Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have previously described the structures of neutral and sialylated O-glycosidic mannose-linked tetrasaccharides and keratan sulphate polysaccharide chains in the chondroitin sulphate proteoglycan of brain. The present paper provides information on a series of related sialylated and/or sulphated tri- to penta-saccharides released by alkaline-borohydride treatment of the proteoglycan glycopeptides. The oligosaccharides were fractionated by ion-exchange chromatography and gel filtration, and their structural properties were studied by methylation analysis and fast-atom-bombardment mass spectrometry. Five fractions containing [35S]sulphate-labelled oligosaccharides were obtained by ion-exchange chromatography, each of which was eluted from Sephadex G-50 as two well-separated peaks. The apparent Mr values of both the large- and small-molecular-size fractions increased with increasing acidity (and sulphate labelling) of the oligosaccharides. The larger-molecular-size fractions contained short mannose-linked keratan sulphate chains of Mr 3000-4500, together with some asparagine-linked oligosaccharides. The smaller tri- to penta-saccharides, of Mr 800-1400, appear to have a common GlcNac(beta 1-3)Manol core, and to contain one to two residues of sialic acid and/or sulphate.
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PMID:Structural studies on sialylated and sulphated O-glycosidic mannose-linked oligosaccharides in the chondroitin sulphate proteoglycan of brain. 366 49

Interleukin-1 alpha (IL-1) stimulated the release of degraded proteoglycan from primary cultures of chondrocyte monolayers in a time- and dose-dependent fashion. Bafilomycin A1, a specific inhibitor of the vacuolar H(+)-ATPase, efficiently blocked acidification of the chondrocyte vacuolar system. Under these conditions IL-1-stimulated proteoglycan degradation was inhibited by bafilomycin A1 with an IC50 of < 10 nM in both chondrocyte monolayers and articular cartilage explants. This concentration was at least 100-fold less than that required to partially inhibit total protein synthesis. In chondrocyte monolayers, bafilomycin A1 could be added several hours after IL-1 and complete inhibition was still observed. Tumor necrosis factor-alpha and retinoic acid also stimulated proteoglycan degradation in chondrocyte monolayers, and in both cases the response was inhibited by bafilomycin A1. These results suggest that maintenance of vacuolar acidity is required for cytokine stimulated proteoglycan degradation and that this requirement is at a point distal to receptor binding and early signal transduction events. IL-1 also stimulated the synthesis and secretion of prostromelysin by chondrocyte monolayers, however, under conditions in which IL-1 stimulated proteoglycan release was totally blocked by bafilomycin A1, there was no effect on IL-1-stimulated stromelysin secretion or stromelysin enzyme activity. These results, in which stromelysin synthesis and proteoglycan degradation were dissociated, suggest that an additional enzyme is responsible for proteoglycan degradation in this chondrocyte monolayer system.
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PMID:Bafilomycin A1 inhibits IL-1-stimulated proteoglycan degradation by chondrocytes without affecting stromelysin synthesis. 786 40

The correlation between serum pepsinogen (PG) levels and the gross types was investigated in 128 consecutive patients with early gastric cancer. Although there was no significant difference in age, gender, cancer location, or cancer depth among gross appearances, the distribution of histological type was significantly different between polypoid and depressed cancers: all polypoid cancers except one were intestinal type, whereas nearly a third of depressed cancers were diffuse type. All the patients in whom Helicobacter pylori status was investigated had Helicobacterpylori infection. Combination of gross appearances and histology (polypoid cancer with intestinal type, depressed cancer with intestinal type and depressed cancer with diffuse type) showed a clear difference in distribution of serum PG levels and a ratio between levels of PG I and PG II (I/II ratio). In polypoid cancer with intestinal type, a PG I level and a I/II ratio were significantly lower than those of the others. In depressed cancer with diffuse type, PG I and PG II levels were significantly higher. These findings revealed that backgrounds such as intragastric acidity and extent of gastric atrophy might differ among early gastric cancers with different morphology and histology.
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PMID:Correlation of serum pepsinogens and gross appearances combined with histology in early gastric cancer. 1691 32

Local acidic areas characterize diffuse intimal thickening (DIT) and advanced atherosclerotic lesions. The role of acidity in the modification and extra- and intracellular accumulation of triglyceride-rich VLDL and IDL particles has not been studied before. Here, we examined the effects of acidic pH on the activity of recombinant human group V secreted phospholipase A(2) (sPLA(2)-V) toward small VLDL (sVLDL), IDL, and LDL, on the binding of these apoB-100-containing lipoproteins to human aortic proteoglycans, and on their uptake by human monocyte-derived macrophages. At acidic pH, the ability of sPLA(2)-V to lipolyze the apoB-100-containing lipoproteins was moderately, but significantly, increased while binding of the lipoproteins to proteoglycans increased >60-fold and sPLA(2)-V-modification further doubled the binding. Moreover, acidic pH more than doubled macrophage uptake of soluble complexes of sPLA(2)-V-LDL with aortic proteoglycans. Proteoglycan-affinity chromatography at pH 7.5 and 5.5 revealed that sVLDL, IDL, and LDL consisted of populations with different proteoglycan-binding affinities, and, surprisingly, the sVLDL fractions with the highest proteoglycan-affinity contained only low amounts of apolipoproteins E and C-III. Our results suggest that in atherosclerotic lesions with acidic extracellular pH, sPLA(2)-V is able to lipolyze sVLDL, IDL, and LDL, and increase their binding to proteoglycans. This is likely to provoke extracellular accumulation of lipids derived from these atherogenic lipoprotein particles and to increase the progression of the atherosclerotic lesions.
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PMID:Acidity and lipolysis by group V secreted phospholipase A(2) strongly increase the binding of apoB-100-containing lipoproteins to human aortic proteoglycans. 2204 Nov 35