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Y Yamaguchi

Publications and source records attributed to Y Yamaguchi.

At least 433 records · Page 24Linked to original sources
PubMed1998

[Beneficial effect of salazosulfapyridine (SASP) in a patient with secondary renal amyloidosis].

A 55-year old female with rheumatoid arthritis (RA) had presented with proteinuria since July 1996. She was referred to us for persistent edema on her face and legs in November 1996. On admission, her 24-hour urinary protein excretion was 4.4 g/day, total serum protein level was 5.3 g/dl, and serum level of amyloid A protein (SAA) was elevated to 45.8 mg/ml. A percutaneous renal biopsy was performed, and light microscopy revealed varying degrees of amyloid deposits in the mesangial areas and arteriolar walls. The diagnosis of secondary amyloidosis (AA amyloidosis) was based on immunohistochemical staining for amyloid A protein using monoclonal antibody against SAA. Four weeks after treatment with salazosulfapyridine (SASP) and dipyridamole, proteinuria began to decrease and the edema had disappeared. Finally she recovered from nephrotic syndrome. AA amyloidosis has been thought to have a poor prognosis, with progression to renal failure. Since there is no specific effective therapy for the disease, it is very important to reduce the activity of the underlying cause. In our patient with renal amyloidosis following RA, SASP was evidently effective for arthritis and improvement of renal function. SASP might have a beneficial effect on AA amyloidosis by suppressing inflammatory cytokines.

Amyloidosis↗
PubMed1998

[Significance of serum surfactant protein-D (SP-D) level in patients with pulmonary tuberculosis].

Elevated levels of serum surfactant protein-D (SP-D) have been previously reported in patients with idiopathic pulmonary fibrosis (IPF) and pulmonary alveolar proteinosis. To determine whether the same change is seen in other pulmonary diseases, especially pulmonary tuberculosis (TB), we measured the serum SP-D levels in active pulmonary TB (smear and/or culture: positive), acute interstitial pneumonia (AIP), IPF, acute exacerbation of IPF, hypersensitivity pneumonitis (HP), pneumoconiosis, bronchiectasis, and bacterial pneumonia by an enzyme-linked immunosorbent assay using monoclonal antibodies to human lung SP-D, and compared them with those of healthy elderly subjects over 50 years of age. The SP-D level in the healthy elderly subjects was 57.6 +/- 38.4 ng/ml (mean +/- SD, n = 287). The levels in patients with active pulmonary TB (140.6 +/- 18.2 ng/ml, n = 49), AIP (1,021 ng/ml, n = 1), IPF (307.0 +/- 180.7 ng/ml, n = 42), acute exacerbation of IPF (817.7 +/- 283.6 ng/ml, n = 3), and HP (716.6 +/- 548.8 ng/ml, n = 4) were significantly higher than those in the healthy elderly controls (p < 0.05), whereas those of pneumoconiosis, bronchiectasis, and bacterial pneumonia, 121.9 +/- 92.8 ng/ml (n = 8), 93.9 +/- 72.9 ng/ml (n = 11), and 72.7 +/- 3.4 ng/ml (n = 4), respectively, showed no significant difference with the controls. In active pulmonary TB, the percentage of patients whose serum SP-D levels were over 134.6 ng/ml (mean + 2SD of healthy elderly controls) was 34.7%, and therefore we considered the serum SP-D level was not useful for the diagnosis of pulmonary TB. However, it was significantly higher in the patients with cavity formation than in those without (p < 0.05), and there was a significant positive correlation between the serum SP-D level and the number of tubercle bacilli in the sputum (r = 0.416, p = 0.00165), erythrocyte sedimentation rate at 1 hr (r = 0.489, p < 0.01), and CRP level (r = 0.383, p = 0.003). These findings suggest that the serum SP-D level is a useful indicator of the disease activity in pulmonary TB.

Aged↗
PubMed1998

Blood concentrations of polymorphonuclear leucocyte elastase and interleukin-6 are indicators for the occurrence of multiple organ failures at the early stage of acute pancreatitis.

We studied potential indicators of severe acute pancreatitis by measuring the blood concentrations of various cytokines, polymorphonuclear leucocyte elastase (PMN-E), acute phase reactants, pancreatic amylase (P-AMY), pancreatic elastase-1 (E-1) and white blood cell (WBC) counts in patients with acute pancreatitis. In addition, the presence of multiple organ damage was assessed. Subjects consisted of 22 patients with acute pancreatitis including severe (n = 11), moderate (n = 4) and mild (n = 7) cases. A significant positive correlation was observed between the number of organs damaged and the peak concentrations of interleukin (IL)-6, PMN-E, C-reactive protein (CRP) and pancreatic secretory trypsin inhibitor (PSTI). Among these markers, blood concentrations of PMN-E and IL-6 rapidly increased and peaked at the early phase of acute pancreatitis whereas CRP and PSTI did not. The elevation of PMN-E and IL-6 was greater the more severe the symptoms. However, no significant correlation was observed between the number of organs damaged and the maximum serum concentrations of P-AMY and E-1, or the WBC count, which have been considered to be markers of pancreatitis. These results suggest that PMN-E and IL-6 concentrations are useful indicators of severity and prognosis and their determination facilitates the selection of appropriate treatment in the early stages of disease to prevent the aggressive progression of acute pancreatitis.

Acute Disease↗
PubMed1997

The brain chondroitin sulfate proteoglycan brevican associates with astrocytes ensheathing cerebellar glomeruli and inhibits neurite outgrowth from granule neurons.

Brevican is a nervous system-specific chondroitin sulfate proteoglycan that belongs to the aggrecan family and is one of the most abundant chondroitin sulfate proteoglycans in adult brain. To gain insights into the role of brevican in brain development, we investigated its spatiotemporal expression, cell surface binding, and effects on neurite outgrowth, using rat cerebellar cortex as a model system. Immunoreactivity of brevican occurs predominantly in the protoplasmic islet in the internal granular layer after the third postnatal week. Immunoelectron microscopy revealed that brevican is localized in close association with the surface of astrocytes that form neuroglial sheaths of cerebellar glomeruli where incoming mossy fibers interact with dendrites and axons from resident neurons. In situ hybridization showed that brevican is synthesized by these astrocytes themselves. In primary cultures of cerebellar astrocytes, brevican is detected on the surface of these cells. Binding assays with exogenously added brevican revealed that primary astrocytes and several immortalized neural cell lines have cell surface binding sites for brevican core protein. These cell surface brevican binding sites recognize the C-terminal portion of the core protein and are independent of cell surface hyaluronan. These results indicate that brevican is synthesized by astrocytes and retained on their surface by an interaction involving its core protein. Purified brevican inhibits neurite outgrowth from cerebellar granule neurons in vitro, an activity that requires chondroitin sulfate chains. We suggest that brevican presented on the surface of neuroglial sheaths may be controlling the infiltration of axons and dendrites into maturing glomeruli.

Animals↗
PubMed1997

The C-type lectin domains of lecticans, a family of aggregating chondroitin sulfate proteoglycans, bind tenascin-R by protein-protein interactions independent of carbohydrate moiety.

The lecticans are a family of chondroitin sulfate proteoglycans including aggrecan, versican, neurocan, and brevican. The C-terminal globular domains of lecticans are structurally related to selectins, consisting of a C-type lectin domain flanked by epidermal growth factor and complement regulatory protein domains. The C-type lectin domain of versican has been shown to bind tenascin-R, an extracellular matrix protein specifically expressed in the nervous system, and the interaction was presumed to be mediated by a carbohydrate-protein interaction. In this paper, we show that the C-type lectin domain of brevican, another lectican that is specifically expressed in the nervous system, also binds tenascin-R. Surprisingly, this interaction is mediated by a protein-protein interaction through the fibronectin type III domains 3-5 of tenascin-R, independent of any carbohydrates or sulfated amino acids. The lectin domains of versican and other lecticans also bind the same domain of tenascin-R by protein-protein interactions. Surface plasmon resonance analysis revealed that brevican lectin has at least a 10-fold higher affinity than the other lectican lectins. Tenascin-R is coprecipitated with brevican from adult rat brain extracts, suggesting that tenascin-R and brevican form complexes in vivo. These results demonstrate that the C-type lectin domain can interact with fibronectin type III domains through protein-protein interactions, and suggest that brevican is a physiological tenascin-R ligand in the adult brain.

Animals↗
PubMed1997

Biochemical characterization of the Wilson disease protein and functional expression in the yeast Saccharomyces cerevisiae.

Wilson disease is a disorder of copper metabolism characterized by hepatic cirrhosis and neuronal degeneration due to inherited mutations in a gene encoding a putative copper-transporting P-type ATPase. Polyclonal antisera generated against the amino terminus of the Wilson protein detected a specific 165-kDa protein in HepG2 and CaCo cell lysates. Further analysis revealed that this protein is synthesized as a single-chain polypeptide and localized to the trans-Golgi network under steady state conditions. An increase in the copper concentration resulted in the rapid movement of this protein to a cytoplasmic vesicular compartment. This copper-specific cellular redistribution of the Wilson protein is a reversible process that occurs independent of a new protein synthesis. Expression of the wild-type but not mutant Wilson protein in the ccc2Delta strain of Saccharomyces cerevisiae restored copper incorporation into the multicopper oxidase Fet3p, providing direct evidence of copper transport by the Wilson protein. Taken together these data reveal a remarkable evolutionary conservation in the cellular mechanisms of copper metabolism and provide a unique model for the regulation of copper transport into the secretory pathway of eucaryotic cells.

Adenosine Triphosphatases↗
PubMed1997

Phenotype and localization of macrophages expressing inducible nitric oxide synthase in rat hepatic allograft rejection.

BACKGROUND: We investigated the phenotype and localization of macrophages expressing inducible nitric oxide synthase (iNOS) in rat hepatic allografts, using double immunostaining with anti-macrophage iNOS (macNOS) and rat anti-macrophage (ED1 or ED2) monoclonal antibodies. METHODS: The animals were divided into three experimental groups: group 1, isografts; group 2, untreated hepatic allografts; and group 3, hepatic allografts treated with FK506. RESULTS: Plasma nitrite/nitrate concentrations in group 2 increased on day 3, peaked on day 5, and decreased thereafter. In contrast, the plasma nitrite/nitrate concentrations in group 1 increased slightly on day 3, but decreased gradually thereafter. The plasma concentrations of nitrite/nitrate did not vary in group 3. The peak nitrite/nitrate values in group 2 were significantly greater than those in groups 1 and 3. The number of macNOS+ cells peaked on day 5 in group 2. In contrast, a few macNOS+ cells were seen in the liver grafts of groups 1 and 3. Double immunostaining revealed that the macNOS+ cells consisted of macNOS+ ED1+ (80%) and macNOS+ ED2+ (40%) in the untreated hepatic allografts on day 5. In addition, a number of macNOS+ cells also were seen in the red pulp of the recipient spleen in the untreated hepatic allografts. CONCLUSIONS: These results suggest that the intense iNOS expression by the monocyte/macrophage lineage among the hepatic infiltrates and by the splenic macrophages after transplantation supports a role for nitric oxide in the immunomodulation of allogeneic responses in local and remote organs, and possibly serves as a mediator of cytotoxic graft damage.

Animals↗
PubMed1997

A phase III randomized study of interleukin-2 lymphokine-activated killer cell immunotherapy combined with chemotherapy or radiotherapy after curative or noncurative resection of primary lung carcinoma.

BACKGROUND: Adoptive immunotherapy with interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells has resulted in response among some patients with advanced malignant disease. However, the relative therapeutic benefit of adoptive immunotherapy as an adjuvant to surgery has not been determined. METHODS: A Phase III prospective randomized controlled study of adjuvant immunotherapy combined with chemotherapy or radiotherapy was conducted for 174 primary lung carcinoma patients postsurgically. After a pathologic examination of resected tissues, patients were divided into curative and noncurative cases and randomized to receive either combined immunotherapy (Group A) or control standard therapy (Group B). Patients who had undergone curative resection of lung carcinoma were stratified according to the stages and histologic types of their disease, and those who had undergone noncurative resection were stratified according to the causes of noncurative resection. The patients of Group A received IL-2 and LAK cells after either chemotherapy or radiotherapy, and those in Group B received either no adjuvant therapy (curative cases) or radiotherapy or chemotherapy alone (noncurative cases), according to the causes of noncurative resection. RESULTS: The 5- and 9-year survival rates of the Group A patients were 54.4% and 52.0%, respectively, and those of the Group B patients were 33.4% and 24.2%, respectively. The difference was statistically significant (P < 0.001, according to the generalized Wilcoxon's test and the Cox-Mantel test). The difference was also statistically significant in the curative cases (65.5% for Group A vs. 40.6% for Group B; 5-year survival rate, P < 0.01), noncurative cases (43.0% for A vs. 20.8% for B; P < 0.01), adenocarcinoma cases (47.5% for A vs. 23.0% for B; P < 0.05), and squamous cell carcinoma cases (62.1% for A vs. 34.8% for B; P < 0.01). CONCLUSIONS: Adoptive immunotherapy with IL-2 and LAK cells combined with chemotherapy or radiotherapy improved the survival of patients after surgical resection of primary lung carcinoma. A multi-institutional group study should be carried out to verify the significance of this study.

Adult↗
PubMed1997

Effects of ginsenosides on maze performance and brain choline acetyltransferase activity in scopolamine-treated young rats and aged rats.

In young adult rats with scopolamine-induced cognitive impairment, choline acetyltransferase activity was increased in the medial septum, but not in the diagonal band, caudate and hippocampus, 30 min after the injection of ginsenosides Rg1 or Re. Rb1 and Rd had no effect on choline acetyltransferase activity. Aged rats showed a smaller number of initial correct responses in the radial-arm maze and a lower choline acetyltransferase activity in the medial septum, diagonal band, caudate and hippocampus than did young adult rats. Repeated i.p. injections of Rg1 increased the number of initial correct responses and the activity of choline acetyltransferase in the medial septum, but not in the diagonal band, caudate and hippocampus, in aged rats. These results suggest that Rg1 and Re may contribute the ameliorative effects through an increase of choline acetyltransferase activity in the medial septum.

Aging↗
PubMed1997

Stimulation of interleukin-8 production by okadaic acid and vanadate in a human promyelocyte cell line, an HL-60 subline. Possible role of mitogen-activated protein kinase on the okadaic acid-induced NF-kappaB activation.

Most types of cells can produce interleukin (IL)-8 in response to various inflammatory stimuli. To study the role of protein phosphatases in the signal transduction leading to IL-8 production, a subline of HL-60 (C-15) was treated with okadaic acid (OA) and sodium orthovanadate (VA), inhibitors of phosphoserine/phosphothreonine phosphatase and phosphotyrosine phosphatase, respectively. Both OA and VA dramatically increased IL-8 secretion up to 200-fold in the HL-60 cells. OA and VA stimulation was accompanied by a marked increase in IL-8 mRNA expression and also by activation of a transcription factor, NF-kappaB. In addition, an essential role of the NF-kappaB site in the IL-8 gene activation was confirmed by the chloramphenicol acetyltransferase assay. IL-8 production by OA or VA was inhibited by protein kinase inhibitors, including staurosporine, H-7, K252a, herbimycin A, and genistein. Both OA and VA induced significant tyrosine phosphorylation of p44, which was presumed to be Erk1, a member of the mitogen-activated protein kinase family, with concomitant activation of the mitogen-activated protein kinase activity. In parallel, rapid degradation of IkappaB-alpha, an inhibitory component of NF-kappaB, was observed. Since OA-activated Erk1 phosphorylated recombinant IkappaB-alpha in vitro, we assumed that Erk1 is involved in the phosphorylation and subsequent degradation of IkappaB-alpha, thus leading to the activation of IL-8 gene transcription.

Base Sequence↗
PubMed1997

Stage specific expression of milk fat globule membrane glycoproteins in mouse mammary gland: comparison of MFG-E8, butyrophilin, and CD36 with a major milk protein, beta-casein.

The expression of mouse milk fat globule membrane (MFGM) glycoproteins, MFG-E8, butyrophilin, CD36 was analyzed by Northern blot analyses. MFG-E8 and butyrophilin mRNAs were specifically detected in the mammary gland of lactating mice, whereas CD36 mRNA was detected in the heart and lung as well as in the mammary gland of lactating mice. The mRNAs of the three MFGM glycoproteins accumulated at mid-lactation were about 2-10-times as much as those of the early and late gestation stages, whereas beta-casein mRNA accumulation was dramatically increased; the mRNA at mid-lactation was no less than 40-times as much as that before lactation. In mouse mammary epithelial cell lines, HC11 and COMMA-1D, only a slight or almost no enhancement for the expression of MFG-E8, butyrophilin and CD36 mRNAs was induced simply by the treatment with the lactogenic hormones such as prolactin, insulin and dexamethasone, whereas the beta-casein mRNA expression was remarkably enhanced only by that treatment. Furthermore, while the beta-casein protein was constantly detected in milk throughout the lactation stage, the content of MFG-E8 and butyrophilin proteins increased during the lactation with an increase in the milk fat content. These results suggest that the stage-specific expression of milk fat globule membrane glycoproteins in mammary epithelial cells is regulated in a similar but not necessarily identical mechanism to that of a major milk protein, beta-casein.

Animals↗
PubMed1997

Evolutionary mechanisms and population dynamics of the third variable envelope region of HIV within single hosts.

Clonal diversifications of HIV virus were monitored by periodic samplings on each of the six patients with regard to 183- to 335-bp segments of the env gene, which invariably included the functionally critical V3 region. Subsequently, six individual phylogenetic trees of viral variants were constructed. It was found that at one time or another during the course of disease progression, viral variants were inexplicably released from a strong negative selection against nonsynonymous base substitutions, possibly indicating positive selection. This resulted in concentrated amino acid substitutions at five specific sites within the V3 region. It was noted that these sites were often involved as antigenic determinants that provoked the host immune response and that these sites were also involved in the determination of viral phenotypes as to their cell tropism, syncytium formation capability, and replication rates.

Amino Acid Sequence↗
PubMed1997

A cholecystokinin-releasing factor mediates ethanol-induced stimulation of rat pancreatic secretion.

The mechanisms by which short-term ethanol administration alters pancreatic exocrine function are unknown. We have evaluated the effects of ethanol administration on pancreatic secretion of digestive enzymes. In our studies, anesthetized as well as conscious rats were given ethanol at a rate sufficient to cause the blood ethanol concentration to reach levels associated with clinical intoxication. Ethanol was administered over a 2-h period during which blood ethanol levels remained stably elevated. We report that intravenous administration of ethanol results in a transient increase in pancreatic amylase output and plasma cholecystokinin (CCK) levels. The ethanol-induced increase in amylase output can be completely inhibited by the CCK-A receptor antagonist L-364,718 and partially inhibited by the muscarinic cholinergic antagonist atropine. The ethanol-induced rise in amylase output can be completely prevented by instillation of trypsin into the duodenum or by lavage of the duodenum with saline during ethanol administration. Furthermore, the intraduodenal activity of a CCK-releasing factor is increased by infusion of ethanol. These studies indicate that administration of ethanol causes rat pancreatic exocrine secretion to increase. This phenomenon is mediated by a trypsin-sensitive CCK-releasing factor which is present within the duodenal lumen. These observations lead us to speculate that repeated CCK-mediated ethanol-induced stimulation of pancreatic digestive enzyme secretion may play a role in the events which link ethanol abuse to the development of pancreatic injury.

Alcoholism↗
PubMed1997

Autologous tumor killing activity as a prognostic factor in primary resected nonsmall cell carcinoma of the lung.

BACKGROUND: Cytotoxic activity of peripheral blood lymphocytes obtained during surgery against autologous fresh tumor cells has been reported. However, the role of lymphocyte autologous tumor killing or natural killer activity during the postoperative period remains obscure. In this article, the authors describe the importance of postoperative autologous tumor killing activity as a prognostic factor in patients with primary resected nonsmall cell lung carcinoma (NSCLC) after long term follow-up. METHODS: Forty-two patients who had resection of NSCLC, with primary culture of autologous tumor cells taken successfully, were studied. Cytotoxic activity against autologous, allogenic NSCLC and K562 leukemia cells was examined using peripheral blood lymphocytes obtained during the 2 weeks immediately following surgery. Factors related to prognosis were analyzed by univariate and multivariate analyses. RESULTS: The overall 5- and 10-year survival rates for the NSCLC patients were 40.5% and 27.5%, respectively. Statistical analysis of survival curves revealed a significant difference with regard to T classification (P = 0.025), N classification (P = 0.0015), stage (P = 0.028), and postoperative autologous tumor killing activity (P = 0.0008); there were no significant differences in relation to age, gender, histology, differentiation, visceral pleural invasion, resectability, surgical method, allogeneic tumor killing activity, or natural killer activity. Multivariate analysis demonstrated a significant correlation between disease recurrence and N classification (P = 0.0003), T classification (P = 0.023), stage (P = 0.001), and autologous tumor killing activity (P = 0.007), indicating independent prognostic significance. The phenotypes of the effector cells involved in autologous tumor killing activity were CD3(+), CD4(-), CD8(+), and CD11b(-). Autologous tumor killing activity was inhibited by competing unlabeled autologous tumor cells. CONCLUSIONS: Autologous tumor killing activity during the 2 weeks immediately following surgery is an important prognostic factor in resected NSCLC.

Adult↗
PubMed1997

Persistent infiltration of CD45RC- CD4+ T cells, Th2-like effector cells, in prolonging hepatic allografts in rats pretreated with a donor-specific blood transfusion.

A single intravenous injection of freshly heparinized blood from a donor-specific blood transfusion (DST) seven days before transplantation significantly prolongs the subsequent survival of hepatic allografts from ACI(RT1a) to LEW(RT1(1)) rats. We used W3/25 (anti-CD4) and OX22 (anti-CD45RC: an isoform of leukocyte-common antigen [CD45R]) monoclonal antibodies to investigate the cellular identity of hepatic allograft infiltrates following transplantation. The number of CD4+ and CD45RC+ cells in untreated allografts increased equally over time by day seven. However, in DST-treated hepatic allografts, CD4+ and CD45RC+ cells also increased over time by day 14, but the increment in the number of CD4+ cells was significantly greater than that in CD45RC+ cells. While the number of CD4+ cells remained persistently elevated in the hepatic allografts of rats pretreated with DST, they did not initiate rejection. Fluorescence-activated cell sorter (FACS) analysis revealed that the accumulated CD4+ T cells could be divided into two subsets, CD45RC- CD4+ and CD45RC+ CD4+ T cells, and that the ratio of CD45RC- CD4+/CD45RC+ CD4+ T cells in the hepatic allografts of recipients pretreated with DST was significantly greater than that in untreated allografts. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis demonstrated that CD45RC- CD4+ T cells expressed interleukin (IL)-4 and IL-10 messenger RNA (mRNA), but not IL-2 and interferon gamma (IFN-gamma). The pattern of messenger RNA expression in hepatic allograft infiltrates from animals pretreated with DST provides compelling evidence for the selective in vivo preservation of T-helper (Th2)-specific cytokines in the rat system. Our studies show that CD45RC leukocyte-common antigen expression can define different populations of hepatic infiltrating CD4+ T cells. A persistent infiltration of CD45RC- CD4+ T cells, Th2-like effector cells, is characteristic of hepatic allografts with a prolonged survival in DST-pretreated rats.

Animals↗
PubMed1997

Pretreatment with activated protein C or active human urinary thrombomodulin attenuates the production of cytokine-induced neutrophil chemoattractant following ischemia/reperfusion in rat liver.

We investigated the role of anticoagulant in the ischemia/reperfusion injury of the liver, using activated protein C (APC), active human urinary thrombomodulin (UTM), and factor Xa blocked at the active site (DEGR-Xa). Liver ischemia was induced in male Wistar rats by occlusion of the portal vein with a microvascular clip for 30 minutes. Each anticoagulant was injected intravenously 10 minutes before clamping the portal vein. Serum concentrations of cytokine-induced neutrophil chemoattractant (CINC) were determined by enzyme-linked immunosorbent assay. The serum levels of CINC increased significantly following reperfusion, reaching a peak in 6 hours, and then decreasing gradually to control levels by 24 hours. CINC levels in rats pretreated with APC (500 U/kg), UTM (3,000 TMU/kg), or DEGR-Xa (10 mg/kg) peaked 3 hours following reperfusion and decreased rapidly to baseline level within 6 and 12 hours, respectively. These peak values were significantly lower than those observed in untreated rats (P < .01). Expression of CINC transcripts in liver tissue of untreated rats was evaluated by Northern blot analysis and peaked 3 hours following reperfusion. Pretreatment with these anticoagulants significantly decreased the expression of CINC messenger RNA transcripts as compared with untreated animals. Myeloperoxidase activity and the number of neutrophils accumulated into the liver 24 hours following ischemia/reperfusion were also significantly decreased in animals pretreated with these anticoagulants. In addition, correlations between the peak values of liver enzymes and serum CINC levels were found to be significant (P < .001). The inactive derivative of factor Xa, a selective inhibitor of thrombin generation, inhibited ischemia/reperfusion-induced increases in the serum concentration and messenger RNA transcript quantities of CINC. The inactive factor Xa also reduced hepatic accumulation of neutrophils after ischemia/reperfusion. These results indicate that the release of CINC is likely related to the hepatic microcirculation disturbance induced by microthrombotic occlusion following ischemia/reperfusion.

Animals↗