Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00691 (EE2)
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The Langerhans cell (LC) migrates between the epidermis and the regional lymph nodes to present antigens. This migration pattern requires the expression of a changing repertoire of cell-surface molecules. In this work, we have investigated the expression of the adhesion molecules CD 11/CD 18 and CD 58 on LCs. Human epidermal cell suspensions were enriched in LCs (mean enrichment 75%) using a two-step technique including a Ficoll-Hypaque gradient followed by Fc receptor panning with IgG-coated sheep erythrocytes. The number of cells obtained per experiment was 750,000 (extremes 280,000-1,800,000), and the following antibodies were tested on fresh suspensions and/or after 48 hours in culture: BB3 (antithyroglobulin negative control IgG2a), OKT6 (anti CD1a, Ortho), anti HLA-DR (Becton-Dickinson), MHM 24 (anti CD 11a, leukocyte typing workshop n(0)3), MO1 and 44 (anti CD 11b, leukocyte typing workshop n(0)3), anti CD 11c (Immunotech), 60.3 and MHM 23 (anti CD 18, leukocyte typing workshop n(0)2), TS2/9.1.1 (anti CD 58, leukocyte typing workshop n(0)3). We found that amongst CD 11 subunits, only CD 11c was expressed in fresh suspensions, but was weaker than CD 18, and disappeared with culture. CD 58 was not detected in fresh suspensions but appeared after 2 days of culture, confirming earlier work. Thus the LC exhibits cell surface characteristics similar to tissue macrophages (CD 18 and CD 11c) prior to culture. The expression of CD 58 after culture is in accordance with the interaction of LC with CD2 bearing T-lymphocytes during antigen presentation in peripheral lymph-nodes.
Clin Exp Dermatol 1992 Jul
PMID:Flow cytometry analysis of adhesion molecules on human Langerhans cells. 145 12

Histologic and clinical improvement of sun-exposed skin following topical treatment with retinoic acid has been reported. Daily application of retinoic acid typically results within 2-5 d in an erythematous scaling reaction, which lessens with continued usage. The cellular, immunologic, and biochemical basis of this retinoid reaction and its role in the repair of photodamaged skin are not known. To investigate the retinoid reaction in man, we have treated non-sun-exposed skin with 0.1% retinoic acid cream (Retin-A, Ortho Pharmaceutical Corporation, Raritan, NJ) under occlusion for 4 d to induce erythema and then examined changes in 1) histology, 2) expression of cell-surface molecules, 3) the enzymes and second messengers of the phospholipase C/protein kinase C signal-transduction system, 4) levels of eicosanoids, and 5) levels of interleukin-1 protein and mRNA. These parameters were chosen for measurement both because they are indicators of epidermal function and previous studies suggest they may be responsive to retinoic acid treatment. Epidermal cell growth as judged by increased epidermal thickness and mitotic figures was significantly increased in retinoic acid-treated skin compared to vehicle-treated controls. Increased numbers of CD4+ T cells accompanied by prominence of dermal dendrocytes in the papillary dermis and focal keratinocyte expression of intercellular adhesion molecule-1 were observed in retinoic acid-treated biopsies. Phosphoinositide-specific phospholipase C activity and 1,2-diacylglycerol content were also elevated in retinoic acid-treated epidermis. Protein kinase C activity was reduced by one third in both the soluble and membrane fraction, suggesting down-regulation. Surprisingly, in view of the inflammatory nature of the retinoid reaction, no increases were observed in arachidonic acid, its metabolites, interleukin-1 alpha, or interleukin-1 beta. To examine the specificity of the retinoid reaction, subjects were treated with the irritant sodium lauryl sulfate, under conditions that resulted in a reaction clinically similar to that observed with retinoic acid. The histologic alterations induced by sodium lauryl sulfate were found to be indistinguishable from those induced by retinoic acid. These data indicate that, although a wide range of cellular and molecular alterations occur in retinoic acid-treated skin, these changes may not be necessarily specific or unique for retinoic acid.
J Invest Dermatol 1991 May
PMID:Cellular, immunologic and biochemical characterization of topical retinoic acid-treated human skin. 167 98

A comparison of the triphasic Triphasil and the combined oral contraceptive Diane 50 for treatment of acne for 6 cycles showed significant improvement in both groups. Triphasil (Wyeth-Ayerst) contains 50 mcg levonorgestrel and 30 mcg ethinyl estradiol, 75 mcg levonorgestrel and 40 mcg ethinyl estradiol for 5 days and 125 mcg levonorgestrel and 30 mcg ethinyl estradiol for 10 days. Diane 50 (Schering Ag) contains 2 mg cyproterone acetate and 50 mcg ethinyl estradiol for 21 days per cycle. 10 women in each group had physical, pelvic, ophthalmologic and neurologic exams, hematologic and biochemical screens, assays of free testosterone, sex hormone binding globulin (SHBG), androstenedione, dehydroepiandrosterone SO4 (DHEAS), progesterone, and computations of acne and hirsutism scores. Subjects had used tetracyclines, isotretinoin, erythromycin, topical clindamycin and benzoyl peroxide previously, but were withdrawn from medication in the cycle before the intervention. The mean acne scores, derived from grading and counting lesions and comedones, fell from 63.3 to 6 in the Diane 50 and from 64.2 to 4.5 in the Triphasil group. Subjective results were excellent for 6, good for 2 and unsatisfactory for 2 in the Diane 50 group, and excellent for 8 and good for 2 in the Triphasil group. In both groups mean free testosterone, androgen index, androstenedione and DHEAS, and an increase in SHBG were documented. 5 Triphasil and 5 Diane 50 subjects had increased cholesterol levels during the trial, the only abnormality detected. Side effects reported were recurrence of varicose veins and hemorrhoids in 1 women who withdrew, and complaints of mastalgia, nausea, dysmenorrhea, migraine, headache, backache and vaginal discharge.
Australas J Dermatol 1991
PMID:An open study of Triphasil and Diane 50 in the treatment of acne. 183 45

Physicians examined a 46 year old woman who came to Lidcombe Hospital in Lidcombe, New South Wales in Australia experiencing recurrent painful eruptions on the skin of her back, chest, and shoulders. General malaise and fever accompanied these eruptions of 2-3 week duration. Due to menstrual irregularities, she began taking the phasic oral contraceptive (OC). Triphasil 6 weeks before the 1st eruption occurred. The findings of laboratory investigations suggested Sweet's syndrome. She then took oral prednisone for 6 months and the lesions disappeared. Upon completion of prednisone, she again suffered from recurrent episodes. This time she did not have a fever. Her ESR levels had fallen from 40-17 mm between initial examination and examination after prednisone use. Neutrophilia was 76% . The physicians then made a diagnosis of Sweet's like dermatosis or drug eruption secondary to the OC. They suggested to the women to cease taking the OC. She then experienced no more lesions. 12 months later her blood count was normal and no more painful episodes occurred. The physicians suggested that the woman had a hypersensitive reaction to the OC. 2 other drugs have also been implicated to cause Sweet's syndrome--hydralazine and trimethoprim-sulphamethoxazole.
Australas J Dermatol 1991
PMID:A neutrophilic reaction of Sweet's syndrome type associated with the oral contraceptive. 183 46

Antibodies to extractable nuclear antigens (ENA) are frequently demonstrated in the serum of patients with cutaneous lupus erythematosus. To gain a better understanding of the influence of sex hormones on cutaneous lupus, we investigated the in vitro binding of anti-ENA antibodies to cultured human keratinocytes. Estradiol-beta augmented the binding of anti-RNP, anti-SS-A/Ro, and anti-SS-B/La antibodies to cultured cells, but produced no enhancement of the binding of anti-Sm antibodies. In addition, we examined the effects of 16-alpha-hydroxyestrone, a highly estrogenic metabolite, on the binding of anti-ENA antibodies to cultured cells. This agent did not produce any augmentation of binding. Based on these experiments, we discuss the influence of estradiol on cutaneous lupus.
Arch Dermatol Res 1991
PMID:Stimulation of anti-RNP antibody binding to cultured keratinocytes by estradiol. 192 44

A case is presented of a 37-year-old Japanese woman who presented to the hospital with arthralgia of the extremities and erythema of the hypothenar and thenar extremities. Also present were pain, swelling of the extremities, general malaise, and erythematous lesions. Abnormal laboratory findings included an elevated erythrocyte sedimentation rate, proteinuria, and weakly positive antinuclear antibodies. A biopsy from the erythematous lesion of the palm revealed mild inflammation of the lymphocytes around dermal small vessels. In addition, the lupus band test was positive in uninvolved skin sites. A month prior to the onset of symptoms, the patient had begun taking an oral contraceptive (OC) that contained 0.5 mg of etynodil acetate and 0.1 mg of mestranol. All symptoms disappeared within 2 weeks of discontinuation of OC use and the laboratory findings returned to normal. This is assumed to be a case of drug-induced lupus erythematosus. Estradiol has been demonstrated to play a significant role in the development of skin lesions in lupus erythematosus, and the estrogen in OCs may trigger a lupus episode. However, this is only the 4th case of OC-induced lupus reported from Japan.
J Dermatol 1991 Jan
PMID:Oral contraceptive-induced lupus erythematosus in a Japanese woman. 205 Sep 10

In a group of healthy, non-vegetarian females currently being treated for diffuse androgen-dependent alopecia with 50 or 100 mg of oral cyproterone acetate for 11 days and 30 or 40 micrograms of ethinyl oestradiol for 20 days of the menstrual cycle, significant decreases in mean serum vitamin B12 (P less than 0.0001), haemoglobin (P less than 0.003) and haematocrit (P less than 0.004) values, were observed after 6 months. Serum folic acid, red-cell folate and mean cell volume remained unchanged within the normal range during this time. All patients responded to oral cyanocobalamin, or intramuscular injections of hydroxocobalamin. In patients with baseline serum vitamin B12 levels below 350 ng/l, we would suggest prophylactic cyanocobalamin concurrent with cyproterone-acetate-ethinyl-oestradiol (CPA EE2) therapy. Studies involving other dose regimens of CPA EE2 (Dianette) or cyproterone acetate alone (Androcur, Cyprostat), may require evaluation of the vitamin B12 status if treatment is to be given for periods of longer than 3 months.
Clin Exp Dermatol 1990 Jul
PMID:Reduced serum vitamin B12 levels during oral cyproterone-acetate and ethinyl-oestradiol therapy in women with diffuse androgen-dependent alopecia. 214 99

The effectiveness of the antiandrogen flutamide in combination with an oral contraceptive was studied in 20 patients with moderate to severe hirsutism. Eight patients had no previous therapy, whereas 12 had failed to respond to oral contraceptives, spironolactone, or dexamethasone therapy. Treatment with the antiandrogen flutamide (250 mg twice daily) and an oral contraceptive (Ortho 1/35) resulted in a particularly rapid and marked decrease in the total hirsutism score, which reached the normal range at 7 months. Seborrhea, acne, and hair loss score were also rapidly corrected. Treatment was associated with a decrease in plasma luteinizing hormone, progesterone, and estradiol levels. Plasma sex hormone-binding globulin levels were initially low in 18 to 20 patients but increased significantly during therapy. No clinically significant side effects were observed.
J Am Acad Dermatol 1990 Sep
PMID:Treatment of hirsutism with the pure antiandrogen flutamide. 221 45

Peripheral blood estradiol, progesterone, testosterone were measured in 100 women with gonorrhea and Gonococcus-Trichomonas infection. Estradiol levels were found reduced in both phases, progesterone level elevated in the follicular and lowered in the lutein phases of the menstrual cycle as against the norm. Elevated testosterone levels were revealed in the peripheral blood of women with gonorrhea, particularly so in chronic gonorrhea and mixed Gonococcus-Trichomonas infection. Therapy did not result in normalization of blood hormone concentrations, this pointing to advisability of including the drugs correcting hormonal disorders into a complex of treatment of such patients.
Vestn Dermatol Venerol 1990
PMID:[The sex hormone content of the peripheral blood in women with gonorrhea and gonorrhea-trichomoniasis infections]. 225 76

Keratinocyte expression of the monocyte/macrophage surface antigens defined by OKM1 and OKM5 antibodies (Ortho Diagnostics) was examined using the peroxidase anti-peroxidase immunohistochemical technique. A range of inflammatory cutaneous disorders were investigated, including lichen planus, psoriasis and atopic dermatitis. Positive suprabasal keratinocyte expression of OKM5 antigen was observed in all disorders, while keratinocyte staining with OKMI antibody was consistently negative. These results provide further evidence that keratinocytes may play an important role in cutaneous immune responses. Furthermore, they are consistent with the recent observation that HLA-DR positive keratinocytes may modulate cutaneous immunological reactions by inducing T-cell unresponsiveness.
Br J Dermatol 1989 May
PMID:Keratinocyte expression of OKM5 antigen in inflammatory cutaneous disease. 247 14


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