PubMed Health⌕ Search

Biomedical subjects

Y Yoshida

Publications and source records attributed to Y Yoshida.

At least 1,207 records · Page 67Linked to original sources

Analysis of structural features of dihydropyridine analogs needed to reverse multidrug resistance and to inhibit photoaffinity labeling of P-glycoprotein.

Synthetic dihydropyridine analogs were screened to determine whether they would reverse multidrug resistance of a multidrug-resistant human KB carcinoma cell line, KB-C1. Among twenty-four dihydropyridine analogs examined, thirteen almost completely overcame drug resistance (group A), nine partially overcame resistance (group B) and two did not reverse resistance (group C). The twenty-two compounds that reversed drug-resistance (groups A and B) were hydrophobic dihydropyridine derivatives. Three compounds that reversed resistance, NK-113, NK-138 and NK-194, increased the accumulation of [3H]vincristine in the resistant KB-C1 cells, but not in the parental KB cells, nor in a revertant cell line, KB-C1-R2. NK-101 (group C), which did not reverse resistance, had no effect on drug accumulation. Enhanced efflux of vincristine from the resistant cells was inhibited completely by NK-194, but NK-194 did not affect vincristine influx. Nine of the twenty-four compounds were screened to determine whether they inhibited photoaffinity labeling of the cell surface protein gp170 (P-glycoprotein) in KB-C1 cells by N-(p-azido-[3-125I]-salicyl)-N'-beta-aminoethylvindesine [( 125I]NASV). All five compounds of group A, NK-138, NK-194, NK-200, NK-203 and NK-220, inhibited the photoaffinity labeling of gp170 at less than 10-100 microM, whereas NK-113 and NK-196 of group B inhibited the labeling at 100-200 microM. By contrast, NK-101 and NK-102 of group C did not inhibit labeling even at 2000 microM. These studies confirm the relationship among reversal of multidrug resistance, decreased efflux of vincristine, and inhibition of [125I]NASV labeling of P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Membrane relationships in murine Meissner corpuscles: cytology of freeze-substituted tissue.

Mechanoreceptive sensory corpuscles (murine Meissner corpuscles) in the toe pad skin of mice, consisting of axon terminals and lamellar cells, were studied following freeze-substitution in order to clarify the plasma membrane relationships between axon terminals and lamellar cells. Tissue preservation of corpuscles was excellent when the corpuscle was located within 10 microns from the contact surface with the precooled metal block. The axolemmata appeared more electron-opaque than did plasma membranes of lamellar cells. The inner leaflet of the unit membranes was thicker than the outer leaflet in the axolemma, and the contour of cell plasma membranes was relatively smooth and straight. Characteristic focal or regional approximations of plasma membranes were noted between the axon and abutting lamellae. Such membrane appositions resembled gap junctions, although no gap junctions were found between the axon and lamellae in chemically fixed materials. Similar gap junction-like close appositions of plasma membranes also were found between neighboring lamellae. These approximations occurred more frequently than typical gap junctions seen in chemically fixed materials. These findings indicate that there may be a relationship of the plasma membranes in the axon terminals and in abutting lamellae as well as between neighboring lamellae that have not been identified as yet in conventional chemically fixed material. Another striking finding was that basal laminae on lamellar cells exhibited the same electron opacity as the surrounding connective tissue matrix and thus the two are indistinguishable from one another. Furthermore, the lamina lucida was not evident, and basal lamina material was directly contiguous with the plasma membrane.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Patterns of intrahepatic recurrence after curative resection of hepatocellular carcinoma.

Using selective angiograms of the liver, we analyzed the patterns of intrahepatic recurrence of hepatocellular carcinomas following curative surgery. In 33 patients with intrahepatic recurrences, seven patients (21%) had a recurrence near the resected hepatic stump. The remaining 26 had either a nodular recurrence in segments away from the resected margin or a widespread multinodular recurrence in the liver remnant. There was a recurrence within the first postoperative year in five of 16 patients with a nodular recurrence and in eight of 10 patients with a widespread multinodular recurrence. In these patients, particularly those with a widespread multinodular recurrence, tumor thrombi in the portal vein present before the operation and/or disseminated during operation from such an advanced main tumor seemed to be the most important and significant factor related to the early recurrence in the remnant liver. This evidence suggests that in cases of surgery for hepatocellular carcinoma it is important to establish a technique to prevent dissemination of cancer cells due to operative manipulation and also adequate adjuvant therapy rather than attempting to obtain an ample resection margin.

Adult↗

A 5-year experience of lipiodolization: selective regional chemotherapy for 200 patients with hepatocellular carcinoma.

Between 1982 and 1987, selective regional cancer chemotherapy using Lipiodol plus an anticancer drug (lipiodolization) was prescribed for 200 patients with hepatocellular carcinoma. One hundred forty-nine patients were given lipiodolization alone, and the remaining 51 underwent hepatic resection following lipiodolization. The grades of deposits of the oily contrast medium in the neoplastic tissue seen on the plain X-ray correlated well with the antitumor effect. In the resected specimens of 17 patients treated with lipiodolization prior to surgery, concentrations of adriamycin in the malignant liver tissues were 13.2 +/- 18.2 micrograms per gm, whereas the adjacent liver parenchyma contained 1.4 +/- 2.0 micrograms per gm of adriamycin; the difference was statistically significant (p less than 0.05). In the 149 patients treated with lipiodolization, 1-, 2-, 3- and 4-year survival rates were 56.1, 28.9, 17.3 and 7.4%, respectively. Thus, lipiodolization was considerably more effective, compared to the results achieved by hepatic artery ligation and cannulation into the hepatic artery for patients in Stages I and II. In this sequential nonrandomized study, the survival rates for patients undergoing hepatic resection were superior to those for patients in Stage I and treated with lipiodolization. The significant difference appeared to depend on incomplete killing of tumor cells, which are most often present in the fibrous capsule, by lipiodolization. We conclude from these data that lipiodolization is an effective treatment for hepatocellular carcinoma when the tumor is not curatively resectable. When the clinical status is good, then surgery is warranted.

Antineoplastic Agents↗

Type I protein kinase C isozyme in the visual-information-processing pathway of monkey brain.

Previously using PKC isozyme-specific antibodies for immunoblot analysis, we demonstrated the heterogeneous distribution of PKC isozymes in various regions of monkey and rat brains and that type I PKC was most abundant in cerebellum, hippocampus, amygdala, and cerebral cortex (Huang et al.: J Biol Chem 262:15714-15720, 1987). Using these antibodies, we have also demonstrated that type I, II, and III PKC are products of PKC genes gamma, beta, and alpha, respectively (Huang et al.: Biochem Biophys Res Commun 149:946-952, 1987). By immunocytochemical analysis, type I PKC-specific antibody showed strong reactivity in various types of neuron in hippocampal formation, amygdala, cerebellum, and neocortex. In hippocampal formation, granule cells of dentate gyrus and pyramidal cells of hippocampus were heavily stained. By immunoblot analysis, relative levels of PKC isozymes in several areas of monkey cerebral cortex involved in the visual information processing and storage were determined. Both type II and III PKCs appeared to be evenly distributed and at moderate levels, type I PKC formed a gradient of increasing concentration rostral along the cerebral cortex of occipital to temporal and then to the limbic areas. Neurobehavioral studies have demonstrated that the neocortical and limbic areas of the anterior and medial temporal regions participate more directly than the striate, prestriate, and posterior temporal regions in the storage of visual representations and that both hippocampus and amygdala are important in the memory formation. As type I PKC is present at high levels in hippocampus, amygdala, and anterior temporal lobe, we predict that the type I protein kinase C may participate in the plastic changes important for mnemonic function.

Animals↗

Glomeruloid blood vessels in ethylnitrosourea-induced rat gliomas. Histological and immunohistochemical studies.

Glomeruloid blood vessels (GBVs), a characteristic histological feature of most human malignant gliomas, were recognized with high incidence in autochthonous rat gliomas induced by transplacental administration of ethylnitrosourea. To evaluate some of the biological properties of these GBVs, we carried out a study using histological methods and immunohistochemical staining for glial fibrillary acidic protein, factor VIII-related antigen (VIII Ag) and bromodeoxyuridine (BrdUrd). Of 22 animals with large, massively growing gliomas in the CNS, GBVs including conglomerate aggregations of small blood vessels with endothelial hyperplasia and strong VIII Ag expression were observed in 13 large gliomas histologically consisting of primitive neuroepithelial neoplasms (PNN; so called ependymoma) and mixed-type gliomas in combination with astrocytoma and PNN or anaplastic astrocytoma. The anaplastic gliomas in our series were devoid of GBVs. These findings indicate that GBV formation takes place in a histological variety of experimental gliomas. Furthermore, the GBVs were frequently associated with the vasculo-mesenchymal stroma in the parent gliomas, suggesting an intimate relationship with the morphogenesis of GBVs. In addition, it was shown that the GBVs had a higher BrdUrd-labelling index than that of other blood vessels in gliomas and also that of neoplastic cells in most parent gliomas, except for anaplastic gliomas. Based on these results, the possible mechanism of GBV morphogenesis is discussed with regard to the roles of macromolecules in the induction and regulation of GBVs.

Animals↗

Cooperative effects of gamma-interferon and 1 alpha, 25-dihydroxyvitamin D3 on in vitro differentiation of the blast cells of RAEB and RAEB-T.

We added recombinant human gamma-interferon (gamma-IFN) and 1 alpha, 25-dihydroxyvitamin D3 (1 alpha, 25 (OH)2D3) to the bone marrow cells from six patients with RAEB or RAEB-T in liquid suspension cultures. After cultivation for 7 to 9 days, numerical, morphological and functional changes of the cells were assessed. gamma-IFN and 1 alpha, 25 (OH)2D3 additively suppressed cell growth, especially the number of blast cells decreased. The expression of alpha-naphthylbutyrate esterase (NBE) activity appeared to be promoted but that of naphthol AS-D chloroacetate esterase (NAE) activity was apparently suppressed by the addition of gamma-IFN and/or 1 alpha, 25 (OH)2D3. The percentage of NBT reduction-positive cells and latex-phagocytizing cells was only slightly increased by both agents. These results indicate that gamma-IFN and 1 alpha, 25 (OH)2D3 cooperate to induce monocytoid differentiation of the patients' blast cells. Combination therapy with both agents merits further study.

Adult↗

Randomized controlled study of mitomycin C/carboquone/5-fluorouracil/OK-432 (MQ-F-OK) therapy and mitomycin C/5-fluorouracil/doxorubicin (FAM) therapy against advanced liver cancer.

We have previously reported that the combination of mitomycin C, carboquone, 5-fluorouracil and OK-432, including the intra-arterial administration of mitomycin C and carboquone (MQ-F-OK therapy), was effective in the treatment of advanced liver cancer. The Cooperative Study Group conducted a controlled study on MQ-F-OK therapy and the combination of mitomycin C, 5-fluorouracil and doxorubicin, including the intra-arterial administration of mitomycin C and doxorubicin (FAM therapy), against advanced liver cancer. Forty patients with advanced primary or secondary liver cancer were enrolled in this study and randomized into the MQ-F-OK group and the FAM group. Seventeen of the 21 cases in the MQ-F-OK group and 16 of the 19 cases in the FAM group were eligible for response evaluation in accordance with the criteria of the Japan Society for Cancer Therapy. There was no significant difference in the patient characteristics between the two groups. Three cases in the MQ-F-OK group and two in the FAM group showed partial response. There was, however, no significant difference in the response rates and the prolongation of life between the two groups. As for the side-effects, only anemia was observed more frequently in the FAM group than in the MQ-F-OK group. In conclusion, we could not preferentially recommend either MQ-F-OK therapy or FAM therapy for advanced liver cancer. The performance status of the patient was one of the most important factors in the treatment of advanced liver cancer because patients with poor performance status showed poorer results.

Adult↗

Endothelial basement membrane and seamless-type endothelium in the repair process of cerebral infarction in rats.

Ultrastructural analysis of capillary changes during the repair process of experimental cerebral infarction induced in rats was carried out with special reference to the endothelial basement membrane (BM) and seamless-type endothelial cells. Following degeneration of endothelial cells and pericytes, their BMs, without any interruption or fragmentation, were left in the lesion. Newly formed capillaries grew from vessels in the surrounding brain tissues into the reactive zone of infarcts. While the capillaries in cross-section possessed multilayered BMs, these membranes in tangential section comprised an outer BM with extremely wavy profile and an inner one showing a normal trilayered structure, uniformly enveloping the endothelial surface. It is therefore suggested that the sprouting of regenerating capillaries might invade the remaining cavities of BM, resulting from endothelial degeneration. In these new vessels, seamless-type endothelial cells lacking interendothelial contacts were observed frequently. These two different and previously unobserved findings appear to be at the heart of the regeneration mechanism of reactive capillary proliferation.

Animals↗

Variations in egg size of Trichuris trichiura.

In patients infected with Trichuris trichiura, large eggs as well as more typical eggs were frequently found in the feces; these large eggs have been attributed to human infection by T. vulpis. To clarify whether the female worms laying the large eggs were T. trichiura or T. vulpis, we examined the morphology of adult worms and the size of whipworm eggs obtained from a patient and from several domestic dogs. Adult female T. trichiura worms were easily and quickly distinguished from those of T. vulpis by their convoluted vaginal tracts and uteri. Eggs obtained from the uteri of T. trichiura were of two sizes, with approximately 80% being of the smaller variety (57 X 26 microns) and 20%, the larger (78 X 30 microns). These percentages were about equal to those found the feces of the patient. T. vulpis uterine eggs were slightly larger (82 X 39 microns) than the large eggs of T. trichiura. The distribution of the 2 populations of eggs in 30 adult female T. trichiura was as follows: 1 worm had only large eggs, 14 had only the typical smaller eggs, and 15 had both varieties in their uteri.

Adolescent↗

Limited atrial compensation to reduced early diastolic filling in hypertensive patients with advanced left ventricular hypertrophy: a Doppler echocardiographic study.

To assess atrial contribution to left ventricular (LV) filling in hypertension, we studied, using pulsed Doppler echocardiography, 22 hypertensive patients without apparent LV hypertrophy (LVH), 12 hypertensive patients with LVH, and 24 age-matched normal subjects. From mitral flow velocity waveform, we determined peak velocity of early diastolic filling flow (peak E), peak velocity of late diastolic filling flow (peak A), and the peak A/peak E ratio (peak A/peak E). Peak E decreased in hypertensives without apparent LVH and showed a further decrease in hypertensives with LVH compared with normal subjects (57 +/- 8 [mean +/- SD]; P less than 0.001, 46 +/- 7; P less than 0.0001, vs 65 +/- 10 cm/s). On the other hand, peak A/peak E increased in hypertensives without apparent LVH, and greatly increased in hypertensives with LVH (1.06 +/- 0.14; P less than 0.001, 1.40 +/- 0.29; P less than 0.0001, vs 0.79 +/- 0.21). However, increased peak A was not significantly different between the hypertensive groups (60 +/- 8 vs 64 +/- 8; NS, both; P less than 0.001 vs 50 +/- 10 cm/s for normal subjects). In hypertensives, we found no significant correlation between peak A and the wall thickness index (WTI, determined as mean LV wall thickness normalized by LV diastolic dimension), whereas peak E was significantly correlated with WTI (r = -0.65; P less than 0.001). Our findings indicate that atrial contraction can not fully compensate the decrease in early diastolic filling caused by advanced LVH. We conclude that atrial compensation for reduced early diastolic filling is limited in hypertensive patients with advanced left ventricular hypertrophy.

Adult↗

Prognostic implication of sequential bone marrow cultures in the myelodysplastic syndromes.

Twenty-five patients with newly-diagnosed myelodysplastic syndromes were studied by the clonal culture method at least three times during the clinical course. Clinical outcomes of the patients were classified into: a stable disease (ten patients); subsequent leukemic transformation (eight patients) and nonleukemic death (seven patients). The growth of the marrow granulocyte-macrophage progenitors (CFU-GM) at the time of diagnosis was significantly related to the survival. In addition, sequential changes in the CFU-GM growth patterns correlated with the different clinical outcome of myelodysplastic syndromes patients.

Aged↗

Quantitative determination of sulfated glycopeptide by two-dimensional electrophoresis on cellulose acetate membrane.

Quantitative determination of the sulfated glycoproteins present in tissue and secretion fluid was performed. After digestion of the specimen with pronase in order to convert glycoproteins to glycopeptides, the sulfated glycopeptides were separated from a mixture of acidic glycans (glycosaminoglycans, sialoglycopeptides and sulfated glycopeptides) by two-dimensional electrophoresis on cellulose acetate membrane [(1986) J. Biochem. Biophys. Methods 12, 239-246]. After staining with alcian blue, the spot of sulfated glycopeptide on the cellulose acetate membrane was cut out, and then only the dye bound to the sulfated glycopeptide was extracted with a 5% cetylpyridinium chloride solution at 100 degrees C for 15 min. The extract was then measured by absorbance at 615 nm using an authentic sulfated glycopeptide as a standard. This method facilitated the determination of sulfated glycopeptides, which were separated from other acidic glycans, within the range 0-25 micrograms.

Animals↗

Cathepsin B and L activities in gastric cancer tissue: correlation with histological findings.

Cathepsin B and L activities in cancerous and noncancerous mucosal tissues from 29 patients with gastric cancer were determined with a small amount of tissue homogenate. Both enzyme activities were significantly higher in cancerous tissues than in noncancerous tissues. The cathepsin B activity was higher with decreasing differentiation of the cancerous tissues, and also with increasing depth of invasion and metastasis to regional lymph nodes. Significantly high cathepsin B activity was observed in specimens of poorly differentiated adenocarcinomas, as well as in specimens from patients with extensive metastasis to n2 or n3 lymph nodes. These results suggest that high cathepsin B activity is characteristic of gastric cancer which invades and metastasizes. Therefore, in cases of marked elevation of cathepsin B activity in cancerous tissues, relatively extensive resection may be necessary to obtain a cure.

Adenocarcinoma↗

Effect of insulin on the production of prostacyclin and cell proliferation in cultured smooth muscle cells.

We have investigated the effects of insulin on the synthesis of prostacyclin and cell proliferation in cultured vascular smooth muscle cells, which have been thought to play important roles in the development of atherosclerosis. Prostacyclin was measured as 6-keto-PGF1 alpha in the culture medium, and cell proliferation as incorporation of [3H]thymidine into DNA. Our studies showed that insulin reduced production of prostacyclin and stimulated cell proliferation in SMC. Like insulin, dibutyryl cAMP inhibited the production of prostacyclin, whereas it did not stimulate cell proliferation. No significant changes in cAMP levels were found on the addition of insulin into the culture medium. Therefore, cAMP does not appear to be involved in the mechanisms of these insulin effects. These results again suggest that hyperinsulinemia could be one of the important factors in atherosclerosis.

1-Methyl-3-isobutylxanthine↗