H 7, 10 microM) did not suppress the changes induced by PDBu, and more importantly H 7 did not affect the inotropic and electrophysiological effects of phenylephrine. Both TPA and PDBu significantly inhibited the phenylephrine-induced phosphoinositide hydrolysis as measured by [3H]inositol monophosphate, and these inhibitory effects were eliminated in the presence of H 7. Our results provide an argument against a role of protein kinase C activation in the alpha 1-adrenoceptor-mediated inotropic and electrophysiological effects.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

Superoxide dismutase recovers altered endothelium-dependent relaxation in diabetic rat aorta.

Experiments were designed to characterize endothelium-dependent relaxation in thoracic aortic rings obtained from streptozotocin-induced diabetic rats. When the degree of the peak relaxation was compared, the endothelium-dependent relaxant responses to acetylcholine, histamine, or ADP in precontracted aortic rings showed that there was no significant difference between diabetic and control vessels. However, the time courses appeared quite different. The endothelium-dependent relaxant responses in diabetic vessels were more transient than those in control vessels. In addition, the rapid fade of the endothelium-dependent responses observed in diabetic vessels was significantly suppressed by pretreatment with superoxide dismutase. Pretreatment with catalase, deferoxamine, allopurinol, or indomethacin did not prevent the rapid fade of the endothelium-dependent relaxation. The endothelium-independent relaxation induced by nitric oxide also faded more quickly in diabetic vessels; this impairment was less pronounced in the presence of superoxide dismutase. These results suggest that the transient nature of the endothelium-dependent relaxation is more marked in diabetic rat aorta as a result of an enhanced accumulation of superoxide anion.

Animals↗