Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although fibrosing alveolitis is a rare complication of dermatomyositis, early detection and treatment are important in preventing pulmonary fibrosis. Anti-Jo-1 antibody, an antibody to the cellular enzyme histidyl-t-RNA synthetase, has been found to correlate closely with the subset of dermatomyositis/polymyositis associated with fibrosing alveolitis. This association is well known to rheumatologists but has received little attention in the dermatologic literature. We wish to alert dermatologists to the importance of the association of anti-Jo-1 antibody in patients with dermatomyositis and present a patient with anti-Jo-1 antibody who had Raynaud's phenomenon and mild arthritis in association with dermatomyositis and pulmonary fibrosis. We suggest screening patients with polymyositis/dermatomyositis for this antibody, to detect the population at high risk of developing pulmonary complications.
J Am Acad Dermatol 1987 Aug
PMID:Dermatomyositis and pulmonary fibrosis associated with anti-Jo-1 antibody. 349 58

Langerhans cells (LC) belong to the dendritic cell lineage and are the principal antigen-presenting cells of squamous epithelia. Short-term cultured LC (cLC) exhibit a marked augmented capacity to stimulate allogeneic T cells and acquire the ability to activate naive T cells, probably in relation to enhanced expression of accessory signals. In this study, we evaluated the expression of B7 costimulatory molecule (CD80) in human freshly isolated (fLC) and cLC at both the protein and mRNA level. Staining of frozen skin sections did not reveal any epidermal dendritic cell reactive with either of two different anti-B7 monoclonal antibodies. fLC in suspension did not exhibit any B7 staining as evaluated by two-color flow-cytometry analysis and immunoelectron microscopy. In contrast, LC that were cultured for 24-72 h displayed strong surface B7 reactivity with a characteristic patchy pattern. Treatment with dispase and trypsin did not reduce B7 staining of cLC. Following warming to 37 degrees C, cLC tagged with anti-B7 monoclonal antibody and gold-conjugated secondary antibody could internalize surface B7 by using the organelles of receptor-mediated endocytosis. B7 mRNA, detected by the reverse-transcriptase polymerase chain reaction technique, was expressed at a low level in purified (> 90% HLA-DR+) fLC but not in LC-depleted epidermal cells, and was markedly upregulated in purified cLC. The results indicate that 1) fLC do not express B7 protein on their surface, but acquire B7 during culture, 2) surface B7 is not sensitive to trypsin, 3) B7 expression is regulated primarily at the mRNA level, and 4) membrane B7 can be internalized within cLC. B7 molecule on CLC may be relevant to their increased antigen-presenting cell potency and ability to stimulate naive T lymphocytes.
J Invest Dermatol 1994 Jul
PMID:Expression of B7 costimulatory molecule in cultured human epidermal Langerhans cells is regulated at the mRNA level. 751 82

We have established a dermal fibroblast-like stromal cell line, DFB-1, and a clone, 12E2, from epidermal sheets prepared from the skin of BALB/c mouse ears by trypsin digestion. They were suggested to be fibroblasts or myofibroblasts, as 1) they were polygonal or spindle-shaped under the phase-contrast microscope, 2) they did not possess any tonofilaments or desmosomes, and 3) they did not express any marker for bone marrow-derived cells or macrophages. Interestingly, these cells showed a unique phenomenon of "pseudo-emperiporesis," which was first recognized in the interaction between thymic nurse cells and thymocytes. Namely, two T-cell clones and one T-cell hybridoma migrated beneath the cytoplasmic projections of the fibroblast-like cutaneous stromal cells in culture. Furthermore, secretion of interleukin 7 by these cells was confirmed by bioassay using an IL-7-dependent cell line and by inhibition with anti-interleukin 7 antibody, and the expression of interleukin 7 mRNA was also demonstrated in these cells by a combination of reverse-transcriptase polymerase chain reaction and Southern blot analysis. These data strongly suggest the presence of unique stromal cells even in the skin, probably at the upper dermis, which can function like the nurse cells in the thymus. These stromal cells may play a crucial role in cutaneous immunophysiology.
J Invest Dermatol 1994 Aug
PMID:Cultured murine dermal cells can function like thymic nurse cells. 751 55

There is increasing evidence that parathyroid hormone (PTH) and PTH-related peptides (PTHrP) are involved in normal skin cell growth; therefore, we investigated whether the PTH/PTHrP receptor was expressed in cultured human keratinocytes and dermal fibroblasts. Northern analyses of poly (A)+ RNA isolated from cultured fibroblasts revealed two PTH/PTHrP receptor transcripts with one major band at 2.5 kb and one minor band at 2.3 kb. These transcripts were consistent with those found in human osteosarcoma cells, which are known to express PTH/PTHrP-R mRNAs. In contrast, after repeated Northern analyses no PTH/PTHrP receptor transcripts were found in poly (A)+ RNA isolated from cultured keratinocytes. Reverse-transcriptase/nested polymerase chain reaction analyses of total RNA isolated from cultured keratinocytes and fibroblasts confirmed the Northern analyses data that the PTH/PTHrP receptor was expressed in cultured fibroblasts but not in cultured keratinocytes. When cultured fibroblasts and keratinocytes were exposed to 10(-7) M PTH (1-34) there was a twofold increase in cAMP levels in the fibroblasts and no demonstrable increase was noted in keratinocytes. These results suggest that skin fibroblasts possess the classical PTH/PTHrP receptor and are target cells for PTH and PTHrP whereas keratinocytes do not have the receptor and are unresponsive to its N-terminal agonist in the stimulation of cAMP formation.
J Invest Dermatol 1995 Jul
PMID:Cultured human fibroblasts and not cultured human keratinocytes express a PTH/PTHrP receptor mRNA. 761 67

Two cases of mycosis fungoides (MF) in the tumor stage were treated with intra-lesional interferon-gamma (IFN-gamma) therapy. After systemic chemotherapy, intra-lesional recombinant interferon-gamma was applied to the residual tumors. Intra-lesional IFN-gamma was sufficiently effective in the treatment of MF tumors, especially small-sized ones. Reverse transcriptase polymerase chain reaction (RT-PCR) analysis of messenger RNA expression of cytokines commonly detected interleukin-6 (IL-6) and IFN-gamma in the tumor cells before intra-lesional IFN-gamma. However, in our study, tumor cells in these cases did not exhibit the definitive cytokine patterns of Th1 or Th2.
J Dermatol 1995 Sep
PMID:Cytokine profile of tumor cells in mycosis fungoides: successful treatment with intra-lesional interferon-gamma combined with chemotherapy. 853 50

Eosinophilic pustular folliculitis (EPF) is characterized clinically by pruritic grouped follicular papules and pustules on the trunk, limbs, and face, and, histologically, by follicular infiltration with eosinophils. The blood eosinophil count is elevated in most patients. Oral minocycline, nonsteroidal anti-inflammatory drugs, diaminodiphenylsulphone, and corticosteroids may induce remission. We report two Japanese men with EPF who responded poorly to the usual therapy. Intravenous injections of recombinant interferon-gamma (rIFN-gamma), 5 x 10(5) to 2 x 10(6) Japan Reference Unit (JRU) (1 JRU roughly corresponds to 4 NIH units) daily for 7 days, cleared the skin lesions and returned the peripheral eosinophil counts to normal in both patients. However, the lesions recurred 2-3 days after rIFN-gamma was stopped. Both patients have received intravenous rIFN-gamma once or twice a week for nearly 1 year without systemic side-effects. Reverse transcriptase-polymerase chain reaction revealed a decreased expression of interleukin 5 (IL-5) mRNA in peripheral mononuclear cells after the rIFN-gamma therapy. rIFN-gamma may become the treatment of choice in recalcitrant EPF, although further studies are needed. It may work by interfering with the immunological function of type 2 T-helper cells, including IL-5 production responsible for the growth and differentiation of eosinophils.
Br J Dermatol 1996 Apr
PMID:Eosinophilic pustular folliculitis effectively treated with recombinant interferon-gamma: suppression of mRNA expression of interleukin 5 in peripheral blood mononuclear cells. 873 89

There are two distinct lineages of T cells: T-cell receptor (TCR) alphabeta-bearing cells (alphabeta T cells) and TCR gammadelta-bearing cells (gammadelta T cells). All of the alphabeta T cells and most subsets of gammadelta T cells develop in the thymus. It has been demonstrated that the protein tyrosine phosphatase CD45 plays a pivotal role in the intrathymic development of alphabeta T cells. Thymocyte maturation is arrested at the transitional stage from immature CD4+ CD8+ double-positive to mature CD4+ or CD8+ single-positive cells after CD45 exon 6 gene disruption. In this study, we examined whether Vgamma3 dendritic epidermal T cells (DETC), a subset of thymus-dependent gammadelta T cells uniquely residing in the murine epidermis, are altered in the CD45 exon 6-deficient mice. In situ immunolabeling on epidermal sheets demonstrated that the CD45-deficient mice had a normal density and immunophenotype of Vgamma3 DETC compared with the wild-type control mice. Reverse transcriptase polymerase chain reaction revealed that similar levels of Vgamma3 TCR mRNA were present in the epidermis of CD45-deficient mice and wild-type controls. Flow cytometry demonstrated no significant difference in the proportion of Vgamma3 T cells in the epidermis between the genotypes. In addition, Vgamma2 T cells, another subset of gammadelta T cells, were also examined by flow cytometry. The frequency of Vgamma2 T cells in lymph nodes was normal in the CD45-deficient mice. Our results indicate that although CD45 is crucial for the development of alphabeta T cells, this molecule is not necessary for the thymic maturation of gammadelta T cells, including Vgamma3 DETC and Vgamma2 T cells.
J Invest Dermatol 1997 Jan
PMID:CD45 molecule in gammadelta T-cell generation: disruption of CD45 exon 6 does not affect Vgamma3 dendritic epidermal T-cell development. 924 17

Spontaneous tumor regression, which is observed clinically and histologically in some primary melanomas, occurs in the absence of any effective therapy. It is probably immunologically mediated, because regressing melanomas are infiltrated with larger numbers of activated T cells, primarily CD4+, than nonregressing melanomas. To investigate the hypothesis that spontaneous regression of melanomas is caused by T-cell cytokine production, cytokine mRNA expression in 20 primary melanomas was examined using a noncompetitive, quantitative reverse-transcriptase polymerase chain reaction method. DNA standards were used to generate known numbers of molecules in each sample. Results were standardized to the internal control, glyceraldehyde-3-phosphate dehydrogenase. mRNA for CD35, lymphotoxin (TNF-beta), and IL-2 were significantly elevated in the ten regressing melanomas compared to the ten nonregressing melanomas. IFN-gamma mRNA was also elevated in regressing melanomas but failed to reach statistical significance. The Th2 cytokines IL-10 and IL-13 did not show differences in the regressing melanomas compared to nonregressing melanomas; neither did the pro-inflammatory cytokines IL-1alpha, IL-1beta, IL-6, IL-8, and TNF-alpha, nor the growth factors, bFGF and TGF-beta or GM-CSF. This study shows an association between Th1 cytokines and spontaneously regressing melanomas. Although we have not shown that these cytokines cause regression, these findings support our hypothesis that activated CD4+ T cells may mediate melanoma regression by secretion of Th1 cytokines.
J Invest Dermatol 1997 Jun
PMID:T helper 1 cytokine mRNA is increased in spontaneously regressing primary melanomas. 918 21

Wells' syndrome, or eosinophilic cellulitis, is a rare dermatosis characterized histologically by a dermal infiltrate of eosinophils, lymphocytes and histiocytes between collagen bundles and amorphous or granular eosinophilic deposits on collagen, constituting flame figures. We report a 54-year-old woman with eosinophilic cellulitis whose peripheral blood showed a marked eosinophilia and a high proportion of CD4+CD7- cells before treatment. Reverse transcriptase-polymerase chain reaction revealed that CD4+CD7- cells, but neither CD4+CD7+ nor CD4-CD8+ cells, in the circulating mononuclear cells expressed mRNA for interleukin (IL)-5, the major cytokine involved in eosinophilia. The proportion of CD4+CD7- cells decreased, and expression of mRNA for IL-5 disappeared in the peripheral blood, when the disease was treated by the administration of intravenous recombinant interferon-gamma. These findings suggest that circulating CD4+CD7- T cells play a pivotal role in the pathogenesis of eosinophilic cellulitis by producing IL-5.
Br J Dermatol 1997 Jun
PMID:Wells' syndrome: a pathogenic role for circulating CD4+CD7- T cells expressing interleukin-5 mRNA. 921 26

Although the TGF-beta family of growth factors probably regulates skin and hair follicle development, its exact role is still quite ill-defined. Here, we characterize the correlative expression pattern of the interdependent high affinity receptor proteins for TGF-beta1 and TGF-beta3, TGF-beta receptor type I (TGF-betaRI) and TGF-beta receptor type II (TGF-betaRII), during hair follicle development and cycling in C57BL/6 mice. During neonatal follicle development, TGF-betaRII immunoreactivity is confined to epithelial cells. Focal epidermal TGF-betaRII expression is seen even before actual hair placode formation. In contrast to the TGF-betaRII immunoreactivity in the outer root sheath, precortical hair matrix and inner root sheath cells were TGF-betaRII negative during hair bulb morphogenesis. TGF-betaRI (Alk-5) immunoreactivity largely overlapped the TGF-betaRII expression pattern, but was more widespread. During hair follicle cycling in adolescent mice, TGF-betaRII immunoreactivity was restricted to follicles, and was strikingly hair cycle dependent (maximal immunoreactivity: anagen VI and early catagen). Again, TGF-betaRI (Alk-5) immunoreactivity co-localized with TGF-betaRII immunoreactivity, but was more extensive. Reverse transcriptase polymerase chain reaction analysis of TGF-betaRII mRNA confirmed peak transcript levels in back skin with most hair follicles in the anagen VI-catagen transformation. mRNA levels of TGF-betaRI (Alk-5) did not vary significantly during the hair cycle, whereas those of TGF-betaRI (threonine-serine kinase 7 L) declined during early anagen, and were maximal during the anagen-catagen transition. This provides a basis for defining the choreography of TGF-beta-related signalling during hair follicle morphogenesis and cycling, introduces intraepidermal TGF-betaRII immunoreactivity as a marker for imminent follicle development, and supports the concept that both TGF-betaRII and TGF-betaRI stimulation is involved in, but not restricted to, the control of catagen induction.
J Invest Dermatol 1997 Oct
PMID:Transforming growth factor-beta receptor type I and type II expression during murine hair follicle development and cycling. 932 84


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