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T Urano

Publications and source records attributed to T Urano.

At least 145 records · Page 8Linked to original sources
PubMed1995

Role of neutrophils and platelets in the pathogenesis of focal hepatocellular necrosis in endotoxaemia.

To clarify whether neutrophils and platelets are implicated in the pathogenesis of focal hepatocellular necrosis in endotoxaemia, we examined the relationship between the changes in neutrophils and platelets in peripheral blood and the degree of focal hepatocellular necrosis and serum transaminase activity in rats after endotoxin injection. The number of neutrophils in the peripheral blood decreased rapidly during the first hour after endotoxin injection and then increased. This initial decrease might be caused by the adhesion of neutrophils to pulmonary capillary walls, and the subsequent increase might be caused by granulocyte colony-stimulating factor mediated by endotoxin. However, there was no relationship between the degree of focal hepatocellular necrosis and the number of neutrophils sticking to the walls of hepatic sinusoids or the changes in the neutrophil count in the peripheral blood. The number of platelets in the peripheral blood decreased rapidly after endotoxin injection. There was a statistically significant relationship between the number of platelets in the peripheral blood and the level of serum transaminase activity: the fewer the platelets, the more severe was focal hepatocellular necrosis. The present study suggests that rapid and extensive consumption of platelets, rather than neutrophils sticking to the sinusoidal walls, is involved in the pathogenesis of focal hepatocellular necrosis in endotoxaemia.

Animals↗
PubMed1995

Expression of CD44 variant exons 8-10 in colorectal cancer and its relationship to metastasis.

Splice variants of CD44 are overexpressed in human lung, breast, and colon carcinoma cell lines. This study was conducted to clarify the association between the expression of CD44 variant exons 8-10 and metastatic potential in human colorectal cancer. We found that the expression of a CD44 splice variant containing exons v8-10 was increased in all of 60 colorectal cancer specimens examined compared with matched normal colerectal mucosa, as determined by Northern blotting. Expression of CD44 variant exons 8-10 did not significantly correlate with histological type, depth of tumor invasion, lymphatic invasion, venous invasion, or lymph node metastasis. However, the level of CD44 variant exon 8-10 expression was significantly higher in carcinomas associated with liver metastasis than in those without liver metastasis. In addition, expression of CD44 variant exons 8-10 in the liver metastases was more intense than that in the primary colorectal cancers. These findings indicated that this domain of the CD44 glycoprotein encoded by exons v8-10 may play an important role in tumor hematogenous metastasis of human colorectal cancer.

Blotting, Northern↗
PubMed1995

Expression of CD44 variant exons 8-10 in gastric cancer.

The expression of CD44 variant containing variant exons 8-10 product (CD44v8-10) was studied by western blot analysis and immunohistochemistry in gastric cancers using a monoclonal antibody, 44-1V. On western blots, a single band of 130 kD was recognized in stomach cancer cell lines. CD44v8-10 expression, with reactivity localized in the cell membrane, was found in 65 (33.5%) of the 194 advanced gastric cancers. There was no correlation between CD44v8-10 immunoreactivity and serosal, lymphatic, or lymph node invasion. However, there was significant correlation with CD44v8-10 immunoreactivity and venous invasion. CD44v8-10-positive cancers were more frequently associated with hematogenous metastasis than those which were immunonegative. There was an inverse association between CD44v8-10 immunoreactivity and peritoneal dissemination, especially in diffuse type adenocarcinomas. These observations indicate that CD44v8-10 may play a role in the metastasis of gastric cancer.

Adenocarcinoma↗
PubMed1995

Effects of pretreatment with SDZ MRL 953, a novel immunostimulatory lipid A analog, on endotoxin-induced acute lung injury in guinea pigs.

SDZ MRL 953 (SDZ), a novel immunostimulatory lipid A analog, has been reported to have immunopharmacological activities similar to those of lipopolysaccharide (LPS) but to have little of the toxicity of LPS. We investigated the effects of pretreatment with SDZ on Escherichia coli endotoxin-induced acute lung injury in guinea pigs. Four experimental groups consisted of saline control (n = 16), SDZ (-12 h) plus LPS (2 mg/kg of SDZ per kg of body weight injected intravenously 12 h before intravenous injection of 2 mg of LPS per kg; n = 15), SDZ (-10 min) plus LPS (SDZ injected 10 min before LPS injection; n = 10), and LPS alone (n = 16). The animals were sacrificed, and lung tissue was sampled 4 h after LPS or saline infusion. Lung injury was assessed by measuring the wet weight-to-dry weight ratio and the level of 125I-labeled albumin accumulation in bronchoalveolar lavage fluid relative to that in plasma. In the SDZ (-12 h) plus LPS group, these two parameters of acute lung injury were decreased compared with those in the LPS alone group. However, they were not decreased in the SDZ (-10 min) plus LPS group. We conclude that SDZ attenuates endotoxin-induced acute lung injury when it is administered 12 h before LPS injection. The attenuating effects of SDZ are speculated to be due to down regulation of the response to endotoxin rather than to receptor blocking.

Adjuvants, Immunologic↗
PubMed1995

Identification and characterization of Ral-binding protein 1, a potential downstream target of Ral GTPases.

Ral proteins constitute a distinct family of Ras-related GTPases. Although similar to Ras in amino acid sequence, Ral proteins are activated by a unique nucleotide exchange factor and inactivated by a distinct GTPase-activating protein. Unlike Ras, they fail to promote transformed foci when activated versions are expressed in cells. To identify downstream targets that might mediate a Ral-specific function, we used a Saccharomyces cerevisiae-based interaction assay to clone a novel cDNA that encodes a Ral-binding protein (RalBP1). RalBP1 binds specifically to the active GTP-bound form of RalA and not to a mutant Ral with a point mutation in its putative effector domain. In addition to a Ral-binding domain, RalBP1 also contains a Rho-GTPase-activating protein domain that interacts preferentially with Rho family member CDC42. Since CDC42 has been implicated in bud site selection in S. cerevisiae and filopodium formation in mammalian cells, Ral may function to modulate the actin cytoskeleton through its interactions with RalBP1.

Amino Acid Sequence↗
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

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

BCG priming enhances endotoxin-induced acute lung injury independent of neutrophils.

Bacillus Calmette Guérin (BCG) is known to increase susceptibility to endotoxin in some animal species. We investigated the effect of BCG-priming and the role of neutrophils in the priming process on the pathogenesis of acute lung injury caused by intravenously administered Escherichia coli endotoxin (LPS). Guinea pigs were divided into seven groups: (1) control (n = 8), (2) BCG-alone (n = 6), (3) cyclophosphamide (CPA)-alone (n = 6), (4) CPA+LPS (n = 6), (5) LPS-alone (n = 6), (6) BCG+LPS (n = 6), and (7) BCG+CPA+LPS (n = 6). A BCG dose of 8 mg/kg was injected subcutaneously 10 d before the study. CPA was administered intraperitoneally to induce peripheral neutropenia. Animals were observed for 4 h after intravenous administration of 0.2 mg/kg of LPS. The plasma TNF level was measured 2 h after LPS challenge. Lung wet-to-dry weight ratio, [125I] albumin leakage in lung tissue, differential cell count in bronchoalveolar lavage (BAL) fluid, and histopathologic features were examined immediately after death. Although the LPS-alone group showed PMN accumulation in lung tissue, neither excess lung water nor increased albumin leakage was induced by this dose of LPS. The BCG+LPS group showed increased lung water, histopathologic edema, and increases in BAL fluid cell counts and plasma TNF in comparison with the LPS-alone group. The BCG+CPA+LPS group also showed enhanced lung injury comparable to that seen in the BCG+LPS group. In both the CPA-alone and the CPA+LPS groups, no parameter was increased as compared with those in the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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

Neutrophil-induced lung protection and injury are dependent on the amount of Pseudomonas aeruginosa administered via airways in guinea pigs.

We investigated the roles of neutrophils in mediating both the protective effect against bacterial infection and the harmful effect of lung injury induced after the intratracheal instillation of live bacteria. We examined the mortality rate, lung injury, and bacterial clearance following the intratracheal instillation of Pseudomonas aeruginosa in low (10(4) colony-forming units [CFU]) and high doses (10(8) CFU) in normal (control) guinea pigs, others made neutropenic with cyclophosphamide (CPA), and guinea pigs made neutrophilic with recombinant granulocyte colony-stimulating factor (rG-CSF). Lung injury was assessed by the ratio of the concentration of 125I-labeled albumin in lung tissue to that in plasma (T/P) and the animals' lung weight-to-body weight (LW/BW) ratio. With 10(4) CFU, the CPA group showed an increased T/P ratio of 0.22 +/- 0.03 versus 0.14 +/- 0.01 in the control and 0.11 +/- 0.01 (mean +/- SEM) in the rG-CSF groups (p < 0.01). Viable bacteria were recovered from bronchoalveolar lavage fluid (BALF) in the CPA group. Neutrophil recruitment was observed in the lungs of animals in the control and rG-CSF groups. With 10(8) CFU, the mortality rate was increased in the rG-CSF group (7 of 10) as compared with the control (0 of 9) and CPA groups (1 of 9) (p < 0.05), which reflected an increased LW/BW (g/kg) ratio (16 +/- 2 versus 12 +/- 1) in the CPA group (p < 0.05). We conclude that neutrophils protect against lung injury during low-level bacterial challenge, but enhance lung injury and contribute to mortality during high-level bacterial challenge.

Animals↗
PubMed1995

Survey of Pseudomonas aeruginosa contamination in human beings and laboratory animals.

Several serotypes of Pseudomonas (P.) aeruginosa were isolated from the oral cavities of researchers, but no positive cases were found among the animals they had contacted or in the environment. These results indicated that researchers are not a source of P. aeruginosa infection for animals. However, P. aeruginosa was detected on the hands of researchers and animal caretakers after they finished their work. The same serotype of P. aeruginosa was found in the animals and the environment. These findings demonstrated that the researchers and the animal caretakers were contaminated with P. aeruginosa by the animals, and then became infective vehicles.

Animal Husbandry↗
PubMed1995

[A case of large cell carcinoma of the lung arising from the inner surface of a pulmonary bulla and complicated by hematoma].

A 64-year-old man with a history of smoking was admitted to our hospital, because he was noted to have a solitary mass lesion at the apex of the right lung on a chest roentgenogram. Eight months before admission, he had come to our hospital because of hemoptysis. At that time, however, no abnormal shadow was seen on his chest roentgemogram, except for multiple bullae at both apexes. Based on chest CT findings on admission, the tumor appeared to be a hematoma growing inside the bulla. The resected tumor was found to contain a large amount of coagulated blood in the bulla. Histopathological examination of the bulla revealed a proliferation of large atypical cells from the inner surface of the bulla toward the inner space. Thus, the diagnosis was large cell carcinoma within the wall of the pulmonary bulla, the inside of which was filled with hematoma. We believe that the hematoma in the bulla allowed us to make an early diagnosis, and thus to succeed in curing the patient.

Carcinoma, Non-Small-Cell Lung↗
PubMed1995

Preferential reduction of nm23-H1 gene product in metastatic tissues from papillary and follicular carcinomas of the thyroid.

The nm23 gene product is a possible mediator of cancer invasion and metastasis, and has been divided into two distinct gene products, NM23-H1 and NM23-H2. It has been shown previously that expression of nm23-H1 messenger RNA is reduced in metastatic lymph nodes from patients with papillary carcinoma of the thyroid (Am J Pathol 142:1938-1944, 1993). Since mAb H1-229 specific for NM23-H1 is now available, we further extended our study to examine the expression of nm23-H1 gene product in various types of thyroid cancer (37 cases of papillary carcinoma, 42 cases of follicular carcinoma, 17 cases of anaplastic carcinoma, and 3 cases of medullary carcinoma). NM23-H1 was expressed in primary papillary and follicular carcinomas (14/15 and 21/22), but weakly or hardly expressed in metastatic lymph nodes and metastatic bone marrow (6/23 and 1/4) (P < 0.01). Expression of NM23-H1 was low or absent in anaplastic and medullary carcinoma (3/17 and 0/3) (P < 0.01).

Adenocarcinoma, Follicular↗
PubMed1995

[A case of Mycobacterium fortuitum pulmonary disease in a healthy young woman successfully treated with ciprofloxacin and doxycycline].

A 22 year-old woman was admitted to our hospital complaining of subtle fever and productive cough. She did not smoke and had no underlying disease. Her chest radiograph showed infiltration in the right upper lung field. A diagnosis of Mycobacterium fortuitum pulmonary disease was made on the basis of isolation of M. fortuitum from repeated sputum cultures. On admission, we administered standard antimycobacterial agents, but found the M. fortuitum isolated in this case to be completely resistant to them. We then administered antibiotics including 600 mg of ciprofloxacin and 200 mg of doxycycline. The pneumonic findings on chest X-ray and her clinical symptoms gradually improved thereafter. The in vitro susceptibility tests confirmed the efficacy of ciprofloxacin and doxycycline. We concluded that these drugs contributed significantly to improve the disease.

Adult↗
PubMed1995

[Effects of intravascular latex injection on factors responsible for acute lung injury].

To study the contribution of phagocytosis to the development of acute lung injury, latex particles (2 x 10(9)/kg; mean diameter, 2.84 microns) were injected intravenously or intra-arterially into guinea pigs. 125I-labelled albumin was injected to estimate the degree of lung injury, and 51Cr-labelled red blood cells were injected to correct for blood contamination in the samples. A control group was given saline. Four hours after the injections, the animals were killed, bronchoalveolar lavage was done, and the lungs were examined histopathologically. Animals that had received intravenous and intra-arterial injections of latex particles had more lung water and more pulmonary albumin leakage than animals that had received saline. Histopathological examination revealed massive accumulation of latex in the reticuloendothelial system. These findings suggest that the phagocytic process in the reticuloendothelial system plays a role in the development of lung injury in guinea pigs.

Acute Disease↗
PubMed1994

N,N,N-trimethylsphingosine modifies aggregatory response and ATP release from platelets in whole blood.

We investigated the influence of N,N,N-trimethylsphingosine (TMS), a potent inhibitor of protein kinase C (PKC), on whole blood aggregation and ATP release from platelets. The preincubation with TMS at 1 microM for 2 min enhanced ATP release during arachidonic acid-induced aggregation. The ristocetin-induced agglutination was inhibited in a TMS concentration-dependent manner, which suggests that TMS may interact with the vWF receptor on platelets. TMS suppressed aggregatory response and ATP release from platelets after the addition of collagen. In contrast, the platelet aggregation induced by ADP and 12-O-tetradecanoylphorbol-13-acetate (TPA) was only slightly inhibited and the ATP release was not influenced after preincubation with TMS. Our results are in contrast to previous reported data, which were obtained using PRP and washed platelets.

Adenosine Diphosphate↗
PubMed1994

Heparin and heparan sulfate enhancement of the inhibitory activity of plasminogen activator inhibitor type 1 toward urokinase type plasminogen activator.

To study effects of glycosaminoglycan on the interaction between two chain urokinase type plasminogen activator (tcu-PA) (EC 3.4.21.31) and plasminogen activator inhibitor type 1 (PAI-1) the second order rate constant (k1) between high molecular weight tcu-PA and active recombinant prokaryotic PAI-1 (rpPAI-1) was determined employing a continuous method using chromogenic substrate S-2444 either in the presence or absence of various kinds of glycosaminoglycans. k1 was (5.9 +/- 1.6).10(6)/mol per s in the absence of effector molecule, and following addition of heparin (1.0 U/ml) k1 was enhanced to (3.22 +/- 0.73).10(7). A significant enhancement of k1 was also obtained by heparan sulfate (1.87 +/- 0.25).10(7). Dermatan sulfate or chondroitin sulfate did not show a significant effect on k1 although a slight decrease was obtained by mono-dextran sulfate (4.2 +/- 1.2).10(6). The intrinsic fluorescence of rpPAI-1 was shown to be slightly increased following addition of heparin (1.49 +/- 0.22%, n = 6), suggesting that heparin may enhance the inhibitory activity of PAI-1 toward tcu-PA both by a template mechanism and by a modification of PAI-1 structure.

Buffers↗