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

Six patients underwent dermabrasion while on or having recently completed isotretinoin (Accutane) therapy. All patients developed keloids in atypical locations; the keloids eventually responded to topical or intralesional steroid therapy. Retinoids have a modulatory effect on connective tissue metabolism, including suppression of collagenase, which may enhance keloid formation. Dermabrasion should be delayed in those patients taking or recently on isotretinoin therapy.
J Am Acad Dermatol 1986 Aug
PMID:Atypical keloids after dermabrasion of patients taking isotretinoin. 301 52

Skin biopsies from patients with pseudoxanthoma elasticum (PXE) were studied by electron microscopy either before or after selective digestions with collagenase, elastase, trypsin, hyaluronidase, chondroitinase AC and ABC, with the aim of identifying an eventual organic component associated with mineralization within the elastin fibers and the chemical nature of the enormous aggregates of filaments very often associated with, but distinct from mineralized elastin fibers. The results obtained, on both embedded thin sections and fresh tissue fragments, showed that elastin fibers, whether mineralized or not, were sensitive only to elastase, and they did not contain significant amounts of materials different from elastin that could be accounted for by ion precipitation; the aggregates of microfilaments in strict connection with altered elastin fibers were mostly sensitive to elastase and hyaluronidase, were partially removed by trypsin and chondroitinase, and were not modified by collagenase, which seems to indicate that the microfilaments consist mainly of abnormally aggregated elastin molecules together with low sulfated proteoglycans. It may be concluded that PXE is a complex genetic disorder of the connective tissue, and that mineralization of elastin is only one of the alterations of the extracellular matrix.
Arch Dermatol Res 1986
PMID:Effect of selective enzymatic digestions on skin biopsies from pseudoxanthoma elasticum: an ultrastructural study. 301 57

Sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis of pepsin-solubilized collagens from post-burn granulation tissues revealed that type V collagen consisted of 3 alpha chains: alpha 1(V), alpha 2(V), and alpha 3(V). The mean value (0.12 +/- 0.01 SD) of the type V/type I ratio in the granulation tissues was significantly higher (p less than 0.001) than that (0.03 +/- 0.01 SD) of the ratio in normal skin. The average ratio of alpha 1(V):alpha 2(V):alpha 3(V) of type V collagen purified from the granulation tissues was determined to be about 5:3:1. SDS-polyacrylamide gel electrophoresis patterns of 3 alpha chains were not affected in the presence or absence of 2-mercaptoethanol. Purified type V collagen was degraded by bacterial collagenase, but remained intact after tadpole collagenase digestion, in contrast to type I and type III collagens. Amino acid analyses of each alpha chain separated on SDS-gel electrophoresis of type V collagen revealed that all 3 alpha chains of type V collagen were poor in alanine, rich in hydroxylysine, and had high ratios of hydroxylysine/lysine, which are typical features of type V collagen. The purified type V collagen was further fractionated by ammonium sulfate into 2 molecular species, [alpha 1(V)]2 alpha 2(V) and alpha 1(V)alpha 2(V)alpha 3(V). Our data demonstrate that type V collagen in preparations from human post-burn granulation tissues consists of 3 alpha chains and can be resolved into 2 distinct heterotrimers.
J Invest Dermatol 1986 Oct
PMID:Isolation and characterization of type V collagen from human post-burn granulation tissues. 302 Jan 32

We performed fetoscopy and skin biopsy on a 19-week fetus at risk for recessive dystrophic epidermolysis bullosa (RDEB). Ultrastructural analysis of the tissue revealed dermolytic blister formation in the skin characteristic of the disease. To develop a biochemical test for use in antenatal diagnosis of RDEB, we established skin fibroblast cultures from the 20-week aborted fetus. The collagenase production by fetal RDEB fibroblast cultures was greater than seen in normal fetal fibroblast cultures. The concentration in culture medium from fetal RDEB cultures was 5.42 +/- 0.74 micrograms/ml (mean +/- SE) compared with 2.24 +/- 1.11 micrograms/ml in normal adult control cultures and 2.05 +/- 0.61 micrograms/ml in cultures from patients with other genetic forms of epidermolysis bullosa (p less than 0.025). In contrast, the concentration of collagenase in the fetal RDEB culture medium was not different from that seen in cell cultures from known patients with RDEB (5.34 +/- 1.12 micrograms/ml). Collagenase activity of the fetal RDEB medium was also increased approximately 3.5-fold. These data indicate that enhanced expression of collagenase by fetal RDEB skin fibroblasts can serve as a biochemical adjunct, and possibly an alternative, to morphologic examination of tissue for antenatal diagnosis.
J Invest Dermatol 1986 Nov
PMID:Antenatal diagnosis of recessive dystrophic epidermolysis bullosa: collagenase expression in cultured fibroblasts as a biochemical marker. 302 61

Selective destruction of connective tissue may be a useful therapeutic tool in conditions associated with abnormal deposition of scar tissue. We have investigated intradermal injections of clostridial collagenase and bovine testicular hyaluronidase alone and in combination in Yucatan miniature hairless pigs. Collagenase in combination with hyaluronidase was quite efficient at destroying the connective tissue matrix, although elastic tissue appeared to be completely spared. Collagenase alone at higher doses degraded collagen, but hyaluronidase had little effect on connective tissue architecture.
Br J Dermatol 1986 Oct
PMID:Degradation of porcine dermal connective tissue by collagenase and hyaluronidase. 302 82

Normal, mature and hypertrophic dermal scars were examined by indirect immunofluorescence for the presence of collagenase, tissue inhibitor of metalloproteinases (TIMP) and cathepsin D. Significant extracellular immunoprecipitation of both collagenase and TIMP were found in areas of all scars judged to be actively remodelling, whereas inactive areas were predominantly negative. TIMP was also present in endothelial cells of patent blood vessels, but found not to be present in the enlarged endothelial cells of occluded vessels. Negligible amounts of extracellular cathepsin D were found.
Br J Dermatol 1986 Oct
PMID:Immunolocalization of collagenase and tissue inhibitor of metalloproteinases (TIMP) in hypertrophic scar tissue. 302 83

Desmoplastic basal cell carcinomas (fibrosing or morphea types) were studied ultrastructurally, immunocytochemically, and biochemically for basement membrane-degrading activity and compared with the common varieties of basal cell (superficial and nodular-ulcerative types). Whereas the latter lesions demonstrated intact basement membranes as evidenced by extracellular laminin and type IV collagen immunoreactivity and the presence of an unusually thickened basal lamina, desmoplastic basal cell carcinomas showed large defects and absences in basal lamina and basement membrane immunoreactivity. Intense tumor cytoplasmic immunoreactivity for type IV collagenase was present in 13 of 15 cases of desmoplastic basal cell but absent in the superficial and nodular-ulcerative varieties. Whereas explant cultures of all the types of basal cell carcinoma studied gave rise to high levels of interstitial (type I) collagenase activity in conditioned media, only the desmoplastic variety exhibited high type IV collagenase activity. These findings suggest that the mechanisms by which the desmoplastic and the common varieties of basal cell carcinoma infiltrate host tissues may be fundamentally different.
J Invest Dermatol 1987 Mar
PMID:Desmoplastic basal cell carcinomas possess unique basement membrane-degrading properties. 302 37

To determine if an altered ability to contract a hydrated collagen lattice is characteristic of fibroblasts from patients with recessive dystrophic epidermolysis bullosa (RDEB), we examined contraction by fibroblasts from normal subjects and patients with RDEB, dominant dystrophic epidermolysis bullosa (DDEB), and dominant epidermolysis bullosa simplex (DEBS). An extremely broad range of contractility (normal, poor, and hypercontraction) was observed in all types of epidermolysis bullosa (EB). When contraction in control fibroblasts was defined as the mean +/- 2 SD, (all control values were within this range) and the data were analyzed by the chi-square test, only 32% of EB cells fell within this range, with 47% poorly contractile and 21% hypercontractile. These data, derived from 34 patients, indicate that no single genetic defect resulting in altered contractility in the 3 distinct types of EB is likely. Neither cell viability, collagenase expression, nor PGE2 synthesis as correlated with gel contraction in any group. Indomethacin had no effect on contraction in RDEB. It is possible that the genetic defects in EB cause blister formation in vivo and may lead in some way to an abnormal interaction of fibroblasts with the extracellular matrix resulting in an altered collagen lattice contraction in vitro.
J Invest Dermatol 1987 Jun
PMID:Behavior of epidermolysis bullosa fibroblasts in a hydrated collagen lattice. 303 32

The correlation between proteinase activities and invasive and metastatic potentials was investigated by comparing three different kinds of tumors. Extracts from tumor homogenate of 11 squamous cell carcinoma (SCC), 5 basal cell epithelioma (BCE), and 8 seborrheic keratosis (SK) were prepared in order to examine the activity of acid phosphatase and proteinases such as cathepsin B and D, type I and IV collagenase, and plasminogen activator (PA). There was no difference observed between acid phosphatase and cathepsin D activities among the three tumors. Cathepsin B and PA activities were slightly elevated in SCC. Type I collagenase activity of SCC was 9-fold higher than that of SK (p less than 0.01), and type IV collagenase was 3-fold higher per tissue DNA (p less than 0.05). Type I and IV collagenase of BCE were elevated per tissue protein but not elevated per tissue DNA. Correlation was found between the level of cell differentiation in SCC and the activities of cathepsin B, PA, and type I collagenase. Poorly differentiated SCC exhibited a tendency to have higher proteinase activities. Proteinases that showed high activities in malignant tumor homogenate may be related to the degradation of the surrounding cell matrix in addition to intracellular metabolism. Type I and IV collagenase, in cooperation with cathepsin B and PA, might play a major role in invading the dermal stroma and basement membrane.
J Invest Dermatol 1988 Jun
PMID:Comparison of proteinase activities in squamous cell carcinoma, basal cell epithelioma, and seborrheic keratosis. 328 80

We describe a patient with Werner's syndrome from whom skin biopsy specimens were sampled for histology and electron microscopy and fibroblasts were cultured. Tissue sampled from five sites that varied in clinical presentation revealed striking changes in the dermoepidermal junction, elastic fibers of the papillary and reticular dermis, and adipose tissue of the hypodermis. The density and organization of the collagenous connective tissue was altered variably depending on the biopsy site. Changes noted in the epidermis were indicative of tissue regeneration and repair. Cells derived from acral areas grew poorly and could not be passed. Collagen synthesis in these cells was enhanced approximately 50%, and collagenase expression was decreased to a similar degree. Cells derived from the skin of the trunk could be passed but had an abbreviated in vitro life span. Collagen synthesis in these cells was unaltered. Serum from the patient with Werner's syndrome or from his obligate heterozygote offspring stimulated collagen synthesis in low-passage normal human skin fibroblast target cells. Sequential passage of these normal cells resulted in a blunting of the stimulatory effect. These observations suggest that a stimulator of collagen synthesis exists in the serum of patients with Werner's syndrome and that as cells (either normal or Werner's syndrome) "age" in vitro they may become hyporesponsive to this as yet undefined stimulatory factor in serum.
Arch Dermatol 1988 Jan
PMID:Werner's syndrome. Evidence for preferential regional expression of a generalized mesenchymal cell defect. 333 48


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