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Biomedical subjects

M Fukuda

Publications and source records attributed to M Fukuda.

1,614 records · Page 90Linked to original sources

Cytologic findings in postpartum and postabortal smears.

A study was undertaken to evaluate the cytologic features of pregnancy-induced cell patterns (PIP) observed in postpartum and postabortal cervicovaginal smears. A total of 3,000 PIP were evaluated and studied by an indirect immunofluorescent technique using human chorionic gonadotropin (HCG). Three characteristic types of PIP were demonstrated. In type I PIP, the cells had a sheetlike arrangement with a fine chromatin pattern and were thought to be of decidual origin. Type II PIP were shed in clumps and had round nuclei, cytoplasmic vacuoles and coarse chromatin. They were thought to originate in the endometrium with the Arias-Stella reaction. Type III PIP were large and had large nuclei with marked atypism. They were thought to be cytotrophoblasts. Almost all of the type III PIP were positive with the anti-HCG stain. It is concluded that this classification and analysis is significant and could reduce the number of false-positive cytology reports on postpartum and postabortal smears.

Abortion, Spontaneous↗

Thymic lesions in chicken infected with infectious bursal disease virus.

Thymic lesions were investigated in specific-pathogen-free chickens infected with the highly virulent HPS-2 strain or virulent reference GBF-1 strain of infectious bursal disease virus (IBDV). Both viruses induced follicular lymphoid necrosis and depletion in the bursa, as well as thymic lesions. However, cortical lymphocyte condensation and depletion in the thymus were more prominent in the HPS-2 group than in the GBF-1 group. Electronmicroscopically, alterations of cortical lymphocytes were characterized by nuclear disintegration resembling apoptosis. Immunohistologically, the virus-antigen-positive epithelial reticular cells in the medulla were more extensive in the HPS-2 group. These results suggest that HPS-2 IBDV persists in the thymic medulla and that cortical lymphocyte depletion is caused by virus-induced apoptosis.

Animals↗

Evaluation of novel platinum complexes, inhibitors of topoisomerase I and II in non-small cell lung cancer (NSCLC) sublines resistant to cisplatin.

We determined the in vitro cytotoxicities of promising new platinum complexes, an inhibitor of topoisomerase I, and novel anthracycline derivatives, and examined using clonogenic assay whether these compounds are cross-resistant in CDDP-resistant sublines derived from human non-small cell lung cancer (NSCLC) cell lines. Cytotoxicities were evaluated by means of the relative antitumor activity (RAA = peak plasma concentration/IC50 values), which we reported previously as a model for predicting antitumor activity. Of the CDDP analogues tested, including carboplatin (CBDCA), [(glycolate-0,0') diammineplatinum (II) (254-S)], ormaplatin [tetrachloro-(d,1-trans)- 1,2-diaminocyclohexaneplatinum (IV) (OP)] and oxaliplatin [oxalato (trans-1-1,2-diaminocyclohexane) platinum (II) (1-OHP)], no agent showed superior antitumor activity compared to CDDP. ME2303 [7-O-(2,6-dideoxy-2-fluoro-alpha-L-talopyranosyl) adriamycinone-14-O -pimelate], a new anthracycline derivative, showed higher antitumor activity than adriamycin (ADM). The CDDPresistant sublines, PC-9/CDDP and PC-14/CDDP, were 18.3- and 7.7-fold more resistant to CDDP compared to the respective parent cell lines. The CDDP analogues were all cross-resistant to CDDP and the order of relative resistance values was CBDCA > 254-S > 1-OHP > OP for PC9/CDDP and 254-S > CBDCA > 1-OHP > OP for PC-14/CDDP. Although OP showed cross-resistance to CDDP, OP was the most active against the CDDP-resistant sublines with relative resistance values of 3.8 and 1.6 for PC-9/CDDP and PC-14/CDDP, respectively. ME2303 and CPT-11, [7-ethyl-10-(4-[1-piperidino]-1-piperidino) carbonyloxycamptothecin], an inhibitor of topoisomerase I, was active against CDDP-resistant human NSCLC cell lines. These results suggest that OP, ME2303 and CPT-11 could be active in patients with, NSCLC clinically resistant to CDDP.

Adenocarcinoma↗

Multidrug resistance-associated protein (MRP) gene expression in human lung cancer.

Multidrug resistance-associated protein (MRP) is a 190 kD transmembrane protein and a potentially important drug-transporter protein in human cancers. While the MRP gene is expressed in normal cells and tissues, the expression in solid tumors is not sufficiently determined. MRP and mdr1 mRNA expressions were examined in normal lung parenchyma and in tumor tissues from six small cell lung cancer (SCLC) patients who had received preoperative chemotherapy and eleven nonsmall cell lung cancer (NSCLC) patients. The reverse transcriptase polymerase chain reaction was used. Normal lung tissues and all SCLCs expressed abundant levels of MRP mRNA, while the NSCLCs expressed a wide range of levels from low to high. Most tumor tissues coexpressed both MRP and mdr1, but the levels of mdrl expression was low except in two SCLCs and one NSCLC. MRP is more likely than mdr1 to be one of the clinical multidrug resistance mechanisms found in lung cancer.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

The clinical role of MDR1 gene expression in human lung cancer.

Human P-glycoprotein (Pgp) encoded by the MDR1 gene confers multidrug resistance to cancer cells. The clinical role of MDR1/Pgp in lung cancer is not fully understood. A total of 87 lung cancer surgical tissue samples, including previously untreated 84 non-small-cell (NSCLC) and three small-cell lung carcinoma (SCLC), were analyzed for levels of MDR1 mRNA determined by Northern blotting and compared with MDR1-positive cell lines. Fifteen percent (13/87) of the tumors were positive for the MDR1 gene, but the level was low in all samples except in one adenocarcinoma which expressed a high level of MDR1. The gene expression in these tumors did not relate with any pathologic factors such as histologic type, pathologic stage and tumor size. The SCLC and only one of the 14 MDR1-negative NSCLC responded to adjuvant chemotherapy after surgery. The present results indicate that the MDR1 gene is not associated in NSCLC with tumor progression and drug resistance.

Blotting, Northern↗

Multidrug resistance-associated protein gene expression and drug sensitivity in human lung cancer cells.

Multidrug resistance-associated protein (MRP) mRNA expression and drug sensitivity in lung cancer cells were examined, and the effects of verapamil, a modulating agent for MRP, on drug sensitivity were also tested. Nine cell lines expressed various levels of MRP gene expression but not the MDR1 gene. The levels were higher in non-small cell carcinoma cells (NSCLC) than in small cell carcinoma cells (SCLC). Clear correlations between the MRP gene level and the sensitivity to etoposide (VP-16) and doxorubicin (Dox) were observed except for one cell line which highly expressed DNA topoisomerase II. Positive correlations between the MRP gene levels in three cell lines and the modulation effects of verapamil in VP-16, Dox, and vincristine were observed. The present results indicate that MRP probably confers intrinsic multidrug resistance in NSCLC rather than in SCLC.

ATP-Binding Cassette Transporters↗

Enhanced expression of metallothionein in human non-small-cell lung carcinomas following chemotherapy.

Metallothioneins (MTs) are induced by various stimuli and probably confer drug resistance in tumor cells in vitro. To investigate whether MT expression in lung cancer is induced by chemotherapy, ninety-seven surgical specimens from patients who had or not received chemotherapy containing cisplatin, were stained immunohistochemically for MT. In untreated tumors, 23% (15/64) of all tumors and 27% (15/56) of non-small-cell carcinoma (NSCLC) stained positive, while all eight small-cell carcinoma (SCLC) were negative. In treated tumors, 52% (17/33) of all tumors, 80% (12/15) of NSCLC and 28% (5/18) of SCLC stained positive. The proportion of positively-stained tumors was significantly higher in treated NSCLC compared with untreated NSCLC (P = 0.0005) and treated SCLC (P < 0.005). Our results indicate that MT expression increases following chemotherapy and that such expression may confer during resistance in lung cancer, especially NSCLC.

Antineoplastic Combined Chemotherapy Protocols↗

Calcium crystal deposition in the ligamentum flavum of the lumbar spine.

OBJECTIVE: To investigate the histological and immunohistochemical properties of the lumbar ligamentum flavum with calcium crystal deposition. METHODS: We examined the histological characteristics of the ligamentum flavum of the lumbar spine containing calcium deposits, obtained from 16 surgical cases with symptomatic lumbar spinal stenosis. Sections of the ligaments were also immunostained for elastase, chymotrypsin and S-100 protein, and examined by energy dispensive X-ray microanalysis and scanning electron microscopy. The results were compared with those of ligaments without calcium deposits. RESULTS: The elastic fibres of ligaments with calcium deposits showed marked degeneration (irregular arrangement and fragmentation of the fibre bundles) and nodular granulomatous lesions. Calcium crystal deposits were present in this area and in the nodular granulomatous areas. The calcified areas were surrounded by neutrophils and new small blood vessels. Immunostaining for elastase and chymotrypsin was positive in these areas, and S-100 protein-containing chondrocytes were detected around and within the calcified areas. Calcium pyrophosphate dihydrate crystals were identified in the calcified areas in all patients. CONCLUSION: Nodular degeneration of the elastic fibres of the ligament is probably caused by the action of proteolytic enzymes. Degeneration results in small granulomatous areas that form the nidus for calcium crystal deposition. Accumulated neutrophils, and S-100 protein-containing chondrocytes appear to precipitate the deposition of calcium crystals in the granulomatous lesions of the degenerated lumbar ligamentum flavum.

Adult↗

Lung resistance-related protein gene expression and drug sensitivity in human gastric and lung cancer cells.

Lung resistance-related protein (LRP) is the human major vault transporter protein and is suggested to confer anticancer drug resistance. We quantitated the level of LRP mRNA expression in 10 gastric and 14 lung cancer cell lines by RT-PCR, and examined the relationship between its level in these cells and their sensitivities to anticancer drugs. HT1080 fibrosarcoma cells were used as positive controls for LRP. LRP mRNA was expressed in all gastric and lung cancer lines, and its level in each cell type was less than two-fold that of HT1080 cells, except for two lung cancer lines. The correlation between the level of LRP mRNA expression and cisplatin sensitivity was significant in lung cancer lines (r = 0.762, P = 0.028), and borderline in gastric cancer lines (r = 0.631, P = 0.129). There was no correlation between the level of LRP mRNA expression and etoposide, doxorubicin, vincristine, or SN-38. Our results suggest that LRP is commonly expressed in gastric and lung cancers, and may confer their resistance to cisplatin.

ATP Binding Cassette Transporter, Subfamily B, Mem↗