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Biomedical subjects

S Fujimura

Publications and source records attributed to S Fujimura.

At least 91 records · Page 5Linked to original sources
PubMed1999

The establishment of sublines with opposite chemosensitivity from a patient with pulmonary large cell carcinoma and the implementation of treatment based on tumor heterogeneity.

Two sublines were established from the primary tumor of a patient with pulmonary large cell carcinoma. These two sublines had different growth characteristics in vitro and different tumor tissue structure in nude mice, and opposite drug sensitivities. Subline 1 was sensitive to a number of drugs, while its sensitivity to cisplatin (CDDP) was not very strong. In contrast, subline 2 was resistant to many drugs, but showed very strong sensitivity to CDDP. When the patient developed recurrence, he was first treated with CDDP-based chemotherapy based on the sensitivity of subline 2, followed by methotrexate-based treatment on the basis of sensitivity for subline 1. Complete remission (CR) was achieved after this alternating chemotherapy. To our knowledge, this is the first report of sublines with opposite sensitivity being established from the same tumor, achieving CR by the treatment of each subline.

Aged↗
PubMed1999

Effects of GABA on noradrenaline release and vasoconstriction induced by renal nerve stimulation in isolated perfused rat kidney.

We examined effects of gamma-aminobutyric acid (GABA) on vasoconstriction and noradrenaline (NA) release induced by electrical renal nerve stimulation (RNS) in the isolated pump-perfused rat kidney. RNS (1 and 2 Hz for 2.5 min each, 0.5-ms duration, supramaximal voltage) increased renal perfusion pressure (PP) and renal NA efflux. GABA (3, 10 and 100 microM) attenuated the RNS-induced increases in PP by 10-40% (P<0.01) and NA efflux by 10-30% (P<0.01). GABA did not affect exogenous NA (40 and 60 nM)-induced increases in PP. The selective GABA(B) agonist baclofen (3, 10 and 100 microM) also attenuated the RNS-induced increases in PP and NA efflux, whereas the RNS-induced responses were relatively resistant to the selective GABA(A) agonist muscimol (3, 10 and 100 microM). The selective GABA(B) antagonist 2-hydroxysaclofen (50 microM), but not the selective GABA(A) antagonist bicuculline (50 microM), abolished the inhibitory effects of GABA (10 microM) on the RNS-induced responses. The selective alpha2-adrenoceptor antagonist rauwolscine (10 nM) enhanced the RNS-induced responses. GABA (3, 10 and 100 microM) potently attenuated the RNS-induced increases in PP by 40-60% (P<0.01) and NA efflux by 20-50% (P<0.01) in the presence of rauwolscine. Prazosin (10 and 30 nM) suppressed the RNS-induced increases in PP by about 70-80%. Neither rauwolscine (10 nM) nor GABA (10 microM) suppressed the residual prazosin-resistant PP response. These results suggest that GABA suppresses sympathetic neurotransmitter release via presynaptic GABA(B) receptors, and thereby attenuates adrenergically induced vasoconstriction in the rat kidney.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed1999

Bilateral pneumothoraces with multiple bullae in a patient with asymptomatic bronchiolitis obliterans 10 years after bone marrow transplantation.

A 16-year-old boy developed bronchiolitis obliterans (BO) 10 years after BMT for myelodysplastic syndrome. Although the patient complained of almost no dyspnea on exertion, he had mild hypercapnea with a markedly reduced forced expiratory volume of 0.32 l. Chest X-rays showed occasional bilateral minimal pneumothoraces, which is in accordance with the existence of multiple small bullae found on the pleural surface at video-assisted thoracic surgery. Histologic examination of the biopsied lung revealed BO. This case indicates that BO in adolescence following BMT and possible chronic GVHD may be masked because of lung immaturity at BMT, and BO after BMT may be associated with multiple pleural bullae.

Adolescent↗
PubMed1999

Purification and amino acid sequence of brevilysin L6, a non-hemorrhagic metalloprotease from Agkistrodon halys brevicaudus venom.

A non-hemorrhagic proteinase, brevilysin L6 (L6), has been purified to homogeneity from Agkistrodon halys brevicaudus venom by gel filtration and DEAE-Toyopearl 650M chromatography. It is an acidic protein with an isoelectric point of 4.8, and its molecular mass was estimated to be 21.5 kDa by SDS-PAGE. The optimum pH of L6 was about 9. EDTA and o-phenanthroline inhibited the proteolytic activity, suggesting that L6 is a metalloprotease. Cysteine also inhibited the activity of L6, but glutathione did not. The protein was stable in the pH range of 5-8.5 and below 40 degreesC. Calcium ions had no effect on the proteolytic activity of L6 or on its thermal stability. The enzyme preferentially cleaved X-Leu, X-Phe, X-Val, and X-His bonds. L6 showed weak alpha-fibrinogenase activity. The complete amino acid sequence of L6 was also determined by manual Edman degradation. L6 is a non-glycosylated single-chain polypeptide consisting of 203 residues with an N-terminal pyroglutamic acid and a calculated molecular weight of 22,713 Da. Its entire sequence is highly homologous to those of other metalloproteases from various snake venoms. A zinc-binding motif, HEXXHXXGXXH, is located at residues 143-153 in the sequence of L6.

Agkistrodon↗
PubMed1999

A general method for rapid purification of soluble versions of glycosylphosphatidylinositol-anchored proteins expressed in insect cells: an application for human tissue-nonspecific alkaline phosphatase.

A soluble form of tissue-nonspecific alkaline phosphatase was purified to apparent homogeneity from the culture media of Sf9 cells which had been infected with recombinant baculoviruses encoding human tissue-nonspecific alkaline phosphatase (TNSALP). To facilitate purification, an oligonucleotide consisting of 6 tandem codons for histidine and a stop codon was engineered into the TNSALP cDNA. The molecular mass of the enzyme purified through a nickel-chelate column was estimated to be 54 kDa by sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis. That of the native enzyme was 90 kDa as estimated by gel filtration, indicating that the purified soluble TNSALP is dimeric. The enzyme was used for production of antibodies specific for human TNSALP. Immunoblotting analysis showed a single 80-kDa band in the cell homogenate prepared from Saos-2 (human osteosarcoma) cells. However, upon digestion with peptide: N-glycosidase F, the 80-kDa TNSALP of human origin and the soluble enzyme of insect origin migrated to the same position on SDS-polyacrylamide gel, indicating that the size difference between the two enzymes is ascribed to N-linked oligosaccharides. The antibodies prepared against the purified TNSALP were found to be useful also for immunoprecipitation and immunofluorescence studies.

Alkaline Phosphatase↗
PubMed1999

In vitro activity of HSR-903, a new oral quinolone, against bacteria causing respiratory infections.

The in vitro activity of HSR-903, an oral quinolone, against 196 recent clinical isolates of respiratory pathogens was evaluated. HSR-903 was 2 to 32 times more active than ofloxacin, ciprofloxacin, and sparfloxacin against Staphylococcus aureus, including methicillin-resistant strains, and Streptococcus pneumoniae and was at least as active as the other quinolones against gram-negative pathogens.

Anti-Infective Agents↗
PubMed1999

Impairment of transalveolar fluid transport and lung Na(+)-K(+)-ATPase function by hypoxia in rats.

We examined whether hypoxic exposure in vivo would influence transalveolar fluid transport in rats. We found a significant decrease in alveolar fluid clearance of the rats exposed to 10% oxygen for 48 h. Terbutaline did not stimulate alveolar fluid clearance, and alveolar fluid cAMP levels were lower than those determined in normoxia experiment. Hypoxia did not influence the alveolar fluid lactate dehydrogenase levels, Evans blue dye fluid-to-serum concentration ratio, or lung wet-to-dry weight ratio, indicating no significant change in the permeability of alveolar-capillary barrier. Histological examination showed no significant fluid accumulation into the interstitium and the alveolar space. Hypoxia did not reduce lung ATP content; however, we found significant decrease in Na(+)-K(+)-ATPase hydrolytic activity in lung tissue preparations and isolated alveolar type II cells. Our data indicate that hypoxic exposure in vivo impairs transalveolar fluid transport, and this impairment is related to the decrease in alveolar epithelial Na(+)-K(+)-ATPase hydrolytic activity but is not secondary to the alteration of cellular energy source.

Adenosine Triphosphate↗
PubMed1999

Prognostic value of nucleolar protein p120 in patients with resected lung adenocarcinoma.

PURPOSE: In this study we investigated the prognostic significance of proliferation-associated nucleolar protein p120 in primary resected lung adenocarcinoma because it reflects tumor growth fractions in vitro. PATIENTS AND METHODS: Expression levels of p120 in tumors were assessed by immunohistochemistry in 74 patients who underwent radical resection. With clinical follow-up data, the prognostic significance of p120 calculated by labeling indices was evaluated using the Cox proportional hazards model. RESULTS: p120 protein was clearly detected in nucleoli of adenocarcinoma cells. Its expression levels widely varied in each sample from 8.5% to 67. 2%, with a mean +/- SD of 35.2% +/- 15.1%. No significant correlation was found between expression levels of p120 and clinicopathologic factors. However, the expression levels of p120 were negatively correlated with the tumor doubling time calculated with retrospective chest roentgenograms. Using a cutoff value of 35% in the labeling index of p120, patients with high expression of p120 experienced early recurrence and shorter survival compared with those who had low expression of p120. Multivariate analysis showed that p120 served as an independent, as well as the strongest, prognostic factor for resected lung adenocarcinoma. CONCLUSION: This report provides the first evidence that expression levels of p120 in tumor tissues can be used as an independent and powerful prognostic marker for resected lung adenocarcinoma.

Adenocarcinoma↗
PubMed1999

Alpha-adrenergic blockade in preventing posttransplant edema of lung allograft.

Effect of alpha-adrenergic blockers on pulmonary edema in lung transplantation was studied with a rat model of syngeneic left lung transplantation. Prior to harvesting, 0.1 mg of Prazosin or 0.4 mg of Yohimbine was given to the donor. Pulmonary and systemic hemodynamics were measured under the right pulmonary arterial occlusion (RPAO) at different time points after grafting. Wet to dry weight ratio (W/D) of all transplants was also calculated. Same procedure was conducted in rats with normal and ischemic lung and in transplanted animals without any treatments. While RPAO did not increase W/D in normal lung with a significant elevation in pulmonary arterial pressure (PAP), both these values significantly increased in transplanted lung. Transplanted animals could not tolerate RPAO 24 hours after grafting, but were tolerable later than 48 hours with elevated W/D and PAP. On the contrary, animals given Prazosin or Yohimbine were all tolerable at 24 hours postsurgery. Yohimbine significantly improved W/D. Consequently, it was demonstrated that pulmonary edema of the graft reached its peak during first 24 to 48 hours after transplantation and was alleviated by the blockade of alpha-adrenergic receptor in the graft vessel.

Adrenergic alpha-Antagonists↗
PubMed1999

Stimulated neutrophils evoke signal transduction to increase vascular permeability in rat lungs.

The mechanisms by which stimulated neutrophils (PMNs) damage pulmonary vascular endothelium were investigated using twenty-four perfused lung preparations isolated from rats. We tested 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) and hemodynamics. To stimulate PMNs, they were gently agitated in a glass vial for 10 seconds. Perfusing lungs with the stimulated PMNs (stimulated group) elicited a 3-fold increase in the filtration coefficient as compared to lungs perfused with unstimulated cells (unstimulated group). This increase in filtration was completely blocked by preincubation of stimulated PMNs with CD18 monoclonal antibody (MoAb group). This increase in filtration coefficient was also completely blocked by GF109203X, a protein kinase C inhibitor (GF group). Pulmonary vascular resistance increased when the stimulated PMNs were injected to the isolated lungs. Although, preincubation of stimulated PMNs with CD18 MoAb successfully blocked and GF109203X partly blocked this increase in pulmonary vascular resistance. The accumulation of stimulated PMNs within the lungs, as assessed by myeloperoxidase (MPO) levels, was blocked by preincubation of stimulated PMNs with CD18 MoAb. However, GF109203X did not decrease MPO levels. These findings suggest that stimulated PMN-induced increases in pulmonary vascular filtration, resulted from endothelial cell injury caused by adhesion to the endothelial cells, evoke intracellular signaling within the endothelial cells.

Animals↗
PubMed1999

The significance of NSE and CEA as a differentiation marker for the cellular heterogeneity of small cell lung cancer.

Neuron-specific enolase (NSE) and carcinoembryonic antigen (CEA) levels in the culture supernatant of the 65 pulmonary carcinoma cell lines: Small cell lung cancer (SCLC) 18, large cell carcinoma 14, squamous cell carcinoma 14, adenocarcinoma 14 and adenosquamous cell carcinoma 5, were measured by a radioimmunoassay (RIA). The mean value of NSE was 30.8+/-22.4 ng/ml and 9.2+/-8.7 ng/ml in SCLC and non-SCLC, respectively. The mean value of CEA was 15.1+/-20.9 ng/ml and 26.6+/-72.3 ng/ml in SCLC and non-SCLC, respectively. A significant difference in NSE levels was obtained between SCLC cell lines and non-SCLC cell lines. In SCLC cell lines, a significant inverse proportional correlation was observed between NSE and CEA levels. The CEA production tended to be higher in cells with low levels of NSE than in those with high NSE production. With respect to correlation between marker production and growth characteristics of SCLC cells in vitro, significantly higher NSE and lower CEA levels were found in cells growing with floating colony or neurite like characteristics (classic cell type) than those in cells with epithelial or intermediate growth characteristics (variant cell type). A significant positive correlation between NSE levels and the survival periods was found in follow-up studies of 10 patients who underwent surgery with complete resection of the primary tumor. All of 4 long term survivors over 3 years after surgery had significantly high NSE and relatively low CEA producing tumors. The relationship of these markers to clinical status of the patient suggests that an analysis for correlation of NSE and CEA levels in SCLC patients may be useful to discriminate between a pure neuroendocrine SCLC tumor and a mixed small cell/large cell tumor, and in monitoring therapeutic effect and prognosis of each patient.

Adult↗
PubMed1999

Adenovirus-mediated delivery of the PTEN gene inhibits cell growth by induction of apoptosis in endometrial cancer.

PTEN, a gene encoding a dual specificity phosphatase, is frequently altered in endometrial carcinoma. Moreover, these alterations are observed even in atypical hyperplasia of the endometrium. This evidence suggests that mutation of PTEN is an early genetic alteration involved in endometrial carcinogenesis. Adenovirus-mediated gene transfer was carried out using Ishikawa 3 H 12 and RL95-2, the endometrial cancer cell lines with completely inactivated PTEN, together with endometrial cancer cell lines HEC1-A and KLE expressing wild-type PTEN as the control. The PTEN transgene significantly suppressed cell growth in vitro through induction of apoptosis in cells lacking wild-type PTEN. Furthermore, the ex vivo tumor formation by Ishikawa 3 H 12 cells was completely inhibited by the introduction of wild-type PTEN. However, neither regression nor progression was observed in inoculated tumors of either cell line by in vivo introduction of the PTEN gene. These results suggest that PTEN may be a good candidate for gene therapy in patients with endometrial carcinoma.

Adenoviridae↗
PubMed1999

[Experience with surgery for congenital esophago-bronchial fistula with esophageal diverticulum in adult].

A 65-year-old female was admitted into our department with complaint of bloody sputum. An upper G-I series examinations and thoracic CT demonstrated an esophago-bronchial fistula with diverticulum located between the mid-esophagus and right B6. Following postero-lateral thoracostomy, the fistula was surgically removed and right lower lobectomy was carried out. No inflammatory changes were found in the surrounding tissues of the fistula and the diverticulum. Histological examination revealed that the fistula wall contained squamous epithelium and muscularis mucosa. These results suggested that this case was congenital esophago-bronchial fistula categorized as Braimbridge type I.

Aged↗
PubMed1999

[Management of mycobacteriosis in general hospital without isolation ward for tuberculosis patients. Clinical study on pulmonary tuberculosis associated with lung cancer patients].

Sixteen of 758 lung cancer in patients (2.1%) were found to have coexisting pulmonary tuberculosis. Of the above 16 of 758 patients (fifteen men and one woman), 4 of 214 patients (1.9%) were found from 1988 to 1989, and 12 of 544 patients (2.2%) from 1991 to 1994. In six patients, pulmonary tuberculosis and lung cancer were found at the same time by clinical work up. In five cases each, pulmonary tuberculosis preceded lung cancer, and lung cancer preceded pulmonary tuberculosis, respectively. Ten patients had adenocarcinoma, 4 had squamous cell carcinoma, and one each had large cell carcinoma and small cell carcinoma, respectively. Five patients were in stage "II", one in "IIIa", two in "IIIb", and eight in "IV" of clinical stage of lung cancer. As regards extent of pulmonary tuberculosis, one patient was in category "II" of the classification of the Japanese Society for Tuberculosis, 13 were in "III", and two were in "IV". Among 544 lung cancer patients from 1991 to 1994, 9 of 151 patients (6.0%) with a past history of pulmonary tuberculosis, had active pulmonary tuberculosis, and 3 of 393 patients (0.8%) with no history of pulmonary tuberculosis, had active pulmonary tuberculosis (statistically significant; p < 0.005). Five smear-positive patients were transferred to a tuberculosis hospital or a tuberculosis ward, and the remaining 11 patients were treated in isolation in the ward where they were. The efficacy of anti-tuberculous chemotherapy was almost comparable to that in patients without lung cancer. However, prognosis was poor, in line with that of lung cancer. Main discussion was devoted to the reason why the incidence (in association with tuberculosis) of adenocarcinoma exceeded that of squamous cell carcinoma in our present study at variance with the studies of other investigators.

Adenocarcinoma↗
PubMed1999

[Investigation of postoperative death after lung resection for lung cancer caused by interstitial pneumonia].

We investigated interstitial pneumonia, one of the most severe postoperative acute complications of respiratory surgery. In sixteen years, from 1982 through 1997, 2,453 cases underwent thoracotomies caused by lung cancers, in our institute. There were 20 cases (0.79%) who died within 30 days after surgery (operative death). Six out of 20 cases died of interstitial pneumonia, one of the most frequent postoperative complications. We examined these six patients and 2 patients with postoperative interstitial pneumonia who died within 32 days. Preoperative lung function tests, laboratory data, chest CT and/or chest X-ray films cannot predict development of postoperative interstitial pneumonia. Those who acquired postoperative interstitial pneumonia had continuous high fever after surgery following reticular shadows on their chest X-ray and increase in LDH levels. We could not detect any characteristic viral infections. Although, they were treated by steroid, elastase inhibitor and/or immune suppressant, they died within 32 days. In conclusion, development of postoperative of interstitial pneumonia cannot be predicted from preoperative laboratory data and/or lung function tests.

Female↗
PubMed1999

Comparative analysis of HPLC profile of cytosolic thymidine kinase activity between hepatoma and regenerating liver in rat with reference to phosphorylation.

Thymidine kinase (TK) activity in rat hepatoma JB1 and AH136B was mainly due to cytosolic TK and was much higher than that in rat regenerating liver. Two forms of cytosolic TK, designated as TK-I and TK-II, were revealed in addition to mitochondrial TK in anion-exchange high performance liquid chromatography (HPLC) of the enzyme extract from hepatoma JB1. During incubation of the enzyme extract at 20 degrees C in the presence of phosphatase inhibitor NaF, TK-II activity remained while TK-I activity almost disappeared. Thus, TK-II appeared to be more stable than TK-I. In Western blot analysis, TK-II was much more phosphorylated and exhibiting higher specific activity than TK-I. Meanwhile, regenerating liver derived from the rat 24 h after partial hepatectomy showed only TK-I activity, which completely disappeared after incubation at 20 degrees C even in the presence of NaF. Consequently, the presence of TK-II might account for the higher TK activity in hepatomas than in regenerating liver.

Animals↗
PubMed1999

[A case report of double roentgenographically occult lung cancer revealed by postsurgical pathological study].

A 66-year-old man admitted to our hospital as a roentgenographically occult lung cancer (ROLC) detected by sputum cytology of class IV. A differential brushing of all branches of the bronchi was performed and squamous cell carcinoma was detected only from the right B8 segmental bronchus. Right lower lobectomy was performed and the microscopic findings of surgical specimen revealed the squamous cell carcinomas were seen at not only B8 bronchus but also B7 bronchus. The frequency of multicentricity of ROLC is reported to be high, and a differential bronchial brushing of all bronchi is a very powerful method to diagnose synchronous multiple lung cancer. However, we failed to detect a cancer lesion of B7 segmental bronchus in this case. Since, the outcomes of surgical treatments for either synchronous or metachronous multiple primary lung cancer are satisfactory, limited surgical treatments might be appropriate as an initial treatment for a ROLC.

Aged↗