Biomedical subjects

M Murakami

Publications and source records attributed to M Murakami.

At least 289 records · Page 16Linked to original sources

PubMed1999

[Clinical usefulness of half-dose gadolinium-enhanced MR angiography of portal venous system (MR portography)--combined use with conventional dynamic MR imaging].

The clinical usefulness of half-dose Gadolinium-enhanced MR portography combined with the conventional full-dose dynamic MR imaging was evaluated on normal volunteers and patients. Half-dose MR portography was performed immediately following conventional full-dose Gd-enhanced dynamic MR imaging. The visualization of the extrahepatic portal system was either good or excellent in most cases excluding the splenic vein which was poor in 20.7%. That of the right and left main portal branches was also excellent. As for segmental branches, the visualization was poor of the left lobe. The comparison with digital subtraction angiography showed that the visualization of the right and left main portal branches was mostly equal. That of the splenic vein alone was worse on MR portography. We conclude that half-dose Gadolinium-enhanced MR portography is useful for the overall assessment of the portal venous system and can be added to the conventional dynamic MR imaging.

Adult↗

PubMed1999

Intraductal spread of invasive breast carcinoma has a positive correlation with c-erb B-2 overexpression and vascular invasion.

BACKGROUND: Studies of the histologic characteristics and biologic behavior of the intraductal spread of breast carcinoma are critically important in that they may lead to the identification of a unique spread pattern rather than a noninvasive lesion. METHODS: Paraffin embedded specimens of 187 primary invasive breast carcinomas and 4 noninvasive ductal carcinomas, obtained by wide excision, quadrantectomy, total glandectomy, or mastectomy, were studied immunohistochemically. The overexpression of c-erb B-2, p53, bcl-2, and MIB-1, as well as the histologic characteristics of intraductal spread (such as histologic features and histologic grade), were assessed. Chi-square and Fisher exact tests were conducted to evaluate significant differences; the Macintosh for Expert StatView 4.0 system was used to conduct these tests. RESULTS: The histologic characteristics of intraductal spread were similar to those of noninvasive ductal carcinoma. However, the expressions of c-erb B-2, p53, and other biologic markers of intraductal spread were similar to those of the main invasive tumor. The overexpression of c-erb B-2 protein was found more often in the group that was positive for intraductal spread than in the group that was negative (P < 0.01). Intraductal spread was found more often in the group that was positive for lymphatic and venous invasion than in the group that was negative (P < 0.005). Subnipple margin positive status was related closely to intraductal spread (P < 0.0001). CONCLUSIONS: The positive correlation between intraductal spread and c-erb B-2 overexpression as well as lymphatic, venous invasion was recognized, and it was determined that intraductal spread of invasive breast carcinoma possesses an invasive and metastatic potential that is distinct from noninvasive ductal carcinoma.

Antigens, Nuclear↗

PubMed1999

Occurrence and identification of UDP-N-acetylmuramyl-pentapeptide from the cyanobacterium Anabaena cylindrica.

UDP-N-acetylmuramyl-pentapeptide (UDP-MurNAc-pentapeptide) is well known to be a key intermediate of bacterial peptidoglycan biosynthesis. We first detected the occurrence of UDP-MurNAc-pentapeptide in the cyanobacterium Anabaena cylindrica (NIES-19), and identified the structure of this pentapeptide by two-dimensional 1H-1H and 1H-13C NMR correlation experiments and mass spectra.

Anabaena↗

PubMed1999

Cellular proteinases trigger the infectivity of the influenza A and Sendai viruses.

It has been proposed that the pathogenicity of the influenza and Sendai virus is primarily determined by host cellular proteases that activate viral infectivity. We isolated trypsin-type serine proteases from rat lungs, candidates for the processing proteases of viral envelope glycoproteins, such as tryptase Clara localized in the Clara cells of the bronchial epithelium and mini-plasmin. These enzymes specifically cleave the precursor of fusion glycoprotein HA of influenza virus at Arg325, and the F0 of Sendai virus at Arg116 in the consensus cleavage motif, Gln(Glu)-X-Arg, resulting in the induction of infectivity of these viruses. Proteolytic activation of viruses by these enzymes occurs extracellularly, probably on the surface and/or in the lumen of the respiratory tract. On the other hand, we isolated two compounds from human bronchial lavage, which inhibit the activity of tryptase Clara. One was a mucus protease inhibitor and the other was a pulmonary surfactant. These compounds inhibited multiple cycles of virus replication in vitro and in vivo, but did not themselves affect the hemagglutination and the infectivity of the virus. Administration of these compounds in the airway may be useful for preventing and treating infection with influenza virus and Sendai virus.

Animals↗

PubMed1999

Polyunsaturated fatty acids potentiate interleukin-1-stimulated arachidonic acid release by cells overexpressing type IIA secretory phospholipase A2.

By analyzing human embryonic kidney 293 cell transfectants stably overexpressing various types of phospholipase A2 (PLA2), we have shown that polyunsaturated fatty acids (PUFAs) preferentially activate type IIA secretory PLA2 (sPLA2-IIA)-mediated arachidonic acid (AA) release from interleukin-1 (IL-1)-stimulated cells. When 293 cells prelabeled with 13H]AA were incubated with exogenous PUFAs in the presence of IL-1 and serum, there was a significant increase in [3H]AA release (in the order AA > linoleic acid > oleic acid), which was augmented markedly by sPLA2-IIA and modestly by type IV cytosolic PLA2 (cPLA2), but only minimally by type VI Ca2(+)-independent PLA2, overexpression. Transfection of cPLA2 into sPLA2-IIA-expressing cells produced a synergistic increase in IL-1-dependent [3H]AA release and subsequent prostaglandin production. Our results support the proposal that prior production of AA by cPLA2 in cytokine-stimulated cells destabilizes the cellular membranes, thereby rendering them more susceptible to subsequent hydrolysis by sPLA2-IIA.

Arachidonic Acid↗

PubMed1999

Anabaenopeptins G and H, potent carboxypeptidase A inhibitors from the cyanobacterium Oscillatoria agardhii (NIES-595).

Anahaenopeptins G (1) and H (2) were isolated from the cultured cyanobacterium Oscillatoria agardhii (NIES-595) as potent carboxypeptidase A (CPA) inhibitors. The gross structure of 1 and 2 were established by spectroscopic analysis including the 2D NMR technique and the absolute configurations of 1 and 2 were determined by the spectral and chemical methods. 1 and 2 inhibited CPA with IC50's of 0.0018 and 3.4 microg/mL, respectively.

Carboxypeptidases↗

PubMed1999

Behavioral and morphologic studies of the chronically compressed cauda equina. Experimental model of lumbar spinal stenosis in the rat.

STUDY DESIGN: An experimental model in rats of chronically compressed cauda equina was produced, and behavioral and morphologic changes were examined. OBJECTIVES: To provide a useful model for analyzing the pathophysiologic changes of the cauda equina by chronic compression and to examine behavioral and morphologic changes in this model. SUMMARY OF BACKGROUND DATA: Several animal models have been reported in which various materials were used to compress the cauda equina. However, the pathophysiology of the cauda equina by chronic compression is not yet well understood. Studies in which rats were used are scarce. METHODS: A silicone sheet was applied to the spinal canal at L4 in the rat. Walking durations on treadmill tests and paw-withdrawal latencies to thermal stimuli were measured before and after the operation for 24 weeks. Histologic changes also were examined. RESULTS: Walking durations decreased after chronic compression. However, paw-withdrawal latencies were not significantly changed. Histologically, the number of large-diameter myelinated axons decreased after compression, whereas the number of small-diameter myelinated axons increased. Electron microscopic observation indicated that the continuous degeneration and regeneration of axons occurred throughout the chronic compression experiment. CONCLUSIONS: The current model and behavioral assessments may be useful in analyzing the pathophysiology of chronically compressed cauda equina.

Animals↗

PubMed1999

High dose chemotherapy with autologous stem cell support in the treatment of patients with ovarian carcinoma: long term results for 105 patients.

BACKGROUND: In this study, the authors reviewed long term results and prognostic factors of high dose chemotherapy (HDC) with autologous stem cell support administered to 105 patients with epithelial ovarian carcinoma. METHODS: Prior to HDC, platinum-based chemotherapy was given to optimize (n = 94) and/or to mobilize peripheral blood stem cells (n = 33). After maximum debulking surgery, HDC with stem cell support was given; it consisted of cyclophosphamide, doxoribicin, and cisplatin (Regimen A, administered to 58 patients) or cyclophosphamide and carboplatin (Regimen B, administered to 47 patients). RESULTS: Five-year overall and disease free survival (OS, DFS) rates (%) according to stage were IC: 92.3, 92.3; II: 73.3, 73.3; III: 58.1, 35.7; IV: 33.7, 22.6; relapsed: 37.5, 31.0; OS, DFS at 8 years were IC: 92.3, 92.3; II: 73.3, 73.3; III: 48.8, 31.7; IV: 33.7, 22.6; relapsed: 37.5, 31.0. There was no difference in survival between patients who received Regimens A and B despite an increase in the total dose of platinum and an increase of more than 1.5- to 3.5-fold in the platinum course of HDC in Regimen B from the equivalence ratio of 4:1 between carboplatin and cisplatin. Among 65 Stage III and IV patients, the best results were obtained for 35 patients with small volume disease: 5-year OS, DFS rates were 74.3, 51.6, and 8-year OS, DFS rates were 66.4, 46.3. CONCLUSIONS: Good long term results were obtained with HDC. Small volume residual disease, platinum sensitivity, and histology excluding mucinous and clear cell adenocarcinoma were important factors for better survival. However, because the results were obtained for selected patients, a prospective, randomized study comparing HDC and standard chemotherapy is necessary if any definitive conclusions are to be drawn.

Adenocarcinoma, Clear Cell↗

PubMed1999

Induction of specific CD8+ T-lymphocyte responses using a human papillomavirus-16 E6/E7 fusion protein and autologous dendritic cells.

When intracellular viral proteins are degraded, only a limited number of peptide epitopes are capable of eliciting specific CD8+ cellular immune responses for a given human leukocyte antigen (HLA) haplotype. We sought to induce CD8+ T-lymphocyte (CTL) responses to human papillomavirus-16 (HPV-16) E6 and E7 proteins using a recombinant E6/E7 fusion protein and autologous human dendritic cells (DCs). CTLs were generated by in vitro stimulation using a recombinant HPV-16 E6/E7 fusion protein and autologous DCs from a healthy HLA-A*0201 donor. CTL specificity was assessed by cytokine release assays when the cells were reacted with autologous DC targets coincubated with the E6/E7 fusion protein. These CTLs were also reacted with the immunodominant E7 peptides (E711-20 and E7(86-93)) and DCs as a target. As a negative control, DCs were incubated with or without an irrelevant control protein (Helicobacter pylori) as target for the E6/E7-induced CTLs. The E6/E7-induced CTLs were capable of specific recognition of target DCs coincubated with E6/E7 but not the control protein. When E6/E7-specific CTLs were reacted with DCs and either E7(11-20) or E7(86-93), specific peptide recognition was also detected. These data demonstrate that specific CTLs can be elicited using autologous human DCs and a HPV-16 E6/E7 fusion protein. Therefore, extracellular viral proteins seem to be engulfed and processed by DCs; then the immunodominant HLA-A2-restricted peptides become available for CD8+ T-lymphocyte recognition. These data suggest that vaccine strategies using recombinant viral proteins may overcome the limitation of peptide epitopes for specific HLA haplotypes and may, therefore, permit more generalized clinical application.

Antigen Presentation↗

PubMed1999

CTLA4IgG treatment induces long-term acceptance of rat small bowel allografts.

BACKGROUND: CTLA4 immunoglobulin (Ig)G that binds to B7 effectively inhibits the signaling of CD28/CTLA4-B7 pathway and induces antigen specific T cell unresponsiveness in vitro and in vivo. Using CTLA4IgG, we examined induction of long-term graft survival and the mechanism of maintenance of tolerance in rat allogeneic small bowel transplantation. METHODS: Small bowels of Brown-Norway rats (RT1n) were heterotopically transplanted into Lewis rats (RT1l). Recipients were treated with an i.p. injection of either CTLA4IgG or control IgG for 7 days. RESULTS: Long-term survival was observed in rats treated with CTLA4IgG, whereas control rats died within 16 days after transplantation. To examine whether a tolerant state was established in long-term survival rats, secondary transplantation was performed using small bowels of Brown-Norway rats or ACI (RT1b) rats. It was demonstrated that small bowels of Brown-Norway rats were accepted; however, those of ACI rats were rejected within 10 days. Serum concentrations of interleukin (IL)-4 were maintained at >50 microg/ml for 7 days after transplantation in rats treated with CTLA4IgG but <15 microg/ml in control rats. IL-2 concentration was reduced to half in CTLA4IgG-treated rats compared with that in control recipients. Serum IFN-gamma in CTLA4IgG-treated recipients increased after transplantation and was not distinguishable from that of control recipients during the first 7 days after transplantation. Conclusion. We demonstrated that CTLA4IgG treatment alone for 7 days induced a long-term donor specific tolerance in rat allogeneic small bowel transplantation. The induction of long-term acceptance of small bowel allografts by CTLA4IgG is not caused by simply the shift of anti-alloimmune responses from Thl to Th2 cytokine production.

Abatacept↗

PubMed1999

Functional coupling between various phospholipase A2s and cyclooxygenases in immediate and delayed prostanoid biosynthetic pathways.

Several distinct phospholipase A2s (PLA2s) and two cyclooxygenases (COXs) were transfected, alone or in combination, into human embryonic kidney 293 cells, and their functional coupling during immediate and delayed prostaglandin (PG)-biosynthetic responses was reconstituted. Signaling PLA2s, i.e. cytosolic PLA2 (cPLA2) (type IV) and two secretory PLA2s (sPLA2), types IIA (sPLA2-IIA) and V (sPLA2-V), promoted arachidonic acid (AA) release from their respective transfectants after stimulation with calcium ionophore or, when bradykinin receptor was cotransfected, with bradykinin, which evoked the immediate response, and interleukin-1 plus serum, which induced the delayed response. Experiments on cells transfected with either COX alone revealed subtle differences between the PG-biosynthetic properties of the two isozymes in that COX-1 and COX-2 were favored over the other in the presence of high and low exogenous AA concentrations, respectively. Moreover, COX-2, but not COX-1, could turn on endogenous AA release, which was inhibited by a cPLA2 inhibitor. When PLA2 and COX were coexpressed, AA released by cPLA2, sPLA2-IIA and sPLA2-V was converted to PGE2 by both COX-1 and COX-2 during the immediate response and predominantly by COX-2 during the delayed response. Ca2+-independent PLA2 (iPLA2) (type VI), which plays a crucial role in phospholipid remodeling, failed to couple with COX-2 during the delayed response, whereas it was linked to ionophore-induced immediate PGE2 generation via COX-1 in marked preference to COX-2. Finally, coculture of PLA2 and COX transfectants revealed that extracellular sPLA2s-IIA and -V, but neither intracellular cPLA2 nor iPLA2, augmented PGE2 generation by neighboring COX-expressing cells, implying that the heparin-binding sPLA2s play a particular role as paracrine amplifiers of the PG-biosynthetic response signal from one cell to another.

Animals↗

PubMed1999

The extracellular processing of HIV-1 envelope glycoprotein gp160 by human plasmin.

Cleavage of the envelope glycoprotein precursor gp160 of HIV-1 is a prerequisite for the infectivity of HIV-1, and occurs at least in part before gp160 reaches the cell surface. Kexin/subtilisin-related endopeptidases are proposed enzyme candidates for this intracellular processing. In this study, we reveal the possibility that plasminogen binds to the cell surface and part of gp160 escaping intracellular processing is cleaved by plasmin extracellularly. Plasmin cleaves gp160 precisely at the C-terminal arginine residue of gp120, and the processing is effectively inhibited by an analogue peptide of the cleavage motif (RXK/RR) and by plasmin inhibitors.

Amino Acid Sequence↗

PubMed1999

Development of a simple, portable carbon dioxide incubator for in vitro production of bovine embryos.

The objective of this study was to develop a simple and portable CO2 incubator using effervescent granules (EG) and to examine the effect of negative and positive air pressure for in vitro maturation (IVM), fertilization (IVF) and culture (IVC) of bovine oocytes. In experiment 1, cumulus-oocyte complexes (COCs) were matured (22 h), fertilized (5 h) and cultured (7 days) using 0.25, 0.5 or 1.0 g of EG per 0.6 l added to maintain an optimum level of CO2 (approximately 3, 6 or 12%, respectively) for in vitro production of embryos. Control oocytes, zygotes and embryos were cultured in a standard CO2 incubator. The blastocyst production rates observed on Days 7 to 9 after insemination were 20.5+/-4.2%, 18.5+/-3.9% and 28.7+/-5.1% for the 0.25 g EG, 0.5 g EG treatments and control, respectively. These rates were significantly higher (P < 0.05) than that of the 1.0 g EG treatment (8.7+/-2.6%). The number of cells in the inner cell mass (ICM) and trophectoderm (TE) produced from blastocysts using the control procedure were 40.8+/-2.9 and 81.2+/-5.3, respectively, and were higher (P < 0.05) compared to the 0.50 g EG (34.6+/-2.9 and 66.8+/-5.7) and 1.0 g EG treatments (33.4+/-3.4 and 67.2+/-7.3). In experiment 2, COCs were placed in a small box with 0.25 g of EG so that the effects on IVM, IVF and IVC of positive or negative air pressure could be compared. The blastocyst production rate observed in the negative air pressure treatment (29.6+/-4.6%) was higher (P < 0.01) than that of the positive air pressure treatment (6.2+/-1.5%) or the normal treatment pressure (P < 0.05; 18.7+/-4.2%) but did not differ from that of the control (30.7+/-4.4%). These results indicate that this simple type of incubator with negative air pressure can be successfully used for in vitro production of bovine embryos and could be used at the field level.

Air Pressure↗

PubMed1999

A longitudinal study of the effect of vitamin K2 on bone mineral density in postmenopausal women a comparative study with vitamin D3 and estrogen-progestin therapy.

OBJECTIVES: To investigate the effect of vitamin K2 treatment for a year on spinal bone mineral density (BMD) in postmenopausal women, comparing with vitamin D3 hormone replacement therapy and to determine the factors which affect the efficacy of vitamin K2 therapy. SUBJECTS AND METHODS: Seventy-two postmenopausal women were randomized into four groups and treated with respective agents. Before the therapy, 6 and 12 months after the treatment, their lumbar spine BMD were measured by dual energy X-ray absorptiometry. The rates of change in BMD (delta BMD) were calculated. Correlations of BMD with age, year since menopause and the initial BMD were determined. RESULTS: Vitamin K2 suppressed the decrease in spinal BMD as compared with no treatment group. BMD in women treated with vitamin K2 was inversely correlated with their age (r = -0.54; P < 0.05). CONCLUSIONS: Vitamin K2 therapy may be a useful method for preventing postmenopausal spinal bone mineral loss. In addition, the therapy should be started early in postmenopausal period.

Bone Density↗

PubMed1999

CD44 variants but not CD44s cooperate with beta1-containing integrins to permit cells to bind to osteopontin independently of arginine-glycine-aspartic acid, thereby stimulating cell motility and chemotaxis.

The expression of osteopontin (OPN), CD44 variants, and integrins has been correlated with tumorigenesis and metastasis. Here we show that these proteins cooperate to enhance cell motility. First, we demonstrate that several different CD44 variants bind to OPN in an arginine-glycineaspartic acid-independent manner, but that the standard form of CD44 does not. These CD44 variants bind to both the amino- and COOH-terminal portions of OPN independently of the arginine-glycine-aspartic acid sequence, suggesting that multiple domains on OPN can be bound by the CD44 variants. Antibodies directed against the integrin beta1 subunit are able to inhibit this binding. The binding of CD44 variants to OPN is significantly augmented by both anti-CD44s and anti-CD44v antibodies. This augmentation by anti-CD44 antibodies is OPN specific and, again, can be blocked by anti-beta1 antibodies. Finally, we show that OPN binding by CD44 variants/beta1-containing integrins promotes cell spreading, motility, and chemotactic behavior.

Animals↗

PubMed1999

The human mucus protease inhibitor and its mutants are novel defensive compounds against infection with influenza A and Sendai viruses.

Tryptase Clara, a trypsin-like protease localized exclusively in and secreted by Clara cells of the bronchial epithelium, is a prime host factor that processes viral envelope glycoproteins and determines the infectivity of influenza A and Sendai viruses (H. Kido, Y. Yokogoshi, K. Sakai, M. Tashiro, Y. Kishino, A. Fukutomi, and N. Katunuma, The Journal of Biological Chemistry, 1992, Vol. 267, pp. 13573-13579). We report here that human mucus protease inhibitor (MPI), a major inhibitor of granulocyte elastase in the lining fluid of the human respiratory tract, significantly inhibited induction of the infectivity of influenza A and Sendai viruses by tryptase Clara in vitro and multicycles of mouse-adapted influenza A virus replication in rat lungs in vivo. Recombinant MPI and the C- but not the N-terminal domain of MPI inhibited both the activity of tryptase Clara and the induction of virus infection by tryptase Clara. The 50% inhibitory concentrations of MPI and the C-terminal domain peptide (Pro50-Ala107) of MPI for tryptase Clara were 7.4 and 61.6 nM, respectively, with Sendai virus envelope glycoproteins as the substrate. Studies on deletion mutants of the C-terminal domain of MPI revealed that the minimal size of MPI required for the inhibition of tryptase Clara is the peptide Lys60-Ala107. Studies involving site-directed mutagenesis of the C-terminal domain of MPI indicated that the Leu72-Met73 site of MPI is the inhibitory site for tryptase Clara. Substitution of residue Leu72 with a basic amino acid significantly increased in the inhibitory activity of the C-terminal domain of MPI, but further substitution of residue Met73 with various amino acids in these mutants reduced the inhibitory activity. Since there is evidence suggesting that the concentration of MPI in respiratory fluid is insufficient for prevention of virus infection, the administration of MPI, the recombinant C-terminal domain of MPI, and their mutants, with residue Leu72 substituted with residues Arg72 and Lys72, may be useful for treatment of such pneumotropic virus infections.

Animals↗

PubMed1999

Mechanisms of ozone-induced inhibitory effect of bronchoalveolar lavage fluid on alveolar macrophage-mediated immunosuppressive activity in rats.

Resident alveolar macrophages (AM) play an important immunomodulatory role via suppression of lymphocyte proliferation, and nitric oxide (NO) plays a crucial role in this immunosuppression of AM. Our previous report suggested that during ozone (O3)-induced lung inflammation, bronchoalveolar lavage fluid (BALF) inhibited AM-mediated immunosuppression and concanavalin A (Con A)-induced proliferation of lymph node cells (LNC) [E. Koike et al. (1998) Toxicol. Sci. 41, 217-223]. In these studies, we investigated the mechanisms of the inhibition of BALF from O3-exposed rats (O3-BALF). We investigated whether BALF might affect (1) the interferon-gamma (IFN-gamma) production by Con A-stimulated LNC and IFN-gamma-induced NO production by AM, and (2) the interleukin (IL)-2 production by Con A-stimulated LNC and IL-2-induced LNC proliferation. These results demonstrated that O3-BALF inhibited IFN-gamma production by Con A-stimulated LNC, IFN-gamma-induced NO production by AM, and IL-2-induced LNC proliferation. In addition, the major inhibitory factor against AM-mediated immunosuppression in O3-BALF may be a protein of greater than 10 kDa.

Animals↗

PubMed1999

Role of type IIA secretory phospholipase A2 in arachidonic acid metabolism.

Recent recognition of the rapidly growing sPLA2 family has led to a suggestion that some of the previously described functions of sPLA2-IIA need to be reevaluated, since studies based upon enzyme activities and using inhibitors or antibodies against sPLA2-IIA may not discriminate these sPLA2s. Our present studies reconfirm the involvement of sPLA2-IIA in biological responses, demonstrated significant crosstalk between the two Ca(2+)-dependent PLA2s (cPLA2 and sPLA2) where one enzyme is required for the induction of the other, and revealed segregated coupling of discrete PLA2 and COX enzymes in the different phases of PG biosynthesis. Based upon the analysis of cells derived from sPLA2-IIA "natural knock-out" mice, it is apparent that sPLA2-IIA is not essential for the initiation of delayed PGE2 biosynthesis. However, it is capable of contributing to the delayed response as an enhancer when appropriately induced by proinflammatory stimuli, leading to optimal COX-2-dependent PGE2 generation. Importantly, in order for sPLA2-IIA (or related sPLA2 isozymes) to attack the biological membranes, so-called "membrane rearrangement" should take place in activated, but not resting, cells. Membrane rearrangement also occurs when cells are undergoing apoptosis, during which acidic phospholipids, the preferred substrates for sPLA2-IIA, are exposed on the outer leaflet of the plasma membranes. Nonetheless, in view of the dramatically elevated levels of sPLA2-IIA in inflamed or ischemic sites, it is likely that this extracellular isozyme participates in the expansion of chronic tissue disorders by augmenting generation of proinflammatory eicosanoids or lysophospholipids, depending upon the states of the inflammatory response.

Animals↗