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Biomedical subjects

S Fujishima

Publications and source records attributed to S Fujishima.

At least 55 records · Page 3Linked to original sources
PubMed1996

A derivative of cationic antimicrobial protein attenuates lung injury by suppressing cell adhesion.

Cationic antimicrobial protein of 18 kD (CAP18) was identified and purified from rabbit granulocytes and shown to inhibit various activities of lipopolysaccharide (LPS). We investigated the effect of a 32-amino-acid C-terminal fragment of CAP18 (CAP18-derived peptide, CDP) on the pathogenesis of acute lung injury caused by intravenous endotoxin. Guinea pigs were divided into six groups: (I) saline control (n = 8), (2) CDP-alone (n = 8), (3) LPS-alone (n = 8), (4) LPS+CDP0m (n = 8), (5) LPS+CDP10m (n = 8), and (6) LPS+CDP60m (n = 8). A CDP dose of 0.2 mg/kg was injected at various time points after LPS injection. Lung wet-to-dry weight ratio, [125I]albumin leakage in lung tissue and bronchoalveolar lavage (BAL) fluid, differential cell count in BAL fluid, and histopathologic features were examined 4 h after intravenous administration of 0.02 mg/kg of LPS. The LPS+CDP0m and the LPS+CDP10m groups showed significantly attenuated lung injury compared to that seen in the LPS-alone group, however the LPS+CDP60m group revealed no attenuation of lung injury. The accumulation of peripheral white blood cells into pulmonary vasculature was attenuated only in the LPS+CDP0m but not in the LPS+CDP10m groups. We examined the effect of CDP on the expression of adhesion molecules using human umbilical vein endothelial cells, the result of which showed that CDP suppressed the LPS-induced expression of adhesion molecules in a dose-dependent manner. We conclude that CDP attenuates inflammatory cell migration into alveoli resulting in the attenuation of lung injury.

Albumins↗
PubMed1996

Serial changes in blood pressure and neurohormone levels after the onset of lacunar stroke.

To assess serial changes in blood pressure and its circadian variation following a lacunar stroke, the authors studied 7 patients who developed a single lacunar infarction in either the internal capsule or the corona radiata. Blood pressure and pulse rate were monitored noninvasively for twenty-four hours by an ambulatory blood pressure monitoring device in the acute, subacute, and chronic phases of the strokes. In the acute and chronic phases, the authors also measured urinary excretion of catecholamines every 6 hr, and serum cortisol concentration at 9:00, 17:00, and 21:00 hr. The patients were free from antihypertensive agents during the study. The twenty-four-hour averages of both systolic and diastolic blood pressure in the chronic phase were lower than those in the acute phase (P < 0.05). A nighttime fall in blood pressure was observed in the subacute and chronic phases (P < 0.05), but not in the acute phase. Urinary excretion of epinephrine at night in the acute phase was significantly higher than that in the chronic phase (P < 0.05). Serum levels of cortisol at 17:00 and 21:00 hr in the acute phase also exceeded those in the chronic phase (P < 0.05 and P < 0.01, respectively). The authors conclude that an increased secretion of epinephrine and cortisol might, at least in part, contribute to a high blood pressure and a lack of circadian variation in blood pressure in the acute phase of lacunar stroke.

Acute Disease↗
PubMed1996

Flow cytometric detection of cell-associated cytokines in alveolar macrophages.

To elucidate the cytokine-producing capacity of alveolar macrophages (AMs), we have introduced a method of flow cytometry combined with saponin treatment to detect the cell-associated cytokines. We studied bronchoalveolar lavage fluid cells from six patients with sarcoidosis (SAR) and six control (CTL) subjects. Cells were either left uncultured, or cultured with and without lipopolysaccharide (LPS), then treated with paraformaldehyde and saponin and analysed for cell-associated interleukin-1 beta (IL-1 beta) and tumour necrosis factor-alpha (TNF-alpha) by flow cytometry. Cell-associated IL-1 beta and TNF-alpha were also analysed by immunoassays. The flow cytometric cytokine values were correlated with the immunoreactive cell-associated cytokines (IL-1 beta: r = 0.45, p < 0.05; TNF-alpha: r = 0.82, p < 0.001). The histograms of cell-associated IL-1 beta yielded a single peak both in the patients and controls, whereas the histograms of cell-associated TNF-alpha exhibited two peaks in SAR patients, but just a single peak in the CTL subjects. The mean value of the cell-associated TNF-alpha in LPS+ AMs was higher in the SAR patients than in the CTL subjects (p < 0.001). In conclusion, the flow cytometric method can be applied to the semiquantitative detection of cell-associated cytokines in alveolar macrophages at the single cell level.

Adult↗
PubMed1996

Purification and characterization of N-acetylglucosamine 6-phosphate deacetylase with activity against N-acetylglucosamine from Vibrio cholerae non-O1.

An enzyme that deacetylates N-acetylglucosamine to glucosamine from Vibrio cholerae non-O1 was purified to homogeneity by sequential procedures. The native enzyme had a molecular mass of 190,000 Da and was predicted to be composed of four identical subunits with molecular masses of 45,000 Da. The purified enzyme hydrolyzed N-acetylglucosamine, N-acetylglucosamine 6-phosphate, and N-acetylglucosamine 6-sulfate, but not chitin oligosaccharides, and N-acetylgalactosamine. The deacetylase activity was completely abolished by N-ethylmaleimide, p-chloromercuribenzoate, EDTA, and Cu2+. On the other hand, the activity was activated by Co2+. The amino-terminal amino acids of the purified enzyme were sequenced. Among the 22 N-terminal amino acid residues, 12 residues of Vibrio deacetylase were identical with that of Escherichia coli GlcNAc 6-phosphate deacetylase.

Acetylglucosamine↗
PubMed1996

[High concentrations of interleukin-8 in bronchoalveolar lavage fluid from a patient with adult respiratory distress syndrome].

A 75-year-old man was admitted to the hospital due to acute onset of a dry cough and dyspnea on exertion. Arterial blood gas analysis showed hypoxemia (PaO2 = 63 Torr) on room air. Chest radiography and computed tomography showed diffuse bilateral infiltrates. Adult respiratory distress syndrome was diagnosed from the findings described above and from the lack of evidence of left heart failure. Diffuse alveolar damage was confirmed at autopsy. During the course of his illness, the patient underwent bronchoalveolar lavage five times. The recovered fluid had high concentrations of interleukin-8 (IL-8), with a maximum of 6260 pg/ml and a minimum of 190 pg/ml, and these values correlated with the number of polymorphonuclear cells in the fluid. Levels of leukotriene B4, another chemotactic factor for PMN, in the lavage fluid were not high. We conclude that IL-8 was a major chemoattractant for PMN in the alveoli of this patient.

Aged↗
PubMed1996

[Cytokine-mediated biological response to severe infections in surgical patients].

Cytokines serve to initiate the acute inflammatory response and to integrate nonspecific and specific immunological responses to infections occurring in perioperative patients. Microbial substances induce macrophages to produce pivotal cytokines (TNF-alpha and IL-1 beta). This results in an activation of other cytokine productions including IL-2, IL-3, IL-4, IL-6, chemokines, and IL-10. Also, other host-originated humoral mediators are released from macrophages, neutrophils, platelets, and endothelial cells Various cytokines are also produced by helper-T (Th) cells, and the Th1/Th2 balance is regulated by cytokines and stress hormones. This nonspecific inflammatory response and specific immunological response which are mediated by cytokines are crucial for the host defense against invading pathogens. On the other hand, the blood levels of TNF-alpha, IL-6, IL-8, and MIP-1 alpha were correlated with the severity and mortality in patients with sepsis. Also we found that in patients with inhalation injury the high IL-8 levels in bronchoalveolar lavage fluid on admission predicted the development of respiratory insufficiency. In severe infection, a systemic release of various cytokines is not properly regulated, and the high blood levels of the proinflammatory cytokines cause an autodestructive systemic inflammatory response syndrome (SIRS). This condition is termed "Cytokine Storm" by the author. In cytokine storm, not only proinflamamtory cytokines, but also anti-inflammatory cytokines appear in circulating blood, leading to septic shock, multiple organ dysfunction, and immunosuppression. With further understanding of the roles of cytokines in sepsis, modulation of cytokine responses could be a new modality of the treatment.

Adult↗
PubMed1995

Secondary exposure of medical staff to sarin vapor in the emergency room.

OBJECTIVE: To clarify the risk of secondary exposure of medical staff to sarin vapor in the emergency room, and to warn emergency room staffs of the hazard. DESIGN: Retrospective observational survey. SETTING: Emergency department of a university hospital in a metropolitan area of Japan. PARTICIPANTS: Fifteen doctors treating victims of a terrorist attack with sarin in the Tokyo subways on the day of the attack. MEASUREMENTS AND RESULTS: Of the 15 doctors who worked in the emergency room treating the victims, 13 became simultaneously aware of symptoms during the resuscitation of two victims who were exposed to sarin. Among 11 doctors (73%) who complained of dim vision, the pupils were severely miotic (<2 mm) in 8 (73%). Other symptoms included rhinorrhea in eight (53%), dyspnea or tightness of the chest in four (27%), and cough in two (13%). Atropine sulfate was given to six, and pralidoxime was given to one of these six doctors. To decontaminate the emergency room of sarin vapor, ventilation was facilitated and all belongings of the patients were sealed up. None of the doctors noticed worsening of their symptoms thereafter. CONCLUSIONS: Careful attention to the risks of secondary exposure to toxic gas in the emergency room and prompt decontamination if such exposure should occur are necessary in the case of large-scale disasters caused by sarin.

Adult↗
PubMed1995

Neutrophil-mediated tissue injury and its modulation.

Neutrophils play a key role in the development of the systemic inflammatory response syndrome (SIRS) and multiple organ dysfunction syndrome (MODS). Since the lungs are the main target in these syndromes, with adult respiratory distress syndrome (ARDS) as the outcome, extensive research has been undertaken to prevent or mitigate ARDS. As evidence of the involvement of neutrophils in ARDS has accumulated, modulation of their function has become a major goal in terms of a therapeutic approach. In this short review, we sought to update our knowledge about neutrophils. Firstly, we summarized the various stimuli which activate neutrophils. Secondly, we described the different mediators, including cytokines, which are released by neutrophils. Lastly, we discussed the possible modulation of their function. Although we cannot assess the clinical usefulness of biochemical substances merely on the basis of their in vitro effects, understanding these mechanisms is fundamental to the success of the new therapeutic approach which is currently under way.

Cytokines↗
PubMed1995

Effect of blood and albumin on pulmonary hypertension and edema in perfused rabbit lungs.

Perfusate composition may alter pulmonary hemodynamics and edema formation in perfused lungs. Perfusion for 3 h with Krebs-Henseleit solution with 3% bovine serum albumin did not produce pulmonary hypertension, pulmonary edema (assessed by lung wet-to-dry wt ratio), or increased macromolecular permeability (assessed by 125I-albumin uptake). Addition of blood to hematocrit levels of 10 or 20% resulted in pulmonary hypertension during the final hour of perfusion but not pulmonary edema or increased macromolecular permeability. Pulmonary hypertension during blood perfusion was primarily due to increased precapillary resistance. Perfusion with buffer solution without albumin produced edema and increased macromolecular permeability but not pulmonary hypertension. In lungs perfused with blood (20% hematocrit), thromboxane B2 levels increased in parallel with the pulmonary hypertension, and inhibition of cyclooxygenase or thromboxane synthase with indomethacin or dazmegrel prevented pulmonary hypertension. Perfusion with leukopenic blood (from prior nitrogen mustard administration or from filtration) also prevented pulmonary hypertension. We conclude that blood perfusion produces pulmonary hypertension via thromboxane A2 generation, which depends on leukocyte activation, and that perfusion with buffer solutions without albumin produces edema and increased permeability without pulmonary hypertension.

Albumins↗
PubMed1995

Attenuation of hyperoxic lung injury by the 21-aminosteroid U-74389G.

Hyperoxic lung injury is attributable to oxygen radicals produced under hyperoxic conditions. The 21-aminosteroid (AS), U-74389G, is a potent antioxidant. We examined the effect of U-74389G on lung injury in guinea pigs during exposure to 90% O2 for 48 h. We injected either vehicle or 10 mg/kg of U-74389G 30 min before the O2 exposure and injected the same dose 12, 24, and 36 h later. We performed two series of experiments after exposure. In the first series, we measured the clearance rate of 99mTc-labeled dialdehyde starch (DAS) from the lungs as an index of pulmonary epithelial damage in three experimental groups consisting of 1) control (n = 6) O2 alone (n = 6), and 3) O2 + AS (n = 6). In the second series, pulmonary endothelial injury was estimated by using 28 guinea pigs divided into four experimental groups consisting of 1) control (n = 8), 2) AS alone (n = 5), 3) O2 alone (n = 6), and 4) O2 + AS (n = 9). In the second series, we measured the wet-to-dry weight ratio (W/D) as an index of lung water and the concentration ratio of 125I-labeled albumin in lung tissue and bronchoalveolar lavage (BAL) fluid compared with plasma (T/P and BAL/P, respectively) as indexes of pulmonary endothelial damage. Cell accumulation in BAL fluid and lung tissue samples was also assessed in the second series.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Long-term course of bronchiectasis and bronchiolitis obliterans as late complication of smoke inhalation.

We describe the long-term course of a patient with bronchiectasis and bronchiolitis obliterans, both of which developed as late complications of a smoke inhalation injury. Sequential chest X-rays obtained during the observation period showed gradual progression of bronchiectasis from the saccular to the cystic type. Symptoms, spirometry and blood gas analysis, however, remained stable for 15 years. We believe that symptoms and physiological derangement were due mainly to bronchiolitis obliterans, and that once the pathophysiological condition had been established following the initial injury, it could be maintained by conservative medical management.

Adult↗
PubMed1995

Soluble form of P-selectin in plasma is elevated in acute lung injury.

A number of adhesion molecules on neutrophils and the pulmonary capillary endothelium mediate the neutrophil accumulation in the lungs at the onset of adult respiratory distress syndrome or acute lung injury (ALI). P-selectin, located on both vascular endothelial cells and platelets, has been shown to be one of these neutrophil-endothelial cell adhesion molecules. In this study, we measured the soluble form of P-selectin in plasma (PPS) from 19 patients (surviving, 11; deceased, 8) with ALI due to various causes and assessed the clinical significance of this measurement. Twelve healthy subjects and 29 patients with other pulmonary diseases, including idiopathic pulmonary fibrosis (IPF) (n = 8), sarcoidosis (n = 5), pneumonia (n = 8), and sepsis without ALI (n = 8) were also studied for comparison. PPS in patients with ALI (474.5 +/- 366.8 ng/ml, mean +/- SD) were significantly higher than those in control subjects (98.8 +/- 39.7, p < 0.01) and in patients with IPF (210.4 +/- 76.6, p < 0.05), sarcoidosis (135.2 +/- 71.5, p < 0.05), pneumonia (225.3 +/- 81.0, p < 0.05), and sepsis without ALI (271.8 +/- 46.5, p < 0.05). There was no significant difference in PPS levels between seven patients with and 12 patients without multiple organ failure. Lung injury scores correlated significantly with the PPS level (r = 0.605, p < 0.05). PPS levels of deceased patients with ALI (841.0 +/- 252.4) were significantly higher than those of surviving patients with ALI (208.0 +/- 109.2, p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

Effect of external negative pressure on pulmonary 99mTc-DTPA clearance in humans.

We studied the mechanisms by which pulmonary solute clearance is affected by lung inflation. We examined the pulmonary clearance of inhaled technetium-99m diethylenetriaminepentaacetic acid (99mTc-DTPA) together with changes in lung volumes in healthy men after applying graded levels of continuous external negative pressure (CNP) and positive end-expiratory pressure (PEEP). The 99mTc-DTPA clearance increased from the baseline during -15 cm H2O CNP (p < 0.005) and during -20 cm H2O CNP (p < 0.001). The 99mTc-DTPA clearance increased during +15 cm H2O PEEP (p < 0.001). However, the changes during both -10 cm H2O CNP and +10 cm H2O PEEP did not differ from the baseline, indicating a threshold effect. On the other hand, changes in FRC during CNP were proportional to the applied pressures and were similar to those during PEEP with corresponding pressures. These results suggest that pulmonary vascular recruitment induced by CNP does not affect pulmonary 99mTc-DTPA clearance. This threshold effect suggests that the increased clearance is due to changes in membrane permeability rather than in the area of the alveolar-capillary interface or the lining layer thickness. We concluded that the effect of lung inflation on solute clearance may be mediated by the changes in membrane permeability.

Adult↗
PubMed1995

Priming of alveolar macrophages for interleukin-8 production in patients with idiopathic pulmonary fibrosis.

We evaluated the contribution of interleukin-8 (IL-8) to the pathogenesis of idiopathic pulmonary fibrosis (IPF) by studying bronchoalveolar lavage fluid (BALF) in eight patients with IPF in the chronically progressive phase, five patients with IPF in the subacutely progressive phase, eight patients with sarcoidosis (SAR), and eight control (CTL) subjects. IL-8 levels were not increased in the BALF of the patients with IPF in the chronic phase (11.3 +/- 8.8 pg/ml), nor in that of the SAR patients (13.8 +/- 7.8 pg/ml), whereas they were increased in the BALF of patients with IPF in the subacutely progressive phase (1.93 +/- 1.10 ng/ml). We then investigated extracellular and cell-associated IL-8 in lipopolysaccharide (LPS)-stimulated BALF cells to determine the IL-8-producing potential of alveolar macrophages (AM). Following LPS stimulation of BALF cells from patients with IPF in the chronic phase, both the extracellular IL-8 in culture fluid and the cell-associated IL-8 in AM were increased as compared with those for the CTL subjects (p < 0.05 and p < 0.05, respectively). These results suggest that AM of patients with IPF are primed for IL-8 production. We conclude that IL-8 may play a role in neutrophilic alveolitis, especially during the subacute phase of IPF.

Acute Disease↗
PubMed1995

Neutrophils activated by granulocyte colony-stimulating factor suppress tumor necrosis factor-alpha release from monocytes stimulated by endotoxin.

We investigated the in vitro effects of granulocyte colony-stimulating factor (G-CSF) on tumor necrosis factor-alpha (TNF-alpha) release from monocytes. Peripheral blood monocytes and neutrophils were obtained from healthy donors (n = 8). Neutrophils alone, neutrophils plus monocytes, and monocytes alone were incubated with and without G-CSF (10 ng/ml) and were studied for TNF-alpha release; monocytes subsequently were stimulated by endotoxin (lipopolysaccharide [LPS] at 10 and 1,000 ng/ml). Neutrophils alone did not produce TNF-alpha after LPS stimulation irrespective of G-CSF treatment. TNF-alpha release from monocytes was suppressed significantly by pretreatment with G-CSF in the presence of neutrophils (P < 0.01). Suppression of TNF-alpha release after LPS was not observed when monocytes were preincubated with G-CSF in the absence of neutrophils. TNF-alpha release from monocytes stimulated by LPS was not inhibited when monocytes were incubated with the supernatant from G-CSF-activated neutrophils. Pretreatment with G-CSF inhibited intracellular TNF-alpha production, as measured by flow cytometry, of monocytes stimulated by LPS (P < 0.05). These data suggest that neutrophils activated by G-CSF directly suppress TNF-alpha release from monocytes stimulated by LPS.

Adult↗
PubMed1995

Effects of intra-arterial infusion of insulin on forearm vasoreactivity in hypertensive humans.

We previously demonstrated that intra-arterial infusion of insulin attenuates vasoreactivity to phenylephrine and angiotensin II in the forearm of normotensive humans, which suggests that the pressor effects of insulin via sympathetic activation may be offset in peripheral arteries. In the present study, we investigated the effects of insulin on vasoreactivity in hypertensive humans. Seven male patients with essential hypertension (age, 26 +/- 2 yr; blood pressure, 159 +/- 4/103 +/- 4 mmHg; mean +/- SEM) were studied. We measured forearm blood flow by a strain gauge plethysmograph while infusing phenylephrine (1, 4, 12 nmol/min) and angiotensin II (5, 10, 20 pmol/min) locally into the brachial artery before and during simultaneous intra-arterial infusion of human insulin (0.15 mU/kg/min). Forearm vascular resistance was calculated from directly measured arterial pressure and forearm blood flow. Intra-arterial infusion of insulin raised the local plasma insulin level without changing the blood glucose level, basal forearm blood flow, or forearm vascular resistance. Phenylephrine and angiotensin II increased forearm vascular resistance dose-dependently before and during insulin infusion. In contrast to the previous results in normotensive subjects, locally infused insulin did not attenuate vasoconstrictive responses to phenylephrine and angiotensin II in patients with essential hypertension. These results suggest that the balance between the pressor and depressor effects of insulin might be altered in favor of a pressor effect in patients with hypertension.

Blood Glucose↗