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Biomedical subjects

S Fujimura

Publications and source records attributed to S Fujimura.

At least 73 records · Page 4Linked to original sources

Effects of intraalveolar oxygen concentration on alveolar fluid absorption and metabolism in isolated rat lungs.

We evaluated the effects of intraalveolar oxygen concentration on alveolar fluid absorption and metabolism in isolated rat lungs. Alveolar fluid absorption was determined by measuring increase in albumin concentration in the instillate solution during 2 h of incubation. Oxidative phosphorylation was assessed by gas analysis of the solution. Glycolysis was assessed by determining glucose escape and lactate release in the solution. We found that alveolar fluid absorption did not change under hyperoxic and hypoxic experimental environments (range 100-10% oxygen). Glycolysis was reduced under hyperoxia and stimulated under hypoxia, however, lung ATP content did not change. When oxidative phosphorylation was inhibited by NaCN, both alveolar fluid absorption and lung ATP content were reduced. Our data indicate that isolated rat lungs maintain optimal energy production for alveolar fluid absorption by stimulating glycolysis, even though glycolysis alone is not enough. We conclude that alveolar fluid absorption determined in isolated rat lungs is not influenced by intraalveolar oxygen concentration in the range above 10% oxygen.

Adenosine Triphosphate↗

Five-year survivors with resected pN2 nonsmall cell lung carcinoma.

BACKGROUND: Some patients with resected pN2 lung carcinoma were long term survivors. To determine appropriate therapeutic modalities for the selected patients, the clinicopathologic characteristics of these patients were examined using the actual number of survivors rather than the cumulative survival rate because the cumulative survival rate occasionally is confounded due to patients with short follow-up periods. METHODS: Between 1981-1990, 178 patients with pN2 nonsmall cell lung carcinoma underwent complete resection with systemic lymph node dissection. The ratios of 5-year survivors to all patients in groups with several clinicopathologic factors were compared. RESULTS: Gender, the side that was operated on, location of the tumor, histologic type, or surgical procedure were not related to the ratio of 5-year survivors. However, T classification, skip metastasis, and the number of levels involved were associated with the ratio significantly. The authors also found that the location of the involved lymph node(s) affected the ratio. CONCLUSIONS: Even in the presence of pN2 disease, lung carcinoma patients with T1 tumors, skip metastasis, or single level mediastinal lymph node involvement, especially Level 4, Level 5, or Level 6 lymph nodes, had a relatively favorable prognosis and may be candidates for primary resection.

Carcinoma, Non-Small-Cell Lung↗

Transalveolar fluid absorption ability in rat lungs preserved with Euro-Collins solution and EP4 solution.

BACKGROUND: Pulmonary reimplantation response, presenting lung edema, is a major obstacle of lung transplantation. Transalveolar fluid absorption mechanism, regulated by active transalveolar Na+ transport via Na+ channel and Na+-K+-ATPase, is considered to be essential for resolution of lung edema. We investigated the effect of lung preservation on this fluid transport mechanism. METHODS: The rat lungs were flushed and preserved with either EP4 solution (EP4) or Euro-Collins solution (EC). First, we determined the basal transalveolar fluid movement by calculating alveolar fluid clearance (AFC) after pulmonary flushing, 24- and 72-hr preservation. Then, we assessed the effects of Na+ channel blocker, amiloride, and Na+-K+-ATPase inhibitor, ouabain, on AFC after 24-hr preservation. We further measured lung ATP content and Na+-K+-ATPase activity after 24-hr preservation to evaluate cellular metabolism and enzymatic activity during preservation. RESULTS: We found that the lungs preserved with EC showed significantly lower AFC and less inhibitory effects of both blockers than with EP4 after 24-hr preservation. Na+-K+-ATPase activity was significantly lower with EC than with EP4, even though lung ATP content was not affected by preservation solution. CONCLUSIONS: EP4 preservation provides a better environment for maintaining transalveolar fluid absorption mechanism than EC preservation. Therefore, lung preservation with EP4 may ensure more reliable ability in resolving pulmonary edema.

Adenosine Triphosphate↗

Superoxide anion mediates pulmonary vascular permeability caused by neutrophils in cardiopulmonary bypass.

During cardiopulmonary bypass (CPB), neutrophils (PMNs) may be stimulated by shear stress which could contribute to the pulmonary injury that occurs after CPB. To elucidate whether mechanically stimulated PMNs increase pulmonary vascular permeability, measured as the pulmonary filtration coefficient (K) and pulmonary vascular resistance, and to elucidate whether superoxide anion mediates this increase, we assessed the effects of stimulated and unstimulated PMNs, and of superoxide dismutase (SOD) on K and resistance in isolated perfused lungs from Sprague-Dawley rats. PMNs were stimulated by gentle agitation in a glass vial for 10 s. Lungs perfused with the stimulated PMNs, being the stimulated group (n = 6), elicited a 5-fold increase in the filtration coefficient compared with lungs perfused with unstimulated cells, being the unstimulated group (n = 6). This increase in filtration was completely blocked by the preincubation of stimulated PMNs with CD18 monoclonal antibody, being the Ab group (n = 6), and also by superoxide dismutase, being the SOD group (n = 6). Pulmonary vascular resistance was not increased by stimulated PMNs, and the accumulation of stimulated PMNs was not blocked by SOD. These findings suggest that stimulated PMNs increase K and that superoxide anion may injure the pulmonary vascular endothelial cells.

Analysis of Variance↗

Left sleeve pneumonectomy performed through a clamshell incision with extracorporeal membrane oxygenation for bronchogenic carcinoma: report of two cases.

We report herein the cases of two patients with bronchial gland carcinomas in the left main bronchus who were successfully treated by left sleeve pneumonectomy performed through a clamshell incision. Adequate oxygenation during pathological examination of tumor invasion at the bronchial stumps and the tracheobronchial anastomoses was achieved by extracorporeal membrane oxygenation (ECMO) in both patients. Tracheobronchial anastomosis was relatively easy to perform in the excellent operative field achieved by this method. The postoperative courses of both patients were uneventful, although they developed temporary pulmonary edema that was effectively controlled by mechanical ventilation and appropriate diuresis. The procedure presented in this paper is considered to be a safe and effective method of performing left sleeve pneumonectomy.

Adult↗

Successful resection of endotracheal papillary adenocarcinoma by endoscopic electrosurgery using a new snare: report of a case.

We report herein the rare case of a patient with endotracheal papillary adenocarcinoma of the goblet cell type. The tumor existed in the upper trachea, obstructing 95% of the airway, and prompt palliation was required. Endotracheal polypectomy was successfully performed in this patient using electrosurgery with a new snare designed for the respiratory tract. The procedure took only a few minutes and the dyspnea was relieved promptly without any complications. The alternative techniques for palliation of bronchial stenosis are also discussed.

Adenocarcinoma, Papillary↗

The marked anticancer effect of combined VCR, MTX, and indomethacin against drug-resistant recurrent small cell lung carcinoma after conventional chemotherapy: report of a case.

In a previous study, we discovered that indomethacin was an effective modulator of the sensitivity of pulmonary carcinoma cells to vincristine (VCR), methotrexate (MTX), adriamycin (ADR), and etoposide (VP-16). We describe herein the case of a 61-year-old-man with multiple brain, lung, liver, and bone metastases from small cell lung carcinoma (SCLC) that recurred after intensive chemotherapy, who showed no signs of remission following conventional chemotherapy. The general condition of the patient deteriorated until he required morphine sulfate to control his severe diffuse pain. In an attempt to improve this patient's quality of life (QOL), he was discharged from hospital and treated at the outpatient clinic with modulation therapy using indomethacin as an anodyne instead of morphine sulfate. Signs of almost complete remission to only one cycle of combination therapy with VCR, MTX, and indomethacin were observed without any obvious adverse effects. This case report serves to demonstrate that modulation therapy combined with VCR, MTX, and indomethacin may be useful in the treatment of patients with drug-resistant recurrent SCLC.

Antineoplastic Combined Chemotherapy Protocols↗

Involvement of the #12u lymph nodes around the upper lobe bronchi in patients with lung cancer of the right middle lobe, right lower lobe, or left lower lobe.

In Japan, the lymph nodes around the upper lobe bronchi, known as the #12u nodes, are not included in the nodes recommended for dissection in patients with right middle lobe carcinoma, right lower lobe carcinoma, or left lower lobe carcinoma. However, histologic examination has revealed involvement of these nodes in pneumonectomy patients whose carcinoma originated in the right lower lobe. We histologically examined the lymph nodes from 152 patients with lung cancer to determine the incidence of involvement of the #12u lymph nodes. These nodes were found to be involved in 14 (9.2%) of the 152 patients. The rate of involvement was significantly higher in those with T2-T4 disease than in those with T1 disease, and was also significantly higher in patients with N2 disease than in those with N1 disease. There were two long-term survivors without recurrence, and one other patient who lived for more than 5 years before succumbing to the disease. In conclusion, to ensure removal of all the cancer tissue, it is recommended that the #12u lymph nodes be included in the nodes routinely dissected in patients with right lower lobe carcinoma, right middle lobe carcinoma, or left lower lobe carcinoma.

Bronchi↗

Functional evaluations for pulmonary resection for lung cancer in octogenarians. Investigation from postoperative complications.

We have reviewed the records of our twenty-four patients aged 80 years or older who underwent lung resections for bronchogenic carcinoma between 1983 and 1997 in our department. Eighteen patients were male and six were female. Adenocarcinoma was the histology in more than half of the cases (13 patients), along with 8 squamous cell carcinoma, 2 large cell carcinoma, and one small cell lung carcinoma. More than single lobectomy was performed in each patient. Unilateral pulmonary occlusion tests were employed in patients with impairment in pulmonary functions. Every patient, who underwent the unilateral pulmonary occlusion test, was certified that the total pulmonary vascular resistance index during unilateral pulmonary arterial occlusion test was less than 700 dyne.sec.cm-5.m2. Postoperative cardiovascular complications, such as paroxysmal atrial tachycardia, premature atrial contraction, premature ventricular contraction or atrial fibrillation, were seen in 10 patients. Postoperative respiratory complications, namely, sputa retention, retained secretions or atelectasis, were seen in 7 patients. The extent of dissection of mediastinal lymph node was not correlated to the postoperative pulmonary complications. However, the incidence of arrhythmias in the patients who received R2 mediastinal lymphnode dissection was much higher than in those who received R1 or R0 dissection. Complete blood counts and serum biochemical analysis performed at about three weeks after operations revealed leukocytosis and increases in levels of serum transaminase. These phenomena in leukocytosis and increases in the levels of serum transaminase in these patients were similar to those in younger patients. There was no operative death. We conclude that some patients over 80 years are candidates for lung resection after careful preoperative cardiopulmonary evaluation.

Adenocarcinoma↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗