Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
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Target Concepts:
Gene/Protein
Disease
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Drug
Enzyme
Compound
Query: EC:3.1.26.9 (
ribonuclease
)
6,589
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Sodium acetate and sulphuric acid extracts of human epidermis can each be separated by chromatographic techniques into three or more fractions with
ribonuclease
activity. Eight of these fractions were compared with respect to molecular weight, pH activity profile, polyribonucleotide hydrolysis, and activity in the presence of low levels of spermidine. Sodium acetate and sulphuric acid extracts were also prepared from callus and from psoriatic lesions and compared with extracts from normal epidermis for their response to exogenous spermidine. All eight human epidermal
ribonuclease
fractions studied had an apparent molecular weight of 15,000 daltons. Seven of the
ribonuclease
fractions were optimally active at alkaline pHs (pH 7.3-7.6 in sodium phosphate and pH 8.I in Tris-HCl) while the eighth
ribonuclease
was most active at pH 5.6 in a citrate-phosphate buffer. All enzymes hydrolyzed polycytidylic acid and five also hydrolyzed polyuridylic acid. None hydrolyzed polyadenylic acid. Seven of the eight ribonucleases studied exhibited greater activity in the presence of added spermidine. The extracts from psoriatic scales showed markedly elevated
ribonuclease
levels which could not be raised further by the addition of spermidine.
Br J
Dermatol
1977 Oct
PMID:Epidermal nucleases. III. The ribonucleases of human epidermis. 2 41
Fifteen patients with epidermal nuclear staining on direct immunofluorescence of normal skin and high titer serum antibody to
ribonuclease
-sensitive extractable nuclear antigen (ENA) had diffuse nonscarring and focal alopecia, abnormal pigmentation, swollen hands with sclerodactyly, and chronic cutaneous lupus erythematosus (LE) as the most common dermatologic features. Direct immunofluorescence of normal, unexposed skin revealed a particulate ('speckled') epidermal nuclear staining pattern in all 15 patients and subepidermal immunoglobulin deposits in 5. Ribonucleoprotein antibodies in high titer are associated with this characteristic type of epidermal nuclear staining. These findings provide easily detectable markers for a less aggressive subset of LE characterized by distinctive clinical and laboratory features consistent with mixed connective tissue disease.
Arch
Dermatol
1977 May
PMID:Mixed connective tissue disease syndrome. 6 24
Theophyllin, an inhibitor of cAMP-degrading phosphodiesterase, stimulates melanin biosynthesis in cultures of RPMI 3460 hamster melanoma cells. Although theophylline does produce an initial transient elevation of intracellular cAMP levels, long-term treatment with theophylline produces a significant decrease in cAMP content. There is an inhibition of the theophylline stimulation by dibutyryl-cAMP; this is apparently caused by interference of dibutyryl-cAMP with the uptake and incorporation of theophylline, as shown by experiments with 3H-theophylline. An alternative theory is that theophylline, being a methylxanthine compound, is metabolized by the cell and possibly causes melanotic stimulation by becoming incorporated into cellular nucleic acids or by altering the normal nucleic acid metabolism. The following observations are consistent with this theory: (u) 3H-theophylline was incorporated into both trichloroacetic acid (TCA)-soluble and TCA-insoluble cell fractions; most of the insoluble label became soluble after digestion with
ribonuclease
and deoxyribonuclease. (2) These nuclease digests of the 3H-theophylline-labeled TCA-insoluble cell fractions contained 3H-labeled material that chromatographed differently from normal nucleotides on ion exchange thin layer sheets. (3) The acid-soluble pool of 3H label disappeared rapidly while both the insoluble label and the induction of melanogenesis remained stable for 50 hr after the removal of exogenous 3H-theophylline.
J Invest
Dermatol
1978 Oct
PMID:Theophylline incorporation into the nucleic acids of theophylline-stimulated melanoma cells. 21 85
There is a deficiency of initiation in protein-synthesizing systems prepared from mammalian epidermis. These systems do not respond to inhibitors of initiation although they remain sensitive to elongation inhibitors and exogenous
ribonuclease
. In spite of this deficiency of initiation, active protein factors which support initiation reactions are present in the potassium chloride extract of mammalian epidermal ribosomes. A factor corresponding to the reticulocyte factor IF-MP has been isolated. An inhibitor of initiation is also present in the epidermal KCl wash.
J Invest
Dermatol
1976 Aug
PMID:Mammalian epidermal protein synthesis: initiation factors. 95 Apr 88
Three patients with mixed connective tissue disease (MCTD) had clinical features that included a high incidence of Raynaud phenomenon, arthritis, myositis, and swollen hands. The diagnostic laboratory test result was the presence of high titers of antibody to extractable nuclear antigen. These antibody titers are notably reduced or abolished in patients with MCTD when the tanned red blood cells that are used in the test are pretreated with
ribonuclease
. Speckled antinuclear antibodies were present in all patients. Patients with MCTD have a low incidence of renal disease, are responsive to treatment with prednisone, and have a good prognosis.
Arch
Dermatol
1976 Nov
PMID:Mixed connective tissue disease. 108 51
A comparative enzyme analysis was performed on 3 pancreatic extracts generally used for dermal-epidermal separation, namely, crude trypsin (Difco), crude trypsin (Sigma) and pancreatin. A fourth pancreatic extract, crude lipase, was subjected to a corresponding analysis. The 4 extracts were assayed for activities of: protease (total), trypsin, chymotrypsin, carboxypeptidase-A, amylase, elastase, lipase, esterase, arylesterase and
ribonuclease
. Relative activities of the different proteolytic enzymes were individualized by utilizing specific inhibitors. Insignificant differences were observed between the enzyme activities of crude trypsin (Difco) and pancreatin. Crude lipase displayed similar enzyme activities as these two extracts in addition to high lipolytic, esterolytic and arylesterolytic activities. Crude trypsin (Sigma) exhibited higher tryptic and chymotryptic activities than the other extracts but lacked all further enzyme activities. Epidermal separation was performed using similar incubation conditions for each extract and skin from the same donor. Ultrastructural examination of the detached epidermis revealed that a more effective separation could be achieved by crude lipase.
Arch
Dermatol
Res 1975 Sep 12
PMID:An analysis of pancreatic enzymes used in epidermal separation. 123 61
Mediators released from injured human skin that initiate the inflammatory response have not been adequately identified. Organ culture of full-thickness skin explants enables us to do so, because injury to the skin can be made in vitro, eliminating the rapid leakage of serum and infiltration of leukocytes that occur in vivo. In our studies, the military vesicant sulfur mustard (SM) (10 microliters of a 0.01 to 1.0% dilution) was topically applied to injure the epidermis of the explant. Then, the explants were cultured in small Petri dishes, usually for 18 h at 36 degrees C, and the organ-culture fluids were assayed for various inflammatory mediators. We found that the culture fluids from SM-exposed and control explants contained similar amounts of angiotensin-converting enzyme, trypsin-like and chymotrypsin-like proteases, acid phosphatase, beta-glucuronidase, beta-galactosidase, lysozyme, deoxyribonuclease,
ribonuclease
, interleukin 1, and lactic dehydrogenase. However, the culture fluids from SM-exposed explants contained increased amounts of histamine and plasminogen-activating activity, and often prostaglandin E2, when compared to culture fluids from control explants. After 3 to 4 d in culture, full-thickness human skin explants, when exposed to 0.2% SM (but not when exposed to 1.0% SM), sometimes showed separation of the epidermis and increased collagenase activity (i.e., hydroxyproline release). Thus, histamine (from local mast cells), and prostaglandin E2 and plasminogen-activating activity (probably from both mast cells and epidermal cells) are apparently involved in early mediation of the inflammatory response.
J Invest
Dermatol
1991 Jun
PMID:Mediators, initiating the inflammatory response, released in organ culture by full-thickness human skin explants exposed to the irritant, sulfur mustard. 171 Jun 39
We have carried out a series of in vitro studies designed to characterize the role of mononuclear phagocytes as regulators of hematopoiesis. The results of these studies have demonstrated that mononuclear phagocytes produce factors, including interleukin-1 (IL-1), that induce the expression of multilineage hematopoietic growth factors by human vascular endothelial cells. In more recent studies we and others have identified these induced factors as G-CSF, GM-CSF, IL-6, and IL-1. Interleukin 1 stimulates expression of these genes by inducing the accumulation of gene transcripts. Moreover, transcript accumulation, at least with GM-CSF, results from prolongation of mRNA half-life. Based on preliminary studies in a cell-free system, we propose that the inductive capacity of IL-1 results from its activation of
ribonuclease
inhibitors in the cytoplasm of IL-1-induced cells and hypothesize that this may be a general mechanism by which IL-1 induces gene expression.
J Invest
Dermatol
1989 Aug
PMID:Human vascular endothelial cells, granulopoiesis, and the inflammatory response. 266 22
In rat skin, type IV is the major 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) isoenzyme expressed. Although types I and II 3 beta-HSD mRNAs are also present in the skin, their level of expression is about two orders of magnitude lower than that of type IV. In this study, we have investigated the control of type IV 3 beta-HSD mRNA levels as well as 3 beta-HSD enzymatic activity in hypophysectomized adult rats of both sexes. Skin 3 beta-HSD activity was measured by the conversion of [14C]-dehydroepiandrosterone into [14C]-androstenedione, whereas
ribonuclease
protection assay using a specific type IV cRNA probe was used to assess mRNA levels. Intact male and female rats show a similar level of skin 3 beta-HSD activity, although hypophysectomy caused opposite effects, a decrease being observed in males while an increase was observed in hypophysectomized female animals. We next studied the effects of hyperprolactinemia, corticosterone and 1-thyroxine in hypophysectomized animals. L-thyroxine was found to stimulate 3 beta-HSD expression and activity in male rats whereas no significant effect was observed on the already elevated levels in hypophysectomized female rats. Corticosterone caused an inhibition of type IV 3 beta-HSD mRNA levels and activity in both male and female animals. Hyperprolactinemia achieved by pituitary implants inserted under the kidney capsule stimulated the expression of type IV mRNA as well as 3 beta-HSD enzymatic activity in hypophysectomized male and female animals. The present data demonstrate the multihormonal regulation of 3 beta-HSD/isomerase expression and activity in the rat skin.
J Invest
Dermatol
1994 Jul
PMID:Opposite effects of prolactin and corticosterone on the expression and activity of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase in rat skin. 802 81
Two patients with histologically proven mycosis fungoides, a malignancy of phenotypically mature T cells, received a topical challenge with mechlorethamine to areas of clinically uninvolved skin to exclude possible hypersensitivity reactions to this chemotherapeutic agent. In both patients, allergic contact dermatitis (ACD) developed at the sites of the application and resolved completely after withdrawal of mechlorethamine. The lesions were biopsied and analyzed for the presence of clonal T-cell receptor (TCR)-gamma gene rearrangements using two polymerase chain reaction (PCR)-based assays involving denaturing gradient gel electrophoresis (PCR/DGGE) and
ribonuclease
protection analysis (PCR/RPA). The former method has a clonal detection threshold of 10(-3)-10(-2), while the latter has a sensitivity of 10(-5). In both cases, the ACD lesions were polyclonal by PCR/DGGE. In contrast, PCR/RPA detected tumor-specific TCR-gamma gene rearrangements in these same lesions. This indicates that the ACD lesions contained tumor cells at a density within the 10(-5)-10(-2) range. Analysis of peripheral blood mononuclear cells from both patients failed to detect the malignant clone and showed the same result as blood from four normal individuals. The normal skin from one skin patient also lacked detectable TCR-gamma gene rearrangements. These results indicate that mycosis fungoides tumor are present within ACD lesions induced in mycosis fungoides patients and that this phenomenon does not appear to be due to the ubiquitous presence of detectable levels of these tumor cells in the blood or skin. These findings might be explained by nonspecific recruitment of malignant T cells to sites of local inflammation mediated by non-neoplastic antigen-specific T cells. Alternatively, they might be due to the local proliferation of very rare tumor cells in apparently normal skin in response to cytokines generated during the ACD reaction. In either case, the present study offers evidence that the malignant cells in myosis fungoides retain at least some capability of responding in vivo to physiologic stimuli.
J Invest
Dermatol
1996 Apr
PMID:Detection of low-level tumor cells in allergic contact dermatitis induced by mechlorethamine in patients with mycosis fungoides. 861 5
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