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Biomedical subjects

D M Carter

Publications and source records attributed to D M Carter.

At least 55 records · Page 3Linked to original sources
PubMed1988

Detection of a gamma interferon-induced protein IP-10 in psoriatic plaques.

The pathologic features of psoriatic plaques are inflammation and increased epidermal turnover. IP-10, a cytokine the expression of which is induced by gamma-interferon, is a member of a family of soluble mediators with inflammatory and growth-promoting activities. IP-10 protein was detected in keratinocytes and the dermal infiltrate from active psoriatic plaques using an affinity-purified rabbit anti-IP-10 antibody in immunoperoxidase studies. Successful treatment of active plaques decreased IP-10 expression in plaques. These results were corroborated by Northern blot analysis with an IP-10 cDNA probe. We have previously detected activated T cells and HLA-DR keratinocytes in active psoriatic plaques. Since IP-10 is detected in delayed cellular immune responses, the present study further points to the role of ongoing cellular immune responses in the pathogenesis of psoriasis.

Blotting, Northern↗
PubMed1988

Sulfur revisited.

Sulfur is a time-honored therapeutic agent useful in a variety of dermatologic disorders. Its keratolytic action is due to formation of hydrogen sulfide through a reaction that depends upon direct interaction between sulfur particles and keratinocytes. The smaller the particle size, the greater the degree of such interaction and the greater the therapeutic efficacy. When applied topically, sulfur induces various histologic changes, including hyperkeratosis, acanthosis, and dilatation of dermal vasculature. One study showed that sulfur was comedogenic when applied onto human and rabbit skin, findings that were not reproduced in other studies. About 1% of topically applied sulfur is systemically absorbed. Adverse effects from topically applied sulfur are uncommon and are mainly limited to the skin. In infants, however, fatal outcome after extensive application has been reported.

Acne Vulgaris↗
PubMed1988

DERM/INFONET: a concept becomes a reality.

The DERMatology INFOrmation NETwork (DERM/INFONET) of the American Academy of Dermatology has become a reality. DERM/INFONET consists of a number of data bases providing information and educational programs for the dermatologist. Currently the components are: DERM/MLS (Medical Literature Search), DERM/RX (dermatologic therapy), DERM/USP (United States Pharmacopeia data base), DERM/ALLERGENS (Food and Drug Administration and Environmental Protection Agency Listings of allergens); Melanoma Prognosis Model; Electronic Mail; Bulletin Board; Meetings Calendar; ICD/CPT (International Classification of Diseases/Current Procedural Terminology) codes; AAD Membership/Committee Directories; and Dermatology Quiz. Additional data bases are planned. As audiovisual and alphanumeric communication systems evolve, newer opportunities for enhancing the DERM/INFONET Biomedical Communication Network will undoubtedly provide even greater opportunities for aiding the dermatologist in delivering state-of-the art management for their patients.

Computer Communication Networks↗
PubMed1988

Wound healing and epidermolysis bullosa.

Wound healing is reviewed in the context of the unique problems of the chronic ulcerating skin lesions associated with epidermolysis bullosa. Management approaches, including treatment of erosions with epidermal autografts, are considered.

Adolescent↗
PubMed1987

Marked increase in the frequency of psoriatic arthritis in psoriasis patients with HLA-DR+ keratinocytes.

Immunocytochemical studies with a monoclonal anti-HLA-DR antibody were performed on skin sections and keratinocyte (KTC) suspensions obtained from suction blisters of active psoriatic plaques. HLA-DR+ KTCs were found in the plaques of 23 of 38 patients with active psoriasis. Of these 23, 16 had clinical findings typical of psoriatic arthritis (PA); none of the 15 patients who lacked HLA-DR+ KTCs had PA. Although KTC HLA-DR expression was more prevalent in patients with severe skin disease, 7 of the 23 patients with HLA-DR+ KTCs in active psoriatic plaques had mild skin disease; 4 of these 7 had PA. Nail pitting or duration of skin disease did not account for increased incidence of PA in patients with HLA-DR+ KTCs. All psoriasis patients with arthritis received nonsteroidal antiinflammatory drug therapy; 14 received additional therapy directed primarily to the cutaneous manifestations of psoriasis. Nine of these noted arthritis improvement with concurrent skin response; however, in 5 patients, arthritis activity increased, despite improvement of the cutaneous disease. Two other patients, treated with methotrexate, also had concurrent skin and joint improvement. These data suggest that psoriasis patients with HLA-DR+ KTCs are at increased risk for the development of associated arthritis.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1987

Treatment of junctional epidermolysis bullosa with epidermal autografts.

We have successfully treated chronic facial erosions in three boys with junctional epidermolysis bullosa. In each patient, keratinocytes were harvested from the roof of suction blisters created on clinically uninvolved skin. They were grown in tissue culture on collagen sponges and grafted onto facial erosions that were previously treated with 2% mupirocin ointment. This experimental antibiotic ointment has proved efficacy in eradicating cutaneous pathogens such as Staphylococcus aureus from chronic wounds. In two patients, complete reepithelialization was achieved over 7 and 10 months, respectively, and partial reepithelialization occurred in another patient in whom treatment is ongoing. Epidermal autografts are a promising means for improving function and appearance in eroded skin caused by junctional epidermolysis bullosa.

Adolescent↗
PubMed1987

RNA, DNA, and cell surface characteristics of lesional and nonlesional psoriatic skin.

We have measured the RNA and DNA content and examined cell surface characteristics of human epidermal cells derived from normal skin, and lesional and nonlesional areas of psoriatic skin prior to and following treatment on a modified Goeckerman protocol. Our results show that cells from active psoriatic lesions contain greater numbers of basal keratinocytes when compared with either nonlesional skin from the same patients or skin from healthy volunteers and individuals with other inflammatory skin lesions. Follow-up measurements 2-3 weeks after the initiation of therapy showed that the numbers of basal keratinocytes in resolving psoriatic lesions had decreased and approached normal levels. Multiparameter RNA/DNA flow cytometric analysis on parallel samples from the same psoriasis patients revealed an increased growth fraction and proportion of cycling cells in both the nonlesional and lesional skin compared with controls. Furthermore, the cellular RNA content was elevated in lesional psoriatic skin when compared with either nonlesional or normal skin. Flow cytometric examination of nonlesional and lesional epidermal cells obtained 2-3 weeks after the commencement of therapy revealed that the growth fraction and mean RNA content of the keratinocytes from resolving psoriatic plaques decreased in response to therapy. In contrast, the proportion of keratinocytes within the S + G2 + M phases of the cell cycle remained elevated. These data indicate that "uninvolved" psoriatic skin exhibits characteristics more closely resembling lesional psoriatic skin than normal skin. The results further suggest that quantitation of cellular RNA content and basal cell number might be sensitive indicators of early treatment response in psoriasis.

Adult↗
PubMed1987

Effect of mupirocin on the growth and lifespan of human fibroblasts.

We have examined the effect of the antibiotic mupirocin on the growth and proliferative lifespan of human fibroblasts. Human embryonic lung fibroblasts were grown in Dulbecco's minimal essential medium, containing 10% fetal bovine serum and various concentrations of mupirocin ranging from 0.5-756 micrograms/ml. There is little difference in the rate of exponential growth and the final saturation density reached between control cultures and those grown in 0.5 microgram, 72 micrograms, or 76 micrograms/ml mupirocin. Growth was retarded or inhibited in cultures containing 650-750 micrograms/ml mupirocin. The proliferative lifespan of adult skin fibroblasts was examined in cultures serially subcultivated in medium containing either 7 micrograms/ml or 100 micrograms/ml mupirocin. Cultures incubated in these concentrations of mupirocin were capable of reaching their full proliferative potential. This study shows that the growth and proliferative lifespan of human fibroblasts is unaltered in the presence of at least 100 micrograms/ml mupirocin although growth of human fibroblasts is inhibited by 700 micrograms/ml mupirocin. These observations suggest that long-term use of low but bactericidal concentrations of mupirocin will not impair growth of fibroblasts in healing wounds.

Cell Adhesion↗
PubMed1987

Abnormalities of plasma and erythrocyte essential fatty acid composition in epidermolysis bullosa: influence of treatment with diphenylhydantoin.

The fatty acid composition of plasma and erythrocyte phospholipids was determined in children with various subtypes of epidermolysis bullosa (EB) and in their parents. Patients with recessive dystrophic, dominant dystrophic, simplex, or junctional forms of EB had a higher percentage composition of arachidonic acid in plasma and/or erythrocyte phospholipids compared to age-matched controls. Epidermolysis bullosa patients treated with diphenylhydantoin had lower levels of arachidonic acid in plasma and erythrocyte phospholipids than did untreated EB patients. Parents of children with the recessive dystrophic or junctional EB subtypes had higher linoleic and arachidonic acids in plasma and erythrocyte phospholipids than did controls. Plasma and erythrocyte total lipids were within the normal range in children with EB. Plasma zinc was also normal but plasma copper was elevated in children with recessive dystrophic EB. We conclude that higher arachidonic acid in plasma and erythrocytes may be related to the pathology of EB.

Adult↗
PubMed1986

Expression of HLA-DR molecules by keratinocytes, and presence of Langerhans cells in the dermal infiltrate of active psoriatic plaques.

Immunoperoxidase staining of skin sections and immunofluorescence analysis of keratinocyte suspensions obtained from suction blisters of psoriatic plaques were performed using an mAb, Josh 524.4.1, and Fab'2 fragments of a rabbit antiserum, both of which are directed against nonpolymorphic determinants of HLA-DR molecules. HLA-DR+ keratinocytes were present in plaques, but not normal-appearing skin, from a significant portion of patients with active psoriasis. Double-labelling immunofluorescence experiments with either the monoclonal or polyclonal anti-HLA-DR antibody, in conjunction with the mAb OKT6, which identifies DR+ Langerhans cells, demonstrated that HLA-DR molecules were present on OKT6- keratinocytes. The dermal infiltrate of psoriatic plaques contained T cells expressing the activation antigens, IL-2 receptor (Tac) and HLA-DR, as well as macrophages and OKT6+ cells. There was little difference in the characteristics of the dermal infiltrate between the lesions with or without HLA-DR+ keratinocytes. OKT6+ presumptive Langerhans cells were also found in the dermal infiltrates of patients with lichen planus, contact dermatitis, spongiotic dermatitis, erythema multiforme, basal and squamous cell carcinoma. Studies of keratinocyte suspensions showed that 7-84% of keratinocytes were HLA-DR+. Flow cytometry experiments showed that keratinocytes at all stages of differentiation were HLA-DR+. However, the stem cell-enriched population contained the highest proportion of HLA-DR+ cells. HLA-DR expression by keratinocytes correlated with disease activity. The expression was reversible with successful medical therapy. HLA-DR+ keratinocytes may activate T cells directly or may present an as yet unknown antigen to T cells. These studies provide further support for the hypothesis that immunological mechanisms play an important role in the pathogenesis of psoriasis.

Dermatitis↗
PubMed1986

Grafting of skin ulcers with cultured autologous epidermal cells.

We treated five adult individuals with six full-thickness chronic ulcerations in the skin caused by venous insufficiency, sickle cell anemia, or surgical wounds. Each patient received applications to the ulcerations of sheets of autologous epidermal cells grown in culture. All patients experienced relief of pain after grafting. Four of the six ulcers healed completely in 21 to 35 days, and three of the four remained healed for up to 2 years. One ulceration recurred within 2 months. Our experience suggests that cultured autologous epidermal grafts can provide continuous covering, relief from pain, and rapid healing of chronic debilitating ulcerations of the skin.

Adult↗
PubMed1986

Effect of oxygen on the growth of human epidermal keratinocytes.

We studied the growth of secondary cultures of neonatal human keratinocytes at oxygen concentrations between 1 and 89%. Keratinocytes were grown in MCDB medium with 5% fetal bovine serum, 10 ng/ml epidermal growth factor, 5 micrograms/ml insulin, 0.5 microgram/ml hydrocortisone, and 0.1 mM ethanolamine and phosphorylethanolamine. Medium in the flasks was equilibrated with gas mixtures containing 5% CO2, various percentages of oxygen from 0-95% and nitrogen to balance. Cells were seeded at 10(4) cells/cm2 in sealed flasks (25 cm2). These were incubated at 37 degrees C in incubators maintained at the experimental oxygen tensions. Cells grew best at PO2 (partial pressure of oxygen) 133 mm Hg (18% O2), with a mean population doubling time of 2.8 days. Growth was retarded by 60% at PO2 38 mm Hg (5% O2) and by 98% at PO2 7 mm Hg (1% O2). However, the oxygen tension that resulted in the best plating efficiency was at PO2 12 mm Hg (2% O2). When oxygen tensions were shifted to 78-133 mm Hg, cells seeded under low oxygen tensions began to proliferate. These data suggest that a better harvest of keratinocytes is obtained when cells are seeded under low oxygen tension and then shifted to ambient oxygen tensions. At high oxygen tensions, above 20%, growth was inhibited by 75% at PO2 241 mm Hg (34% O2) and 98% at PO2 374 mm Hg (52% O2). At PO2 637 mm Hg (89% O2) no cell growth occurred. These findings showed that high oxygen tensions, above 20%, have no beneficial effect on the growth of keratinocytes.

Cell Adhesion↗
PubMed1986

Plasminogen activator secreted by cultured human melanocytes.

A plasminogen activator (PA), Mr 72,000, was detected in conditioned medium from human melanocyte cultures by fibrin autography. The electrophoretic mobility was identical to that of tissue PA produced by Bowes melanoma cells. PA activity in human melanocyte culture medium was inhibited by anti-tissue PA IgG, but not by anti-urokinase IgG. Our results are the first to show that normal human melanocytes in culture secrete tissue plasminogen activator.

Cells, Cultured↗