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Biomedical subjects

S Fujimura

Publications and source records attributed to S Fujimura.

At least 217 records · Page 12Linked to original sources

[Transport of ions across alveolar epithelial cells in resected human lungs].

Little information is available regarding the effect of ion transport agonists and antagonists on ion transport in the human lung. Therefore, we studied ion transport in lungs resected from patients with lung cancer. A test solution of 45 ml of isosmotic albumin was instilled into one segment of a resected lobe within 10 min of resection. Because protein leaves the air space very slowly, the concentration of alveolar protein over 4 h was used to quantify the volume of alveolar fluid. Ion transport was measured from the changes in ion concentrations and the volume of alveolar fluid. In the basal condition, the net efflux of Na+ and Cl- were 4.66 +/- 0.83 mEq/l/h and 3.52 +/- 0.84 mEq/l/h, respectively. In contrast, the net influx of K+ was 0.44 +/- 0.07 mEq/l/h. Amiloride (10(-5) M), an inhibitor of apical Na+ uptake, ouabain (10(-3) M), an inhibitor of Na(+)-K+ ATPase, and hypothermia (8 degrees C) reduced the efflux of Na+ and Cl-. Ouabain and hypothermia increased the net influx of K+. Terbutaline (10(-3) or 10(-4) M) increased the efflux of Na+ and Cl-, but did not affect the influx of K+. Propranolol (10(-4) M) and amiloride (10(-5) M) inhibited the terbutaline-induced increase in the transport of Na+ and Cl-. Alveolar fluid clearance was closely correlated with Na+ transport and with Cl- transport. However, the values of Na+ transport were greater than those of Cl- transport. These data suggest that Na+ transport is accompanied by Cl- transport and fluid movement out of the alveolar space in resected human lungs.

Adrenergic beta-Agonists↗

[Role of cyclooxygenase metabolites in the increase in pulmonary vascular permeability caused by mechanically activated white blood cells].

To study the role of cyclooxygenase metabolites in changes in the pulmonary vasculature induced by mechanically activated white blood cells (WBCs), the effects of activated and inactive WBCs, and of a cyclooxygenase inhibitor, were studied in isolated perfused lungs from Sprague-Dawley rats. WBCs were activated by gentle agitation in a glass container for 10s. Baseline measurements were made, and then activated or inactive WBCs were added to the perfusate. Perfusion was stopped for 90 minutes, and then started again. The effects of the cyclooxygenase inhibitor meclofenamate on the pulmonary vascular filtration coefficient and on pulmonary vascular resistance were also measured. In the group that received activated WBCs, the pulmonary vascular filtration coefficient and the pulmonary vascular resistance were about 2.5 times and 3.3 times higher, respectively, than those in the group that received inactive WBCs. However, this apparent increase in the filtration coefficient caused by activated WBCs was partly blocked by meclofenamate. Histological examination indicated that meclofenamate did not prevent the adhesion of WBCs to the pulmonary vascular endothelium. These date indicate that WBCs that have been made to adhere to vessel walls can induce pulmonary vascular injury via cyclooxygenase products.

Animals↗

[Contribution of oxidative stress to pulmonary hypertension induced by chronic hypoxia].

Chronic hypoxia causes pulmonary hypertension and right ventricular hypertrophy associated with media wall thickening of pulmonary arteries in rats. Platelet-activating factor plays an important role in the pulmonary vascular remodeling induced by chronic hypoxia, and reactive oxygen species are involved in tissue injury induced by platelet activating factor. We therefore hypothesized that reactive oxygen species contribute to the pulmonary hypertension induced by chronic hypoxia, and examined the effect of N-acetyl-L-cysteine (NAC), a free radical scavenger and the precursor of glutathione sulfhydryl (GSH), on hypoxia-induced pulmonary hypertension. We used a chemiluminescence-HPLC assay to measure the levels of phosphatidylcholine hydroperoxide (PCOOH) in the rat lungs exposed to hypoxia. Three weeks of normobaric hypoxia (FiO2 = 0.1) with NAC significantly reduced pulmonary hypertension, right ventricular hypertrophy, and media wall thickening of the pulmonary arteries. NAC had no effect on the hematocrit of normoxic or chronically normobaric hypoxic rats. Lung PCOOH levels were significantly higher in the hypoxic rats than in the control rats, and those in the NAC-treated rats were significantly lower than those in the hypoxic rats that were not given NAC. Lung PCOOH levels were significantly higher in the hypoxic rats than in the control rats, and those in the NAC-treated rats were significantly lower than those in the hypoxic rats that were not given NAC. These results indicate that hypoxia induces oxidative stress in the lung tissue, and that oxidative stress may have a role in the development of pulmonary hypertension induced by chronic hypoxia in rats.

Acetylcysteine↗

[Leukocyte-mediated production of eicosanoids in rat lungs: modulation by a calcium antagonist].

Formyl peptide (fMLP) by itself does not increase eicosanoid levels in rat lungs, but eicosanoid levels and edema do increase if endotoxin (ETX) is given before an fMLP challenge. The role of pulmonary intravascular leukocytes in fMLP-induced eicosanoid production in rat lungs was studied, as was the effect of a calcium antagonist (Ro 40-5967). ETX increased the levels of 6-keto PGF1 alpha, but not the levels of TXB2 or LTB4. A second challenge with fMLP in ETX-primed rats resulted in increased production of these three eicosanoids, and increased neutrophil accumulation, as assessed by myeloperoxidase assay. The calcium antagonist attenuated both the production of eicosanoids and the accumulation of neutrophils in the lung. The levels of both 6-keto PGF1 alpha and TXB2 correlated well with lung neutrophil accumulation. Leukocytes isolated from the pulmonary vasculature released TXB2 and LTB4 when stimulated with fMLP in vitro. The amount of these eicosanoids released from pulmonary intravascular leukocyte suspension was well correlated with neutrophil counts in a leukocyte suspension. These data indicate that fMLP-induced production of eicosanoids in the lung, especially production of TXB2, is mediated by pulmonary intravascular neutrophils, and that calcium antagonists can attenuate eicosanoid production by decreasing the accumulation of neutrophils in the lung.

6-Ketoprostaglandin F1 alpha↗

[A true aneurysm of the right internal mammary artery, accompanied by diminished grasping power of the right hand].

A 69-year-old man was admitted to our hospital after an abnormal shadow was found on a chest radiograph. The preoperative diagnosis was right subclavian aneurysm. Loss of grip in the right hand developed, and the patient underwent surgery. During surgery, the aneurysm was found to have originated from the right internal mammary artery. The root of the right internal mammary artery was tied and the right subclavian artery, which had been compressed and displaced by the aneurysm, was replaced. A chest radiograph obtained 6 months after surgery showed that the trachea was no longer displaced. However, the gripping force of the right hand had not recovered.

Aged↗

[An experience of surgery for thymolipoma in a patient with amyotrophic lateral sclerosis].

A 48-year-old male with amyotrophic lateral sclerosis (ALS) was revealed to have an anterior mediastinal tumor, occupying left hemithorax on a chest CT. The tumor compressed the left lower lobe, resulting in a hypoventilation, which required a continuous ventilatory support. Although ALS has poor prognosis in general, we decided to remove the tumor surgically. Because the symptoms related to ALS was limited to his extremities, indicating he could potentially reestablish his life under ventilator-free condition, when a remove of the tumor improved a hypoventilation. A remove of the tumor was performed via antero-axillar thoracotomy, and reexpansion of the left lower lobe was achieved, followed by improvement of lung function and of respiratory symptoms. Histological examination revealed that the tumor was composed of mature adipose tissue and thymic tissue, diagnosed as thymolipoma. Postoperative course was uneventful.

Amyotrophic Lateral Sclerosis↗

[Role of peptide leukotrienes in monocrotaline-induced lung disease].

Monocrotaline (MCT) causes lung inflammation and right ventricular hypertrophy associated with lung vascular thickening in rats. We hypothesized that peptide leukotrienes play a role in MCT-induced lung disease, and examined the effect of ONO 1078, a specific antagonist of LTC4, D4 and E4 receptors on MCT-induced right ventricular hypertrophy and on lung vascular thickening. Next, we measured leukotriene C4 (LTC4) levels in the lung tissue of MCT-treated rats. Within 3 weeks after the injection MCT had caused an increase in the ratio of right ventricular weight to left ventricle+septum weight (RV/(LV+S)) and an increase in media wall thickness of the muscular arteries of the lung. In rats given both ONO 1078 and MCT, these changes were significantly less severe than in rats given MCT only. The LTC4 levels in MCT-treated rats were significantly higher than in saline-treated control rats. These results indicate that this antagonist of peptide leukotriene receptors inhibits right ventricular hypertrophy induced by MCT, and suggest a role for peptide leukotrienes in the inflammatory process that contributes to lung vascular remodeling in MCT-treated rats.

Animals↗

Tumor doubling time and prognostic assessment of patients with primary lung cancer.

BACKGROUND: Relationships between tumor doubling time (DT) and other prognostic factors and the risk of death related to these factors are not yet fully understood. METHODS: Tumor doubling time of primary lung carcinomas of 174 patients, detected in a limited number of local municipalities during a limited period, was calculated using the Schwartz formula. Survival rate of the 174 patients was compared with reference to categories of prognostic factors (univariate analyses) and significant factors affecting survival were identified by multivariate analyses using the Cox proportional hazard model. RESULTS: Tumor doubling time had a log normal distribution. There was a significant difference in mean DT in relation to sex, smoking history, presence of symptoms, cell type, primary tumor factor, and stage. Univariate analyses showed a significant difference in survival in relation to DT, age, sex, method of tumor detection, smoking history, symptoms, therapy, cell type, primary tumor (T) factor, regional lymph node (N) factor, distant metastasis (M) factor, and stage. Multivariate analyses using the Cox's proportional hazard model in a stepwise fashion identified a final set of five significant variables: N factor (P = 0.0001); therapy (P = 0.0016); M factor (P = 0.0017); T factor (P = 0.0018), and DT (P = 0.0152). CONCLUSIONS: Tumor doubling time was an independent and significant prognostic factor for lung cancer patients.

Adult↗

The granulocyte colony-stimulating factor produced in the human lung and its effect on liquid movement in the rabbit lung.

Levels of the granulocyte colony-stimulating factor (G-CSF) were determined in the plasma and resected lung tissue from patients who underwent pulmonary resection. Moreover, the effect of recombinant human (rh) G-CSF on the permeability of pulmonary endothelium and on liquid clearance from the alveolar spaces was investigated in rabbits. The plasma levels of G-CSF increased from 30 pg/ml preoperatively to 409 +/- 236 pg/ml 3 h postoperatively (P < 0.05), while the levels of G-CSF in the resected lung tissue were increased in the alveolar fluid, to 1,834 +/- 1,054 pg/ml, and in the pulmonary blood, to 5,466 +/- 2,019 pg/ml. It was found that rh G-CSF 25 micrograms administered into the subcutaneous tissue of rabbits increased extravascular lung water to 3.45 +/- 0.26 vs 2.98 +/- 0.20 in control experiments (P < 0.05); however, rhG-CSF 0.75 microgram/kg administered into the alveolar spaces did not affect liquid clearance from the alveolar spaces. The findings of this study led us to conclude that G-CSF is synthesized in the human lung and increases the permeability of pulmonary endothelium, but not liquid clearance across the alveolar epithelium.

Animals↗

Use of the sandwich method with an ultra-high-molecular-weight polyethylene prosthesis and Marlex mesh in sternal reconstruction: report of a case.

A 52-year-old Japanese man with a slow-growing chondroma originating from the sternal bone was referred to our hospital. A subtotal resection of the sternum was performed, hereafter termed the "sandwich method," and an originally designed prosthesis made from ultra-high-molecular-weight polyethylene and Marlex mesh was used for reconstruction. The postoperative course was uneventful without any symptoms due to paradoxical movement of the chest or regional abscess, and no disturbance in the movement of the upper limbs, such as a surgical sequelae, was observed.

Bone Neoplasms↗

Prostaglandin E2/parathyroid hormone-induced suppression of alkaline phosphatase activity is mediated by protein kinase C.

1. Bone resorptive factors, prostaglandin E2 and parathyroid hormone are shown to suppress alkaline phosphatase activity in a rat osteoblastic cell line. 2. Phorbol myristate acetate, but not dibutyryl cAMP or calcium ionophore can suppress alkaline phosphatase activity. 3. The protein kinase C inhibitors (H89, staurosporine) are able to block the suppression of alkaline phosphatase activity induced by prostaglandin E2 and parathyroid hormone. 4. These data suggest that protein kinase C is involved in the inhibition of alkaline phosphatase activity induced by prostaglandin E2 and parathyroid hormone.

Alkaline Phosphatase↗

Purification and characterization of two Kunitz family subtilisin inhibitors from seeds of Canavalia lineata.

Two subtilisin inhibitors (CLSI-II and -III) were purified from seeds of Canavalia lineata by extraction with water, ammonium sulfate precipitation, and chromatographies on DEAE-Toyopearl and hydroxyapatite. The two inhibitors have the same molecular weight of about 22,000, and quite similar amino acid compositions. They contain five half-cystine residues and tend to dimerize through an intermolecular disulfide bridge due to the presence of a single cysteine residue. CLSI-III only inhibited subtilisin-type serine proteases, while CLSI-II showed a wider inhibitory specificity. Though the two inhibitors have almost identical thermal labilities, CLSI-II is more stable as to extreme pH than CLSI-III. They are considered to be Kunitz type inhibitors on the basis of several properties.

Amino Acid Sequence↗

Amino acid sequences of Kunitz family subtilisin inhibitors from seeds of Canavalia lineata.

The amino acid sequences of two subtilisin inhibitors (CLSI-II and -III) from Canavalia lineata seeds were determined by manual Edman degradation using the DABITC/PITC double coupling method after enzymatic digestions and CNBr degradation. CLSI-II and -III consist of 190 and 183 amino acids, respectively, and have identical amino acid sequences except for in the C-terminal regions: an elongated sequence, Gly-Thr-Ile-Arg- Ser-Asp-Gly, was found at the C-terminus of CLSI-II. A short-chain analog protein without an N-terminal Asn residue was also detected in each inhibitor preparation. The inhibitors showed significant homology to Kunitz type inhibitors, but differed from them with respect to the half-cystine content. Among five half-cystine residues present in CLSI-III, two disulfide bonds link Cys44 to Cys88 and Cys142 to Cys149, Cys106 being present as a free cysteine residue. Phenylglyoxal treatment abolished the inhibitory activity of CLSI-III, indicating the participation of an Arg residue in the interaction with the enzyme. The reactive-site peptide bond was deduced to be Arg68-Gly69.

Amino Acid Sequence↗

Characterization of nicotinamide methyltransferase in livers of mice bearing Ehrlich ascites tumors: preferential increase of activity.

There was a 2- to 7-fold increase in nicotinamide methyltransferase activity in the livers of mice and rats bearing seven different kinds of tumors compared with the respective control normal livers, while activity in the tumors themselves was hardly detectable. The activity in the liver started to increase markedly 3-7 days after i.p. transplantation of Ehrlich ascites tumors into the mice, maintaining a plateau up to death. Metabolic conversion of 14C-nicotinamide to 14C-N1-methylnicotinamide was 3-fold higher in the slices of the ascites tumor host liver than in the normal liver, but the conversion to other radioactive metabolites was not significantly different. Nicotinamide methyltransferase was finally purified 20,000-fold with a yield of 4% from the cytosolic fraction of the ascites tumor host liver by means of five purification steps. At every purification step, only one enzyme fraction was detected. The enzyme finally isolated exhibited a single protein band in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, with a molecular weight of 26,000. As for the compounds investigated, including the substrates for methyltransferases other than nicotinamide methyltransferase, only quinoline could be the substrate for enzyme activity. It is suggested that the increase in enzyme activity in the tumor host liver probably derived from the endogenous enzyme preexisting in the liver before tumor transplantation.

Animals↗

Alveolar fluid clearance in the resected human lung.

Although the mechanisms responsible for alveolar liquid clearance have been studied in several species, there has not been any information regarding the effect of ion transport agonists or antagonists on alveolar liquid clearance in the human lung. Therefore, we studied alveolar liquid clearance in the recently resected human lung from patients who underwent surgery for lung cancer. A test solution of 40 ml of isosmolar albumin solution was instilled into one segment of a resected lobe within 10 min of resection. Because protein leaves the air spaces very slowly, the concentration of alveolar protein over 4 h was used to quantify alveolar liquid clearance. Basal alveolar liquid clearance was 12 +/- 2% over 4 h. Amiloride (10(-5) M), an inhibitor of apical Na+ uptake, and ouabain (10(-3) M), an inhibitor of Na,K-ATPase activity, reduced alveolar liquid clearance by 40 and 49%, respectively (p < 0.005). Terbutaline (10(-3) or 10(-4) M) doubled alveolar liquid clearance to 28 +/- 9% over 4 h (p < 0.05). Propranolol (10(-4) M) and amiloride (10(-5) M) inhibited the terbutaline-induced increase in alveolar liquid clearance. In conclusion, (1) alveolar liquid clearance in the human lung can be markedly reduced by inhibition of apical sodium channel uptake or Na,K-ATPase activity, and (2) beta-adrenergic stimulation markedly increases the rate of alveolar liquid clearance in the resected human lung without pulmonary perfusion.

Aged↗

Property and amino acid sequence of a subtilisin inhibitor from seeds of beach canavalia (Canavalia lineata).

A subtilisin inhibitor was purified from the seeds of Canavalia lineata by ammonium sulfate precipitation, ultrafiltration on a YM-30 membrane, column chromatography on DEAE-Toyopearl and SP-Toyopearl, followed by reverse-phase HPLC. The inhibitor (CLSI-I) is a low molecular weight protein (M(r) about 6500) containing no half-cystine residue, and quite stable as to extreme heat and pH treatment. CLSI-I inhibited subtilisin-type serine proteases including S. griseus alkaline protease. The amino acids of CLSI-I were sequenced by manual Edman degradation after enzymatic digestion with Achromobacter lyticus lysyl endopeptidase and Staphylococcus aureus V8 protease. CLSI-I contains 65 amino acid residues and showed a high homology to potato inhibitor I family proteins.

Amino Acid Sequence↗

Purification and characterization of three proteinase inhibitors from Canavalia lineata seeds.

Three proteinase inhibitors (CLTI-I, -II and -III) were purified from the seeds of Canavalia lineata by DEAE-Toyopearl, hydroxyapatite, and anhydrotrypsin-Sepharose column chromatographies. All the inhibitors bound to trypsin at a 1:1 molar ratio and inhibited the enzyme with dissociation constants of 3-7 x 10(-9) M. They also showed the inhibitory activities on chymotrypsin. CTLI-I and -II had an identical M(r) of 8000 and very close isoelectric points (4.57 and 4.50), and existed mainly as trimers under physiological conditions. The high content of half-cystine residues and the high stability to pH and heat have suggested that these are Bowman-Birk type inhibitors. On the other hand, CLTI-III, with an M(r) of 20,500 was classified as a Kunitz (soybean) family inhibitor on the basis of the amino acid composition as well as the homology of its N-terminal 17 residues to other Kunitz inhibitors.

Amino Acid Sequence↗