Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Onchocerca volvulus worms, extracted from nodules by collagenase digestion, stained with haematoxylin and cleared in glycerol, were unravelled for longitudinal examination and later embedded in brain blocks for study of serial transverse sections. A classification system for female worms is proposed, based on the reproductive status of 446 worms from Guatemala, 94 from Liberia and 125 from Mali. They were categorized into fecund, inseminated specimens; uninseminated, but potentially fertile specimens, shedding ova destined to degenerate; worms changing from the uninseminated to the inseminated state and vice versa, which were few in number; old worms, with degenerate ovaries, whose genital tracts were either empty or had disappeared; and moribund or dead worms, characterized by loss of turgor, collapse and degeneration, calcification, or invasion by polymorphic, basophilic cells. Potentially fertile worms shed oocytes continuously and, when they were inseminated, embryonic development ensured. No evidence was found of a periodic cycle of reproduction. Inseminated worms were found in nodules without a male worm, and uninseminated worms in nodules harbouring male worms. Measurements are recorded of portions of the female reproductive tract and of the length of uterus occupied by the various embryonic stages in fully fecund worms. A significant difference in the length of the body behind the first and second ovaries was observed as between worms from West African savanna (Mali) and forest (Liberia). Limited observations were also made on meiosis in the oocyte, penetration of the oocyte by sperm, formation of the ovum, syngamy and zygote formation.
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PMID:On the reproductive activity of the female Onchocerca volvulus. 207 83

Rabbit synovial fibroblasts respond to changes in cell shape and cytoskeletal architecture by altering specific gene expression. We have tested the ability of acrylamide, a neurotoxin that alters the distribution of intermediate filaments in cultured PtK1 cells, to induce metalloprotease expression in synovial fibroblasts. Cells treated with 2-20 mM acrylamide for 5 to 24 h underwent shape changes similar to cells treated with the tumor promoter phorbol myristate acetate. Intermediate filaments visualized with anti-vimentin antibodies did not collapse into a perinuclear cap in these rounded cells, but were still present in the extended cell processes. Unexpectedly, when actin was visualized in acrylamide-treated cells, extensive dissociation and clumping of microfilaments was observed. Concentrations of acrylamide greater than 10 mM were cytotoxic, but cells recovered completely after 24 h incubation with 5 mM acrylamide. Like other agents that alter cell shape and actin distribution in synovial fibroblasts, acrylamide also induced expression of the secreted metalloprotease collagenase. Although some recent evidence suggests that acrylamide may be able to exert its collagenase-inducing effects extracellularly, perhaps through transmembrane matrix receptors, our observation that this neurotoxin dramatically alters protein synthesis in synovial fibroblasts suggests that direct effects on cell metabolism may also play a role in acute acrylamide intoxication.
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PMID:Cytoskeletal dynamics in rabbit synovial fibroblasts: I. Effects of acrylamide on intermediate filaments and microfilaments. 216 39

The orientation of collagen fibres in bovine secondary osteons has been investigated in the scanning electron microscope (SEM) by removal independently of firstly the mineral component and secondly the collagen fibres. Demineralization of polished transverse sections reveals a lamellar structure for the collagen component but the precise orientation of the collagen in each ring is not unequivocably determined. However, by using a collagenase solution to etch away the collagen component of a polished surface, holes are produced in the mineral revealing the former position of the fibres. The greater rigidity of the mineral component ensures that the structure does not collapse and produce artifacts. A specimen cut so that transverse and longitudinal sections are simultaneously observed allows the relationship between the structural features on each surface to be revealed. Analysis of such micrographs indicates a model for the collagen component of osteons in which the lamellar structure contains fibres with orientations alternately parallel to and circumferential to the long axis of the osteon. Tilting the samples to look directly down the holes shows that the fibres are not precisely longitudinal and circumferential but are tilted from these ideals by a variable angle (typically 20 degrees) the precise angle probably being an important factor related to the in vivo mechanical property requirements.
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PMID:Collagen fibre orientation in bovine secondary osteons by collagenase etching. 282 98

The structural roles of cardiac jelly components were examined in the early developing chick embryonic heart. Cardiac jelly matrix components were enzymically removed in situ by injecting nanogram quantities of enzymes directly into the cardiac jelly. Injection of ovine testicular hyaluronidase caused shrinkage and the heart became flaccid, but overall heart shape did not change. These responses were the result of enzymatic removal of glycosaminoglycan sugar moieties and were not due to lumenal collapse. Although purified collagenase did not cause any noticeable change, enzymes with non-specific proteolytic activity induced marked cardiac shape changes. In such hearts the dorsal mesocardium opened completely, and the myocardium as well as splanchnic mesoderm of foregut detached from their substrate and the entire heart region swelled. Consequently the shape of the heart was altered completely. The results suggested that in the normal condition the myocardial envelope was under an internal pressure due to the presence of glycosaminoglycans in the cardiac jelly space, and that some matrical non-collagenous protein components were essential to control the internal pressure. Therefore it is suggested that the internal pressure of cardiac jelly may be the direct driving force for the looping process and protein components of cardiac jelly may be important in directing the force for the morphogenetic process.
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PMID:An experimental study of the relation of cardiac jelly to the shape of the early chick embryonic heart. 627 43

The effects of tenotomy on the surface morphology of muscle fibers including myotendinous junctions in the rat soleus muscle were studied by scanning electron microscopy (SEM). Using potassium hydroxide (KOH) and collagenase, the extracellular materials were successfully removed to expose the surface of muscle fibers. When the soleus muscle was tenotomized at both proximal and distal ends, virtually all muscle fibers showed marked alterations of the fiber surface characterized by the formation of numerous transverse grooves and folds along their length. Narrow longitudinal grooves and folds of the sarcolemma were also observed. At myotendinous junctions, the fiber ends showed an over-all rounded shape with several short sarcoplasmic processes, indicating that the processes were significantly retracted. These changes were clearly recognizable at 5 days after tenotomy, and most apparent at one week. Thin-section electron microscopy of the same SEM samples demonstrated that such folding of the sarcolemma was not directly related to the sarcomere pattern of the underlying myofibrils, suggesting that, once formed, the folds and grooves were retained for a certain period of time. At 2 and 3 weeks the surface morphology of the fibers underwent a recovery process of restoring the smooth surface on which the cross-striations of the underlying myofibrils were seen. At the fiber ends, sarcoplasmic processes regrew into slender, wavy and short forms. Such sarcoplasmic processes were greater in number and more elaborate than those in the control muscle. At 5 and 6 weeks the fiber surface resumed an almost normal morphology, except that the sarcoplasmic processes at the fiber end were still shorter and more numerous than those in the control. These observations support our previous results obtained by thin-section electron microscopy that the myotendinous junction undergoes a series of morphological changes of collapse and regrowth of the sarcoplasmic processes, reflecting changes in the underlying myofibrils. In conclusion, the changes in the surface morphology of tenotomized muscle fibers were well correlated chronologically to those of myofibrils such as the central core lesion.
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PMID:Scanning electron microscopy of tenotomized soleus muscles of the rat. 849 25

Renal tubulointerstitial fibrosis may result from a loss of tubulointerstitial volume, which produces a disproportionate increase in the density of matrix. This study examines the relationship between fibrogenesis and collapse in scar formation after experimental renal infection. Escherichia coli were inoculated into the renal cortex of Sprague Dawley rats, with saline substituted in a control group. Glomerular, tubular, and interstitial profile areas were determined. Density of glomerular profiles was used as a measure of tubulointerstitial collapse. Collagen type I, III, and IV expression was examined by in situ hybridization and immunohistochemistry. Myofibroblasts were identified by alpha smooth muscle actin immunohistochemistry, and matrix metalloproteinase-1 (MMP-1) and MMP-2 were localized with appropriate antisera. Acute interstitial edema was followed by increasing density of glomerular profiles, paralleled by loss of interstitial volume and progressive tubular atrophy. Glomerular profile area remained unchanged. Density of glomerular profiles was not temporally related to myofibroblast accumulation. Procollagen alpha 1(I), alpha 1(III), and alpha 1(IV) transcription was focal, spatially related but temporally ordered. Collagen I, III, and IV immunostaining was increased from days 3, 24, and 100, respectively (P < 0.05 versus day 0 and day 100 saline). However, when corrected for glomerular density, collagen I immunostaining decreased between days 24 and 100, whereas collagen III and IV no longer differed from day 0. MMP staining within the lesion was confined to occasional interstitial and epithelial cells throughout. It is concluded that in this model, contraction and collapse of the tubulointerstitial parenchyma has a greater influence than new collagen production on final fibrotic density.
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PMID:Evolution of tubulointerstitial fibrosis in experimental renal infection and scarring. 955 66

The systemic response to endotoxin is characterized by hypotension and severe reductions in blood pressure, leading to cardiovascular collapse that can accompany septicemia. The renin/angiotensin system would normally be expected to respond to hypotensive challenge; however, inflammation appears to modify this response. This study identifies a strong acute phase response of the kidney that is characterized by enhanced expression of serum amyloid A, haptoglobin and tissue inhibitor for metalloproteinase-1 and a reduced expression of renin. Equivalent regulatory effects were observed for the immortalized As4.1 kidney cell line that models certain features of juxtaglomerular cells. Oncostatin M, a known endotoxin-responsive proinflammatory cytokine, proved to be an effective inhibitor of renin gene expression. Suppression by oncostatin M involves activated STAT5 and requires an inhibitory element in the renin promoter that functions separately from cell type-specific enhancer elements. The renal acute phase reaction, unlike the liver acute phase reaction, is more strongly dependent on locally produced inflammatory factors.
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PMID:Endotoxin-induced renal inflammatory response. Oncostatin M as a major mediator of suppressed renin expression. 1080 9

A crude filtrate from a culture of Clostridium perfringens, type A, was fractionated by a heavy metal-alcohol technique, and some degree of concentration of biologically active factors was achieved. Both the crude material and the fractions obtained were characterized in terms of their alpha toxin, theta toxin, hyaluronidase, and collagenase activities. The filtrate and fractions were tested for their effect on the peripheral circulation of the rat, using the epinephrine threshold technique. The crude material and several fractions caused a sharp increase in epinephrine sensitivity of the capillary bed of the meso-appendix of the rat; fraction R3B1 giving an 86-fold increase in sensitivity. This reaction could be inhibited by specific antitoxic serums but not by normal serum. The "circulation factor" was shown to be heat-labile and appears to be independent of either the alpha or theta toxins. Bilateral nephrectomy greatly reduced, but did not abolish, the effect of the toxin, while the threshold response to epinephrine was not materially changed following bilateral adrenalectomy. The crude filtrate and several fractions were shown to inhibit the phagocytosis of heat-killed B. anthracis to the extent of 40 to 50 per cent. Fraction R3C2 was devoid of all biological properties studied here, except phagocytosis inhibition, suggesting that the factor responsible for this activity is distinct from the "classical" toxins and the "circulation factor." Moreover, a 1:5000 dilution of an antiserum prepared against this fraction would completely neutralize the phagocytosis inhibition factor but failed to inhibit any of the other toxic activities. Since cardiovascular collapse and absence of phagocytosis are two significant clinical findings in gas gangrene, the possible roles of the "circulation" and "phagocytosis inhibition" factors in the pathogenesis of this disease are discussed.
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PMID:The relationship of toxic fractions of a filtrate of Clostridium perfringens type A to the pathogenesis of clostridial myonecrosis. 1436 82

Previous work has shown that endothelial cell (EC)-derived matrix metalloproteinases (MMPs) regulate regression of capillary tubes in vitro in a plasmin- and MMP-1 dependent manner. Here we report that a number of serine proteases can activate MMP-1 and cause capillary tube regression; namely plasma kallikrein, trypsin, neutrophil elastase, cathepsin G, tryptase and chymase. Plasma prekallikrein failed to induce regression without coactivators such as high molecular weight kininogen (HMWK) or coagulation Factor XII. The addition of trypsin, the neutrophil serine proteases (neutrophil elastase and cathepsin G) and the mast cell serine proteases (tryptase and chymase) each caused MMP-1 activation and collagen type I proteolysis, capillary tubular network collapse, regression and EC apoptosis. Capillary tube collapse is accompanied by collagen gel contraction, which is strongly related to the wound contraction that occurs during regression of granulation tissue in vivo. We also report that proMMP-10 protein expression is markedly induced in ECs undergoing capillary tube morphogenesis. Addition of each of the serine proteases described above led to activation of proMMP-10, which also correlated with MMP-1 activation and capillary tube regression. Treatment of ECs with MMP-1 or MMP-10 siRNA markedly delayed capillary tube regression, whereas gelatinase A (MMP-2), gelatinase B (MMP-9) and stromelysin-1 (MMP-3) siRNA-treated cells behaved in a similar manner to controls and regressed normally. Increased expression of MMP-1 or MMP-10 in ECs using recombinant adenoviral delivery markedly accelerated serine protease-induced capillary tube regression. ECs expressing increased levels of MMP-10 activated MMP-1 to a greater degree than control ECs. Thus, MMP-10-induced activation of MMP-1 correlated with tube regression and gel contraction. In summary, our work demonstrates that MMP-1 zymogen activation is mediated by multiple serine proteases and MMP-10, and that these events are central to EC-mediated collagen degradation and capillary tube regression in 3D collagen matrices.
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PMID:MMP-1 activation by serine proteases and MMP-10 induces human capillary tubular network collapse and regression in 3D collagen matrices. 1587 Jan 7

Methimazole is an antithyroid drug widely used in the treatment of hyperthyroidism. Administration of this drug, often in a chronic manner, is associated with several adverse drug reactions in humans, including life-threatening hepatotoxicity. This study attempted to investigate the cytotoxic mechanism(s) of methimazole toward isolated rat hepatocytes. In addition, the role of proposed methimazole intermediary metabolites, such as N-methylthiourea and glyoxal, in the toxicity induced by this drug was evaluated. Isolated hepatocytes were prepared by the collagenase enzyme perfusion method. Cells were treated with methimazole, N-methylthiourea, and other chemicals and markers, such as cell viability, mitochondrial membrane potential (MMP), reactive oxygen species (ROS) formation, lipid peroxidation (LPO), and cellular glutathione (GSH) content, were measured. Methimazole-induced cytotoxicity was accompanied by collapse in MMP, increase in ROS formation, and LPO. Further, methimazole caused reduction in GSH reservoirs, and the cytotoxic effect of the drug was much more severe in GSH-depleted cells. N-methylthiourea caused toxicity in lower concentrations than methimazole and reduced hepatocytes glutathione content. The specific flavin-containing monooxygenase inhibitor, N,N-dimethylaniline, attenuated toxicity induced by N-methylthiourea. Administration of glyoxal trapping agents, such as metformin, hydralazine, or N-acetyl cysteine, effectively prevented methimazole toxicity in intact or GSH-depleted rat hepatocytes. This study indicates that methimazole reactive metabolites are responsible for the cytotoxicity induced by this drug, but the role of glyoxal as a metabolite, which causes ROS formation, LPO, and mitochondrial injury, is predominant because the glyoxal-trapping agents diminished these adverse effects.
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PMID:Mechanisms of methimazole cytotoxicity in isolated rat hepatocytes. 2325 69


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