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Biomedical subjects

N Koike

Publications and source records attributed to N Koike.

At least 19 recordsLinked to original sources

Invasive potentials of gastric carcinoma cell lines: role of alpha 2 and alpha 6 integrins in invasion.

The potentials of the two major histological types of gastric carcinoma to invade through extracellular matrices were studied with cell lines. We found that the invasive potential of intestinal-type carcinoma cells (MKN-28 and MKN-74) were higher than those of diffuse-type carcinoma cells (MKN-45 and KATO-III). To investigate whether the alpha 2 and alpha 6 integrin adhesion molecules are responsible for, or involved in carcinoma invasion. We further studied alpha 2 and alpha 6 expression patterns in these two types of cell line. Although fluorescence-activated cell sorting analysis revealed that all cells examined invariably expressed these integrin molecules, their expressional patterns were different among different cell lines. The intestinal-type carcinoma cells expressed integrins mainly along the cell-cell contact region, whereas the diffuse-type carcinoma cells showed a diffuse cytoplasmic pattern of integrin expression. Invasion by MKN-28, MKN-74 and MKN-45 cells through reconstituted basement membrane or type I collagen gel was significantly inhibited (P < 0.05) by 50 micrograms/ml anti-(alpha 2 integrin) or anti-(alpha 6 integrin) monoclonal antibodies. Our results suggest that active invasiveness is stronger in the intestinal-type than in the diffuse-type carcinoma cells and that alpha 2 and alpha 6 integrins play important roles in invasion of both types of gastric carcinoma cell lines.

Antigens, CD

Papillary carcinoma of the thyroid with exuberant nodular fasciitis-like stroma.

We describe a rare case of papillary carcinoma with extensive proliferation of stromal cells. The stromal cells were immunocytochemically positive for vimentin, alpha-smooth muscle actin and desmin, but negative for cytokeratin, epithelial membrane antigen, S-100, thyroglobulin and CD34. These results and the ultrastructure of the stromal cells, which exhibited the characteristics of both fibroblasts and smooth muscle cells, indicated an origin from myofibroblasts. We conclude that myofibroblastic proliferation may contribute to the stromal response in the slow growth of the papillary carcinoma.

Carcinoma, Papillary

Rapid and differential detection of two analogous enterotoxins of Vibrio cholerae and enterotoxigenic Escherichia coli by a modified enzyme-linked immunosorbent assay.

The principle of a novel ELISA (nylon-slip immuno-test, NSIT) was applied to the differential detection of two analogous enterotoxins, cholera toxin (CT) of Vibrio cholerae and heat-labile enterotoxin (LT) of enterotoxigenic Escherichia coli. The results obtained for CT and LT detection by a single test were sufficiently sensitive (87.9 and 100%) and specific (100 and 94.7%) in the differential detection test, when compared with the result of a colony hybridization test with DNA probes. The results suggest that the novel ELISA is applicable to the diagnosis of bacterial infections, by means of differential immunological detection of toxins in a single test.

Bacterial Toxins

Distribution of 1,25-dihydroxyvitamin D3[22-oxa] in vivo receptor binding in adult and developing skin.

Because of the therapeutic potential of oxacalcitriol (OCT, 22-oxa-dihydroxyvitamin D3), in vivo studies were conducted in adult and neonatal rats to identify the nuclear receptor sites of action in different tissues of the skin. Results were compared with those for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and oestradiol from previous studies. Autoradiograms were prepared from the dorsal skin of adult rats and the skin of the leg and head regions of neonatal rats 1 or 2 h after the injection of 3H-OCT. Specific nuclear concentrations of radioactivity, eliminated by competition with unlabelled OCT or 1,25(OH)2D3, were found in cells of the epidermis, outer hair sheath, hair bulb and sebaceous glands, but were absent or low in most fibroblasts of the dermis and hypodermis. The strongest nuclear binding of OCT was conspicuous in outer hair sheaths, where it was 1.5 to 3.2 times higher than in keratinocytes of the epidermis. The distribution of nuclear receptors for OCT was similar to that for 1,25(OH)2D3 but in part dissimilar to that for oestradiol. Oestradiol binding was found in the epidermis and hair sheaths, and also predominantly in fibroblasts of the dermis and hair dermal papillae. The results suggest genomic regulatory effects of OCT, similar to the effects of vitamin D, on proliferation, differentiation and activity of keratinocytes, growth and maintenance of hair, and proliferation and secretion of sebaceous glands. This may be utilized therapeutically, since OCT has a lower calcaemic effect than 1,25(OH)2D3.

Animals

Nuclear receptors for 1,25-dihydroxy-22-oxavitamin D3 (OCT) and 1,25-dihydroxyvitamin D3 in gastric gland neck mucous cells and gastrin enteroendocrine cells.

22-Oxacalcitriol the analog with low calcemic effect and the original hormone 1,25(OH)2 vitamin D3 were localized by autoradiography in mouse stomach at different time intervals after intravenous injection. Both compounds showed a distinct nuclear concentration and retention in neck mucous cells of gastric and pyloric glands, and in dispersed endocrine cells in the antrum region. When the nuclear binding of radioactively labelled compound was compared between gastric neck cells and duodenal absorptive cells, binding was low but sustained in neck cells. Peak uptake after the injection was between 8 and 12 h in neck cells, but between 15 min and 30 min in duodenal villous epithelium. In the duodenum, weak nuclear labelling appeared at 8 h and was undetectable at 12 h under the conditions of the experiment. Nuclear labelling of neck cells remained detectable at 12 h and even after 24 h, similarly for both OCT and 1,25(OH)2 vitamin D3. These results suggest that the stomach is an important target tissue for vitamin D and its analog OCT. Regulation of neck cell functions is suggested, such as proliferation and differentiation of surface epithelium and gastric gland epithelium, and neck cell secretion of acidic mucus. Regulation is also indicated of G-cell gastrin secretion associated with gastrin paracrine effects on parietal cell HCl and intrinsic factor secretion, chief cell pepsinogen secretion, neck cell proliferation, as well as endocrine effects on systemic calcium homeostasis.

Animals

[Effects of antiseptics against methicillin-resistant Staphylococcus aureus].

Various antiseptics, commonly used in hospital, were tested against methicillin-resistant Staphylococcus aureus (MRSA) at high concentrations (approximately 10(9) CFU/ml) and in short time exposures. The antiseptic solutions of 0.05% alkyldiaminoethylglycine hydrochloride, 0.05% benzalkonium chloride, 0.2% povidone-iodine gargle and 0.03% dominophen bromide produced 1,000 to 1/100,000 reduction after a 30 sec exposure. 7.5 % povidone-iodine scrub and 0.2% benzalkonium chloride in 83% ethanol were most effective, reducing MRSA under detection limits. (less than 10 CFU/ml) 0.05% chlorhexidine gluconate was less effective, producing no evident reduction even after 1 min of exposure. Though 0.2% povidone solution reduced MRSA under detection limits at 37, 24 hrs incubation, colonies of several strains were detected after 48 hrs extended incubation. This suggests the existence of strains resistant to the antiseptic solution of povidone-iodine. We recommend that the disinfection for these strains should be repeated short time disinfection, because repeated short time exposure (15 sec 2 times) of antiseptics was more effective than one long time exposure (30 sec once).

Anti-Infective Agents, Local

A novel method to chemically immobilize antibody on nylon and its application to the rapid and differential detection of two Vibrio parahaemolyticus toxins in a modified enzyme-linked immunosorbent assay.

A new method of chemically immobilizing antibody on nylon was developed. The method consists of serial treatments with HCl, polyethylene imine, and maleic anhydride methylvinyl ether copolymer, which resulted in the stable immobilization of sufficient amounts of antibodies on nylon. This principle was used to differentially detect two immunologically related but nonidentical hemolysins (thermostable direct hemolysin [TDH] and TDH-related hemolysin [TRH]) of Vibrio parahaemolyticus in a modified enzyme-linked immunosorbent assay with antibodies immobilized on nylon slips (NSIT). The results (dark purple color on nylon slips) were easily evaluated by the naked eye. The results with NSIT were compatible with those obtained by using DNA probes or a conventional bacterial culture test, not only with cultured specimens but also with clinical specimens (diarrheal stool samples). Furthermore, the NSIT differentially detected TDH and TRH in a single test. The antibody immobilization method developed here is applicable to various immunological detection methods and may improve their sensitivity and specificity.

Animals

Effect of sucrose monostearate, an emulsifier, on polyamine metabolism and phosphatidylinositol turnover in Ehrlich ascites tumor cells.

Sucrose esters of fatty acids have antitumor activity. We studied the effect of sucrose monostearate (SS), an emulsifier, on polyamine metabolism and phosphatidylinositol turnover in Ehrlich ascites tumor cells. The activity of ornithine decarboxylase (ODC) was increased in the cells by changing the medium. This increase in the activity was inhibited by adding sucrose stearate, but not sucrose or stearate to the medium. The activity of spermidine/spermine N1-acetyltransferase (SAT), a rate-limiting enzyme of polyamine biodegradation, was enhanced with the addition of SS in a time- and dose-dependent manner. The elevation of SAT activity was completely prevented when cycloheximide was added to the culture simultaneously. In in vitro studies, SS at various concentrations up to 1 mM hardly affected the activities of ODC or SAT. The incorporation of [3H]inositol into both fractions of inositolphospholipid and inositol phosphates was inhibited by SS. These results suggest that the perturbation of polyamine metabolism and phosphatidylinositol turnover is involved in the mechanism of antitumor activity of SS in Ehrlich ascites tumor cells.

Acetyltransferases

Efficacy of the Cytobrush method in aged patients.

To evaluate the efficacy of the Cytobrush method in aged patients, a comparative study between the Cytobrush smears and cotton swab smears from the uterine cervix was performed. Consecutive 319 cotton swab smears of the endocervix were attempted on aged patients (60-98 yr, average 77.5 yr) from 1987 to 1988 (A group). Subsequently 391 endocervical smears were attempted by the Cytobrush on aged patients (60-100 yr, average 76.9 yr) from 1988 to 1990 (B group). The Cytobrush method was more effective in the following two points: (1) The rate of insert-impossible case in B group (7.2%) was lower than A group (12.5%). (2) The rate of case containing endocervical columnar cells increased in B group (64.7%) compared with A group (47.7%). In contrast, benign epithelial fragments (BFs) were observed in 6.8% of A, in 28.4% of B group. In smears positive for squamous cancer, malignant epithelial fragments (MFs) were noted in 24.5% of A, and 55.1% of B group. Consequently, the differential diagnosis of MFs from BFs is of more importance on the Cytobrush smears of aged patients.

Aged

1,25-Dihydroxyvitamin D3 and 22-oxa-1,25-dihydroxyvitamin D3 in vivo nuclear receptor binding in developing bone during endochondral and intramembranous ossification.

Target cells for 3H-labeled 1 alpha, 25(OH)2 vitamin D3 [1,25(OH)2D3, vitamin D] and its analog 3H-labeled 22-oxa-1 alpha, 25(OH)2 vitamin D3 (OCT) have been identified during endochondral and intramembranous ossification in developing, undecalcified, unembedded bone, using thaw-mount autoradiography. Two-day-old neonatal rats were injected with [3H]1,25(OH)2D3 or [3H]OCT; after 2 h leg, spine, and head were frozen and sectioned. In the epiphyseal-metaphyseal region specific nuclear concentrations of [3H]1,25(OH)2D3 and [3H]OCT were observed in identical cell populations, being low in cells of the articular and resting zone, intermediate in the proliferating zone, and highest in hypertrophic chondrocytes and in osteoblasts and precursor cells. In the primary spongiosa intertrabecular spaces there were a large number of cells with nuclear labeling--probably osteoblasts and precursor cells. In contrast, in the secondary spongiosa intertrabecular spaces, apparent blood-forming cells were mostly unlabeled. Osteoblasts along bone spicules and compact bone in long bones, vertebrae, and head also showed strong nuclear labeling, as did cells of the periosteum. These data suggest that 1,25(OH)2D3 and OCT regulate development, differentiation, and activities of chondrocytes and osteoblasts, including differentiation of resting chondrocytes into proliferating and hypertrophic chondrocytes that involve "chondroclastic" enlargement of lacunae and "trans-differentiation" of surviving hypertrophic chondrocytes; differentiation of stroma cells into osteoblasts; and in periosteum and other regions of intramembranous ossification differentiation of precursor cells and osteoblasts. Nuclear receptor binding and their selective and hierarchical distribution during cell differentiation appear to correspond to multiple genomic effects toward growth, regeneration and repair. The findings indicate a physiological significance and therapeutic potential of 1,25(OH)2D3 and in particular of its less hypercalcemic analog OCT.

Animals

[Immunohistochemical study of VLA integrins in human gastric carcinoma].

Using an immunohistochemical technique, we investigated expression of collagen receptor VLA-2 integrin and laminin receptor VLA-6 integrin in human gastric carcinoma. The expression of VLA integrins was compared in carcinoma of each histologic type and invasion/growth pattern. VLA-2 and VLA-6 were expressed more weakly in undifferentiated carcinoma than in non-cancerous epithelium. Non-localized invasion was observed in 89% of undifferentiated carcinoma. In differentiated carcinoma, expression of VLA-2 was weak in the mucosal layer. In the submucosal layer, however, VLA-2 expression was significantly different according to the invasion/growth pattern (p < 0.01); weak expression of VLA-2 in the localized invasion type and strong expression of VLA-2 in the non-localized type. VLA-6 was strongly expressed in the mucosal and submucosal layers of the differentiated carcinoma, regardless of the invasion/growth pattern. The present study suggested that VLA-6 contributed to the histologic type and VLA-2 affected the invasion/growth pattern of the gastric carcinoma in varied manners according to the histologic type.

Carcinoma

Dependence of the thymidylate synthase inhibition rate on the interval after the last administration of tegafur in sigmoid colon cancer patients.

The thymidylate synthase (TS) inhibition rate was measured after tegafur (FT) administration (1.5 g/day, at least 10 days) in 7 sigmoid colon cancer patients. The TS inhibition rate decreased as the interval between the time of the last administration and the time of the tumor resection increased longer. This study provides basic data for considering methods of drug administration and assessment of modification, for example, by leucovorin.

Adenocarcinoma