Biomedical subjects

S Fujimura

Publications and source records attributed to S Fujimura.

At least 145 records · Page 8Linked to original sources

PubMed1997

Identification of a receptor-type protein tyrosine phosphatase expressed in postmitotic maturing neurons: its structure and expression in the central nervous system.

We have isolated a rat cDNA encoding a receptor-type protein-tyrosine-phosphatase (RTP) expressed in brain and kidney (RPTP-BK) and characterized its expression in the developing central nervous system. RPTP-BK has seven fibronectin type III-like repeats in the extracellular region and a unique catalytic phosphatase domain in the cytoplasmic region. Bacterial expression of its phosphatase domain showed that the dephosphorylation of phosphotyrosine residues was mediated by the cytoplasmic catalytic domain. Sequence comparison revealed that RPTP-BK is homologous with GLEPP1, a rabbit PTP expressed in renal glomerular epithelia, and has the same phosphatase domain as murine PTPphi expressed in macrophages. RPTP-BK has also significant homology with Drosophila DPTP10D in the phosphatase domain, whose expression is localized exclusively in growth cones of the embryonal brains. The gene for RPTP-BK is well conserved among other species, and the expression in the brain but not in the kidney is developmentally regulated during the neonatal stage. Hybridization in situ showed that RPTP-BK is highly expressed in the postmitotic maturing neurons of the olfactory bulb, developing neocortex, hippocampus and thalamus. Because the expression of RPTP-BK in the developing neocortex is correlated with the stage of axonogenesis in cortical neurons, RPTP-BK might be crucial in neural cell development of the mammalian central nervous system.

Amino Acid Sequence↗

PubMed1997

Increased alveolar fluid clearance following thoracotomy: report of a case and results of an analysis.

Alveolar fluid clearance was studied in the resected lung of a 58-year-old man who had undergone exploratory thoracotomy 9 days earlier. An isosmolar albumin solution was instilled into the distal air spaces, and the albumin and electrolyte concentrations were measured over 4 h. Alveolar sodium and fluid clearance had increased by nearly 200% from the control values in the resected lungs of patients without prior thoracotomy (n = 5), and histological examination showed that the number of alveolar type II epithelial cells was markedly elevated. These results suggest that an increase in the number of alveolar type II cells may accelerate alveolar fluid clearance under certain clinical conditions.

Aged↗

PubMed1997

Hypothermia inhibits the alveolar epithelial injury caused by hyposmotic albumin solution during preservation of the resected human lung.

This study was conducted to determine whether hypothermia inhibited alveolar epithelial injury in the resected human lung during preservation. Hyposmotic albumin solution, 248 mOsm/kg, was instilled into the alveolar spaces of resected human lungs which were inflated with an airway pressure of 7 cmH2O and stored at either 37 degrees C or 8 degrees C for 4 h. Alveolar fluid was aspirated and the influx of lactate dehydrogenase (LDH) and globulin into the alveolar spaces, as markers of alveolar epithelial injury, was measured. Ion transport and fluid clearance across the alveolar epithelium were calculated by the changes in electrolyte and albumin concentrations in the alveolar fluid, respectively. While the LDH levels and globulin concentrations increased significantly in the hyposmotic experiments at 37 degrees C, hypothermia inhibited these increases. Alveolar fluid clearance at 37 degrees C increased to 20% in the hyposmotic experiments compared with 12% in the control isosmotic experiments; however, sodium and chloride transport in the hyposmotic experiments was not significantly different from that in the isosmotic experiments. Thus, we conclude that hypothermia at 8 degrees C inhibits alveolar epithelial injury caused by the hyposmotic solution in resected human lungs. Moreover, alveolar ion and fluid clearance mechanisms were preserved across the injured alveolar epithelial cells.

Epithelium↗

PubMed1997

Bone morphogenetic protein-2 stimulates differentiation of cultured spinal ligament cells from patients with ossification of the posterior longitudinal ligament.

Ossification of the posterior longitudinal ligament (OPLL) of the spine is characterized by heterotopic bone formation occurring in spinal ligament, causing severe compression myelopathy. In order to investigate the mechanism of OPLL development, we isolated spinal ligament cells from OPLL patients as well as non-OPLL patients, and established 10 OPLL cell lines and 7 non-OPLL cell lines, respectively. We analyzed the effects of bone morphogenetic protein-2 (BMP-2) on these cells with respect to alkaline phosphatase (AP) activity, DNA synthesis, and collagen production. BMP-2 caused a significant increase of AP activity in 4 OPLL cell lines, whereas the activity did not change in any non-OPLL cells. Among OPLL cells, BMP-2 stimulated DNA synthesis in four cell lines and procollagen type I carboxyl-terminal peptide (PICP) synthesis in five cell lines. Some non-OPLL cells also responded to BMP-2, as there was an increase of DNA synthesis in three cell lines and PICP synthesis in one cell line. These data collectively indicate that BMP-2 preferentially induces osteogenic differentiation in OPLL cells rather than in non-OPLL cells. OPLL cells, therefore, exhibit a different response to BMP-2 than non-OPLL cells, suggesting that the expression of BMP receptor(s) and/or the signal transduction initiated by BMP-2 in the spinal ligament cells of OPLL patients somewhat deviate from those in normal spinal ligament cells. Such abnormal characteristics of OPLL cells as described here provide some clues to the clarification of the pathogenesis of OPLL.

Alkaline Phosphatase↗

PubMed1997

Promotion of proliferation of murine BALB/C3T3 fibroblasts mediated by nitric oxide at lower concentrations.

This study showed that nitric oxide (NO)-generating S-nitrosothiols, S-nitroso-N-acetylpenicillamine (SNAP) and S-nitrosoglutathione (GSNO), increased proliferation of BALB/c 3T3 (clone A31-1-1) fibroblasts in vitro. Treatment with SNAP at a relatively low concentration (0.005-0.02 mM) induced an increase in cell number compared to control. SNAP (0.005-0.02 mM) and GSNO (0.025-0.05 mM) both showed an increase of [3H]thymidine incorporation in exponentially growing cells in a dose-dependent manner. The maximal effect was observed at about 40 and 90% above control at 0.02 mM and 0.05 mM, respectively. The increase induced by 0.02 mM SNAP was abolished by the addition of 0.01 mM oxyhemoglobin, a scavenger of NO. [3H]Thymidine incorporation in stationary cells was also increased by SNAP. In addition, 0.02 mM SNAP produced a 1.8-3.2-fold increase of thymidine kinase activity in exponentially growing cells.

3T3 Cells↗

PubMed1997

Infrequent genetic alterations of the PTEN/MMAC1 gene in Japanese patients with primary cancers of the breast, lung, pancreas, kidney, and ovary.

In the present study, we searched for genetic alterations of the entire coding region of PTEN/MMAC1, a recently isolated candidate tumor suppressor gene, in 178 specimens from Japanese patients with various malignant tumors by the polymerase chain reaction-single strand conformation polymorphism method. The samples consisted of 11 glioblastoma multiformes (GBMs), 14 astrocytomas, 47 breast cancers, 25 non-small cell lung cancers, 9 small cell lung cancers, 8 pancreatic cancers, 24 renal cell carcinomas, 20 ovarian cancers, and 20 metastatic lung tumors from various organs. Only one somatic frameshift mutation at codon 319 was observed in one (9%) of eleven GBMs. Our results suggest that mutation of the PTEN/MMAC1 gene does not play a major role in carcinogenesis, at least in the tumor types from Japanese patients analyzed in this study.

Base Sequence↗

PubMed1997

Vasoactive intestinal peptide causes nitric oxide-dependent pulmonary vasodilation in isolated rat lung.

Vasoactive intestinal peptide (VIP) is one of the chief neurotransmitters of nonadrenergic noncholinergic nerve fibers. In this study, we investigated the effect of VIP on the pulmonary circulation in isolated perfused rat lungs. Baseline pressures of the pulmonary artery for the isolated rat lungs were not affected by 3 x 10(-8) M VIP. VIP caused dose-dependent pulmonary vasodilation when the pulmonary vascular bed was constricted with 20 mM KCl. This vasodilative effect of VIP was inhibited by 1 x 10(-6) M L-n omega-nitro-arginine, an endothelium-derived relaxing factor (nitric oxide) inhibitor, and was restored by the addition of 10(-4) M L-arginine, a substrate of nitric oxide. VIP also caused suppression of the ANG II pressor response, and this VIP-induced suppressive effect was reduced when L-N omega-nitro-arginine or 3 x 10(-6) M meclofenamate was added to the perfusate. These results indicate that VIP causes pulmonary vasodilation in isolated rat lung and suggest the possible involvement of NO and/or cyclooxygenase metabolites in VIP-induced pulmonary vasodilation.

Angiotensin II↗

PubMed1997

Beta-adrenergic agonist stimulated alveolar fluid clearance in ex vivo human and rat lungs.

Because beta-adrenergic agonist therapy may be useful clinically as a treatment to hasten the resolution of alveolar edema, this study was designed to examine the dose-dependent effects of beta-adrenergic agonist therapy on alveolar epithelial fluid clearance. The studies were done by instilling an isosmolar 5% albumin solution into the distal air spaces of both ex vivo rat and ex vivo human lungs that were inflated with 8 to 10 cm H2O with 100% oxygen and placed in a 37 degrees C humid incubator. Alveolar fluid clearance was measured by the progressive increase in concentration of protein over 1 or 4 h. Salmeterol, a new long-acting lipophilic agent, was more potent than terbutaline in stimulating alveolar fluid clearance from the ex vivo human lung. Therefore, salmeterol was used for these studies. The results indicated that: (1) basal, unstimulated alveolar fluid clearance in rat lungs was significantly faster than in human lungs (24 +/- 4% over 4 h in rat lungs compared with 11 +/- 2% over 4 h in human lungs, p < 0.05); (2) comparison of equivalent doses of beta-adrenergic stimulation indicated that stimulated clearance rates were also faster in rat lungs than in human lungs; (3) very low doses of salmeterol were effective in ex vivo rat lungs (10(-8) M); and (4) relatively low doses were effective in the ex vivo human lungs (10(-6) M) as a treatment for increasing alveolar fluid clearance. In summary, there are significant differences in the basal and stimulated rates of alveolar epithelial fluid clearance in rat and human lungs, although the ex vivo human studies may have underestimated maximal alveolar fluid clearance in the intact human lung. The human lung responds well to relatively low doses of beta-adrenergic agonist therapy, a finding with potentially important clinical implications for hastening the resolution of alveolar edema.

Adrenergic beta-Agonists↗

PubMed1997

Indomethacin enhances the cytotoxicity of VCR and ADR in human pulmonary adenocarcinoma cells.

The ability of anti-inflammatory agents to modulate cellular sensitivity to anticancer drugs was investigated for pulmonary carcinoma cells in vitro. We examined the drug sensitivity of two pulmonary adenocarcinoma cell lines (76-2, 77-4) in the presence of two drugs, an anticancer drug and an anti-inflammatory agent, for 72 hr by the 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay with 96 well plates. Anticancer drugs used for screening test were cyclophosphamide (CPM), mitomycin C (MMC), adriamycin (ADR), 5-fluorouracil (5FU), vindesine (VDS), cisplatin (CDDP), cytarabine (Ara C), methotrexate (MTX), etoposide (VP-16), and vincristine (VCR). Anti-inflammatory agents examined as modulators to anticancer drugs were aspirin, mefenamic acid, ibuprofen, sulindac, piroxicam, phenacetin, dicrofenac, ketoprofen, tolmetin and indomethacin. Screening tests showed indomethacin to be the most effective modulator, resulting in more than a 3-fold increase in cytotoxicity of VCR as compared with that produced by VCR alone. Study of each of the ten anticancer drugs in combination with indomethacin showed VCR to be the most effective anticancer drug in this combination. In 76-2 cells, the concentration of VCR producing 50% growth inhibition (IC50) for VCR alone and VCR in combination with 2 micrograms/ml indomethacin were 1.58 +/- 0.16 and 0.52 +/- 0.1 ng/ml respectively, which represents a 3-fold decrease. In 77-4 cells, the IC50 for VCR alone and VCR in combination with 2 micrograms/ml indomethacin were 2.86 +/- 0.2 and 0.52 +/- 0.11 ng/ml respectively, which represents a 3.8-fold decrease. Our studies indicate that clinically achievable concentrations of indomethacin may be useful in modulating VCR resistance in human pulmonary adenocarcinoma cells, so that combined use of VCR and indomethacin may be of potential clinical significance in the treatment of lung cancer.

Adenocarcinoma↗

PubMed1997

Roles of the visceral pleura in the production of pleural effusion in permeability pulmonary edema.

We investigated the roles of the mesothelium of the visceral pleura on hydraulic conductivity in dogs under normal conditions and condition of permeability pulmonary edema. Nineteen mongrel dogs were divided into following 4 groups: thoracotomy alone (control group, n = 7); thoracotomy and striping of the mesothelium using Gelfilm (C + G group, n = 4); injection of oleic acid to increase the permeability of the pulmonary vessels (OA group, n = 4); injection of oleic acid and striping of the mesothelium (OA + G group, n = 4). A hemispherical capsule filled with physiological saline was attached to the visceral pleura. The transpleural fluid flow (delta V) was measured at given incremental or decremental hydrostatic pressures (delta Pcap) in the capsule. Hydraulic conductivity was calculated from the slope of linear regression line obtained from relationship between delta Pcap and the fluid flow rate (v) according to the Starling's equation. The conductivity obtained were 1.49 +/- 0.69 (nl.min-1.cmH2O-1.cm-2) in the control group, 1.37 +/- 0.88 in the C + G group, 3.75 +/- 0.74 in the OA + G group, and 7.07 +/- 2.49 in the OA + G group. The hydraulic conductivity was not increased by striping of the mesothelium (1.49 +/- 0.69 [nl.min-1.cmH2O-1.cm-2] vs. 1.37 +/- 0.88, in the control group vs. C + G group, respectively). Visceral pleural hydraulic conductivity following OA injection was increased by striping of the mesothelium (3.75 +/- 0.74 vs. 7.07 +/- 2.49 in OA group vs. OA + G group, respectively). These findings suggest that the wall of pulmonary vessels acts as a barrier to movement of pleural effusion under normal conditions, whereas the mesothelium of the visceral pleura acts as that under condition of permeability pulmonary edema.

Animals↗

PubMed1997

Cyclooxygenase metabolites possibly produced by endothelial cells mediate the lung injury caused by mechanically stimulated leukocytes.

To determine whether mechanically stimulated leukocytes increase pulmonary vascular permeability and resistance and, if so, whether cyclooxygenase metabolites mediate the increase, we assessed the effects of stimulated and unstimulated leukocytes, and of a cyclooxygenase inhibitor on pulmonary vascular permeability and resistance in isolated perfused lungs from Sprague-Dawley rats. Leukocytes were stimulated by gentle agitation in a glass container for 10 seconds. After baseline measurements were made, stimulated or unstimulated leukocytes were added to the perfusate. The effects of the cyclooxygenase inhibitor, meclofenamate, on the pulmonary vascular filtration coefficient and pulmonary vascular resistance were measured. In the rats that received stimulated leukocytes, the pulmonary vascular filtration coefficient and the vascular resistance were about 2.5 times and 3.3 times higher, respectively, than those in the rats that received unstimulated leukocytes. These increases were completely and partly blocked by meclofenamate. Histological examination indicated that meclofenamate did not prevent the adhesion of leukocytes to the pulmonary vascular endothelium. These findings suggest that mechanically stimulated leukocytes increase pulmonary vascular permeability and that cyclooxygenase metabolites produced by endothelial cells may injure the cells.

Animals↗

PubMed1997

[The significance of surgical treatment for T4 lung cancer].

A total of 114 pT4 patients underwent pulmonary resection from January 1980 to December 1993 at our hospital. The overall five-year survival rate of the 114 cases was 17%. There was no significance between the five-year survival rate of squamous cell carcinoma and that of adenocarcinoma. Five-year survival rates of 17 patients with N0 disease, 29 patients with N1 disease, 51 patients with N2 disease, 1 patients with N3 disease, and 16 patients with NX disease were 40%, 21%, 21%, 0%, and 0%, respectively. Five-year survival rate of 89 cases with single factor of T4 was 24% and that of 25 cases with more than one factor was 4% (0.05 < P < 0.1). In the patients with only single factor of T4, five-year survival rates of 6 patients with left atrium invasion, 13 patients with major vessel invasion, 9 patients with trachea/carina invasion, and 18 patients with vertebral body, were 50%, 38%, 22%, and 0%, respectively. Furthermore, in 38 pT4 patients with involvement only to single adjacent structure, five-year survival rates were 47% in curative operation (n = 17) and 10% in non-curative operation (n = 21) (P < 0.05). We conclude that surgical treatment for T4 lung cancer should be performed to patients with single structure invasion which is expected to have a curative operation. N0 disease is more favorable than N1 or N2 disease.

Adenocarcinoma↗

PubMed1997

[A case of systemic origin of an aberrant artery to the basal segment of the lung].

We report on a rare case of systemic origin of an aberrant artery to the basal segment of the lung (Pryce I type intralobar pulmonary sequestration) that caused occasional bloody sputum. The patient was admitted to our hospital after an abnormal image was discovered in Chest X-ray film. The chest MRI showed an abnormal vessel originating from the descending aorta. The aortagram showed an abnormal artery originating from the descending aorta and entering the left lower lobe, and the left pulmonary angiogram revealed a poorly blood supply to the left basal segments. The preoperative diagnosis of systemic origin of an aberrant artery to the basal segment of the lung was given. The patient was subjected to surgical treatment. During surgery, it was found that the abnormal artery, 12 mm in diameter, which was connected from the descending aorta to the left basal segments. The abnormal artery was dissected, and the left basal segments was removed. The postoperative course was uneventful.

Aorta, Thoracic↗

PubMed1997

[Role of leukotriene B4 in monocrotaline-induced pulmonary hypertension].

Monocrotaline (MCT) causes lung inflammation and chronic pulmonary hypertension associated with lung vascular thickening in rats. We hypothesized that leukotriene B4 (LTB4) and LTB4-induced accumulation of leukocytes in the lung play a role in MCT-induced lung disease, and therefore measured LTB4 and myeloperoxidase (MPO) levels in lung tissue of MCT-treated rats. Next, we examined the effect of an orally active LTB4 receptor antagonist (ONO4057) on MPO levels in lung tissue, on pulmonary hypertension, and on pulmonary vascular remodeling induced by MCT. Lung LTB4 and MPO levels had increased by 3 days after MCT injection. In the ONO4057-treated MCT rats, lung MPO levels were significantly lower than in the rats given MCT but not ONO4057. By the third week after injection. MCT had caused increases in mean pulmonary arterial pressure, in the ratio of right ventricular weight to left ventricle+septum weight (RV/[VS + S]), and in media wall thickness of the muscular arteries of the lung. Treatment with ONO4057, either for 3 weeks or during the first week after MCT injection, significantly reduced pulmonary hypertension, right ventricular hypertrophy, and lung vascular thickening induced by MCT. These results indicate that ONO4057 reduces both the accumulation of leukocytes in lung tissue and the chronic pulmonary hypertension induced by MCT, and they suggest a role for LTB4 in the inflammatory process that contributes to pulmonary hypertension and lung vascular remodeling induced by MCT in rats.

Animals↗

PubMed1997

[Early postirradiation changes in Na+ and fluid transport across alveolar epithelium in rats].

To study changes in Na+ and fluid transport that occur soon after irradiation of the thorax, we used fluid-filled isolated rat lungs. Irradiation 15 Gy of 60Co doubled the fluid absorption rate across the alveolar epithelium within 2 weeks, but fluid absorption had returned to the baseline values by 3 weeks after irradiation. The timing of this change in fluid absorption was parallel to the time course of Na+ escape across alveolar epithelium and the two correlated closely. These data suggest that a dysfunction of alveolar epithelial Na+ transport is involved in the development of pulmonary edema after irradiation of the thorax.

Animals↗

PubMed1997

[Effect of thoracoscopic procedure versus standard posterolateral/muscle-sparing thoracotomy on pulmonary lung function].

To understand the effects of thoracoscopic approach to thoracotomy on lung function, we investigated the changes in lung function after thoracoscopic operation (n = 7) and compared them to those after standard posterolateral (n = 5) or muscle-sparing thoracotomy (n = 6). In 18 patients with benign lung tumor in which surgical treatment resected in partial resection of the lung tissue, we measured TLC, VC, RV, FEV1.0, FEV1.0%, Peak Flow and DLco preoperatively and at 2, 4 weeks postoperatively. In the standard posterolateral or muscle-sparing thoracotomy groups, FVC, TLC, FEV1.0 and Peak Flow decreased to about 80% of preoperative value at 2 weeks. At 4 weeks after operation, these values showed to increase some what, but did not reach to the preoperative value. Whereas, the thoracoscopic procedure group, did not show the decrease in lung function through the time course. There was not significant different between standard posterolateral and muscle-sparing thoracotomy. We conclude that thoracoscopic approach is an useful technique to thoracotomy because of its minimizing after thoracotomy effect of lung function loss.

Adult↗

PubMed1997

[Increase in pulmonary vascular permeability caused by increased expression of Mac-1 on the surface of polymorphonuclear leukocytes].

We studied the expression of adhesion molecules on the surface of human polymorphonuclear leukocytes (PMNs). The effects of mechanical stimulation were measured with a flow cytometer and pulmonary vascular injury due to accumulation of PMNs in the lungs was assessed by a gravimetric method. The accumulation of PMNs in the lungs was studied by measuring the amount of myeloperoxidase. PMNs were stimulated by gentle agitation in a glass container for 10 s. Mac-1 (CD11b/CD18) was upregulated on the surface of PMNs that were mechanically stimulated. When unstimulated PMNs were exposed to isolated rat lungs, the filtration coefficient did not change from that under baseline conditions. However, when mechanically stimulated PMNs were exposed to isolated rat lungs, the filtration coefficient was about 5 times higher than that measured at baseline. When mechanically stimulated PMNs treated with anti-CD18 antibody were used, the increase in the filtration coefficient was completely blocked. The assay of myeloperoxidase revealed that PMNs stuck to isolated rat lungs only after stimulated PMNs were added. We conclude that when the adhesiveness of PMNs is increased by mechanical stimulation, these cells adhere to pulmonary vessels and increase pulmonary vascular permeability.

Animals↗

PubMed1997

[A child of malignant lymphoma diagnosed by transbronchial aspiration cytology under general anesthesia with a laryngeal mask].

A 8-year-old male with Wiskott-Aldrich syndrome was admitted to our hospital because of left hilar swelling on a chest roentgeonogram. Bronchofiberscopy and transbronchial aspiration cytology (TBAC) was performed under general anesthesia with a laryngeal mask. The specimen obtained by TBAC was immediately stained and diagnosed as malignant lymphoma. One month later, thoracotomy was performed in order to get more detail diagnosis, which is necessary to determine the regimen of chemotherapy, and the nodal specimen were diagnosed as Hodgkin's disease. The ABVD therapy was performed which induced the complete remission. The laryngeal mask is a useful device for bronchofiberscopy in children.

Anesthesia, General↗