Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0009443 (cold)
 92,137 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study was undertaken to determine whether the blood-brain barrier (BBB) breakdown and cerebral edema occurring post-trauma are associated with overexpression of the endothelial (e) and inducible (i) nitric oxide synthases (NOS), enzymes responsible for nitric oxide (NO) biosynthesis. These enzymes were determined quantitatively at the mRNA level and qualitatively at the protein level in the rat cerebral cortical cold injury model, during a period up to 6 days post-injury. In addition, peroxynitrite generation at the lesion site was detected by immunolocalization of nitrotyrosine as a marker of NO-superoxide interactions. These studies were correlated with the permeability status of the BBB by immunohistochemical detection of endogenous fibronectin extravasation in the same brains. BBB breakdown was immediate in lesion vessels, it was present as early as 10 minutes post-lesion and delayed in perilesional vessels that showed maximal BBB breakdown between 2-4 days. The BBB was restored to normal at 6 days post-lesion. An increase in both eNOS and iNOS mRNA was observed at the lesion site as compared with the contralateral hemisphere at 12 hours, 2 days, and 4 days. The mRNA returned to resting levels by 6 days. Increased eNOS protein was observed in the endothelium of permeable perilesional vessels and neovessels and in the endothelium of the hyperplastic pial vessels overlying the lesion site. iNOS protein was observed initially in polymorphonuclear leukocytes at the lesion site and later in macrophages, endothelial cells, and the smooth muscle cells of the overlying pial vessels. Furthermore, nitrotyrosine was demonstrated at the lesion site up to 5 days. Up-regulation of the NO synthases at both the mRNA and protein level accompanied by presence of nitrotyrosine during BBB breakdown and angiogenesis suggests that NO has a role in the pathogenesis of these processes.
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PMID:Expression of nitric oxide synthases and nitrotyrosine during blood-brain barrier breakdown and repair after cold injury. 1120 72

The role of nitric oxide (NO) in blood-brain barrier (BBB) breakdown and edema formation was investigated in the rat cortical cold injury model over a period of 10 min to 6 days post cold-injury by immunolocalization of fibronectin as a marker of BBB permeability alterations and endothelial (e) and inducible (i) nitric oxide synthases (NOS), which are markers of NO biosynthetic activity. BBB breakdown to fibronectin in lesion vessels was observed at 10 minutes post-injury, was maximal between 60 minutes and 3 hours and declined gradually thereafter, while perilesional vessels remained permeable up to 5 days. Increased eNOS immunoreactivity was observed in endothelium of perilesional permeable vessels starting at 12 hrs and was maximal between 4-6 days, after which immunoreactivity decreased reaching basal levels by 5-6 days. Immunoreactivity for iNOS was absent in normal brain and was first observed in polymorphonuclear leukocytes and endothelium of lesion vessels at 3 hrs. Maximal iNOS immunoreactivity was observed in endothelial cells and macrophages during the period of angiogenesis. Smooth muscle cells of overlying hyperplastic pial vessels showed iNOS immunoreactivity up to 6 days. The demonstration of increased NO synthases at the lesion site during BBB breakdown and edema formation and angiogenesis suggests that NO plays a role in these processes.
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PMID:Increased immunolocalization of nitric oxide synthases during blood-brain barrier breakdown and cerebral edema. 1145 93

For understanding the immunological functions of the peritoneum, spatial localization of integrins and their ligands was studied by immuno-SEM on the peritoneal surface of mice with cecal perforation-induced peritonitis. The cecal peritoneum 24 hr after perforation was stained with specific antibodies against LFA-1, Mac-1, VLA-4, ICAM-1, VCAM-1, and fibronectin diluted with cold University of Wisconsin (UW) solution in conjunction with immuno-gold labeling. The spatial localization of those cell adhesion molecules was detected by backscatter electron (BSE) imaging with field emission scanning electron microscope (FESEM). Numerous leukocytes with diverse surface ultrastructure were observed on the peritoneal surface by FESEM. Some leukocytes were in contact with mesothelial cells, and others adhered to the exposed underlying connective tissue. The BSE imaging showed the ubiquitous distribution of Mac-1 on all membrane domains of leukocytes, i.e., cell body, ruffles, and microvilli. In contrast, predominant expressions of LFA-1 and VLA-4 were discernible on ruffles/microvilli of some leukocytes. The mesothelial cells remaining in the inflamed area expressed both ICAM-1 and VCAM-1 on their microvilli. The fibronectin was detected on presumable collagen fibers and/or fibrin over the exposed smooth muscle layer as well as on fibrin extending between leukocyte aggregation. The spatial microlocalization of integrins was clarified on the leukocytes emigrated in peritonitis, and their ligands were detected on the inflamed peritoneum.
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PMID:Spatial distribution of cell adhesion molecules on the peritoneal surface in the cecal perforation-induced peritonitis. 1159 May 97

In the last 40 years, therapeutic plasmapheresis techniques have been improving considerably. These include cryofiltration technologies providing novel ways of removing large amounts of cryoproteins from plasma. The concept of cryofiltration involves exposure of plasma to below core (37 degrees C) and room temperatures (25 degrees C) without freezing. It was initially used to treat diseases such as cryoglobulinemia with systemic vasculitis, rheumatoid arthritis, systemic lupus erythematosus, and ABO-incompatible transplants. There are 2 basic types of cryofiltration. The first method removes cryoproteins, namely cryoglobulins that precipitate at 4 degrees C. Several filters have been used for this procedure like the AP06M (Asahi Medical, Tokyo, Japan) with a 0.2 microm pore size, a 0.65 m2 surface area, and a cellulose diacetate (CDA) membrane. It has been used in the United States and Japan for treatment of rheumatoid arthritis and cryoglobulinemia. A major disadvantage was frequent filter plugging, which was cumbersome and it is no longer used in the United States. The G3 cryofilter (Gelman Sciences, Ann Arbor, MI, U.S.A.) with a 3 microm pore size was tried in vitro but proved inadequate by design. Currently in our institution, the cryoglobulin filter (Pall Medical, Ann Arbor, MI, U.S.A.) is used with a 4.3 microm pore size, a 0.135 m2 surface area, and an acrylic co-polymer pleat membrane. We performed over 1,200 procedures in 40 patients in the last 8 years. The second type of cryofiltration removes cryogel, which is an agglutination complex of fibrinogen, fibronectin, fibrin split products, and cold insoluble proteins with a heparin core, at temperatures between 2 and 10 degrees C. The AP06M, the AC1740 (Asahi Medical) with a 0.02 microm pore size, a 1.70 m2 surface area, and a CDA membrane, and the Evaflux-4A (Kuraray Company, Osaka, Japan) with a 0.03 microm pore size, a 2 m2 surface area, and an ethylene vinyl alcohol membrane are used to remove cryogel to treat ABO-incompatible transplants as well as rheumatoid arthritis and other previously mentioned diseases. This article will discuss each cryofiltration treatment modality.
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PMID:Current topics on cryofiltration technologies. 1172 13

We have previously shown a biochemical interaction between fibronectin (Fn) and polymeric immunoglobulins (Igs), that we localized to the fourth and fifth N-terminal type I repeats (4F1.5F1) in Fn and the Fc portion of IgG. Therefore, we hypothesized that Fn, as a constituent of the extracellular matrix (ECM) may directly bind circulating immune complexes (ICs) causing their deposition, thereby contributing to the pathogenesis of IC diseases. As an in vitro paradigm to test this idea, we have generated Fn-containing ECMs from varied cells in culture and demonstrated a saturable dose-dependent binding of aggregated (agg) IgG, as a prototype of ICs, as well as the binding of both heat and cold aggregated purified type I cryoglobulins (CGs) to these ECMs. No binding was observed to ECMs (Matrigel) that do not contain Fn. Characteristic of our previous findings, polymeric but not monomeric IgG bound to the acellular Fn-containing ECMs. To further demonstrate the specificity of the interaction and implicate matrix Fn in the binding of aggIgG, complete inhibition of binding of aggIgG to Fn was achieved by blocking Fn on the ECMs with anti-Fn antiserum and by preincubation of the Ig aggregates with anti-human IgG antibodies. By competing the binding interaction with fluid phase Fn and the Ig-binding site on Fn, 4F(1).5F(1), 70% inhibition was obtained. Additional experiments performed with purified CGs show that an identical dose-dependent increase in Fn binding occurred using both preformed and forming cryoprecipitates suggesting that Fn does not confer cryoprecipitation of CGs and that the specific association of Fn with cryoprecipitates probably results from their polymeric configuration. Our results support the notion that Fn, as it exits in expanding ECMs characteristic of glomerulonephropathies and rheumatoid synovial disease, specifically interacts with complexed/polymeric Igs, thereby perpetuating IC deposition and playing a role in the pathogenesis of IC diseases.
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PMID:Binding of polymeric IgG to fibronectin in extracellular matrices: an in vitro paradigm for immune-complex deposition. 1204 77

Our previous study demonstrated that vascular endothelial growth factor (VEGF), now referred to as VEGF-A, plays a significant role in blood-brain barrier (BBB) breakdown and angiogenesis after brain injury. In this study, VEGF-A expression was compared with that of VEGF-B in the rat cortical cold injury model over a period of 6 hours to 6 days post-injury. VEGF-A and VEGF-B mRNA were detected by in situ hybridization and their protein was detected by immunohistochemistry. The presence of VEGF-A and VEGF-B proteins in endothelium of lesion vessels was related to BBB breakdown by double labeling for either of these growth factors and fibronectin, which was used as a marker of BBB breakdown. Significant induction of both VEGF-A and VEGF-B mRNA occurred at the lesion site during the period of maximal endothelial proliferation. VEGF-A mRNA levels peaked at 3 and 4 days post-injury and returned to basal expression by day 6, while VEGF-B mRNA levels remained elevated up to day 6. VEGF-B protein was constitutively expressed in endothelium of all cerebral vessels. After brain injury, there was increased immunoreactivity for VEGF-B at the lesion site, this protein being present in the endothelium and vascular smooth muscle cells of pial vessels, in inflammatory cells, and later in proliferating endothelial cells, endothelium of neovessels, and astrocytes. Lesion vessels showing BBB breakdown to fibronectin showed endothelial VEGF-A protein but not VEGF-B protein. Constitutive expression of VEGF-B in normal endothelium suggests that it may have a role in maintenance of the BBB in steady states, while its induction at both the gene and protein level post-injury indicates that it has an essential role in angiogenesis and the repair processes after brain injury.
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PMID:Differential expression of vascular endothelial growth factor-A (VEGF-A) and VEGF-B after brain injury. 1223 Mar 24

The chitinase B (ChiB) secreted by Alteromonas sp. strain O-7 was purified, and the corresponding gene (chiB) was cloned and sequenced. The open reading frame of the chiB gene encodes a protein of 850 amino acids with a calculated molecular mass of 90,223 Da. ChiB is a modular enzyme consisting of two reiterated domains and a catalytic domain belonging to chitinase family 18. The reiterated domains are composed of chitin-binding domain (ChtBD) type 3 and two fibronectin type III (Fn3)-like domains. Expression plasmids coding for ChiB or deletion derivatives thereof were constructed in Escherichia coli. Deletion analysis showed that the ChtBD of ChiB plays an important role in efficient hydrolysis of insoluble chitin. The optimum pH and temperature of ChiB were 6.0 and 30 degrees C, respectively. The enzyme showed relatively high catalysis, even at low temperatures close to 0 degrees C, and remarkable thermal lability compared to ChiA and ChiC, which are the mesophilic chitinases of the same strain. The kca)/Km value for the ChiB reaction at 10 degrees C was about 4.7 times higher than that of ChiC. These results suggest that ChiB is a cold-adapted enzyme. The RNA transcript of chiB was induced by 1% GlcNAc, and along with a rise in temperature, the RNA transcript showed a tendency to decrease. Thus, among the ChiA, ChiB, and ChiC chitinases, production of ChiB may be advantageous for the strain, allowing it to easily acquire nutrients from chitin and to survive in cold environments.
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PMID:Molecular analysis of the gene encoding a novel cold-adapted chitinase (ChiB) from a marine bacterium, Alteromonas sp. strain O-7. 1256 83

We tested a hypothesis that interactions between fibronectin (FN), the major extracellular matrix component, and its integrin alpha 4 beta 1 receptor is important in the development of ischemia/reperfusion injury of steatotic liver transplants. We examined the effect of connecting segment-1 (CS1) peptide-facilitated blockade of FN-alpha 4 beta 1 interaction in a well-established steatotic rat liver model of ex vivo cold ischemia followed by iso-transplantation. In this model, CS1 peptides were administered through the portal vein of steatotic Zucker rat livers before and after cold ischemic storage. Lean Zucker recipients of fatty liver transplants received an additional 3-day course of CS1 peptides after transplant. CS1 peptide therapy significantly inhibited the recruitment of T lymphocytes, neutrophil activation/infiltration, and repressed the expression of proinflammatory tumor necrosis factor-alpha and interferon-gamma. Moreover, it resulted in selective inhibition of inducible nitric oxide synthase expression, peroxynitrite formation, and hepatic necrosis. Importantly, CS1 peptide therapy improved function/histological preservation of steatotic liver grafts, and extended their 14-day survival in lean recipients from 40% in untreated to 100% in CS1-treated OLTs. Thus, CS1 peptide-mediated blockade of FN-alpha 4 beta 1 interaction protects against severe ischemia/reperfusion injury experienced otherwise by steatotic OLTs. These novel findings document the potential of targeting FN-alpha 4 beta 1 in vivo interaction to increase the transplant donor pool through modulation of marginal steatotic livers.
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PMID:Fibronectin-alpha 4 beta 1 integrin-mediated blockade protects genetically fat Zucker rat livers from ischemia/reperfusion injury. 1265 15

We have demonstrated that Cre-loxP-mediated gene-switch transgenesis is an effective approach to achieve targeted and temporally regulated gene manipulation in the heart. Using this approach, we have established animal models with targeted activation of different MAPK pathways. From these animal models, we identified distinct features of cardiac pathology associated with individual MAPK branches (summarized in Fig. 8). Specifically, Ras activation appears to promote cardiac hypertrophy, whereas p38 and JNK activation does not. Whereas Ras activation leads to depressed diastolic function associated with suppressed calcium transients and SR calcium uptake, p38 activity seems to modulate cellular contractility without affecting intracellular calcium cycling. Although all three models displayed extensive remodeling in the myocardium, the extent and the composition of interstitial fibrosis are different among them, with Ras- and p38-activated hearts promoting collagen-based fibrosis, and JNK activation leading to induction in fibronectin-based reticular fiber. In addition, JNK activation leads to loss of Cx43 expression and abnormal cell-cell communication. Therefore, ERK, p38, and JNK are three distinct intracellular signaling pathways that contribute to different aspects of cardiac pathology during heart failure. Combining sophisticated genetic manipulation with comprehensive analysis at physiological, molecular, and genomic levels, the transgenic animals established in these studies should serve as valuable model systems to identify and dissect the underlying mechanisms for different aspects of cardiac pathology such as hypertrophy, contractile dysfunction, and abnormal cell-cell communication. The insights learned from these investigations may help to develop novel therapeutic approaches to confront this devastating disease.
Cold Spring Harb Symp Quant Biol 2002
PMID:Using a gene-switch transgenic approach to dissect distinct roles of MAP kinases in heart failure. 1285 68

Angiopoietin-1 (Ang-1) and angiopoietin-2 (Ang-2) belong to a novel family of endothelial growth factors that function as ligands for the endothelial-specific receptor tyrosine kinase, Tie-2. Ang-1 reduces endothelial permeability of noncerebral vessels and has a major role in vascular stabilization and maturation, whereas Ang-2 is thought to be an endogenous antagonist of the action of Ang-1 at Tie-2. Expression of these ligands at the mRNA and protein level were studied during both blood-brain barrier (BBB) breakdown and cerebral angiogenesis occurring in the rat cortical cold-injury model by RT-PCR analysis and immunohistochemistry respectively, during a time course of 6 hours to 6 days. In addition, immunohistochemical detection of fibronectin was used to detect BBB breakdown at the lesion site and dual labeling was used to determine whether the vessels demonstrating BBB breakdown expressed endothelial Ang-1 or Ang-2. Endothelial Ang-1 and Tie-2 proteins were present in all cerebral vessels of normal brain including those of the choroid plexuses, whereas both these proteins as well as Ang-2 were present in choroid plexus epithelium and in ependymal cells, suggesting that angiopoietins have an autocrine effect on these cell types as well. In contrast, in the early phase after injury during the known period of BBB breakdown, increased Ang-2 mRNA and protein and decreased endothelial Ang-1 and Tie-2 proteins were observed. Two to 6 days after injury, the progressive increase in Ang-1 mRNA and protein and the decrease in Ang-2 coincided with cerebrovascular angiogenesis. Confocal microscopy showed colocalization of both Ang-1 and Ang-2 in endothelium of lesion vessels, and our observation of colocalization of Ang-1 and Ang-2 in polymorphonuclear leukocytes and macrophages has not been reported previously. This study demonstrates that Ang-1 is an important factor in maintaining normal homeostasis in the brain. Thus Ang-1 therapy may have therapeutic potential in reducing BBB breakdown and the ensuing edema after massive brain injury.
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PMID:Altered expression of angiopoietins during blood-brain barrier breakdown and angiogenesis. 1292 Feb 50


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