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Biomedical subjects

M Kaneko

Publications and source records attributed to M Kaneko.

At least 289 records · Page 16Linked to original sources

Inhibitory effects of tetrandrine and hernandezine on Ca2+ mobilization in rat glioma C6 cells.

The effects of tetrandrine (TET), a Ca2+ antagonist of Chinese herbal origin, and hernandezine (HER), a structural analogue of TET, on Ca2+ mobilization were studied in rat glioma C6 cells. TET and HER alone did not affect the resting cytoplasmic Ca2+ concentration ([Ca2+]i). TET and HER inhibited the peak and sustained elevation of [Ca2+]i induced by bombesin and thapsigargin (TG), a microsomal Ca2+ ATPase inhibitor, in a dose-dependent manner. The doses of TET or HER needed to abolish the sustained and peak increase in [Ca2+]i induced by bombesin and TG were 30 microM and 300 microM, respectively. TET and HER did not increase inositol 1,4,5-trisphosphate (IP3) accumulation by themselves but inhibited IP3 accumulation elevated by bombesin. In permeabilized C6 cells, the addition of IP3 and TG released Ca2+ from intracellular stores. Pretreatment with TET or HER abolished Ca2+ release from intracellular stores induced by bombesin and TG. In the absence of extracellular Ca2+, the addition of 3 mM Ca2+ to extracellular medium slightly increased [Ca2+]i, which indicated Ca2+ entry due to leakage of Ca2+ at the plasma membrane but not Ca2+ influx through Ca2+ channels. TET and HER did not affect this leakage entry of Ca2+. The present results suggest that TET and HER inhibit Ca2+ release from intracellular stores as well as Ca2+ entry from extracellular medium evoked by bombesin and TG. In addition, TET and HER inhibit IP3 accumulation induced by bombesin in rat glioma C6 cells.

Alkaloids↗

[Experimental study of detection of brain tumor at surgery using fluorescent imaging under a surgical microscope after fluorescein administration].

Total resection is the optimal treatment for malignant gliomas. However, we sometimes find an unexpected residual tumor mass on magnetic resonance imaging performed after an operation because of a macroscopically unclear margin of the tumor during operation. This study was designed to evaluate the effect of fluorescein sodium on imaging of glioma in combination with a surgical microscope for detection of the tumor at surgery in a rat glioma model. For this study, we produced two filters for the excitation and emission of fluorescein that can be easily fitted to and removed from a surgical microscope manually during the operation. For the in vivo study, Wistar rat brains bearing C6 glioma were removed at appropriate intervals after the intravenous administration of 10-20 mg/kg body weight of fluorescein sodium, and their surface and coronal sections through the tumor were observed using a surgical microscope with the filters. For the in vitro study, the cultured C6 glioma cells were exposed to 5 micrograms/ml of fluorescein sodium for 2 hours and then observed by confocal laser scanning microscopy. In the in vivo study, the C6 glioma itself and the brain within 2-3 mm of the gross surface of the tumor (probably indicating part of the perifocal edema) were well stained a brilliant yellowish green for a few hours. The normal brain was not stained. The intensity of the fluorescence was dose-dependent and was stronger under the xenon than under the halogen lamp. The in vitro study demonstrated almost no uptake of fluorescein by the C6 glioma cells. This fact indicates that the fluorescein in the stained tumor exists in extracellular spaces due to the disruption of the blood-brain barrier. These results suggest that this staining technique using fluorescein sodium and a surgical microscope with special filters during the operation may be the intravenous administration of 10 useful for detection of gliomas and warrants evaluation of clinical application.

Animals↗

[Developmental dyslexia and dysgraphia--a case report].

We reported a 7-year-old, right-handed boy whose reading and writing of kana and kanji were impaired. He also showed a severe deficit in visuo-spatial perception skills. Nevertheless, his ability to read and write kana characters was facilitated by means of the Japanese Syllabaries. It is generally considered that the Syllabary involve two kinds of language modalities: auditory-verbal and visuo-verbal language systems. In spite of his intact auditory-verbal language system, his visuo-verbal language skills involved in writing kanji were severely impaired. It was suggested that a severe deficit of visuo-spatial perception skills influenced performance of visuo-verbal language systems. Accordingly, we inferred that the patient recalled a kana character by use of the Japanese Syllabaries based on his good auditory-verbal language system, and supposed that his reading and writing disorders were similar to alexia with agraphia in adult patients with angular lesions.

Agraphia↗

[Tumor seeding to the neck through percutaneous applicators of interstitial high-dose-rate brachytherapy for cancer of the tongue: a case report].

We report the case of a 46-year-old woman with cancer of the tongue. She underwent interstitial high-dose-rate brachytherapy of 50 Gy in 10 fractions for 5 days following telecobalt therapy of 20 Gy in 10 fractions for 2 weeks. Seven applicators were percutaneously implanted into the tongue. Radical neck dissection was carried out because a tumor rapidly developed on the neck 2.5 months after the treatment. Pathological examination revealed tumor seeding to the soft tissue of the neck where applicators were placed. To the best of our knowledge, there have been no reports presenting tumor seeding through percutaneous applicators of interstitial brachytherapy for head and neck tumor.

Brachytherapy↗

[Effects of amrinone on oxygen demand-supply relationship after cardiopulmonary bypass in patient undergoing coronary bypass surgery].

We evaluated the effects of amrinone on oxygen demand-supply relationship after cardiopulmonary bypass (CPB) in patient undergoing coronary bypass surgery comparing with the patients not receiving amrinone. In amrinone treated patients bolus dose of amrinone 1.5 mg.kg-1 was administrated into the reservoir of CPB and followed by continuous infusion at a rate of 5 micrograms.kg-1.min-1. Hemodynamics and blood gas (arterial and mixed venous) measurements were carried out immediately after CPB, 1 hour after CPB and after the chest closure. After the chest closure, cardiac index and oxygen supply in amrinone treated group were significantly higher and systemic vascular resistance was significantly lower than in non-treated group. Left ventricular stroke work index, rate pressure product and oxygen consumption showed no significant difference between the two groups. These data indicate that the amrinone treated patients preserved better oxygen demand-supply relationship after CPB compared with the non-treated patients undergoing coronary bypass surgery.

Amrinone↗

Role of spinal gamma-aminobutyric acidA receptors in formalin-induced nociception in the rat.

This study investigated the role of gamma-aminobutyric acid (GABA) and GABA(A) receptors in the spinal cord in the expression of pain behaviors evoked by injection of formalin in concentrations ranging from 0.25 to 2.5% in the hindpaw of the rat. Two approaches were used. The first approach compared the effect of drug treatment to saline at each concentration of formalin. The second approach examined the effect of drug treatment on the concentration-response functions of formalin, i.e., its EC50. Intrathecal (i.t.) pretreatment with 0.03 to 0.3 microg of bicuculline, a GABA(A) receptor antagonist, dose-dependently increased the number of flinches and weighted pain scores in the interphase and phase 2, but did not alter responses in phase 1. In the interphase, the EC50 values of formalin for number of flinches or weighted pain score in bicuculline-pretreated rats were decreased to one-third or one-fourth, respectively, of their values in saline-pretreated rats. In phase 2, the EC50 values of formalin for number of flinches or weighted pain score in bicuculline-pretreated rats were similarly decreased to one-half of their value in saline-pretreated rats. These results suggest that formalin was a significantly more noxious stimulus in the presence of bicuculline. Pretreatment with the GABA(A) receptor agonists, muscimol (0.3 microg) or isoguvacine (10 or 30 microg i.t.), significantly decreased the number of flinches in phase 1 and phase 2, but produced only a marginal decrease in the weighted pain score at the highest doses. These findings suggest that there is little tonic activation of GABA(A) receptors by GABA in the spinal cord before or immediately after the injection of formalin. However, approximately 10 min after the induction of injury by formalin, there is a release of GABA and activation of GABA(A) receptors in the spinal cord that 1) contributes to the period of quiescence between phase 1 and phase 2 and 2) coincidentally diminishes the magnitude of pain behaviors in phase 2, possibly by limiting the development of central sensitization in the spinal cord.

Animals↗

MR angiography of aneurysm models of various shapes and neck sizes.

PURPOSE: To investigate the signal intensity of lateral and terminal saccular aneurysm models with differing neck sizes using three-dimensional time-of-flight (TOF) MR angiography with various imaging parameters. METHODS: The study included four lateral and four terminal saccular aneurysm models with pulsatile flow. The height and fundus diameter were 10 mm; the neck diameters were 2.5 mm, 5 mm, 7.5 mm, and 10 mm, respectively. Each aneurysm model was examined with fast imaging with steady-state precession MR sequences with parameters of 20-140/7 (repetition time/echo time) and flip angles of 10 degrees to 30 degrees. Signal intensity was measured and compared among the models. RESULTS: Three-dimensional TOF MR angiography with the shorter repetition time and/or larger flip angle showed weaker signal intensity in the aneurysm models. Stronger signal intensity was obtained in the terminal saccular aneurysm models and/or the models with a wider neck than in the lateral saccular aneurysm models and/or the models with a narrower neck. In some aneurysm models, longer repetition times produced greater signal intensity than that of background brain models, but not in aneurysms with narrow necks. CONCLUSION: Noncontrast 3-D TOF MR angiography delineated terminal saccular aneurysms and/or aneurysms with wider necks and did not delineate lateral saccular aneurysms and/or aneurysms with narrower necks. Longer repetition times are recommended to allow the spins flowing into the aneurysms to recover.

Artifacts↗

[Studies on the taste perceptive threshold for 4 basic taste qualities at various sites of lingual surface].

Using filter-paper-disk method for 20 approximately 23 year-old 60 healthy females, taste perceptive thresholds for 4 basic taste qualities (sweetness, saltiness, sourness and bitterness) were measured detailedly at various sites of the lingual surface (lingual apex, lingual center, lingual margin, lingual radix). Sucrose, sodium chloride, sodium tartarate and quinine hydrochloride as taste-producing substances were used for the sweetness, saltiness, sourness and bitterness, respectively. The results revealed the apical site to be most sensitive to all of the sweetness, saltiness and sourness (and especially to the saltiness) and to be followed by marginal and radical sites in sensitiveness. The radical site was revealed to be most sensitive only to the bitterness, and the central site was remarkably hyposensitive to all of these taste qualities. These experimental results differ, in many respects, from those results of study which have been published by Kiesow in 1894 and are already established today (lingual sensitivity to taste qualities is found separately by site: sweetness, sourness and bitterness and highly perceptible at apical, marginal and radical sites, respectively, and saltiness is not very differently perceptible by site), indicating that further detailed reexamination will be needed to know how taste perceptive thresholds for 4 basic taste qualities are distributed in the lingual surface.

Adult↗

Involvement of tyrosine kinase in capacitative Ca2+ entry pathway in rat glioma C6 cells.

Capacitative Ca2+ entry, a main pathway of Ca2+ entry evoked by receptor activation, is widely confirmed in various types of cells. However, the mechanism of the activation of capacitative Ca2+ entry is unknown. We checked the several candidates for the mechanism of capacitative Ca2+ entry pathway in rat glioma C6 cells using thapsigargin (TG), a microsomal Ca(2+)-ATPase inhibitor. Pretreatment with pertussis toxin did not affect the peak and sustained elevation of [Ca2+]i evoked by TG. Sodium nitroprusside and 8-bromo cyclic GMP did not affect an elevation of [Ca2+]i induced by TG. Phorbol 12-myristate 13-acetate, an activator of protein kinase C (PKC), and staurosporine, an inhibitor of PKC, did not modify an increase in [Ca2+]i induced by TG. Okadaic acid, an inhibitor of phosphatase, did not affect an increase in [Ca2+]i evoked by TG. Pretreatment with colchicine and cytochalasin D, drugs disrupting cytoskeleton, had no effect on a rise of [Ca2+]i induced by TG. Genistein and erbastatin analog, inhibitors of tyrosine kinase, inhibited an elevation of [Ca2+]i evoked by TG in a dose-dependent manner. The present results suggest that tyrosine kinase regulates capacitative Ca2+ entry into rat glioma C6 cells.

Animals↗

Lansoprazole elevates the ratio of serum pepsinogen I v.s. pepsinogen II.

In order to investigate the mechanism by which proton pump inhibitor increases serum pepsinogen levels, we evaluated the effects of ulcer location and IgG antibody against Helicobacter pylori on lansoprazole-induced elevations. Patients with endoscopically proven peptic ulcer received lansoprazole 30 mg/day for 6 or 8 weeks; pepsinogen I and II levels, along with antibody to H. pylori, were measured in fasting blood samples. We found that whether or not antibody to H. pylori was present, pepsinogen I and II levels and the I/II ratio rose significantly in lansoprazole-treated patients. Patients with stomach-body ulcers showed smaller increases in both pepsinogens than did those with ulcers in the gastric angle/antrum or in the duodenum. In conclusion, lansoprazole increases serum levels of both pepsinogens I and II, although a larger increase in pepsinogen I elevates the pepsinogen I/II ratio. The relatively small increases seen in patients with stomach-body ulcers suggest atrophic changes in the gastric mucosa in patients with stomach-body ulcer.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Expression of bcl-2 Protein in Breast Carcinoma with Correlation to Expression of p53 Protein and Clinicopathological Factors.

Expression of bcl-2 gene product was examined in 204 breast carcinomas in order to ascertain its clinicopathological significance. The bcl-2 protein was detected by immunohistochemistry on paraffin embedded tissue sections and its presence was confirmed by Western blot analysis of whole cell lysates. A strong positive correlation was noted among expression of bcl-2 protein in carcinoma cells, positivity of progesterone receptor (PR) and expression of p53 protein. However, no correlation could be observed among expression of bcl-2 protein, histological type of carcinoma, tumor size, lymph node metastasis and positivity of estrogen receptor (ER).

Journal Article↗

Multicentric Breast Carcinoma: Evaluation of Clinicopathological and Immunohistochemical Characteristics.

Multicentric breast carcinomas not diagnosed clinically, were examined by serial step-cut sectioning of the whole breast, and multicentric carcinoma cases were compared with single carcinoma cases with regard to histological and clinicopathological findings. In 7(3.7%) out of 187 surgically resected breasts, latent carcinomas apart from the main carcinoma were noted. The size of the latent carcinoma varied from 0.2 to 5 cm in diameter. The histological type was noninvasive ductal carcinoma in six cases and invasive ductal carcinoma in one case. When the main carcinoma was small in size (less than 2.5 cm in diameter), and showed papillotubular carcinoma as the histological type or had estrogen receptor (ER) by the dextran-coated charcoal (DCC) method, the incidence of latent carcinoma was high. In 5 of 6 cases with latent carcinoma examined by immunohistochemistry, latent carcinomas showed expression of ER. Concerning Ki-67, proliferating cell nuclear antigen (PCNA) and p53 protein, there was no significant difference between the main and latent carcinomas, as well as with other clinicopathological factors.

Journal Article↗

Sequence analysis of presenilin-1 gene mutation in Japanese Alzheimer's disease patients.

The mutations of presenilins (PSs) gene and their clinicopathological correlations to Alzheimer's disease (AD) have lately attracted considerable attention. In this report we analyzed fifteen Japanese familial Alzheimer's disease (FAD) including 12 early-onset FAD and 13 sporadic AD patients for the mutation of PS-1 gene by direct sequence analysis. We found the mutations, G384A, E280A in two FAD and H163R in one sporadic AD patient, and no N1411 or M239V mutation in PS-2 gene, and no mutation in exons 16 and 17 in amyloid precursor protein (APP) gene. Families in which we failed to find the mutation by this screening may have mutations elsewhere in PSs or in APP gene, or yet unidentified other AD loci may exist. This is the first report to find a sporadic AD patient having PS-1 mutation.

Adult↗

New graft-implanting method for thoracic aortic aneurysm or dissection with a stented graft.

BACKGROUND: To alleviate the invasiveness of surgical treatment for thoracic aortic aneurysm or dissection involving the distal arch, we developed a new method of implanting a graft in the distal anastomotic portion that does not require dissection, suture, or lateral thoracotomy. METHODS AND RESULTS: The tight circumferential attachment between the graft and the aortic inner wall, produced by the hoop strength of a self-expanding (Gianturco) stent that is anchored into the woven polyester graft, takes the place of the conventional anastomotic suture at the distal end of the graft. This new surgical method requires only a median sternotomy and relatively short circulatory arrest time to repair a thoracic aneurysm or dissection involving the distal arch. In a 12-month period in 1994 and 1995, we applied this new method in 10 cases (seven true aneurysms and three dissections). Complete thrombosis of the aneurysms or false lumens surrounding the grafts resulted in all 10. There were no surgical deaths, and the major complications were two cerebral infarctions due to inappropriate protection of the brain and dissecting procedure of an aortic arch, respectively. CONCLUSIONS: These preliminary results indicate that this new graft-implanting method with the stented graft should be considered one of the less-invasive surgical treatments for thoracic aneurysm and dissection involving the distal arch.

Aged↗

Mitochondrial DNA is required for regulation of glucose-stimulated insulin secretion in a mouse pancreatic beta cell line, MIN6.

To determine whether mtDNA and mitochondrial respiratory function in pancreatic beta cells are necessary for the phenotypic expression of glucose-stimulated insulin secretion, we used a cultured mouse pancreatic beta cell line, MIN6, and two derivative lines, mtDNA knockout MIN6 (rho0 MIN6) and mtDNA repopulated cybrid MIN6. The MIN6 cells retain the property of glucose-stimulated insulin secretion, but their mtDNA knockout induced the loss of mitochondrial transcription, translation, and respiration activity, without inhibition of transcription of the insulin gene or loss of succinate dehydrogenase activity, indicating that the observed mitochondrial dysfunction in rho0 MIN6 cells was not due to a cytotoxic side effect derived from the mtDNA knockout. Moreover, the mtDNA depletion also inhibited both the glucose-stimulated increase in the intracellular free Ca2+ content and the elevation of insulin secretion. The possibility of the involvement of nuclear genome-encoded factors in this process was excluded by the observation that the missing sensitivity to extracellular glucose stimulation in rho0 MIN6 cells was restored reversibly by repopulation with foreign mtDNA and isolating cybrid MIN6 clones. Therefore, these findings provide unambiguous evidence for the involvement of the mitochondrial dysfunction induced by mtDNA impairment in developing pathogeneses of some forms of diabetes mellitus.

Animals↗

Lysophosphatidic acid-sensitive intracellular Ca2+ store does not regulate Ca2+ entry at plasma membrane in Jurkat human T-cells.

In Jurkat T cells, the anti-CD3 antibody OKT3 and thapsigargin (TG) elevated the cytoplasmic free Ca2+ concentration ([Ca2+]i), after which it decreased to a sustained, elevated level. In contrast, lysophosphatidic acid (LPA) increased [Ca2+]i only briefly and transiently, after which it declined to the resting level of [Ca2+]i even in the presence of extracellular Ca2+. OKT3 increased Ins(1,4,5)P3 formation but neither LPA nor TG did. In the absence of extracellular Ca2+, the addition of OKT3 did not affect an elevation of [Ca2+]i induced by the subsequent addition of LPA and vice versa. In permeabilized Jurkat cells, the addition of Ins(1,4,5)P3 released Ca2+; this was inhibited by heparin, whereas LPA released Ca2+ even in the presence of heparin. cADP-ribose released Ca2+; this was additive with LPA-induced Ca2+ release and vice versa in permeabilized Jurkat cells. LPA did not stimulate Ca2+ entry and 45Ca2+ uptake but OKT3 and TG did. LPA, OKT3 and TG did not affect the sustained elevation of [Ca2+]i induced by ionomycin. The present results suggest that at least three kinds of intracellular Ca2+ stores, which are Ins(1,4,5)P3,-cADP-ribose- and LPA-sensitive, exist in Jurkat T cells, and that the LPA-sensitive intracellular Ca2+ store does not regulate Ca2+ entry at the plasma membrane.

CD3 Complex↗

Molecular cloning and sequencing of a cDNA encoding dihydropyrimidinase from the rat liver.

A cDNA encoding dihydropyrimidinase has been isolated from a rat cDNA library. The N-terminal and an internal amino acid sequences were determined, and PCR primers were designed based on these sequences. Using a cDNA fragment amplified by RT-PCR with these primers, three cDNA clones were isolated from a rat liver library. The clone with the longest insert of 2129 bp contained a 1557 bp open reading frame encoding a polypeptide of 519 residues with a molecular mass of 56,832 Da.

Amidohydrolases↗