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Biomedical subjects

M Kanno

Publications and source records attributed to M Kanno.

371 records · Page 21Linked to original sources

Diminishment of contractions associated with depolarization-evoked activation of Ca2+ channels in diabetic rat aorta.

Alterations in contractile responses of aortic rings mediated by activation of Ca2+ channels were investigated in rats with streptozotocin-induced diabetes. Eight to 12 weeks of diabetes resulted in a marked decrease in the contractile response of aortic rings to high K+. In contrast, diabetic aortas exhibited significantly greater contractions in response to noradrenaline compared to age-matched controls. In the presence of 15 mM K+, the Ca2+ channel agonist Bay K 8644 consistently produced concentration-dependent contractions in control aortas. On the other hand, the half of diabetic aortas did not respond to Bay K 8644. As a result, the contractile response to Bay K 8644 was significantly less in diabetic aortas compared to controls. There was no significant difference in basal 45Ca2+ uptake between control and diabetic aortas. However, the uptake of 45Ca2+ induced by high K+ was significantly less in diabetic aortas than in controls, and pretreatment with the Ca2+ channel antagonist nifedipine abolished both responses. The resting membrane potentials were not significantly different between control and diabetic aortas. Furthermore, no difference was found in the magnitude of depolarization evoked by increasing K+ concentrations between the two groups of tissues. There were no significant differences in the density and the dissociation constant for [3H]-(+)-PN200-110, a radiolabeled Ca2+ channel antagonist, between aortic membranes from control and diabetic rats. These data indicate that the contractile responses to high K+ and Bay K 8644 are specifically diminished in diabetic aortas. These diminished responses are not due to a difference in the number of Ca2+ channels, but may be related to an alteration in activation of the channels by membrane depolarization.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

Prognostic value of nucleolar organizer regions in endoscopically biopsied tissues of colorectal cancers.

We studied the proliferative activity in endoscopically biopsied tumors by means of argyrophil-protein nucleolar organizer region (AgNOR) scores. AgNOR scores of 109 colorectal cancers ranged from 2.48 to 6.72 (mean: 3.27 +/- 0.52). The 109 tumors were divided into two groups by the median value of AgNOR counts. There was no significant correlation between the AgNOR scores and the histologic type, invasion of bowel wall, lymph node metastases or peritoneal metastases. There was a significant association between the AgNOR scores and lymphatic invasion or liver metastases. Patients with higher AgNOR score tumors had significantly poorer prognoses than those with lower AgNOR score tumors. In Dukes' stage C, especially, the survival rate for patients with higher AgNOR score tumors was significantly lower than for those with lower AgNOR score tumors. Recurrence was found in 8.7% of the tumors with lower AgNOR scores and 19.4% of the tumors with higher scores. Aneuploid tumors had higher AgNOR scores than tumors with the diploid pattern. The results suggest that the AgNOR scores may possibly be a useful prognostic marker of colorectal cancer.

Biopsy↗

Implications of flow cytometry in preoperative detection of biologic variables of gastric cancer and malignant condition of gastric remnant cells obtained by endoscopic biopsy.

Flow cytometric (FCM) DNA studies were performed on cell suspensions obtained by endoscopic biopsy in 73 patients with gastric cancer and in 61 patients with gastric remnant. In cancer, DNA aneuploidies were detected in 49 tumors (67.1%), including 51.7% (15/29) of early gastric cancers and 77.3% (34/44) of advanced gastric cancers. Nuclear DNA content of biopsy materials had a significant correlation with that of surgically obtained ones, providing the estimation of the original ploidy pattern and DNA index (p < 0.01). The serosal invasion, lymph node metastasis, lymphatic invasion, and vascular invasion of the DNA aneuploidy were significantly higher than those of the DNA diploidy (p < 0.05). In patients with gastric remnant, 9 biopsy specimens in the anastomotic site showed DNA aneuploidy (13.9%). The DNA measurement of the endoscopically obtained specimens may provide additional preoperative information and help to identify biologic variables.

Adult↗

Cardiac Na(+) channel dysfunction in Brugada syndrome is aggravated by beta(1)-subunit.

BACKGROUND: Mutations in the gene encoding the human cardiac Na(+) channel alpha-subunit (hH1) are responsible for chromosome 3-linked congenital long-QT syndrome (LQT3) and idiopathic ventricular fibrillation (IVF). An auxiliary beta(1)-subunit, widely expressed in excitable tissues, shifts the voltage dependence of steady-state inactivation toward more negative potentials and restores normal gating kinetics of brain and skeletal muscle Na(+) channels expressed in Xenopus oocytes but has little if any functional effect on the cardiac isoform. Here, we characterize the altered effects of a human beta(1)-subunit (hbeta(1)) on the heterologously expressed hH1 mutation (T1620M) previously associated with IVF. METHODS AND RESULTS: When expressed alone in Xenopus oocytes, T1620M exhibited no persistent currents, in contrast to the LQT3 mutant channels, but the midpoint of steady-state inactivation (V(1/2)) was significantly shifted toward more positive potentials than for wild-type hH1. Coexpression of hbeta(1) did not significantly alter current decay or recovery from inactivation of wild-type hH1; however, it further shifted the V(1/2) and accelerated the recovery from inactivation of T1620M. Oocyte macropatch analysis revealed that the activation kinetics of T1620M were normal. CONCLUSIONS: It is suggested that coexpression of hbeta(1) exposes a more severe functional defect that results in a greater overlap in the relationship between channel inactivation and activation (window current) in T1620M, which is proposed to be a potential pathophysiological mechanism of IVF in vivo. One possible explanation for our finding is an altered alpha-/beta(1)-subunit association in the mutant.

Amino Acid Substitution↗

Effects of genistein and daidzein on enhanced vascular contractile reactivity and Ca2+ sensitivity in cardiomyopathic hamsters.

We investigated the contribution of tyrosine kinase activity to the enhanced vasoreactivity in cardiomyopathic (CM) hamsters. The contractile response of the aorta to phenylephrine was greatly enhanced in CM in comparison to control hamsters. Genistein, a tyrosine kinase inhibitor, did not affect the maximum contractile response to phenylephrine in control aortas, although the sensitivity to phenylephrine was significantly diminished. In contrast, genistein markedly inhibited both the sensitivity and the maximum contractile response to phenylephrine in CM aortas. Daidzein, an inactive form of genistein, also inhibited the sensitivity to phenylephrine in both strains although the maximum contractile response was not altered even in the CM aorta. The Ca2+ sensitivity of tension was significantly augmented in alpha toxin-permeabilized smooth muscle from the mesenteric artery of CM hamsters. Furthermore, phenylephrine enhanced myofilament sensitivity to Ca2+ more in CM than control hamsters. The enhancement of myofilament Ca2+ sensitivity by phenylephrine was markedly inhibited by genistein only in CM hamsters. The inhibition by daidzein of the phenylephrine effect on the Ca2+ sensitivity in CM hamsters was less pronounced. These results suggest that an increase in tyrosine kinase activity may lead to enhanced vascular reactivity in CM hamsters possibly due to an increased Ca2+ sensitivity of the contractile apparatus.

Animals↗

Anomalous union of the pancreaticobiliary ductal system without dilation of the common bile duct or tumor: case reports and literature review.

Among 698 patients subjected to endoscopic retrograde cholangiopancreatography, an anomalous union of the pancreaticobiliary ductal system (AUPBD) was found in 6 patients (0.9%). One of these 6 patients had an associated congenital choledochal cyst, and 4 did not. Two of these 4 patients, however, had advanced gallbladder cancer. The remaining 2 patients had no associated carcinoma of the biliary tract. A clinicopathological study was performed on these 2 patients and 26 such cases have been reported in the literature. The diagnosis of AUPBD was made by direct cholangiography. Regarding the type of union, the Pancreatic-Biliary type was present in 15 of 18 (83.3%) of these patients. Fifteen of 28 patients (53.6%) had right upper abdominal pain. Thickness of the gallbladder wall was visualized in 26 of the 28 (92.9%) patients. Gallstones were present in 4 (14.3%). AUPBD should always be kept in mind when a patient with abdominal pain is diagnosed as having gallbladder wall thickness without gallstones. ERCP should be performed in these patients in order to detect AUPBD without dilation of the bile duct. This may allow early detection of carcinoma of the biliary tract.

Adult↗

Extracorporeal circulation with perfluorochemicals (Fluosol-DA).

Experimental studies on extracorporeal circulation (ECC) with perfluorochemicals (Fluosol-DA) as a perfusate was performed to examine oxygen carrying capacity and its organ distribution using eight calves. Approximately 80% of the circulating blood volume was withdrawn before ECC and reinfused after completion of ECC. ECC time was 60 minutes in five of the calves and 120 minutes in three of the calves. Hct and Hb decreased to 4-12% and 1.7-6.6 g/dl during ECC. Fct (Fluorocrit: volume percentage of Fluosol-DA) ranged between 5 and 10%. PaO2 and PvO2 were 432-543 mmHg and 93-164 mmHg. Sixty-seven to 86% of the oxygen consumed by the tissues was delivered by Fluosol-DA. One of the complications of ECC with Fluosol-DA, hemolysis was observed in four of the calves which had a relatively high level of Fluosol-DA retention (13.9 g/kg) in the body after ECC. The retention volume of the other four calves which did not show hemolysis was 10.0 g/kg. Retention of Fluosol-DA after ECC was found to be greater in the reticuloendothelial system of the calves sacrificed earlier and became trace or minimal after 10 months.

Alanine Transaminase↗

Analysis of hepatic recurrence of colorectal cancer after resection of hepatic metastases.

Forty patients with history of resected hepatic metastases of colorectal cancer were examined for pattern of recurrence. The 5-year survival rate was 41.3% for 40 patients. Recurrences of the malignancy were seen in 25 of the patients, with hepatic recurrence in 42.5% of them. The hepatic recurrence rate did not correlate with the lobar distribution of metastases or surgical methods. The pathological margins of less than 1 cm, 3 or more liver metastatic lesions, and the metastatic lesions of greater than 5 cm were at increased risk of hepatic recurrence. The recurrence rate was high, or 56% for aneuploid tumors, while it was 18.5% for diploid tumors.

Aneuploidy↗

Intrabiliary pressure measurement by duodenal pressure loading for the evaluation of duodenal parapapillary diverticulum.

BACKGROUND/AIMS: We report a method of intrabiliary pressure measurement by duodenal pressure loading for evaluating the effects of duodenal parapapillary diverticulum. MATERIAL AND METHODS: Forty-eight patients with primary choledocholithiasis were investigated based on usual intrabiliary pressure measurement developed at our department. RESULTS: Ten of these patients with parapapillary diverticulum showed higher intrabiliary residual pressure (P) and biliary resistance (R) values than the remaining patients without diverticulum, but the difference were not significant. There were no significant differences in the frequency of patterns of the B zone angulation of the pressure curve between the two groups with and without parapapillary diverticulum. Intrabiliary pressure was measured while maintaining a manometer pressure of 250 mm H2O by infusing or aspirating physiologic saline. CONCLUSION: From the results of this measurement for 6 patients, when P and R values show increases of 50 mm H2O or more and 3.5 units or more, respectively, additional surgery for parapapillary diverticulum was considered to be indicated.

Biliary Tract↗

Breast conserving treatment versus modified radical mastectomy in Japanese patients with operable breast cancer.

From January, 1988 to October, 1995, 96 patients with operable breast cancer were treated by breast conserving treatment (BCT) including wide excision and axillary dissection followed by breast radiation. During the same period, 188 patients were treated by modified radical mastectomy (MRM) with or without breast reconstruction. In order to compare the survival of BCT and MRM groups, univariate and multivariate analyses were performed in this retrospective study. Univariate analysis revealed that the 5-year survival rates in the BCT and MRM groups were 97% +/- 2% and 87% +/- 3%, respectively (p < 0.05 with the Cox-Mantel test). However, the baseline variables were different between the groups. The adjusted Cox regression analysis revealed that the results of BCT were almost equivalent with those of MRM. Moreover, no breast recurrence was found in the BCT group. Therefore, it is suggested that our technique of BCT is as effective as modified radical mastectomy in treating operable breast cancer in Japanese patients.

Adult↗

Apoptotic index correlates to bcl-2 and p53 protein expression, histological grade and prognosis in invasive breast cancers.

Apoptosis is considered to play a critical role in tumorigenesis. In order to clarify the significance of apoptosis in breast cancers, we quantitated apoptotic cells by light microscopy in 126 patients with invasive breast cancers. The expression of bcl-2, and p53, as regulators of apoptosis, was immunohistochemically analyzed. Apoptotic index (AI) detected in the patients ranged from 0 to 48 per mm2 of breast cancer cells (mean +/- SE, 11.0 +/- 0.97). Significantly highly AI was found for the tumors with grade 3 (p < 0.0001), high mitotic index (p < 0.0001), and bcl-2 negatively (p = 0.004) compared with those with grade 1 or 2, low mitotic index, and bcl-2 expression, respectively. Moreover, high AI was associated with larger tumor size (p = 0.008), positive lymph nodes (p = 0.01), p53 positivity (p = 0.01), and advanced TNM stage (p = 0.03). In survival analysis, we found that low AI, like bcl-2 and other conventional prognostic indicators, was significantly predictive of better prognosis in terms of both disease-free survival (DFS) and overall survival (OS) (each, p < 0.0001). In multivariate analysis, AI failed to retain an independent significant value for DFS or OS. Our results indicate that low AI is related to a number of clinicopathologic and biologic parameters known to predict a lower risk of recurrence and is associated with a favourable survival in invasive breast cancer. However, it was not an independent prognostic factor for clinical outcome in this patient series.

Apoptosis↗