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Biomedical subjects

S Toyoshima

Publications and source records attributed to S Toyoshima.

At least 127 records · Page 7Linked to original sources
PubMed1986

Partial purification and characterization of membrane-bound and cytosolic phosphatidylinositol-specific phospholipases C from murine thymocytes.

Membrane-bound and cytosolic phosphatidylinositol (PI)-specific phospholipases C in murine thymocytes have been partially purified and characterized. The membrane-bound enzyme was extracted from microsomes with sodium cholate and purified by sequential column chromatographies on Sephadex G-100, heparin-Sepharose CL-6B, and Sephadex G-100. The cytosolic enzyme was purified from the cytosol by sequential column chromatographies on Sephadex G-100 and FPLC-Mono S. Specific activities of the membrane-bound enzyme and the cytosolic enzyme increased more than 1,800- and 1,400-fold, respectively, compared with those of microsomes and the cytosol. The molecular weights of the both enzymes were estimated to be about 70,000 by gel filtration. These purified enzymes also hydrolyzed phosphatidylinositol 4,5-bisphosphate (PIP2). At neutral pH and low Ca2+ concentrations, the membrane-bound enzyme hydrolyzed PIP2 in preference to PI and showed higher activity than the cytosolic enzyme. These activities were also affected differently by various lipids. For PIP2 hydrolysis, all lipids investigated except lysophosphatidylcholine enhanced the activity of the membrane-bound enzyme, while phosphatidylcholine (PC) and phosphatidylserine (PS) did not significantly affect the activity of the cytosolic enzyme. PC, PE, and PS inhibited the activities of the membrane-bound and cytosolic enzymes for PI hydrolysis. The physiological implications of these results are discussed.

Animals↗
PubMed1986

Invasive lobular carcinoma of the breast. An analysis of 29 cases.

Twenty-nine cases of invasive lobular carcinoma were analyzed, based on three aspects of the histology: 1) cellular features such as a monotonous proliferation of uniform small cells, 2) a single file or targetoid arrangement, and 3) loss of cell cohesion or dissociation of tumor cells. Twenty-four tumors which fulfilled these three criteria were appraised as cases of conventional lobular carcinoma, in a classic sense, while five others were a variant of this tumor. Individual tumor cells of lobular carcinoma were estimated to be well differentiated, both morphologically and functionally, revealing well developed intracytoplasmic organelles and a high percentage of alpha-lactalbumin content in the cytoplasm. Nevertheless, the tumor itself was characterized by a lack of any particular structural differentiation in the arrangement of cells. Based on the observation of the histologic features, invasive lobular carcinoma was subclassified into three groups, in situ predominant, intermediate, and diffuse infiltrating and with a definite correlation to the age of the patient and to the prognosis. Validity of this classification indicates that lobular carcinoma progresses gradually, even in the invasive phase, and can be categorized as a slowly growing subset of mammary carcinoma.

Adult↗
PubMed1986

The effect of food dye and other environmental substances on the host defense reaction in mice in relation to virus infection.

Environmental substances were examined for their effect on interferon induction and delayed type hypersensitivity (DTH) responses in mice. Amaranth, safrole, phenacetin and nicotine suppressed the DTH response, and suppressed the serum interferon titers induced by virus infection. However, they did not affect the interferon titers which were induced by tilorone, a chemical inducer. The peak of interferon titer was 12 hours after infection with herpes simplex virus type 2 (HSV-2). Therefore, amaranth, safrole, phenacetin and nicotine were given to mice intraperitoneally 24 hours before, and 2 and 18 hours after infection with HSV-2. It was found that safrole and nicotine shortened the mean survival time of HSV-2 infected mice when they were given to mice 2 hours after virus inoculation. Amaranth and phenacetin showed similar effects. However it was not definite statistically. In biochemical and hematological tests, these four substances did not affect the functions of liver, kidney and carbohydrate metabolism in normal mice. These results suggest that substances which may often be taken into the body have the potential to affect the onset of virus infectious diseases as a result of the suppression of the host defense reaction.

Animals↗
PubMed1986

Inhibition of experimental pulmonary metastasis of mouse colon adenocarcinoma 26 sublines by a sialic acid:nucleoside conjugate having sialyltransferase inhibiting activity.

The total and sialidase-releasable sialic acid contents of murine colon adenocarcinoma 26 sublines of high (NL-17) and low (NL-44) metastatic potential were found to be positively correlated with their ability to undergo metastasis. Furthermore, sialyltransferase activity of intact NL-17 cells was higher than that of NL-44 cells. These findings suggest that sialic acid on the cell surface may play a role in the metastasis of these cells. Therefore, the effect of a sialyltransferase inhibitor, 5-fluoro-2',3'-isopropylidene-5'-O-(4-N-acetyl-2,4-dideoxy-3,6,7,8-tetra -O -acetyl-1-methoxycarbonyl-D-glycero-alpha-D-galactooctapyranosyl)u ridine (Kl-8110), on the experimental lung metastasis of NL-17 or NL-44 cells was examined. Kl-8110 inhibited the transfer of sialic acid to its endogenous acceptor in NL-17 and NL-44 cells. NL-17 or NL-44 cells were injected into the tail veins of mice, and the metastasis-inhibiting activity of Kl-8110 was evaluated on the basis of both the lung weight and the number of pulmonary surface nodules about 3 wk after the tumor cell injection and of the survival ratio of mice inoculated with the tumor cells. Pretreatment of tumor cells with Kl-8110 together with i.v. injection of Kl-8110 caused significant inhibition of pulmonary metastasis of both NL-17 and NL-44 cells. Inhibition of metastasis and prolongation of survival were also observed on i.v. injection of Kl-8110 without pretreatment of the tumor cells with Kl-8110, but the degree of inhibition was lower than that in the case of the two treatments together. Kl-8110 itself had neither cytostatic nor cytotoxic effects on NL-17 and NL-44 but reduced the retention of tumor cells in the lungs. This antimetastatic effect of Kl-8110 may be due to modification of the tumor cell surface resulting from inhibition of sialyltransferase by Kl-8110. In addition, a beta-linked sialic acid:nucleoside conjugate (Kl-8111) and an equimolar mixture of Kl-8110 and Kl-8111 (Kl-414) also inhibited the metastatic ability of NL cells to the same extent as Kl-8110 did.

Adenocarcinoma↗
PubMed1985

Glandular or mucus-secreting components in squamous cell carcinoma of the esophagus.

A review of 195 patients with carcinoma of the esophagus disclosed 41 cases (21.0%) with glandular and/or mucus-secreting components, in addition to the ordinary component of squamous cell carcinoma. These tumors could be grouped into three types according to representative histologic features of glandular and mucus-secreting portions: glandular type (23 cases), cribriform type (11 cases), and mucoepidermoid type (7 cases). The histologic features of the three types were reminiscent of those of adenocarcinoma, adenoid cystic carcinoma, and mucoepidermoid carcinoma of salivary glands, respectively. Moreover, areas showing glandular or mucus-secreting differentiation were in greater part located in the submucosa and the lamina propria mucosae, thereby suggesting that such differentiation had arisen in the esophageal glands or their ducts. In all 41 cases, the ordinary element of squamous cell carcinoma, invasive, or noninvasive, was admixed in various proportions with the glandular components, indicating that this type of esophageal tumor had originated not only from the covering squamous epithelium but also from esophageal mucous-gland or ductal epithelium. The findings also support the concept of the field origin of carcinogenesis in esophageal carcinoma.

Carcinoma↗
PubMed1985

Partial purification and characterization of phospholipid N-methyltransferases from murine thymocyte microsomes.

Significant amounts of phospholipid N-methyltransferase activity in murine thymocytes were found to be distributed on the plasma membrane. The enzyme activity had an optimum pH of 9. The presence of divalent cations, Mg2+ (10 mM) or Ca2+ (1 mM), and EGTA separately in the assay had only a small effect on the enzyme activity. However, addition of both 10 mM Mg2+ and 1 mM Ca2+ increased the enzyme activity. The presence of two enzymes for each conversion of phosphatidylethanolamine (PE) to phosphatidylmonomethylethanolamine (PME) and PME to phosphatidylcholine (PC) was suggested by the result of the determination of the incorporated radioactivity into PME, phosphatidyldimethylethanolamine (PDE) and PC; the apparent Km values for S-adenosyl-L-methionine were 20 and 400-500 microM for the conversion of PE to PME and for the conversion of PME to PC they were 5 microM and 40 microM. S-Adenosyl-L-homocysteine (AdoHcy), a known inhibitor of enzymatic methylation, competitively inhibited [14C]methyl incorporation into total lipid. The apparent Ki value for AdoHcy was 44.7 microM. Two phospholipid N-methyltransferases were partially purified by extraction with sodium deoxycholate, gel filtration on Sephadex G-75, and affinity column chromatography on AdoHcy-Sepharose. One enzyme, mainly catalyzing the formation of PME, was purified approximately 1548-fold and the other catalyzing the formation of PDE and PC, was purified approximately 629- to 703-fold. However, the former still contained a little activity for PDE and PC formation and the latter contained a little activity for PME formation. In these partially purified phospholipid N-methyltransferase preparations, little contaminating protein O-carboxylmethyltransferase activity was observed; however, significant PC-phospholipase A2 activity was detected. This result may suggest that phospholipid N-methyltransferases associate with phospholipase A2 in the thymocyte plasma membrane.

Animals↗
PubMed1985

Extremely well-differentiated adenocarcinoma ("adenoma malignum") of the cervix in a patient with Peutz-Jeghers syndrome.

In a 29-year-old woman with the Peutz-Jeghers syndrome (PJS), an extremely well differentiated adenocarcinoma (adenoma malignum) of the uterine cervix was detected. The cervical lesion consisted of a polypoid mass, measuring 3.5 cm in greatest diameter, composed of extremely well differentiated tubules resembling those of the endocervical glands, yet containing a few Paneth cells. Immunohistochemical stains displayed cytoplasmic carcinoembryonic antigen in this tumor. The ovaries had no apparent abnormality. The diagnosis of the PJS was based on the presence of numerous hamartomatous polyps of the rectum and cutaneous pigmentation around the lips, fingers, and toes. The patient underwent a simple total hysterectomy and was subsequently treated with chemotherapy. In an 11 year follow-up, there has been no recurrence of the cervical tumor and she is currently well. The clinicohistopathologic differences of this cervical tumor in patients with and without PJS are briefly discussed.

Adenocarcinoma↗
PubMed1984

Lectin-like molecules on the murine macrophage cell surface.

Lectin-like molecules on the surface of murine peritoneal exudate macrophages induced by thioglycolate or an anti-tumor streptococcal preparation, OK-432, were investigated and isolated. Furthermore, their sugar-binding specificities and their role in macrophage-mediated tumor cytotoxicity were examined. A neoglycoprotein, D-galactose (Gal)-bovine serum albumin, bound to these murine peritoneal macrophages. This binding of Gal-bovine serum albumin was inhibited by D-galactose, and by complex-type oligosaccharides (unit B) and high mannose-type oligosaccharides (unit A) prepared from porcine thyroglobulin. When thioglycolate-elicited macrophages were activated by lipopolysaccharide and/or the culture supernatant of concanavalin A-activated mouse spleen cells, they became tumoricidal and the number of the lectin-like molecules on the macrophage surface was found to increase. Since the binding and cytotoxic activities of these tumoricidal macrophages toward tumor cells were partially inhibited by D-galactose, the D-galactose-binding lectin-like molecules on the surface of tumoricidal macrophages might play an important role in macrophage-mediated cytotoxicity. These lectin-like molecules were then isolated from solubilized murine peritoneal exudate cells labeled with pyridoxal 5'-phosphate and sodium [3H]borohydride by affinity chromatography on columns of asialo unit B oligosaccharide-Sepharose 4B and/or beta-D-galactose-Bio-Gel P-100. The proteins bound to the asialo unit B oligosaccharide-Sepharose 4B column and eluted specifically were found to have approximate molecular weights of 79 000 and 18 000, and the protein bound to and eluted from the beta-D-galactose-Bio-Gel P-100 column had an approximate molecular weight of 77 000. These isolated proteins bound to the surface of glutaraldehyde-fixed tumor cells, and their binding was inhibited by D-galactose and also by D-mannose. Since most of the 77 kDa protein bound to the asialo unit B oligosaccharide-Sepharose 4B, this protein was assumed to be identical with the 79 kDa protein. These results suggest that the lectin-like molecules on murine macrophages have wide specificity and that one lectin-like molecule can bind both D-galactose and D-mannose.

Animals↗
PubMed1984

Simultaneous occurrence of primary carcinoma and chondrosarcoma in the liver. A case report and a review of the literature.

We treated a 67-year-old man with primary carcinoma and sarcoma arising from the different areas of the cirrhotic liver. Histologically the carcinoma was of hepatocellular origin and the sarcoma consisted mainly of poorly differentiated mesenchymal cells partly with a chondrosarcomatous component. Among nine similar cases reported in the literature, only one was a rhabdomyosarcoma and the others were described simply as of spindle cell variety without evidence of mesenchymal differentiation. In the present case, the sarcoma consisted of mesenchymal cells with distinctive areas of unequivocal chondrosarcoma.

Aged↗
PubMed1984

Binding of bile acids with rat colon and resultant perturbation of membrane organization as studied by uptake measurement and 31P nuclear magnetic resonance spectroscopy.

The mode of interaction of deoxycholate (DOC) or lithocholate (LC) with F344 rat colon was examined by measurements of uptake, 31P nuclear magnetic resonance (NMR) spectroscopy and observation of morphological changes. DOC as well as LC was taken up by the colon in a nonsaturable manner with respect to concentration and time, up to 30 min. None of several metabolic inhibitors reduced the uptake of the bile acids, nor did pretreatment of colon segments with chloroform-methanol (2:1, (v/v), heat or trypsin. Further, the bile acids were not transported by the colon against concentration gradients, and they were bound to both the mucosa and serosa equally. From these findings, it is concluded that the bile acids are transported in a passive manner, and no specific receptor for them is contained in colonic mucosa. The uptake of the bile acids by the colon varied with temperature and was related to the fluidity of the colonic membranes. The extent of uptake of dehydrocholate and taurocholate, which do not induce ornithine decarboxylase (ODC) activity, was almost the same as that of LC. The 31P NMR spectra of the colonic mucosal cells indicated that the proportion of the bilayer structure is increased by 0.5 mM DOC. Among a variety of bile acids examined, the extent of membrane alteration was in parallel with the extent of ODC induction. Treatment of the colonic mucosa with 0.5 mM DOC caused marked degeneration of the surface but not the deeper layers of the mucosa. Thus, physiological concentrations of bile acids influence the membrane organization of the colonic mucosa in a nonspecific manner that is possibly related to the tumor-promoting activity.

Animals↗
PubMed1984

[Analysis of gastric biopsy specimens group III by a revised group classification].

A revised group classification of histology in gastric biopsy specimens was recently proposed by the Japanese Research Society For Gastric Cancer. The specimens judged as Group III by the revised classification contained; adenoma that used to be judged as Group III by the former classification, lesions difficult to distinguish between adenoma and carcinoma, lesions difficult to distinguish between atypical regenerative epithelium and carcinoma, and so on. Pathologists are requested to describe whether the lesion is adenoma or not and to consult with clinicians about the lesion in order to reduce the possibility that a case of well-differentiated adenocarcinoma is misdiagnosed as Group III by the revised classification.

Adenocarcinoma↗
PubMed1983

Mammary carcinoma with argyrophil cells.

In a series of 253 cases of carcinoma of the breast, nonargentaffin, argyrophil cells were seen among the tumor cells in 27 cases (10.7%). An electron microscopic examination in one such case revealed dense cored secretory granules surrounded by a limiting membrane within the cytoplasm of the argyrophil tumor cells. Tumors with argyrophil cells, particularly when these cells were abundant, histologically showed a uniform appearance of relatively small constituent cells with oval or round nuclei of a regular size, forming solid alveolar nests or sheets. In one of these tumors, a delicate vascular stroma separated the sheets of tumor cells to form a ribbonlike pattern, simulating the feature of a carcinoid tumor. This tumor, however, is preferably interpreted at present as a mammary carcinoma with features of a carcinoid tumor, because of an incomplete characterization of argyrophil granules in the tumor cells. Other tumors with argyrophil cells were examples basically of ordinarily featured invasive ductal carcinoma. In a search for the origin of these cells, 99 breasts with various noncancerous lesions were examined; however, these argyrophil cells were never detected in any component of these mammary tissues.

Adult↗
PubMed1983

Phospholipase A2 of chicken erythrocyte membranes.

Chicken erythrocytes have been found to have at least two kinds of phospholipase A2. The first is a soluble enzyme from the cytosole fraction and has no calcium sensitivity. The second can be extracted from the plasma membrane fraction with the nonionic detergent Triton X-100. In this study the membrane-bound enzyme was partially purified by affinity chromatography on phosphatidylcholine-Sepharose, and its specific activity was increased 1100-fold compared with that of the cell homogenate without nuclei. It has an optimum pH of 8.5 and required calcium for maximum activity. It showed the specificity for both phosphatidylcholine and phosphatidylethanolamine, but reacted preferentially on the former substrate. Analysis by concanavalin A-Sepharose affinity chromatography revealed that the membrane-bound phospholipase A2 was retained on the resin and could be eluted specifically with a haptenic sugar, methyl alpha-D-mannopyranoside. The enzyme seems to be either a concanavalin A-binding glycoprotein or a part of a complex with certain concanavalin A-binding glycoproteins.

Animals↗
PubMed1983

Induction of increased calcium uptake in liposomes having membrane proteins of chicken erythrocytes by S-adenosylmethionine.

Liposomes having membrane proteins of chicken erythrocytes were prepared and the effect of S-adenosylmethionine on 45Ca2+ uptake into the liposomes was investigated. S-Adenosylmethionine, a donor of methyl groups in enzymatic methylation, induced an increase of 45Ca2+ uptake into the proteoliposomes with membrane proteins but not into the liposomes without membrane proteins. Increased release of 45Ca2+ from the inside of the proteoliposomes was also induced by S-adenosylmethionine. These increases of uptake and release of 45Ca2+ were inhibited by S-adenosylhomocystein, an inhibitor of enzymatic methylation. Furthermore, membrane proteins from chicken erythrocytes showed protein and phospholipid methyltransferase activities. The uptake of other materials, 3-0-[methyl-3H]glucose, alpha-[1-14C]aminoisobutyric acid, 42K+ and 54Mn2+, into the proteoliposomes was not increased by S-adenosylmethionine. These results suggest that enzymatic methylation of membrane components may have an important role in the regulation of calcium transport in the chicken erythrocyte membrane and this regulation is rather specific for calcium.

Animals↗