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Biomedical subjects

S Fujimura

Publications and source records attributed to S Fujimura.

At least 55 records · Page 3Linked to original sources
PubMed2000

Long-term survival of a patient with stage IV pulmonary large cell carcinoma achieved by combined-modality therapy: report of a case.

We describe herein the case of a 59-year-old-man with stage IV pulmonary large cell carcinoma and a giant brain metastasis, in whom two sublines with different growth characteristics and drug sensitivities in vitro were established from the primary tumor. Disease-free survival for more than 5 years after surgery was achieved by combined-modality therapy together with surgery to remove the primary tumor, radiation to the brain metastasis, and chemotherapy to presumed hematogenous dissemination. Subline 1 proliferated in a monolayer of epithelial-like cells, while subline 2 showed a floating colony pattern of proliferation, resembling the typical growth characteristics of small cell lung cancer (SCLC) cells in vitro. Subline 2 was sensitive to a number of drugs, namely, vincristine (VCR), cyclophosphamide (CPM), adriamycin (ADR), and cisplatin (CDDP), whereas subline 1 was resistant to many drugs. The patient was treated with a combination of 44 Gy of whole-brain irradiation and a number of cycles of chemotherapy comprised of ADR, VCR, and CPM, followed by CDDP, VCR, and CPM, based on the results of sensitivity testing of the subline 2 cells. As a result, the patient has been disease-free for more than 5 years postoperatively. In conclusion, this case report serves to demonstrate that meticulous combined-modality treatment taking tumor heterogeneity in human cancers into account may be necessary to achieve breakthroughs in current cancer therapy for advanced lung cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2000

Transition from squamous cell carcinoma to adenocarcinoma in adenosquamous carcinoma of the lung.

The heterogeneity of tumor cells is frequently observed in lung cancer, but the clonality of these cells has not yet been established. The distinct components of 12 lung adenosquamous carcinomas were compared by genetic alterations of p53 and K-ras, chromosomal abnormalities at 9p21 and 9q31-32, and immunohistochemical reactions. The immunoreactivity of p53 was consistent in both adenocarcinomatous and squamous cell carcinomatous components as well as in the transitional areas, retaining the morphological characteristics of the distinct components. The same p53 mutation was found in both components of each tumor with p53 overexpression. No K-ras mutations were detected in any of the tumors examined. Three of the four tumors with chromosomal abnormalities detected, one at 9p21 and two at 9q31-32, had coincident abnormalities between the distinct components, whereas one tumor deleted homozygously at 9p21 (D9S259) in the adenocarcinomatous component with loss of heterozygosity in the other component. The expression of squamous cell carcinoma-related antigen in adenocarcinomatous components was significantly higher than that of lung adenocarcinomas (57 +/- 5.8% vs. 1.0 +/- 0.5%, P < 0.0001), whereas Mucin 1 expression is less in these components (9.0 +/- 4.9% vs. 55 +/- 8.2%, P = 0.003). These results suggest monoclonal transition from squamous cell carcinoma to adenocarcinoma in lung adenosquamous carcinoma.

Adenocarcinoma↗
PubMed2000

Superoxide possibly produced in endothelial cells mediates the neutrophil-induced lung injury.

BACKGROUND: The mechanism by which stimulated neutrophils (polymorphonuclear leukocytes [PMNs]) damage pulmonary vascular endothelium was investigated. METHODS: The ability of unstimulated and mechanically stimulated PMNs to adhere to pulmonary endothelial cells and, thereby, alter pulmonary vascular permeability was tested. Each series was conducted on 6 rats. To stimulate PMNs, they were agitated gently in a glass vial for 10 seconds. RESULTS: Perfusing lungs with the stimulated PMNs elicited a fivefold increase in permeability compared with lungs perfused with the unstimulated cells. This increase in permeability was blocked completely by preincubation of stimulated PMNs with CD18 monoclonal antibody. This increase in permeability was also blocked completely by superoxide dismutase (SOD) or the xanthine oxidase (XO) inhibitor allopurinol. Pulmonary vascular hemodynamics were unaffected by any treatment protocol. The accumulation of stimulated PMNs within the lungs was not inhibited by SOD but was partially blocked by allopurinol. CONCLUSIONS: These findings suggest that stimulated PMN-induced increases in pulmonary vascular filtration resulted from endothelial cell injury caused by superoxide anion possibly generated by XO, exclusively present in the endothelial cells.

Animals↗
PubMed2000

Effects of EP4 solution and LPD solution vs Euro-Collins solution on Na(+)/K(+)-ATPase activity in rat alveolar type II cells and human alveolar epithelial cell line A549 cells.

BACKGROUND: Intact alveolar epithelial Na(+)/K(+)- adenosinetriphosphatase (ATPase) function is important in preventing alveolar fluid accumulation after lung transplantation. We examined whether the type of preservation solution used influences Na(+)/K(+)-ATPase activity in alveolar epithelial cells. METHODS: Rat alveolar type II cells were preserved with EP4, low-potassium dextran (LPD), or Euro-Collins solution at 7 degrees C for 5 and 20 hours. To assess cell toxicity, we measured cell viability and lactate dehydrogenase release. Na(+)/K(+)-ATPase activity was measured as ouabain-sensitive ATPase hydrolysis. We also examined the effect of terbutaline (10(-3) mol/liter) and dibutyryl cyclic adenosine monophosphate (dbcAMP) (10(-3) mol/liter) on Na(+)/K(+)-ATPase activity in A549 cells preserved for 5 hours. RESULTS: All solutions caused significant damage of rat alveolar type II cells at 20 hours. However, Na(+)/K(+)-ATPase activity was preserved at normal levels with EP4 and LPD over 20 hours. Terbutaline and dbcAMP significantly increased Na(+)/K(+)-ATPase activity in A549 cells preserved with EP4 and LPD solutions for 5 hours. However, we observed no activation in the cells preserved with Euro-Collins solution. We found no significant difference in intracellular cAMP levels after terbutaline challenge among the types of preservation solution. CONCLUSIONS: We conclude that extracellular-type solutions such as EP4 and LPD may be preferable for maintaining not only the basal activity but also the ability to activate Na(+)/K(+)-ATPase in response to beta-adrenergic agonists, in alveolar epithelial cells.

Animals↗
PubMed2000

Endothelial signal transduction system enhances neutrophil-induced pulmonary vascular permeability.

The mechanism by which stimulated polymorphonuclear leukocytes and neutrophils (PMNs) damage pulmonary vascular endothelium was investigated. The authors assessed the ability of unstimulated and mechanically stimulated PMNs to adhere to pulmonary endothelial cells and, thereby, alter pulmonary vascular permeability, measured as the pulmonary filtration coefficient (K) and haemodynamics. PMNs were stimulated by gentle agitation in a glass vial for 10 s. Perfusing lungs with the stimulated PMNs (n=6) resulted in significant accumulation of PMNs within the lungs, assessed by myeloperoxidase levels, and elicited a 4-fold increase in K and a 2-fold increase in pulmonary vascular resistance as compared to lungs perfused with unstimulated cells (n=6). The increases in K were completely blocked by GF109203X, a protein kinase C inhibitor (n=6); however, GF109203X only partially attenuated the increase in vascular resistance and had little effect on the accumulation of stimulated PMNs. An agonist of protein kinase C, phorbol myristate acetate, elicited dose dependent increases in both K and pulmonary vascular resistance even in the absence of PMNs (n=6). These findings indicate that the increases in pulmonary filtration coefficient and pulmonary vascular resistance induced by polymorphonuclear neutrophils result from endothelial cell injury mediated by activation of protein kinase C within the endothelial cells themselves.

Animals↗
PubMed2000

Results of surgical treatment of lung cancer involving the diaphragm.

OBJECTIVES: Lung cancers with diaphragmatic invasion are categorized as T3 lesions, but the surgical results have not been well known. We retrospectively surveyed patients with resected primary lung cancers involving the diaphragm. METHODS: A total of 16,771 patients underwent surgical resection for lung carcinoma between 1986 and 1995 at 31 institutions of the Lung Cancer Surgical Study Group in Japan. By investigating the database, we identified 63 patients (0. 38%) who underwent resection of T3 lung cancer invading the diaphragm. These patients constituted the study population, and their clinical and pathologic records were retrospectively analyzed. RESULTS: Tumor invasion to the diaphragm was diagnosed before operation only in 17 patients (27.0%). Complete resections of the primary lung tumors with the invaded diaphragm were performed in 55 patients (87.3%), of whom 26 had T3 N0 M0 diseases and 29 had T3 Nl-2 M0 diseases. The operative mortality was 1.6% in all patients. The 5-year survival of patients with complete resection was 22.6%, but there was no 4-year survivor in patients with incomplete resection (P =.024). The survivals of patients with completely resected T3 N0 M0 and T3 N1-2 M0 tumors were 28.3% and 18.1%, respectively (P =.013). In those patients, the depth of diaphragmatic involvement significantly affected the prognosis. The 5-year survival of the patients with shallow invasion (parietal pleura or subpleural tissue involvement) was 33.0%, whereas that of the patients with deep invasion (muscle or peritoneal infiltration) was 14.3% (P =.036). CONCLUSIONS: In selected patients with lung carcinoma and diaphragmatic invasion, combined resection of the lung and diaphragm offers the prospect of cure with acceptable mortality. However, primary lung tumors with diaphragmatic invasion, especially invasion of the muscle layer or deeper tissue, are not considered to be T3 lesions, because these cancers are generally technically resectable but oncologically almost incurable.

Aged↗
PubMed2000

Primary structure and autoproteolysis of brevilysin H6 from the venom of Gloydius halys brevicaudus.

The complete amino acid sequence of brevilysin H6 (H6), a zinc-protease isolated from Gloydius halys brevicaudus venom, was determined by a manual Edman degradation method. H6 has an amino-terminal pyroglutamic acid and consists of a total of 419 residues. An N-linked sugar chain is attached at Asn-181. The molecule is composed of three domains (metalloprotease, disintegrin-like and cysteine-rich domains), as commonly found in other high molecular mass metalloproteases from snake venoms. In the absence of calcium ions, H6 is autocatalytically degraded with a half-life of 47 min to give 29 and 45 kDa fragments, which correspond to residues 208-419 and 99-419 of H6, respectively. Thus, the autoproteolysis seemed to start from the cleavage of either the Leu(98)-Leu(99) or Asp(207)-Ile(208) bond. Calcium ions suppressed both the formation of the 45 kDa fragment and the rate of autoproteolysis. Calcium ions also contributed to the stability of H6 against pH, heating, urea and cysteine. More than twenty-five peptide bonds adjacent to hydrophobic residues in the metalloprotease domain were progressively cleaved during the autoproteolysis.

Amino Acid Sequence↗
PubMed2000

Difference in the effects of low temperatures on the tension of human pulmonary artery and vein ring segments.

BACKGROUND: Although limited data suggest that pulmonary flushing with organ preservation solutions should not be performed at too low temperatures, the influence of temperature on pulmonary vascular tone is unclear. OBJECTIVE: The purpose of this study was to examine the effect of low temperatures of the tension of human pulmonary artery and vein ring segments and the vascular resistance of perfused rat lungs. METHODS: 5 sets of human pulmonary artery and vein ring segments were suspended from a force displacement transducer at 37, 24 and 8 degrees C, and the effect of 30 mM K(+) on the tension was monitored. The effect of 30 mM K(+) on vascular resistance was also examined at low temperatures in 5 perfused rat lungs. RESULTS: Pulmonary artery segments dilated at 24 degrees C, and more significant vasodilatation was observed at 8 degrees C. In contrast, there was a significant constriction of pulmonary veins at 8 degrees C. Vasoconstriction induced by 30 mM K(+) at 37 degrees C was significantly inhibited at low temperatures in both pulmonary arteries and veins. In rat lungs, perfusion at 8 degrees C caused a significant increase in pulmonary vascular resistance, even though no further increase was observed in the presence of 30 mM K(+). CONCLUSIONS: Our data indicate that pulmonary arteries dilate and the veins constrict at 8 degrees C and may increase pulmonary vascular resistance. We conclude that the different effect of low temperatures between pulmonary arteries and veins may explain why pulmonary vascular flushing with organ preservation solutions at room temperature is more satisfactory.

Adult↗
PubMed2000

Infiltration of CD8+ T cells in non-small cell lung cancer is associated with dedifferentiation of cancer cells, but not with prognosis.

CD8+ T cells infiltrating within cancer cell nests in human colorectal cancer were associated with a favorable patients' survival, suggesting the presence of anti-tumor immunity. The present study was designed to examine this concept in non-small cell lung cancer (NSCLC) by a retrospective analysis of 128 surgically resected cases. Immunohistochemical analysis showed that the number of CD8+ T cells within cancer cell nests in NSCLC was related to the histological subtype (large cell carcinoma or squamous cell carcinoma > adenocarcinoma) and the degree of dedifferentiation (undifferentiated type > differentiated type). In contrast to colorectal cancer, the number of CD8+ T cells in NSCLC had no statistically significant impact on the patients' survival. The present study demonstrated that the degree of infiltration of CD8+ T cells within cancer cell nests is dependent on the dedifferentiation of cancer cells in NSCLC, which could be one of the important aspects for the study of tumor immunity.

Adenocarcinoma↗
PubMed2000

Differences in TNF-alpha producing activity from murine peritoneal macrophages induced by lipopolysaccharides of Prevotella heparinolytica and Porphyromonas gingivalis.

We compared the effects of LPSs from P. gingivalis and P. heparinolytica on the induction of tumor necrosis factor-alpha (TNF-alpha) production by murine peritoneal macrophages. The lipopolysaccharide (LPS) preparation from P. gingivalis showed a typical ladder pattern in SDS-PAGE, whereas that from P. heparinolytica formed several stained bands without a ladder pattern. When the macrophages from C3H/HeJ mice were incubated with P. gingivalis LPS, the level of TNF-alpha released in the culture supernatants was significantly higher than that with P. heparinolytica. All tested reagents except genistein strongly inhibited the production of TNF-alpha by the macrophages after induction by either LPS. These results suggested the following possibilities, i) the induction level of TNF-alpha by P. heparinolytica is similar to that of Salmonella minnesota, ii) tyrosine phosphorylation is not the only pathway for the TNF-alpha production induced by these LPSs, iii) different regulatory mechanisms are involved in TNF-alpha production in P. gingivalis LPS stimulated and P. heparinolytica LPS stimulated cells.

Animals↗
PubMed2000

MDM2 expression is associated with progress of disease and WAF1 expression in resected lung cancer.

Although MDM2, p21/WAF1, and p53 are considered as regulating each other based on in vitro studies, the relation in human lung cancer is not fully understood. The expressions of these proteins were examined immunohistochemically in 112 resected non-small cell lung cancer specimens and the correlation between them were analyzed. MDM2 was expressed in 45% of all lung cancers. In advanced stage, MDM2-positive cases were observed more frequently than in early stage, showing significant difference. No significant difference was observed in the prognosis of the patients regardless of the expression of any protein. Although no correlation was observed between MDM2 expression and p53 expression, or between p21/WAF1 expression and p53 expression, MDM2 expression was strongly related with p21/WAF1 expression. Therefore, MDM2 expression may relate to the progress of the stage of lung cancer, and MDM2 expression and p21/WAF1 expression may be associated not through the p53-related pathway.

Adenocarcinoma↗
PubMed2000

Regulation of the activity and polymerization status of recombinant human cytosolic thymidine kinase by thiols and ATP.

The cDNA clone encoding human thymidine kinase (hTK), was expressed in E. coli using a prokaryotic expression vector, pKK 223-3. The kinetics of the recombinant hTK (rhTK) were similar to those of cytosolic TK but not of mitochondrial TK. rhTK was highly purified in the presence of either ATP or dithiothreitol (DTT). The specific activity of rhTK purified in the presence of ATP [rhTK(ATP)] was lower than that of rhTK purified in the presence of DTT [rhTK(DTT)]. Activity of the purified rhTK(ATP) was enhanced by addition of thiols including DTT, cysteine, homocysteine and beta-mercaptoethanol but inhibited by various sulfhydryl reagents such as 5,5'-dithio-bis(2-nitrobenzoic acid). Hence, it was suggested that rhTK is a thiol-type enzyme. Apparent Mr of purified rhTK(ATP) was 100 kDa, which corresponds to the size of a tetramer (25 kDa subunit), while that of purified rhTK(DTT) was 50 kDa, the size of a dimer. The tetramer form of rhTK(ATP) was converted to the dimer by replacement of ATP by DTT. On the other hand, the dimer form of rhTK(DTT) was converted to the tetramer by addition of ATP. Thus, the catalytic activity of human cytosolic TK might be regulated by thiols as well as ATP via its polymerization status.

Adenosine Triphosphate↗
PubMed2000

[An office technique for myringoplasty without the use of fibrin glue].

A simple method for office closure of eardrum perforation using an atero-collagen graft used for dermal defects (Terdermis) without fibrin glue was developed. Eardrum perforations were successfully closed in 71.4% of all cases (63 ears) after the initial treatment. Neither skin incision nor the use of temporal fascial grafts was necessary in this method. The merit of the method is that there is no possibility of blood infection because no blood materials are used.

Adolescent↗
PubMed2000

[Assessment of systematic nodal dissection by VATS lobectomy for lung cancer].

The feasibility of the complete systematic nodal dissection by the video-assisted thoracic surgery was prospectively assessed in 22 cases of clinical stage I lung cancer (16 right, 6 left cases). Resection of the designated lobe with the mediastinal lymph node dissection was carried out by the small thoracotomy with the aid of the thoracoscope, followed by the standard surgery to verify the completeness of systematic nodal dissection. Although residual lymph nodes were found in 14 of 22 cases, the residual rate was 2.9% and 2.7% by the number and 2.3% and 2.1% by the weight in right and left cases, respectively. Average time and hemorrhage for performing the procedure were 196 minutes, 216.7 minutes and 157.5 g, 145 g in right and left cases, respectively. As a consequence, sufficient systematic nodal dissection in lung cancer was suggested to be feasible by VATS lobectomy.

Humans↗
PubMed2000

[A case of right B2 hillar lung cancer treated by sleeve segmentectomy].

A 47-year-old male, a heavy smoker, was referred to our hospital after Class IV was detected by screening of sputum cytology. His chest X-ray film showed no abnormalities, but bronchoscopy revealed a small nodular lesion at the orifice of right B2. Squamous cell carcinoma was diagnosed by transbronchial biopsy. The clinical stage was I (T1N0M0), and S2 sleeve segmentectomy with lymph node dissection (R 2 b) was performed. The pathological stage was I (T1N0M0), and it was confirmed as early hilar lung cancer. There were no post operative complications and he is well without any evidence of recurrence 5 months after surgery. It may well be considered that this segmental bronchoplastic procedure is useful for cases with early stage squamous cell carcinoma of the segmental bronchus to preserve pulmonary function.

Carcinoma, Squamous Cell↗
PubMed2000

[Strategy of treatment for roentgenographically occult lung cancer].

Roentgenographically occult bronchogenic squamous cell carcinomas(ROCs) are very small hilar type lung cancer that grow superficially and localize mainly in the bronchial wall, and these patients are expected to have an excellent prognosis after resection. When a ROC is limited within bronchoscopic visibility and less than 10 mm in longitudinal extension and its bronchoscopic findings are slight thickening and flat or wavelet, the tumor is a good candidate for photodynamic therapy. When a ROC is limited within bronchoscopic visibility, the tumor is a good candidate for segmentectomy with curative intent. The tumor invading beyond bronchial wall and/or nodal involvement should be treated by standard operation.

Bronchoscopy↗