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K Yanagihara

Publications and source records attributed to K Yanagihara.

At least 37 records · Page 2Linked to original sources
PubMed2001

Apoptosis and p53 status predict the efficacy of postoperative administration of UFT in non-small cell lung cancer.

To examine whether efficacy of postoperative oral administration of UFT, a 5-fluorouracil derivative chemotherapeutic agent, may be influenced by incidence of apoptosis (apoptosis index) or apoptosis-related gene status (p53 and bcl-2) of the tumour, a total of 162 patients with pathologic stage I non-small cell lung cancer were retrospectively reviewed. UFT was administrated postoperatively to 44 patients (UFT group), and not to the other 118 patients (Control group). For all patients, 5-year survival rate of the UFT group (79.9%) seemed higher than that of the Control group (69.8%), although without significant difference (P = 0.054). For patients with higher apoptotic index, 5-year survival rate of the UFT group (83.3%) was significantly higher than that of the Control group (67.6%, P = 0.039); for patients with lower apoptotic index, however, there was no difference in the prognosis between these two groups. Similarly, UFT was effective for patients without p53 aberrant expression (5-year survival rates: 95.2% for the UFT group and 74.3% for the Control group, P = 0.022), whereas not effective for patients with p53 aberrant expression. Bcl-2 status did not influence the efficacy of UFT. In conclusion, apoptotic index and p53 status are useful factors to predict the efficacy of postoperative adjuvant therapy using UFT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2001

A new variant neuropathic type of Gaucher's disease characterized by hydrocephalus, corneal opacities, deformed toes, and fibrous thickening of spleen and liver capsules.

We report a new variant type of Gaucher's disease characterized by hydrocephalus, corneal opacities, deformed toes, gastroesophageal reflux, and fibrous thickening of splenic and hepatic capsules. This patient had 1 D409H allele. He differed from other reported cases with a 1342G to C (D409H) homozygous mutation (onset at 4 months, no cardiac involvement until the age of 12 years, and massive hepatosplenomegaly with fibrous thickening of spleen and liver capsules). Enzyme replacement therapy was given for 4 years, resulting in an improvement of visceral and hematologic abnormalities but no neurologic improvement.

Biopsy↗
PubMed2001

Effects of parenterally administered ciprofloxacin in a murine model of pulmonary Pseudomonas aeruginosa infection mimicking ventilator-associated pneumonia.

BACKGROUND AND METHODS: We compared the bacteriological, pharmacological and histopathological effects of parenterally administered ciprofloxacin (CPFX) to those of imipenem/cilastatin (IMP/CS) and cefozopran (CZOP) in a murine model of mucoid Pseudomonas aeruginosa pneumonia mimicking ventilator-associated pneumonia. RESULTS: The minimum inhibitory concentrations (MICs) of CPFX, IMP and CZOP were 1.0, 1.0 and 4.0 mg/l, respectively. Treatment with CPFX resulted in a significant decrease in the number of viable bacteria [control, IMP/CS, CZOP and CPFX (mean +/- SEM): 5.02 +/- 0.20, 4.96 +/- 0.38, 5.44 +/- 0.13 and 3.27 +/- 0.02 log(10) colony-forming units lung, respectively]. Histopathological examination revealed that inflammatory changes in the CPFX-treated group were less marked than in other groups. Of the drugs analyzed, the pharmacokinetic parameters of area under the time-concentration curve (AUC)/MIC, AUC exceeding MIC and the time that lung concentrations of drug remained above the MIC were highest for CPFX. CONCLUSION: Our results suggest that parenterally administered ciprofloxacin is effective in ventilator-associated P. aeruginosa pneumonia.

Animals↗
PubMed2001

Lipopolysaccharide Induces Mucus Cell Metaplasia in Mouse Lung.

A murine model of lipopolysaccharide (LPS)-induced airway inflammation and epithelial cell phenotypic change, and the time courses of these events are described. A single intratracheal instillation of Pseudomonas aeruginosa LPS in mice resulted in massive recruitment of neutrophils to the lung 2 d after treatment as assessed by differential cell counts of the inflammatory cells in bronchoalveolar lavage fluid and histologic assessment of hematoxylin and eosin (H&E)-stained lung sections. The LPS-induced neutrophilic inflammation subsided substantially on Day 4 and essentially vanished by Day 7. Airway epithelial mucus cells were not detected by Alcian blue periodic acid-Schiff staining until Day 4 after LPS treatment and became more abundant in number as well as in mucus content on Day 7. The expression of Muc5ac messenger RNA (mRNA) as well as glycoprotein was enhanced on Day 2, peaked on Day 4, and decreased on Day 7, whereas enhanced expression of mucin core 2 beta6 N-acetylglucosaminyltransferase (C2GnT)-M mRNA was not detected until Day 4 and peaked on Day 7. The expression of C2GnT-L mRNA in the lung, a marker for activated leukocytes as well as mucus cells, peaked on Day 2 and remained moderately high until Day 7. C2GnT-L mRNA expression in LPS-treated lung correlated with the presence of neutrophils and the appearance of mucus cells in the airway epithelium. We conclude that mucus cell metaplasia and hyperplasia can be generated in mouse lungs with a single intratracheal instillation of LPS. In addition, C2GnT-M may serve as a marker for mucus cells in mouse lung. This LPS-induced mucus cell metaplasia and hyperplasia model should be useful for the study of Pseudomonas-induced airway mucus hypersecretory diseases.

Animals↗
PubMed2001

[Two-step tuberculin skin test in nurse students].

The tuberculin skin test (TST) was conducted in 243 nurse students (19.4 +/- 1.3 years old). The second TST were carried out in 240 students who did not show blister or necrosis in the first TST. The size of erythema was 16.5 +/- 9.4 mm in the first TST (T1) and 24.3 +/- 15.6 mm in the second TST (T2). The negative reactors, whose size of erythema was below 10 mm, were decreased from 53 to 25, whereas, the strong reactors, whose size of erythema was more than 30 mm, were increased from 11 to 71. The difference of the size of erythema (T2-T1) was 9.7 +/- 11.9 mm in the group I (190 students) who received the latest TST in junior high school, whereas, that was 0.5 +/- 9.2 mm in the group II (50 students) who received the latest TST 14 months before this study. T2-T1 in the group I was weakly correlated with T1. Twenty-four negative reactors received BCG vaccination, and 23 of them converted to positive. Seventy-one strong reactors were checked by chest X-ray, and none showed the findings of tuberculosis, and required the administration of anti-TB drug. The two-step TST is an essential means to know the baseline reactivity to TST, and to distinguish newly infected tuberculosis from booster phenomenon.

Adolescent↗
PubMed2001

Evaluation of angiogenesis in non-small cell lung cancer: comparison between anti-CD34 antibody and anti-CD105 antibody.

PURPOSE: Angiogenesis is an essential process in the progression of malignant tumors. Whereas pan-endothelial markers, such as CD34, are generally used in evaluation of angiogenesis, pan-endothelial antibodies react with not only "newly forming" vessels but also normal vessels just trapped within tumor tissues. It has been recently reported that anti-CD105 antibody preferentially reacts with "activated" endothelial cells in angiogenic tissues. Thus, the superiority of anti-CD105 monoclonal antibody (mAb) in evaluation of angiogenesis of non-small cell lung cancer (NSCLC) was assessed. EXPERIMENTAL DESIGN: A total of 236 patients with resected NSCLC were retrospectively reviewed. Intratumoral microvessel density (IMVD) was determined with an anti-CD34 mAb (CD34-IMVD) and with an anti-CD105 mAb (CD105-IMVD). RESULTS: The mean CD34-IMVD and CD105-IMVD were 179.9 and 41.6, respectively. Whereas CD34-IMVD was significantly correlated with the expression of vascular endothelial growth factor (P = 0.003), CD105-IMVD was more closely correlated with vascular endothelial growth factor expression (P < 0.001). The 5-year survival rate of the lower CD105-IMVD patients was 74.9%, significantly higher than that of the higher CD105-IMD patients (60.4%, P = 0.018). Whereas the 5-year survival rate of the lower CD34-IMVD patients seemed higher than that of the higher CD34-IMVD patients (63.7%), the difference did not reach a statistical significance (P = 0.137). Multivariate analysis confirmed that higher CD105-IMVD was a significant factor to predict poor prognosis (P = 0.029), whereas CD34-IMVD was not (P = 0.070). CONCLUSIONS: Anti-CD105 mAb proved to be superior to anti-CD34 mAb in evaluation of angiogenesis in NSCLC.

Aged↗
PubMed2000

Characterization of a mutant E-cadherin protein encoded by a mutant gene frequently seen in diffuse-type human gastric carcinoma.

The cell-cell adhesion molecule E-cadherin plays an essential role in the maintenance and function of epithelial tissues. Altered expression of E-cadherin has been implicated in tumor invasion. Analysis of mutations of the human E-cadherin gene in gastric carcinoma of the diffuse type has revealed that deletion of exon 8 or 9 in its cDNA appears to be predominant. In this study, we carried out structural and functional analyses of a mutant form of E-cadherin in a cell line, HSC45-M2, established from a human signet ring-cell carcinoma. Although immunohistochemical analysis showed that the mutant cadherin was localized at cell-cell contact sites as usually seen with the wild type, these cells did not form compact colonies. HSC45-M2 cells expressed aberrant E-cadherin with an m.w. larger than that of the wild type. In these cells, we found deletion of the exon 9-intron 9 boundary including the splicing donor site in E-cadherin genomic DNA. RT-PCR indicated 2 transcripts, which appeared to be caused by the splicing defect. Northern blotting, however, showed that the transcript lacking exon 9 was predominantly detected in these cells. The electrophoretic mobilities on SDS-PAGE of the mutant E-cadherin protein in HSC45-M2 cells and the protein expressed from cDNA lacking exon 9 appeared identical. Analysis of the amino-terminal region of the mutant E-cadherin protein revealed that the cadherin was capable of becoming a mature form by removal of its amino-terminal peptide. However, the mutant E-cadherin was susceptible to trypsinization in the presence of Ca(2+), which is not the case for wild-type E-cadherin, suggesting that the mutant E-cadherin frequently found in diffuse-type gastric carcinoma may have lost its Ca(2+)-binding ability, leading to disruption of the tight cell-cell association.

Animals↗
PubMed2000

Expression of polysialic acid and STX, a human polysialyltransferase, is correlated with tumor progression in non-small cell lung cancer.

Polysialic acid (PSA) is a carbohydrate composed of a linear homopolymer of alpha-2-8-linked sialic acid residues and is mainly attached to the neural cell adhesion molecule (NCAM). Because of the large negative charge of PSA, presence of PSA attenuates the adhesive property of NCAM and increases the cellular motility. PSA expression on NCAM is developmentally regulated, and PSA plays important roles in formation and remodeling of the neural system through regulation of the adhesive property of NCAM. Expression of the polysialated form of NCAM has been also demonstrated in some malignant tumors, such as Wilms' tumor and small cell lung cancer. Despite the possible importance as an onco-developmental antigen, however, significance of PSA expression in most malignant tumors has not been revealed. Therefore, PSA expression in non-small cell lung cancer was assessed in the present study. PSA was expressed only in 5 (20.8%) of 24 pathological stage I cases, whereas it was expressed in most stage IV cases (76.8%, 11 of 14 cases). PSA expression was correlated with nodal metastasis and distant metastasis, but not with local extent of the primary tumor. Next, expression of polysialyltransferase genes (PST and STX genes) which controlled formation of PSA, was examined. The PST gene was constantly expressed in both normal lung tissue and tumor tissue of all cases. In contrast, the STX gene was not expressed in normal lung tissue of any case, and STX gene expression in tumor tissue was closely correlated with tumor progression. The STX gene was expressed only in 1 (4.2%) of 24 stage I cases, whereas it was expressed in most stage IV cases (85.7%, 12 of 14 cases). These results suggested that the PSA and STX genes could be new targets of cancer therapy as well as important clinical markers.

Adult↗
PubMed2000

CD44 is a potential target of amplification within the 11p13 amplicon detected in gastric cancer cell lines.

Classical cytogenetic approaches have revealed many of the chromosomal aberrations that may occur in gastric cancers (GC), although few alterations of specific genes have been identified so far. Genes that affect progression of this disease need to be identified if clinicians are to achieve optimal management of patients with GC. As the first step toward the cloning of gene(s) that may be involved in gastric carcinogenesis, we examined 25 GC cell lines for aberrations in DNA copy number to detect chromosomal gains and losses, as well as gene amplifications, by comparative genomic hybridization (CGH). Our CGH study revealed high-level amplifications in chromosomal regions that had been well defined in GC but also in sites that had not, including 3p24, 5p15, 11p11.2-14, 13q34, 15q26, Xp24, and Xq26-28. The minimal common region at 11p13, within the 11p11.2-14 amplicon, harbors the CD44 gene. Northern and Western blot analyses showed that an alternatively spliced form of CD44, with variant exons 8-10 (CD44E), was overexpressed in all cell lines bearing the 11p13 amplicon. However, cell adhesion activity was no greater in these lines than in cell lines without amplifications at the CD44 locus, suggesting that the major property of upregulated CD44 in these cases might be to transduce signals critically associated with growth and proliferation of the tumor cells.

Blotting, Northern↗
PubMed2000

Antifungal activity of a new triazole, voriconazole (UK-109496), against clinical isolates of Aspergillus spp.

Voriconazole is a new triazole antifungal agent with potent activity against yeast and molds. We investigated the in-vitro activity of voriconazole compared with that of other antifungal agents against 50 clinical isolates of Aspergillus spp., measured by the National Committee for Clinical Laboratory Standards (NCCLS) reference method described in the M27-A document, and by an alamar blue colorimetric method. Voriconazole was the most potent agent against Aspergillus fumigatus (minimum inhibitory concentration [MIC]90, 0.5 mg/l) and Aspergillus niger (MIC90, 1.0 mg/l). Voriconazole was less active (MIC90, 1.0 mg/l) against Aspergillus flavus than itraconazole (MIC90, 0.5 mg/l). Voriconazole was more active than itraconazole against Aspergillus fumigatus and Aspergillus flavus by the alamar blue indicator method for the measurement of MIC. Based on these results, voriconazole has promising activity against commonly encountered isolates of Aspergillus spp., and its clinical usefulness should be established by further studies.

Antifungal Agents↗
PubMed2000

Polychlorinated biphenyls and metals in marine species from French Frigate Shoals, North Pacific Ocean.

Polychlorinated biphenyls (PCBs) and metals were analyzed in coral (Porites lobata), fish (Stegastes fasciolatus), crab (Grapsus tenuicrustatus), and sediment samples collected from Tern Island, and the reference samples from Trig and La Perouse Islands. All three islands are part of French Frigate Shoals, a national wildlife refuge in the North Pacific Ocean. Average concentrations of total PCBs ranged from 154 to 274 ng/g in the sediments, from 120 to 267 ng/g in the corals, from 387 to 4,500 ng/g in the crabs, and 1,340 to 46,000 ng/g, dry weight, in the fishes. High concentrations in marine species indicate there is PCB source(s) in French Frigate Shoals, especially Tern Island. Tetra- and pentachlorobiphenyls were 64-66% of the total PCB levels in the sediments, and they accounted for 57-65% of total PCBs in the corals. Penta- and hexachlorobiphenyls were 76-84% of total PCBs in the fishes, and they accounted for 79-85% in the crab samples. The sediment and coral were predominated by lower chlorinated PCB congeners, whereas the fish and crab bioaccumulated mainly higher chlorinated congeners. Selenium concentrations (16-23 microg/g) in sediments were much higher than some reported baseline values (0.4-2.5 microg/g). The average concentrations of arsenic, cadmium, lead, and selenium in the coral and fish were about equal to or less than those in the sediments. Concentrations of arsenic and cadmium in the crabs (49-51 and 3-4 microg/g, respectively) were approximately twofold of those in the sediments.

Animals↗
PubMed2000

Synergistic effect of ofloxacin and fluconazole against azole-resistant Candida albicans.

We investigated the combination effects of ofloxacin and fluconazole against azole-resistant Candida albicans strains in vitro and in vivo. Ofloxacin alone showed no efficacy against the azole-resistant C. albicans strain, C26. The in-vitro combination effects were evaluated by the checkerboard method, calculated as the fractional inhibitory concentration (FIC) index, but there was no synergistic effect of the combination. The activity of the drug efflux pump in the azole-resistant C. albicans strains was measured by intracellular rhodamine 6G concentration. When the cells were incubated with ofloxacin or grepafloxacin, the intracellular rhodamine 6G concentration was significantly increased in the azole-resistant C. albicans strain. In-vivo combination effects were evaluated in murine disseminated candidiasis. The survival of the mice was not prolonged, but counts of the yeast cells in the kidney and spleen were reduced following treatment with the combination of ofloxacin (20 mg/kg) and fluconazole (20 mg/kg). The combination of ofloxacin and fluconazole may represent an effective strategy to treat infections caused by azole-resistant C. albicans.

Anti-Infective Agents↗
PubMed2000

Biological features and preoperative evaluation of mediastinal nodal status in non-small cell lung cancer.

BACKGROUND: To examine whether biological features of primary tumor can help preoperative evaluation of mediastinal nodal status in non-small cell lung cancer. METHODS: A total of 450 patients who underwent tumor resection and mediastinal dissection were reviewed. p53 status and proliferative fraction (PI) were evaluated immunohistochemically. RESULTS: The accuracy of preoperative evaluation of mediastinal nodal status with computed tomography (CT) was 72.2%; mediastinal nodal metastases had not been revealed until operation in 59 patients (13.1%) (false-negative), and no metastasis was revealed in 66 patients (14.7%) although mediastinal nodal enlargement had been demonstrated by CT (false-positive). The number of false-negative patients was significantly larger when p53 aberrant expression was positive or when PI was higher. Combined with p53 status and PI, there were 27 false-negatives (24.1%) among patients with aberrant p53 expression and higher PI, whereas only two false-negatives (1.5%) among those with negative p53 expression and lower PI. CONCLUSIONS: Mediastinoscopy may be recommended for tumor showing aberrant p53 expression and higher PI, even when CT demonstrates no mediastinal nodal enlargement.

Aged↗
PubMed2000

Integrin alpha6beta4 as a suppressor and a predictive marker for peritoneal dissemination in human gastric cancer.

BACKGROUND & AIMS: Because alterations of integrin expression in cancers contribute to cancer cell biology, we analyzed the association between the potential for peritoneal dissemination and integrin expression. METHODS: The dissemination potential of 10 human gastric cancer cell lines in mice with severe combined immunodeficiency (SCID) was compared with the expression of various integrins. The relationship between integrin expression and peritoneal dissemination was also investigated in surgically resected gastric cancer cases. RESULTS: The level of integrin beta4 subunit expression was inversely correlated with dissemination potential. Introduction of a full-length complementary DNA (cDNA) for beta4 subunit into cancer cells showing negligible beta4 subunit expression markedly suppressed peritoneal dissemination and inhibition of endogenous integrin alpha6beta4 by introduction of a cytoplasmic domain-deleted beta4 subunit cDNA into cells showing high expression of beta4 subunit promoted peritoneal dissemination. Apoptosis, which was histologically evident in peritoneal nodules of SCID mice, was induced in the cells with high beta4 subunit expression by attachment to laminin and stimulation with growth factors in vitro. An immunohistochemical study of specimens from 120 cases of primary gastric cancer showed that patients with beta4 subunit-positive tumors exhibited peritoneal dissemination only infrequently (P < 0.0001) and had a better outcome (P < 0.01). CONCLUSIONS: These results indicate that integrin alpha6beta4 is both a suppressor and a predictive marker for peritoneal dissemination in gastric cancer.

Animals↗
PubMed2000

Surgery for non-small cell lung cancer: postoperative survival based on the revised tumor-node-metastasis classification and its time trend.

OBJECTIVE: To clarify results of surgery for non-small cell lung cancer (NSCLC) based on the new tumor-node-metastasis (TNM) classification revised in 1997 and its time trend. METHODS: A total of 921 patients operated from 1980-1994 were retrospectively reviewed. For analysis of time trend, they were grouped into three periods by the year of operation (period (1): 1980-1984, period (2): 1985-1989, and period (3): 1990-19-94). RESULTS: Concerning patients' characteristics, recent increase in the ratio of patients whose tumor was discovered at mass screening (31% in period (1), 40% in period (2), and 50% in period (3)), and increase in the ratio of p-stage IA patient (16, 20, and 29%, respectively) were marked. Decrease in the ratio of operation-related death and the ratio of exploratory thoracotomy was significant. Concerning level of operation, decrease in the ratio of pneumonectomy, increase in the ration of sublober resection and that of tracheal or bronchoplastic procedures were significant. Postoperative survival for all patients was significantly better in period (2) or (3) than that in period (1); no significant difference was demonstrated between period (2) and (3) (5-year survival rates: 35% for period (1), 56% for period (2), and 56% for period (3)). Stratified p-stage, improvement of postoperative survival in recent years was demonstrated in p-stage IIA, IIB, IIIA, and IIIB diseases. CONCLUSIONS: Postoperative survival for all NSCLC patients has been improved with significant increase of early-stage (p-stage IA) patients. Concerning level of resection, recent increase in patients who underwent sublobar resection and bronchoplastic procedures was marked.

Adult↗
PubMed2000

Pressurized fluid extraction for quantitative recovery of chloroacetanilide and nitrogen heterocyclic herbicides in soil.

Pressurized fluid extraction (PFE) is a new sample extraction method operated at elevated temperatures and pressures with liquid solvents. The use of PFE was investigated for the extraction of four Hawaiian clayey soils fortified with the selected chloroacetanilide and nitrogen heterocyclic herbicides Alachlor, Bromacil, Hexazinone, Metribuzin, and Tebuthiuron. The effects of operation temperature, pressure, flush volume, and static cycles on PFE performance were studied. Water was the most effective modifier of PFE for quantitative recoveries of the five herbicides in soils. The simple extraction method required pretreatment of the soil with 37.6% water and subsequent two-static-cycle extraction with a total of 32 mL of acetone at 1500 psi and 100 degrees C. Average recoveries of Alachlor, Bromacil, Hexazinone, Metribuzin, and Tebuthiuron ranged from 93 to 103% by the water-assisted PFE, compared with only 68-83% recoveries of the corresponding chemicals when no water was used. The extraction time and total organic solvent consumption were reduced from 18 h and 300 mL by Soxhlet to 22 min or less and 80 mL or less of organic solvent by PFE.

Acetamides↗
PubMed2000

Effects of epidermal growth factor, transferrin, and insulin on lipofection efficiency in human lung carcinoma cells.

Poor transfection efficiency is the major drawback of lipofection. We showed previously that addition of transferrin (TF) to Lipofectin enhanced the expression of a reporter gene in HeLa cells by 120-fold and achieved close to 100% transfection efficiency. The purpose of this study was to determine whether TF and other ligands could improve the efficiency of lipofection in lung carcinoma cells. Confluent A549, Calu3, and H292 cells were transfected for 18 hours with a plasmid DNA (pCMVlacZ) using Lipofectin plus TF, insulin, or epidermal growth factor as the vector. The transfected cells were assessed for transfection efficiency by beta-galactosidase activity (light units/microg protein) and the percentage of blue cells following 5-bromo-4-chloro-3-indolyl beta-D-galactopyranoside staining. Lipofectin supplemented with epidermal growth factor yielded the largest enhancement of lipofection efficiency (< or =23-fold over that by Lipofectin alone) in all three cell lines. Insulin significantly enhanced the lipofection efficiency in A549 and Calu3 cells but not in H292 cells, whereas TF showed significant lipofection efficiency-enhancing effect in Calu3 and H292 cells but not in A549 cells. The transfection efficiency correlated well with the amounts of DNA delivered to the nucleus as well as the amounts of the receptor. These results indicate that the gene delivery strategy employing ligand-facilitated lipofection can achieve high transfection efficiency in human lung carcinoma cells. In addition, enhancement of the expression of the receptor may be a possible strategy for increasing the efficiency of gene targeting.

Cell Nucleus↗