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Biomedical subjects

S Fujimura

Publications and source records attributed to S Fujimura.

At least 37 records · Page 2Linked to original sources
PubMed2000

A novel nuclear phosphoprotein, GANP, is up-regulated in centrocytes of the germinal center and associated with MCM3, a protein essential for DNA replication.

Antigen (Ag) immunization induces formation of the germinal center (GC), with large, rapidly proliferating centroblasts in the dark zone, and small, nondividing centrocytes in the light zone. We identified a novel nuclear protein, GANP, that is up-regulated in centrocytes. We found that GANP was up-regulated in GC B cells of Peyer's patches in normal mice and in spleens from Ag-immunized mice. GANP-positive cells appeared in the light zone of the GC, with coexpression of the peanut agglutinin (PNA) (PNA)-positive B220-positive phenotype. The expression of GANP was strikingly correlated with GC formation because Bcl6-deficient mice did not show the up-regulation of GANP. GANP-positive cells were mostly surrounded by follicular dendritic cells. Stimulation with anti-micro and anti-CD40 induced up-regulation of ganp messenger RNA as well as GANP protein in B220-positive B cells in vitro. GANP is a 210-kd protein localized in both the cytoplasm and nuclei, with a homologous region to Map80 that is associated with MCM3, a protein essential for DNA replication. Remarkably, GANP is associated with MCM3 in B cells and MCM3 is also up-regulated in the GC area. These results suggest that the up-regulation of GANP might participate in the development of Ag-driven B cells in GCs through its interaction with MCM3.

Acetyltransferases↗
PubMed2000

Binding and utilization of myoglobin by Porphyromonas gingivalis.

Myoglobin was found to bind reversibly to the envelope of Porphyromonas gingivalis in a pH-dependent manner; the binding took place below neutral pHs of the incubation mixtures and myoglobin bound released from the envelope at high pHs. The amounts of myoglobin bound to 1 mg of the envelope at pH 5.0 per min under the presence of sufficient myoglobin were 1.4 microg. K(d) for the reaction at pH 5.0 was 2.2 x 10(-10) M. From the dot blot assay, myoglobin obviously bound to hemoglobin-binding protein (HbBP) of P. gingivalis, however, the amounts of myoglobin that bound to HbBP were half those of hemoglobin. One of the fractions, separated by gel filtration, of the digested materials of myoglobin by the detergent-solubilized envelope containing proteinases was found to support the growth of P. gingivalis in the iron source-depleted medium.

Bacterial Proteins↗
PubMed2000

Combined modality therapy including surgery for stage III small-cell lung cancer on the basis of the sensitivity assay in vitro.

Fifty-nine consecutive patients with clinical stage (cStage) I-III resectable small-cell lung cancer (SCLC) underwent surgery with adjuvant chemotherapy based on an in vitro sensitivity assay between April 1982 and March 1992. In 42 (71%) of these patients, a stable passage of cancer cells from resected specimens was possible and the sensitivity of these cultured SCLC cells to anticancer drugs was examined by the MTT method. In the sensitivity assay, vincristine (VCR) showed the most intense specific efficacy for SCLC, followed by cyclophosphamide (CPM) and cisplatin (CDDP). The 5-year survival rates for pathological stage (pStage) I, pStage II, and pStage III were 55%, 33%, and 23%, respectively. The 5-year survival of the patients with pStage III operated on in the first 5 years was 7% (1/14). On the other hand, 6 of the 16 pStage III patients (38%) operated on during the second 5-year period, who were generally treated with pre- and postoperative adjuvant chemotherapy combined with three drugs, survived over 5 years. In conclusion, these results suggest that combined modality therapy including surgery is necessary, and adjuvant chemotherapy combined with VCR, CPM, and CDDP may be useful in the treatment of Stage III SCLC disease, for the purpose of achieving a long-term survival with both a good performance status and quality of life for the patients.

Adult↗
PubMed2000

Long-term survival of a poor-risk octogenarian following wedge resection under VATS for small-cell lung cancer: report of a case.

We describe herein the case of an 81-year-old man who has remained disease-free for more than 3 years after undergoing a wedge resection of cStage I small-cell lung cancer (SCLC) under video-assisted thoracoscopic surgery (VATS), with no adjunct chemotherapy or radiotherapy. The patient had compromised pulmonary function and was a poor surgical risk. As he could not have endured a conventional lobectomy or intensive chemotherapy, a nonanatomical wedge resection of the area of lung involved by the primary tumor was carried out under VATS. Cancer cells from the resected tumor were cultured and the growth characteristics and sensitivity to 12 anticancer drugs were examined. The majority of primary cultured cells proliferated in a monolayer, like paving stones, resembling the growth pattern of non-small-cell carcinoma cells in vitro. The subcultured cells were resistant to most of the drugs, but showed weak sensitivity to cisplatin (CDDP), adriamycin (ADR), and vincristine (VCR). Therefore, the patient was discharged with no adjunct postoperative therapy and was followed up at an outpatient clinic. He has remained alive and disease-free for more than 3 years. Thus, we considered that performing wedge resection under VATS for a primary tumor could be appropriate treatment for selected patients with cStage I SCLC in a peripheral region, especially if they are elderly and a poor surgical risk.

Age Factors↗
PubMed2000

The significance of surgery for bulky N2 small-cell lung cancer: a clinical and in vitro analysis of long-term survivors.

Until recently, stage III small-cell lung cancer (SCLC) has not been considered an indication for surgical treatment, however, stable subculture has become possible in about 80% of the patients with SCLC in our hospital. Therefore, we have been performing surgery for all patients with cStage I-III resectable tumors and giving combined-modality therapy based on the sensitivity assay in vitro since April 1982. In the present study, we reviewed 30 consecutive patients with cStage III and pStage III SCLC, including 27 with N2 disease who underwent surgery between 1982 and 1992, 7 of whom (23%) survived disease-free for over 5 years. We examined the cell characteristics in vitro and the actual treatment of five patients with bulky N2 lesions, four of whom were long-term survivors and one of whom died 11 months after surgery, as controls for comparison with the long-term survivors. Based on the results of the cell characteristics in vitro, SCLC was determined to be a heterogeneous tumor. Thus, surgical excision of the primary tumor with adjuvant therapy might be necessary to achieve long-term survival and maintain good performance status, and to improve quality of life in patients with bulky N2 SCLC by eliminating drug-resistant tumor cells within the primary tumor.

Aged↗
PubMed2000

Allelic loss on 17p13 (TP53) and allelic loss on 3p21 in early squamous cell carcinoma of the lung.

Roentgenographically occult bronchogenic squamous cell carcinomas are early lung cancers that localize in the bronchial wall, and are thought to be a good model to elucidate the carcinogenesis of lung cancer. In the present study, we analyzed the incidence of allelic losses on chromosome regions 3p21 and 17p13 in 40 cases of roentgenographically occult bronchogenic squamous cell carcinomas, using three microsatellite dinucleotide polymorphic markers. We also investigated the relationship between such allelic loss and the clinicopathological findings of those cases. These chromosome regions showed frequent losses. Moreover, the incidence of loss on 17p13 increased gradually along with the advance of the depth of invasion, while the incidence of loss on 3p21 increased along with the advancing length of the longitudinal extension. These results suggested that these chromosome regions play different roles in lung cancer progression, i.e., the 3p21 chromosome region was related to the longitudinal extension of the carcinoma while the 17p13 (p53) region was related to the depth of invasion.

Carcinoma, Squamous Cell↗
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↗