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Biomedical subjects

S Nagai

Publications and source records attributed to S Nagai.

At least 109 records · Page 6Linked to original sources
PubMed1998

Bradykinin stimulates type II alveolar cells to release neutrophil and monocyte chemotactic activity and inflammatory cytokines.

In the present study, we evaluated the potential of bradykinin (BK) to induce the release of neutrophil and monocyte chemotactic activity (NCA and MCA) and cytokines from an alveolar type II epithelial cell line, A549 cells. BK stimulated A549 cells to release NCA and MCA in a dose- and time-dependent manner (P < 0.001). Checkerboard analysis revealed that both NCA and MCA involved chemotactic and chemokinetic activity. Molecular sieve column chromatography showed three molecular weight masses (near 19 kd, 8 kd, and 400 d) for NCA and several molecular weight peaks (near 66 kd, 25 kd, 19 kd, 16 kd, and 400 d) for MCA. The release of NCA and MCA was inhibited by cycloheximide and lipoxygenase inhibitors (P < 0.01). The NCA and MCA were inhibited by leukotriene B4 (LTB4) receptor antagonist (P < 0.01), and the concentration of LTB4 was high enough for NCA and MCA. Antibodies to interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF) attenuated NCA (P < 0.01), and antibodies to monocyte chemotactic protein-1 (MCP-1), G-CSF, and transforming growth factor (TGF)-beta attenuated MCA (P < 0.01). The levels of IL-8, G-CSF, MCP-1, and TGF-beta increased time dependently (P < 0.01). BK also stimulated the release of ILeukin-6 from A549 cells (P < 0.001). The receptors responsible for the release of NCA, MCA, and individual chemokines involved both BKB1 and BKB2 receptors. These data suggest that BK may stimulate alveolar type II pneumocytes to release inflammatory cytokines, which then may modulate the lung inflammation.

Antibodies↗
PubMed1998

Smoke extract stimulates lung epithelial cells to release neutrophil and monocyte chemotactic activity.

Inflammatory cells accumulate within the lungs of cigarette smokers. Current concepts suggest that these cells can induce protease-antiprotease and/or oxidant-antioxidant imbalance(s), which may damage the normal lung alveolar and interstitial structures. Because type II pneumocytes line the alveolar space, and because the inflammatory cells migrate and reside at the alveolus, we postulated that the type II pneumocytes might release chemotactic activity for neutrophils and monocytes in response to smoke extract. To test this hypothesis, A549 cells were cultured and the supernatant fluids were evaluated for the neutrophil and monocyte chemotactic activity (NCA and MCA) by a blind-well chamber technique. A549 cells released NCA and MCA in response to smoke extract in a dose- and time-dependent manner (P < 0.05). Checkerboard analysis showed that the activity was chemotactic. Partial characterization of NCA and MCA revealed that the activity was partly heat labile, trypsin sensitive, and ethyl acetate extractable. Lipoxygenase inhibitors and cycloheximide inhibited the release of NCA and MCA. Molecular sieve column chromatography showed multiple peaks for both NCA and MCA. NCA was inhibited by anti-human-interleukin (IL)-8 antibody, granulocyte colony-stimulating factor (G-CSF) antibody, or leukotriene (LT)B4 receptor antagonist. Monocyte chemoattractant protein (MCP)-1 antibody or LTB4 receptor antagonist inhibited MCA. Immunoreactive IL-8, G-CSF, MCP-1, and LTB4 significantly increased in the supernatant fluids in response to smoke extract. These data suggest that the type II pneumocytes may release NCA and MCA and modulate the inflammatory cell recruitment into the lung.

Antibodies↗
PubMed1998

A canine model of intracranial arteriovenous shunt with acute cerebral venous hypertension.

Increased pressure of draining veins in intracranial arteriovenous fistula is considered an important cause of clinical symptoms. To investigate hemodynamic changes in intracranial arteriovenous fistula with cerebral venous hypertension, we developed a new canine model of this condition. A lingual artery-superior sagittal sinus (SSS) shunt was constructed using a section of the femoral artery as an interposed graft; immediately after which, monitoring of SSS pressure (SSSP) and regional cerebral blood flow (rCBF) was started. The baseline SSSP was 4.1 +/- 3.7 mmHg. After shunt opening, it increased slightly but not significantly. When the SSS was occluded with a clip with the shunt closed, SSSP rose to 20.3 +/- 9.0 mmHg (p < 0.01). Finally, on shunt opening, with the SSS caudal (downstream) to it occluded, the SSSP increased to 59.5 +/- 22.9 mmHg (p < 0.01, multiple analysis of variance, contrast). The frontal lobe rCBF decreased as the cerebral perfusion pressure (CPP) (mean blood pressure minus SSSP) fell. However, cerebral vascular resistance decreased significantly and proportionately to the reduced CPP (r = 0.66, p < 0.0001). In conclusion, when an intracranial arteriovenous shunt was present, venous outflow obstruction was shown to be necessary for cerebral venous hypertension to occur. In acute venous hypertension, decreases in rCBF occurred, but the autoregulatory vasodilating response was also active.

Animals↗
PubMed1998

Three dimensional electron spin resonance (ESR) imaging of internal organs in living mice.

In vivo electron spin resonance imaging (ESR imaging) was applied to living mice after peroral administration of a nitroxide radical spin probe. A 3D ESR imaging procedure was applied in vivo in order to obtain the exact distribution of the spin probe in a living animal. The imaging pictures demonstrated that the administered spin probe was firstly located in the stomach, then delivered to the liver, kidney and heart of the animal.

Animals↗
PubMed1998

Moderate hypothermia reduces hypotensive, but not hypercapnic vasodilation of pial arterioles in rats.

Two types of acid-base strategies are available for the blood gas management of patients during hypothermia: alpha-stat and pH-stat management. However, the more suitable strategy for therapeutic hypothermia is unclear. We studied the effects of hypothermia (30 degrees C) and acid-base management on reactivity to hypercapnia and hypotension in rat pial arterioles, using a closed cranial window. The baseline diameter during hypothermia decreased in the alpha-stat (PaCO2 was maintained at 35 mm Hg when measured at 37 degrees C, n = 8), but not in the pH-stat (PaCO2 was maintained at 35 mm Hg when corrected to the animal's actual temperature, n = 7). Vasodilation induced by hypotension was significantly reduced in hypothermic groups compared with the normothermic group (n = 7), whereas responses to hypercapnia were preserved. Moreover, hypotensive vasodilation was more attenuated in the pH-stat, than the alpha-stat, management. These findings show that moderate hypothermia and acid-base management alter cerebrovascular autoregulation.

Animals↗
PubMed1998

Chronic bronchioloalveolitis associated with human T-cell lymphotrophic virus type I infection.

The lung is a preferential site for human T-cell lymphotropic virus type I infection. This peculiar tropism for the lung is responsible for the high incidence of pulmonary involvement in patients with human T-cell lymphotropic virus type I infection. A variety of pulmonary manifestations may be present in human T-cell lymphotropic virus type I-associated pulmonary diseases, but the characteristic features of this disorder appear to be chronic bronchioloalveolitis with or without fibrotic changes of surrounding parenchyma. As for the pathogenesis of pulmonary involvement associated with human T-cell lymphotropic virus type I infection, immunologic mechanisms through T-cell activation may play an important role. Such attractive interpretations need further verification.

Adult↗
PubMed1998

Classification and recent advances in idiopathic interstitial pneumonia.

Idiopathic interstitial pneumonia (IIP) is a heterogeneous group of diseases comprising acute interstitial pneumonia, bronchiolitis obliterans organizing pneumonia (BOOP), nonspecific interstitial pneumonia, desquamative interstitial pneumonia, and idiopathic pulmonary fibrosis and usual interstitial pneumonia (IPF/UIP). We review the clinicopathological spectrum of IIP and introduce recent advances in classification, treatment, and prognosis. BOOP can be clinically categorized as an interstitial pneumonia, though prominent granulation tufts are seen in the airspaces. Though differences between the nonspecific interstitial pneumonia and other lips can be histopathologically clarified, the focus of clinical research on NSIP is differentiation from BOOP, or from IPF and UIP. IIP can be categorized into two groups: groups with acute or subacute lung injuries or fibrosis, such as in acute interstitial pneumonia, BOOP and nonspecific interstitial pneumonia, and groups with chronic injuries or fibrosis, such as IPF/UIP. This classification accords well with the maturity of fibrosis, CT findings, bronchoalveolar lavage fluid cell findings, and prognosis. The most critical problem is the treatment of IPF/UIP, because of its high mortality.

Acute Disease↗
PubMed1998

MPB70 and MPB83 as indicators of protein localization in mycobacterial cells.

Culture fluids after growth of Mycobacterium bovis BCG on Sauton medium contain actively secreted proteins and proteins released by bacterial lysis. BCG culture fluids and sonicates of Mycobacterium tuberculosis and Mycobacterium paratuberculosis were tested after separation by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The localization of marker proteins was determined by enzyme-linked immunosorbent assay and Western blotting with selected monoclonal antibodies of known specificities. Soluble secreted proteins (MPB64 and proteins of the antigen 85 complex) and three heat shock proteins (DnaK, GroEL, and GroES) were recovered in a single peak after gel filtration, indicating their occurrence as a free monomer in the culture fluid and cytosol, respectively. Other constituents eluted in two distinct peaks during gel filtration. The first peak corresponded to the void volume, indicating complex formation between several proteins or attachment to lipids in the surface layer or the cytoplasmic membrane; the second peak corresponded to the expected monomer size indicated by SDS-PAGE under conditions that separate proteins from each other during sample preparation. The two-peak group contained constituents with known lipid contents, the 19- and 38-kDa lipoproteins and lipoarabinomannan. The 26-kDa form of MPB83 behaved similarly. After extraction with Triton X-114, these constituents entered into the detergent phase, confirming the lipoprotein nature of 26-kDa MPB83. The MPB83 molecule was shown to be available on the surface of BCG Tokyo bacilli for reaction with monoclonal antibody MBS43 by flow cytometry.

Antibodies, Monoclonal↗
PubMed1998

Human lung fibroblasts release chemokinetic activity for monocytes constitutively.

We determined whether human lung fibroblasts (HLFs) might release mediators that are responsible for monocyte chemokinetic activity (MCA) constitutively. HLF supernatant fluids showed MCA in a time-dependent manner (P < 0.001). Checkerboard analysis of 24- and 72-h supernatant fluids showed that the activity was chemokinetic. Partial characterization of 24- and 72-h supernatant fluids revealed that the mediators released after 24 h were predominantly composed of lipid-soluble activity, and MCA was blocked by lipoxygenase inhibitors. The mediators released after 72 h were predominantly trypsin sensitive and blocked by cycloheximide. Molecular-sieve column chromatography identified four peaks of MCA. A polyclonal antibody to monocyte chemoattractant protein-1 (MCP-1) inhibited MCA by 20% after 24 h and by 40% after 72 h. Granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor-beta (TGF-beta) antibodies attenuated MCA released after 72 h by 30 and 10%, respectively. These antibodies inhibited corresponding molecular-weight peaks separated by molecular-sieve column. The concentrations of MCP-1, GM-CSF, and TGF-beta were 4,698 +/- 242, 26.8 +/- 3.8, and 550 +/- 15 pg/ml, respectively. A leukotriene B4 (LTB4)-receptor antagonist attenuated the total MCA and the lowest molecular weight peak of MCA. The concentrations of LTB4 were 153.4 +/- 12.4 (24 h) and 212 +/- 16.6 (72 h) pg/ml. These findings suggest that HLFs may modulate the recruitment of monocytes into the lung by releasing MCP-1, GM-CSF, TGF-beta, and LTB4 constitutively.

Adult↗
PubMed1998

Alveolar type II-like cells release G-CSF as neutrophil chemotactic activity.

We evaluated the potential of A549 cells, an alveolar type II epithelial cell line, to release granulocyte colony-stimulating factor (G-CSF), in addition to interleukin (IL)-8 and leukotriene B4, as neutrophil chemotactic activity (NCA). Human recombinant IL-1beta stimulated A549 cells to release NCA in a time- and dose-dependent fashion. The released NCA was blocked by mouse anti-human G-CSF polyclonal antibody. Molecular-sieve column chromatography revealed that IL-1beta induced the release of a 19- to 20-kDa chemotactic mass that was inhibited by anti-human G-CSF antibody. IL-1beta stimulated the release of G-CSF in a dose-dependent fashion, but the time-dependent profile of G-CSF showed that the concentration of G-CSF declined after 48 h. Tumor necrosis factor (TNF)-alpha, Escherichia coli lipopolysaccharide (LPS), and bradykinin (BK) stimulated A549 cells to release NCA that was inhibited by anti-G-CSF antibody. The release of G-CSF in response to TNF-alpha, LPS, and BK was significantly increased. The similar concentrations of human recombinant G-CSF (10-1,000 pg/ml) as in the supernatant fluid induced neutrophil chemotaxis. G-CSF mRNA was expressed time and dose dependently at 4 h and declined after 4 h in response to IL-1beta as evaluated by RT-PCR. The expression of G-CSF mRNA was also observed by TNF-alpha, LPS, and BK stimulation. These data suggest that type II alveolar epithelial cells may produce G-CSF as NCA and may participate in the regulation of leukocyte extravasation.

Animals↗
PubMed1998

Acetylcholine and substance P stimulate bronchial epithelial cells to release eosinophil chemotactic activity.

We investigated a role of neuroregulation in the release of eosinophil chemotactic activity (ECA) from bovine bronchial epithelial cells (BBEC). BBEC were stimulated with acetylcholine (ACh) and substance P (SP), and the supernatant fluids were tested for ECA by a blind-well chemotactic chamber technique. BBEC released ECA in response to ACh and SP in a dose- and time-dependent manner. Checkerboard analysis showed that ECA in regard to ACh and SP was chemotactic rather than chemokinetic. Partial characterization revealed that ECA involved both lipids and peptides. The release of ECA in response to ACh and SP was inhibited by nonspecific and 5-specific lipoxygenase inhibitors and by cycloheximide (P < 0.01). Molecular-sieve column chromatography revealed that these mediators induced three molecular mass peaks (near 25 kDa, 9 kDa, and 400 Da, respectively). The lowest peak, which represented the predominant activity, was blocked by leukotriene B4-receptor antagonist (P < 0. 01) but not by platelet-activating factor-receptor antagonist. The release of leukotriene B4 in the supernatant fluids was increased in response to ACh and SP stimulation (P < 0.01). Platelet-activating factor was not detected. These results raise the possibility of a role of neuroregulation for the elaboration of ECA in the airway.

Acetylcholine↗
PubMed1998

Ionized calcium and 1,25-dihydroxyvitamin D concentration in serum of patients with sarcoidosis.

The aim of this study was to evaluate alterations in calcium metabolism in sarcoidosis. The serum concentrations of calcium (sCa), ionized calcium (sCa2+), 1,25-dihydroxyvitamin D (s1,25(OH)2D3) and parathyroid hormone (sPTH), serum angiotensin-converting enzyme activity (sACE) and urinary excretion of calcium (uCa) were studied in 36 Japanese patients with pulmonary sarcoidosis, aged 48.1+/-15.3 yrs (mean+/-SD), 15 males and 21 females. During the study the patients were on a daily diet with 500 mg calcium and 1000 mg phosphorus for a total of 6 days. sCa2+ was above the normal range (>1.26 mmol x L(-1)) in 10 patients (27.8%), 12 patients (33.3%) were hypercalciuric, and 16 patients (44.4%) showed alteration in calcium metabolism, with an increase in values of sCa, sCa2+ or uCa. There was a significant correlation between sCa2+ and s1,25(OH)2D3 (p<0.001), as well as between sCa2+ and sACE (p<0.001). s1,25(OH)2D3 in patients with extrathoracic involvement (ETI) tended to be higher than in patients without ETI. sCa2+ was less than 1.23 mmol x L(-1) (p<0.05) in the majority of patients without ETI, and sCa2+ was less than 1.24 mmol x L(-1) in the majority of normocalciuric patients. In conclusion, a disease-related alteration in calcium metabolism was seen in about 40% of patients with sarcoidosis, and 1,25-dihydroxyvitamin D probably plays a crucial role in this abnormality. The serum concentration of ionized calcium was considered to be a useful index for the disease activity of sarcoidosis.

Adult↗
PubMed1998

Pulmonary epithelioid haemangioendothelioma in 21 patients, including three with partial spontaneous regression.

This investigation studied the general conditions and prognostic factors of pulmonary epithelioid haemangioendothelioma (PEH), which is a rare disease. Twenty-one patients were collected throughout Asia by a questionnaire. Age at the detection or onset of symptoms of PEH was 14-64 yrs (mean 44 yrs). Males were more likely to be detected by symptoms (4/8, 50%) than were females (1/13, 8%). Fifteen showed bilateral multiple nodular opacities. Partial spontaneous regression occurred in three asymptomatic patients (one male and two females, all with bilateral multiple nodular opacities) 5, 13 and 15 yrs after detection. Two of the three patients with pleural effusion died within 1 yr, while the 16 patients with no effusion were alive more than 1 yr later (p<0.05). Histologically, two patients with fibrinofibrous pleuritis and extrapleural proliferation of tumour cells died within 2 yrs, while only one of 14 patients lacking such manifestations died within the same period (p<0.05). All three patients without spindle tumour cells survived for 12 yrs after the diagnosis, while all four patients with such cells died during the same period (p<0.05). In conclusion, 21 patients with pulmonary epithelioid haemangioendothelioma were reported, of whom three demonstrated partial spontaneous regression, and adverse prognostic features were identified.

Adolescent↗
PubMed1998

Idiopathic nonspecific interstitial pneumonia/fibrosis: comparison with idiopathic pulmonary fibrosis and BOOP.

Based on past difficulties in clinically differentiating patients with idiopathic pulmonary fibrosis (IPF), bronchiolitis obliterans-organizing pneumonia (BOOP), and nonspecific interstitial pneumonia/fibrosis (NSIP), which all manifest clinically as interstitial lung disease, experience with pathologically confirmed examples of the three diseases was reviewed to compare clinical profiles and prognosis and to define NSIP more clearly. Thirty-one patients (15 males and 16 females) were pathologically identified as NSIP and subclassified into either the cellular (n=16) or fibrotic group (n=15). All 31 patients were clinically considered to be idiopathic NSIP cases. Patients with idiopathic BOOP (n=16) and IPF (n=64) were compared with the NSIP patients. Subacute presentation of interstitial lung disease characterized both idiopathic NSIP and idiopathic BOOP. NSIP patients showed volume loss on a chest radiograph (29.0%) and honeycombing on a computed tomography scan (25.8%); these features were not found in BOOP patients. Bronchoalveolar lavage lymphocytosis was characteristic of both BOOP and NSIP. Two subgroups of NSIP can be recognized histologically: patients in the fibrotic group had a less favourable outcome than those in the cellular group. BOOP and NSIP had a more favourable outcome than IPF. In conclusion, idiopathic nonspecific interstitial pneumonia can be differentiated from other types of idiopathic interstitial pneumonia, both pathologically and clinically.

Adult↗
PubMed1998

Selective inhibition of Src protein tyrosine kinase by analogues of 5-S-glutathionyl-beta-alanyl-L-dopa.

Twelve analogues of the antibacterial phenolic peptide 5-S-glutathionyl-beta-alanyl-L-dopa (5-S-GA-L-D: 1) were synthesized via orthoquinones using tyrosinase. Several synthesized compounds inhibited the v-Src autophosphorylation tyrosine kinase reaction with an IC50 value comparable to that of herbimycin. The inhibition of c-Src substrate phosphorylation was much less active than v-Src autophosphorylation inhibition. The analogues showed no effects on substrate phosphorylation by epidermal growth factor receptor (EGFR), and this selectivity is the most characteristic feature of the analogues (1-12).

Enzyme Inhibitors↗
PubMed1998

Successful treatment of infertility due to anejaculation with in vitro fertilization and embryo transfer: a report of two cases.

We investigated the efficacy of assisted ejaculation in combination with in vitro fertilization and embryo transfer (IVF-ET) in two couples with infertility due to anejaculation. Case 1 was in an anejaculatory condition associated with a spinal cord-injury. We performed intrauterine insemination (IUI) three times using motile sperm obtained by intrathecal injection of neostigmine, but no pregnancy followed. The couple then entered IVF-ET. The semen volume obtained by assisted ejaculation was 4.5 ml. The sperm count was 33 x 10(6)/ml with 33% motility. At 35 weeks of gestation she delivered three healthy babies by cesarean section. Case 2 was in an unexplained retrograde ejaculatory condition. We performed IUI eight times before changing to IVF-ET. We then used sperm obtained from urine or sperm recovered from the bladder after administration of human tubal fluid, but no pregnancy followed. At the fifth IVF-ET attempt, using sperm obtained from urine, we succeeded. We prepared the sperm by the Percoll gradient method. The sperm count was 36 x 10(6)/ml with 64% motility. At 39 weeks of gestation she delivered a healthy baby. Deficient seminal quality contributes to the decreased fertility potential in patients with anejaculation. With the use of IVF-ET methods, pregnancies can be achieved in these couples.

Adult↗
PubMed1998

Superior sagittal sinus thrombosis associated with primary antiphospholipid syndrome--case report.

A 36-year-old female with a history of recurrent pregnancy loss experienced sudden onset of disturbance in consciousness, with right hemiparesis and total aphasia. Computed tomography revealed a massive hemorrhage in the left frontal lobe, and angiography showed occlusion of the anterior two-thirds of the superior sagittal sinus. Laboratory investigations detected the presence of lupus anticoagulant, elevation of the anticardiolipin beta 2-glycoprotein I complex antibody level, and a decreased protein S activity level. There were no underlying conditions, such as connective tissue disorders, malignancies, infectious diseases, and drug-induced disorders, so the diagnosis was primary antiphospholipid syndrome. Primary antiphospholipid syndrome should be considered in the evaluation of patients with "idiopathic" or "primary" sinus and cerebral venous thrombosis.

Adult↗