Biomedical subjects

K Soejima

Publications and source records attributed to K Soejima.

At least 73 records · Page 4Linked to original sources

PubMed1998

[Acute exacerbation of subacute interstitial pneumonia after thoracoscopic lung biopsy].

A 55-year-old woman was admitted to our hospital with progressive dyspnea that had begun one month before. Chest rentogenogram revealed groundglass appearance and reticular shadows bilaterally. Pulmonary function tests showed both decreased vital capacity and diffusing capacity. Bronchoalveolar lavage fluid had a high lymphocyte fraction with a low CD4+/CD8+ ratio. Thoracoscopic lung biopsy revealed thick, fibro-edematous interstitium and diffuse infiltration of lymphocytes. We also observed an intra-alveolar exudate with infiltration of histiocytes and lymphocytes. The clinical features and pathological findings were consistent with subacute interstitial pneumonia, which was the entity proposed by Kawabata and colleagues. The patient developed acute respiratory failure four days after lung biopsy and died despite steroid pulse therapy. Although subacute interstitial pneumonia has been reported to respond to steroid therapy, and to have a good prognosis, we believe that subacute interstitial pneumonia could fatally worsen when associated with lung biopsy, infection, or some other stimulus.

Acute Disease↗

PubMed1998

[Pulmonary emphysematous changes associated with Pneumocystis carinii pneumonia in an AIDS patient].

A 60-year-old man was admitted to our hospital complaining of non-productive cough. He had worked in Africa and received a blood transfusion after a traffic accident in 1985. On admission, the patient had remarkable hypoxemia and a decreased CD4+ lymphocyte count. A serological test for human immuno-deficiency virus (HIV)-1 was positive. His chest radiographs showed diffuse reticular and linear opacities, and broncoalveolar lavage findings established a diagnosis of Pneumocystis carinii pneumonia (PCP). A high-resolution CT of the chest revealed peripheral infiltrates and low attenuation areas (LAA) consistent with severe emphysematous alterations. We administered high-dose methylprednisolone and trimethoprim-sulphamethoxazole (TMP-SMX). Because of marked eosinophilia, TMP-SMX was discontinued, and the patient was given inhaled pentamidine isothiocyanate. Although there was a striking clinical improvement, the emphysema-like lesion on chest CT remained unaltered. LAA on CT had been modest in 1994, but had markedly enlarged during the three years thereafter, leading us to speculate that most of the LAA lesions recognized on admission might have developed in association with PCP. Pulmonary function tests showed an obstructive ventilatory defect and impaired diffusing capacity. Although PCP classically presents with diffuse ground-glass or fine granular opacities, thin-walled cavities or other atypical findings have recently been reported, especially in AIDS patients. There have been several reports about emphysema-like lesions associated with PCP. It was suggested that these lesions might be due to lung parenchyma destruction induced by HIV itself or increased elastase release from HIV-infected macrophages. This is the first report of PCP with pulmonary emphysematous lesions in Japan.

AIDS-Related Opportunistic Infections↗

PubMed1997

Increase in heart rate after radiofrequency catheter ablation is mediated by parasympathetic nervous withdrawal and related to site of ablation.

To assess the mechanism for the increased sinus rate after radiofrequency catheter ablation performed for atrioventricular nodal reentrant tachycardia (AVNRT), we studied heart rate variability before and after radiofrequency catheter ablation in 17 patients with AVNRT and in 38 patients with an accessory pathway. The accessory pathway was located at the left ventricular free wall, the right ventricular free wall, or the posterior interventricular septum. An increased sinus rate was observed in patients with AVNRT or with the accessory pathway at the posterior septum or left free wall after radiofrequency ablation. In these groups, high-frequency power, root mean square of successive difference and percent of adjacent cycles that were more than 50 ms apart, all of which are indices reflecting parasympathetic nervous activity, were decreased. The ratio of low-frequency to high-frequency power reflecting sympathovagal balance, was increased in patients with AVNRT or with an accessory pathway at the posterior septum or left free wall. Increases in sinus rate were correlated with decreases in high-frequency power, and percent of adjacent cycles more than 50 ms apart that the increase in heart rate was due to parasympathetic nervous withdrawal.

Adolescent↗

PubMed1997

Reconstruction of burn deformity using artificial dermis combined with thin split-skin grafting.

Twelve patients with post-burn contracture were treated using artificial dermis combined with thin split-skin grafting during the period January 1994 to April 1996. Bilayer artificial dermis was grafted onto full thickness open wounds of the skin, after excision of scar contracture tissue. About 3 weeks later, the silicone layer was removed and thin split-skin, 8/1000 in. thick, was grafted onto the newly synthesized dermis-like tissue in the wound bed. Scalp was chosen as the donor site in 11 of the 12 cases. Artificial dermis grafting was undertaken to ensure that morbidity at the donor site could be reduced as much as possible in the treatment of burn deformity. The skin grafts took completely in all cases. Postoperative management was performed in accordance with conventional skin grafting. Postoperative contraction or hypertrophic scar was observed in three cases, but a soft, favorable quality was obtained in the other nine cases. Treatment of burn deformity with artificial dermis may be beneficial in selected cases.

Adolescent↗

PubMed1997

Treatment of giant pigmented nevus using artificial dermis and a secondary skin graft from the scalp.

From January 1994 to October 1995, 5 patients with congenital giant pigmented nevi were treated using artificial dermis with a secondary skin graft from the scalp. The nevus was excised in full thickness and the open wound was grafted with artificial dermis. About 3 weeks later, thin split-thickness skin grafting on the newly synthesized, dermis-like tissue was required. We chose the scalp as the donor of the secondary skin graft. Epithelialization of each donor site was completed within 1 week. In addition, the donor site was not complicated with alopecia or hypertrophic scars. Morbidity at the donor site was minimized and favorable tissue quality of the grafted skin was obtained. The clinical results revealed that the scalp was a favorable donor of a secondary skin graft for the treatment of giant pigmented nevus with artificial dermis.

Adolescent↗

PubMed1997

A case of widely split double P waves with marked intra-atrial conduction delay.

We report a 78-year-old man as the first documented case of double P waves separated by 400 msec on 12-lead ECG. These P waves had different polarities on lead V1. The first P wave represented activation of the lateral wall of the right atrium, and the latter P wave represented activation of the medial right atrium and the left atrium. Widely spaced double potentials were recorded craniocaudally along the line, presumably corresponding to the crista terminalis during sinus rhythm. For this to occur, conduction disturbance has to be present both in the upper and lower right atrium. Conduction disturbance in the upper right atrium would interrupt excitation from the sinus node to the medial wall, and conduction disturbance in the lower right atrium would interrupt excitation spreading from the lower lateral right atrium to the isthmus area where fragmented potentials were recorded. These multiple discrete lesions appear to constitute a unique electrical atriopathy in this patient.

Aged↗

PubMed1997

Downmodulation of IL-8 receptors, type A and type B, on human lung neutrophils in vivo.

We examined the expression of interleukin (IL)-8 receptors (Rs), type A (IL-8-RA) and type B (IL-8-RB), on peripheral blood and bronchoalveolar lavage (BAL) fluid neutrophils; we also examined IL-8 and other chemoattractants in the epithelial lining fluid (ELF) of patients with chronic lower respiratory tract infection (CLI) to elucidate the in vivo regulation of IL-8Rs. Neutrophils were stained with monoclonal antibodies specific for IL-8-RA and IL-8-RB. We detected higher levels of IL-8 (81.6 +/- 25.4 ng/ml, mean +/- SE), leukotriene (LT) B4, and IL-1 beta in the ELF of the CLI patients than in their serum (P < 0.05). The expression of IL-8Rs on BAL neutrophils was significantly lower than that on peripheral blood neutrophils (P < 0.01 for both). In vitro analysis showed that low-level IL-8 (50 ng/ml) alone did not affect IL-8R expression but that it was downregulated by high-level IL-8 (500 ng/ml) alone and by low-level IL-8 in combination with LTB4 or IL-1 beta. Staurosporine reduced the downmodulation by low-level IL-8 plus LTB4 or IL-1 beta but not by high-level IL-8 alone. We speculate that pulmonary IL-8-RA and IL-8-RB may have been downmodulated by the combined effect of local chemoattractants through, in part, a protein kinase C-dependent mechanism.

Adult↗

PubMed1997

Fatal diffuse alveolar damage from bird fanciers' lung.

A 68-year-old man, who had continuing exposure to budgerigars, developed fatal acute respiratory failure following years of slowly progressive pulmonary deterioration. His lung function was characterized first by mild airflow obstruction and later by progressive loss of lung volume. Computed tomography showed progressive development of pulmonary fibrosis and honeycombing. His serum disclosed precipitins to pigeon antigen. During his final illness his chest radiograph showed widespread patchy consolidation. At autopsy, his lungs revealed left lower lobe bronchopneumonia, fibrosis and honeycombing at the bases and widespread evidence of diffuse alveolar damage with organized exudate in some alveoli. To our knowledge, this is the second reported fatality due to acute alveolar injury in bird fanciers' lung.

Acute Disease↗

PubMed1997

[A case report of angiomyolipoma arising from the renal capsule].

A case of angiomyolipoma arising from the renal capsule is reported. A 49-year-old female was admitted to our hospital with a complaint of abdominal mass pointed out by ultrasonography during her yearly health check. The tumor was 10 cm in size. On abdominal enhanced CT, the tumor was existed behind the left kidney. The capsule of the tumor was enhanced and the septums were seen inside of the tumor. MRI revealed a hemorrhage in the tumor and selective renal angiography showed the tumor was fed by the renal capsular artery. A tumor of the renal capsule was suspected and a laparotomy was done. Pathological results by the frozen section suggested malignancy and radical nephrectomy was performed. Angiomyolipoma was diagnosed histologically. Tumors of the renal capsule are uncommon and angiomyolipoma of the renal capsule is extremely rare. We have found only two cases in Japanese medical literature.

Angiomyolipoma↗

PubMed1997

[Effect of barnidipine hydrochloride on the autonomic nervous system: difference between short- and long-acting components of calcium antagonist].

Short-acting calcium antagonists have a deleterious effect on the prognosis for patients with myocardial ischemia, possibly caused by overactivation of sympathetic nerves due to vasodilatation, negative inotropism, or coronary steal. However, there is considerable debate about whether long-acting calcium antagonists as well as the short-acting calcium antagonists have the same effect. Barnidipine-HCl is a newly-developed calcium antagonist with 1:2 short- and long-acting particles. This study evaluated the changes of autonomic tone due to barnidipine. Both the short- and long-acting effect of the calcium antagonist was evaluated. Eleven patients with primary hypertension underwent 24-hour ambulatory electrocardiogram and blood pressure monitoring before and after the treatment with barnidipine. Heart rate and blood pressure were compared before and after the medication. Heart rate variability was analyzed with a Marquette 8000/T. High frequency power (HF), as a parameter of vagal tone, and the ratio to low frequency power (LF), as a parameter of sympathetic tone, were obtained. Twenty-four-hour average blood pressure decreased significantly during the day, but nocturnal hypotension was not observed. Heart rate did not increase. HF decreased at the peak of the short- and long-acting components. LF/HF increased at the peak of the short-acting component. Short-acting particles of barnidipine had a deleterious effect on the autonomic tone, that is overactivation of sympathetic tone and suppression of vagal tone. Long-acting particles of barnidipine suppressed the vagal tone. These findings suggest that short-acting calcium antagonists may cause arrhythmia or deterioration of coronary ischemia.

Autonomic Nervous System↗

PubMed1997

[Normal predicted values of CT indices reflect emphysematous alterations in the lung].

In order to obtain normal values and 95% confidence limits of various CT indices, healthy adult subjects with no history of smoking (n = 36) underwent CT scanning under a variety of conditions. By then applying the normal limits thus obtained to CT images of COPD patients (n = 45), we examined the sensitivity for detecting abnormal emphysematous changes in the lung fields. To measure emphysematous alterations, we used the average value of lung CT densities (ROI), the maximally appearing value in a CT histogram (Hist. Peak), the relative area with low CT densities below -910 HU (%LDA) and the total cross-sectional area (Area) in each lung section. Regardless of the section thickness (10 mm or 1 mm), the lung volume level at which the breath was held or the site from which CT images were taken (upper, middle or lower lung field), no significant correlation was observed between the CT indices associated with emphysematous changes and the subjects' age. This allowed us to define, independently of the subjects' age, normal values and 95% confidence limits for the CT indices. Among the CT indices surveyed, %LDA was found to be the most sensitive indicator for detecting emphysematous abnormalities. In so far as the extent of emphysema may be determined by lung CT density, classical CT images of 10-mm section thickness appear to have a sufficiently high sensitivity for the detection of emphysematous abnormalities, such that high-resolution CT may be unnecessary.

Adult↗

PubMed1997

[A case of interstitial pneumonia induced by intravesical administration of bacillus Calmette-Guerin (BCG)].

A 61-year-old man with superficial bladder cancer, which was detected after he complained of hematuria, was treated three times with intravesical BCG administration. Since liver dysfunction was detected thereafter, he was admitted to our hospital. Three days after admission, he complained of dyspnea on exertion associated with severe hypoxemia, as well as abnormal findings on chest X-ray, i.e. extensive bilateral lung densities. We performed bronchoscopic examination and obtained bronchoalveolar lavage fluid (BALF) and lung biopsy specimens (TBLB). In the BALF, a marked increase in the total cell number, particularly lymphocytes with a high CD4/CD8 ratio was noted. TBLB specimens revealed the lesions to be numerous non-caseating granulomas. We failed to obtain definite evidence of BCG in the sputum, urine, blood, and BALF. Instead, we found that a lymphocyte stimulation test for BCG (DLST) was strongly positive. Based on these findings, severe interstitial pneumonia probably induced by hypersensitivity against BCG, was diagnosed. Anti-tuberculous agents, and steroid-pulse therapy followed by oral administration of relatively low dose of steroid ameliorated the abnormal conditions, including chest X-ray film findings and hypoxemia. The population of lymphocytes and CD4/CD8 ratio in the BALF were reduced as well. Serious interstitial pneumonia was induced by the intravesical administration of BCG, which resulted in transitional changes in the BALF cell component.

Administration, Intravesical↗

PubMed1996

Cell-associated IL-8 in human blood monocytes: analysis by flow cytometry.

Several cell-associated cytokines, such as interleukin-1 (IL-1) and tumor necrosis factor, exist on the cell surface and are biologically active. Although extracellular IL-8, a potent chemotactic factor for primarily neutrophils, has been studied extensively, cell-associated IL-8 has barely been studied. In this study, we analyzed the intracellular and cell-surface IL-8 in human blood monocytes in vitro by using flow cytometry and predicted the biological activity of the cell-associated IL-8 in vivo. After fixation with paraformaldehyde, mononuclear cells were divided into two subgroups. One subgroup was left untreated to study cell-associated antigens, and the other subgroup was permeabilized with saponin to detect intracellular antigens. In lipopolysaccharide (LPS)-stimulated monocytes, IL-8 was detected solely intracellularly, whereas both the intracellular and cell-surface IL-1 beta was detectable. In a time-course study, the intracellular IL-8 increased in response to LPS stimulation, but the cell-surface IL-8 was undetectable throughout the course. In an LPS-stimulated monocytic cell line, both ELISA and flow cytometry detected the quantitative change of the intracellular IL-8. The dissimilar localization between IL-8 and IL-1 beta within cells was confirmed by the immunohistochemical analysis. In summary, LPS stimulation induced a time-dependent increase in intracellular but not cell-surface IL-8 in monocytes. Thus, it is unlikely that the cell-associated IL-8 is functioning physiologically. The semiquantitative flow cytometric procedure may be useful for simultaneous examination for cell-surface and intracellular cytokines.

Antibodies, Monoclonal↗

PubMed1996

Autonomic and antiarrhythmic drug modulation of ST segment elevation in patients with Brugada syndrome.

OBJECTIVES: We examined the modulatory effects of autonomic nervous system and antiarrhythmic drugs on the ST segment in patients with Brugada syndrome to gain an insight into the mechanism of ST segment elevation. BACKGROUND: Right bundle branch block, ST segment elevation and ventricular tachyarrhythmias define a distinct clinical and electrocardiographic (ECG) syndrome (Brugada syndrome). However, the mechanism of ST segment elevation and the causes of this syndrome are unknown. METHODS: The study included four patients in whom structural heart or coronary artery disease was excluded by noninvasive and invasive tests. High take-off ST segment elevation of either the coved or saddle-back type in precordial leads V1, V2 and V3 was seen in all patients. Three patients experienced recurrent episodes of syncope or aborted sudden cardiac death, and the remaining patient had palpitation. Autonomic receptor stimulation and blockade and intravenous administration of antiarrhythmic drugs were performed during sinus rhythm while the 12-lead ECG was recorded. Metaiodobenzylguanidine (MIBG) scanning and Holter monitoring were also performed. RESULTS: Beta-adrenoceptor stimulation by intravenous isoproterenol consistently reduced (> or = 0.1 mV) ST segment elevation at or 80 ms after the J point in all four patients. Selective alpha-adrenoceptor stimulation by intravenous norepinephrine in the presence of propranolol or by intravenous methoxamine consistently augmented, whereas alpha-adrenoceptor blockade reduced, ST segment elevation in three patients. Intracoronary acetylcholine or intravenous edrophonium or neostigmine augmented ST segment elevation without inducing coronary spasm in three of four patients. Class IA antiarrhythmic drugs also consistently augmented (three patients), whereas class IB drugs had no effect on (two patients) ST segment elevation. No abnormality was found on MIBG imaging or heart rate variability in three patients, suggesting that autonomic dysfunction is not a primary disease process. Class IA drugs had no effect on ST segment in three control patients, suggesting that the ST segment elevation seen in patients with Brugada syndrome in response to the drugs is not a nonspecific response. CONCLUSIONS: ST segment elevation in patients with Brugada syndrome was augmented by selective stimulation of alpha-adrenoceptors or muscarinic receptors or by class IA drugs but was mitigated by beta-adrenoceptor stimulation or alpha-adrenoceptor blockade. These responses might be explained by postulating the presence of an area of early repolarization or a local "depolarized" area in the ventricle causing ST segment elevation in this syndrome. Because only a small number of patients were studied, these possibilities need further evaluation.

Adult↗

PubMed1996

Augmentation of endotoxin-induced pulmonary responses by mononuclear cell phagocytosis in the reticuloendothelial system.

OBJECTIVE: To test the hypothesis that the effects of intravenous injection of latex particles would demonstrate the contribution of phagocytosis by mononuclear phagocytes to the development of Escherichia coli-induced acute lung injury in neutropenic guinea pigs. DESIGN: Prospective, controlled, experimental study. Intravenously injected the latex particles into 41 guinea pigs to investigate the contribution of the phagocytosis in acute lung injury. SUBJECTS: Forty-one guinea pigs. INTERVENTIONS: Forty-one guinea pigs were divided into five experimental groups: a saline group (n=9); an endotoxin group (n=10) receiving 2 mg/kg of intravenous E. coli endotoxin; a latex group (n=7) receiving 2 x 10(9)/kg of intravenous polystyrene latex (mean diameter 3.19 micrometers); an endotoxin + latex group (n=8); and an E. coli group (n=7) receiving 2 x 10(9) live E. coli/kg. MEASUREMENTS AND MAIN RESULTS: The lung wet/dry ratio was increased in the live E. coli-treated guinea pigs (6.71 +/- 0.16 [SEM], p < .01) as compared with the saline control (5.40 +/- 0.16, whereas the ratio was not increased in the endotoxin (5.52 +/- 0.14) or latex (5.58 +/- 0.20) groups. However, the lung wet/dry ratio was greater in the endotoxin + latex group (6.11 +/- 0.16, p < .05) than in the saline control. The 125I albumin lung tissue/plasma ratio was greater in the E. coli (2.00 +/- 0.29, p < .01) and endotoxin + latex (0.84 +/- 0.12, p < .05) groups than in the saline group (0.18 +/- 0.07), whereas no increases were observed in the endotoxin group (0.22 +/- 0.10) and the latex (0.34 +/- 0.13) group. More than 40% of the injected radiolabeled latex was observed to have accumulated in the reticuloendothelial system (liver and spleen), in both the saline control (40.1 +/- 2.3%, n=4) and endotoxin (57.3 +/- 6.8%, n=5) groups, with 2.6 +/- 1.5% and 3.1 +/- 1.7% in the lungs for the saline control and the endotoxin groups, respectively. The percent deposition of radiolabeled latex in the liver was greater in the endotoxin group (51.7 +/- 3.8%, p < .05) than in the saline group (37.6 +/- 5.9%). CONCLUSIONS: These findings suggest that, in neutropenic guinea pigs: a) the combination of endotoxin and latex particles induces acute lung injury; and b) the phagocytic properties of mononuclear phagocytes in the reticuloendothelial system augment endotoxin-induced pulmonary responses and may play a role in the development of live E. coli-induced acute lung injury.

Animals↗

PubMed1996

Heat-killed Corynebacterium parvum enhances endotoxin lung injury with increased TNF production in guinea pigs.

Corynebacterium parvum (CP) is known to increase susceptibility to endotoxin, which is associated with increased production of tumor necrosis factor (TNF). We investigated the effect of CP-priming on the pathogenesis of acute lung injury caused by intratracheal Escherichia coli endotoxin (lipopolysaccharide [LPS]). Guinea pigs were divided into four groups: (1) control (n=6), (2) CP-alone (n=6), (3) LPS-alone (n=6) and (4) CP + LPS (n=6). A CP dose of 4 mg/kg was injected intraperitoneally 7 d before the study. Animals were observed for 4 h after intratracheal administration of 0.02 mg/kg of LPS. The lung wet-to-dry weight ratio (W/D), [125I] albumin concentration ratio of lung tissue to plasma (T/P) and of bronchoalveolar lavage (BAL) fluid to plasma (B/P) and differential cell count in BAL fluid were examined. In the LPS-alone group, neither excess lung water nor increased albumin leakage was observed. The CP + LPS group showed increased lung water and albumin leakage as compared with the other three groups (p<0.05). We also observed increased cell counts in BAL fluid (p<0.05), in the CP + LPS group. The spleen weight was increased in guinea pigs pretreated with CP, indicating reticuloendothelial system (RES) activation. In the CP + LPS group, the TNF level was increased in both plasma and BAL fluid. We conclude that pretreatment with CP enhances LPS-induced acute lung injury in parallel with increasing TNF production, which suggests that the activation of mononuclear phagocytes contributes to increased susceptibility to intratracheal endotoxin in guinea pigs.

Administration, Topical↗

PubMed1996

Local Pseudomonas instillation induces contralateral lung injury and plasma cytokines.

We investigated whether local bacterial instillation leads to lung injury in noninstilled lung regions and examined local and systemic cytokine accumulation. Rats were challenged by intrabroncheal instillation of Pseudomonas aeruginosa, 10(7) colony-forming units (CFU) (HD group, n = 11), 4 x 10(6) CFU (LD group, n = 10), or saline (control group, n = 12). 99mTc-labeled macroaggregated albumin was added to the P. aeruginosa or saline solution for later documentation of the instilled area. At 4 h the right lung, including instilled segment, and the left lung were sampled. Lung injury was assessed by lung tissue to plasma 125I-labeled albumin (T/P) and lung wet-dry (W/D) ratios. We measured plasma and bronchoalveolar lavage fluid (BALF) levels of tumor necrosis factor (TNF) and cytokine-induced neutrophil chemoattractant (CINC). HD bacterial instillation induced neutrophil recruitment and TNF and CINC elevation in BALF (p < 0.05) associated with increased T/P (p < 0.005) and W/D (p < 0.05) ratios in both instilled and the noninstilled lungs as compared with the saline-instilled and noninstilled controls. LD bacterial instillation induced neutrophil recruitment and TNF and CINC elevation only in the instilled lung (p < 0.05), and not in the noninstilled lung, and did not increase the T/P or W/D ratio. Plasma levels of TNF and CINC were increased in the HD, but not the LD, group when compared with the saline controls (p < 0.05). These data indicate that, when the dose is high enough to cause an excess inflammatory response, local bacterial instillation leads to neutrophil sequestration, lung injury, and cytokine elevation in the noninstilled lung associated with systemic cytokine release.

Albumins↗

PubMed1996

Protective effect of B464, a lipid A analog, on endotoxin-induced cellular responses and acute lung injury.

B464 is a novel synthetic analog of lipid A, a toxic component of endotoxin (LPS; lipopolysaccharide). We investigated the effects of B464 on both LPS-induced cellular responses in vitro and acute lung injury in vivo. In the in vitro study, B464 inhibited tumor necrosis factor-alpha (TNF-alpha) production from human monocytes, priming and stiffening of neutrophils, and expression of adhesion molecules on endothelial cells induced by LPS. We then studied the effects of B464 pretreatment on acute lung injury elicited by intravenous LPS administration in vivo. Guinea pigs were divided into saline control, B464 alone, LPS alone, and LPS + B464 groups. Animals were observed for 4 h after LPS administration, and lung injury was evaluated by extravascular lung water, 125I-albumin leakage in lung tissue, and lung neutrophil accumulation. In the LPS alone group, rapid and sustained peripheral neutropenia (p < 0.001 versus saline at 15 min and at 1, 2, and 4 h), an increased plasma TNF-alpha concentration (p < 0.005 at 1 h), and increases in lung injury parameters (p < 0.05) were observed. In the LPS + B464 group, no changes were observed in either plasma TNF-alpha or lung injury parameters. Transient peripheral neutropenia and subsequent rapid recovery (p > 0.05, p < 0.001, p < 0.01, and p > 0.05 at 15 min and 1, 2, and 4 h, respectively) were observed in the LPS + B464 group. These in vivo data, together with in vitro evidence of suppressed cellular responses, suggest that B464 (1) inhibits neutrophil accumulation in lung tissue, and (2) attenuates the development of acute lung injury by blocking the activation of neutrophils and mononuclear cells as well as the interaction between neutrophils and endothelial cells.

Animals↗