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Biomedical subjects

E Robb

Publications and source records attributed to E Robb.

6 recordsLinked to original sources
PubMed1995

Isolation of a unique melanogenic inhibitor from human skin xenografts: initial in vitro and in vivo characterization.

Previously, split-thickness human skin grafted onto athymic mice has been shown to become markedly hyperpigmented, but the factor(s) responsible for this hyperpigmentation had not been isolated. The present study describes the isolation and characterization of a potent melanogenic inhibitor from grafted human skin. Extracts from grafted skin inhibited, in a concentration-dependent manner, tyrosinase activity of normal human melanocytes and of Cloudman S91 murine melanoma in culture. Sodium dodecylsulfate-polyacrylamide gel electrophoresis analysis of extracts from pre- and post-grafted skin demonstrated the presence of a protein doublet of approximately 14 kD exclusively in the post-grafted skin. This protein inhibited both tyrosinase activity and cellular proliferation in a concentration-dependent manner. The inhibition of tyrosinase activity in normal human melanocytes was 53% at 0.5 microgram/ml concentration, whereas this inhibition was almost complete in murine melanoma cultures at 1.0 microgram/ml. The protein did not inhibit either cellular proliferation or protein synthesis in normal human fibroblast cultures, and therefore may act specifically on melanocytes. Injections of the inhibitor corresponded with a delay and reduction in the quantity of pigment in human skin 2 weeks after grafting. Multiple injections of the inhibitor into the hyperpigmented xenografts (20 weeks after grafting) reversed the hyperpigmentation with no observable inflammatory or toxic responses. The results indicate that hyperpigmented human skin xenografts contain a potent inhibitor of melanogenesis and melanocyte proliferation.

Animals↗
PubMed1993

Histological, biochemical, and ultrastructural studies on hyperpigmented human skin xenografts.

The mechanisms for hyperpigmentation observed in human cutaneous xenografts placed on athymic nude mice was investigated. Histologic, biochemical, histochemical, and ultrastructural examinations were performed on human skin prior to grafting and at various times ranging from 2 weeks to 30 weeks post-grafting (PG). Hyperpigmentation was macroscopically visible on the graft as early as 4-6 weeks. The number of Dopa-positive melanocytes per unit area was increased at 2 weeks PG and remained elevated until 20 weeks PG. The surface area of the melanocytes, a measure of the activity of the cells, also increased significantly and remained above the pre-grafting size throughout the study. Western blot analysis using tyrosinase specific antibody (alpha Ty-SP) revealed the presence of tyrosinase exclusively in the grafted skin from 2 weeks to 12 weeks PG tested. Histological and ultrastructural observations revealed the presence of numerous dendritic melanocytes, indeterminant clear cells suggestive of Langerhans cells, and dermal melanophages. The results of this study suggest that the observed hyperpigmentation in grafted tissue is caused by an increase in the number of Dopa-positive melanocytes and probably from enhanced melanin production. Extracts of proteins from the xenografts exhibited prominent differences in low and high molecular proteins between pre- and post-grafted skin. Among them, the exclusive appearance of a protein doublet with apparent mw approximately 14 kDa was found in grafted skin, and subsequent studies indicate it has potent effects on melanocyte function.

Animals↗
PubMed1987

Effect of transfusion on immune function in a traumatized animal model. II. Effect on mortality rate following septic challenge.

It is well established that transfusions given prior to transplantation diminish rejection, and recent reports suggest that transfused patients having surgery for cancer developed more metastases than those who did not receive transfusions. To our knowledge, however, there are no studies evaluating whether transfusions result in increased rates of infections. To investigate this, 295 Lewis rats were subjected to a 25% total body surface area burn and were given either 3 mL of Lewis blood, 3 mL of A'Solagoft Cancer Institute rat blood, or 9 mL of lactated Ringers' solution intravenously on day 1 before burn or on the day of burn. One additional group received 1-mL transfusions on days 9, 7, and 5 before burn. The burns were painted with 1 X 10(8) Pseudomonas aeruginosa lot No. 1244 on postburn days 0, 1, or 2. All rats were followed up for 28 days and survival and mean survival times were recorded. Transfusion of A'Solagoft Cancer Institute blood increased mortality unless given within 24 hours prior to Pseudomonas challenge, when it diminished mortality. Transfusion with syngenic Lewis blood had no effect. We conclude that transfusions may adversely affect survival when given before bacterial challenge, possibly due to immunosuppression from exposure to non-self-histocompatibility antigens.

Animals↗
PubMed1986

The effect of the thromboxane synthetase inhibitor Dazmegrel (UK-38,485) on wound healing, dermal ink perfusion and skin blood flow measurements in deep partial thickness burns.

A guinea-pig model was used to evaluate the effect of Dazmegrel (UK-38,485), a new highly selective inhibitor of thromboxane synthetase, on burn wound healing. Dazmegrel had a beneficial effect on wound healing when given systemically at a dosage of 3.4 mg kg-1 day-1 but higher doses had no effect. There was no change in dermal perfusion measured by India ink injection or by 133Xe injection in any of the groups receiving parenteral Dazmegrel. Neither was the number of hair follicles in the healing burn wound significantly different between the treated and control animals. When Dazmegrel was applied topically, it inhibited wound healing. These findings are consistent with previous reports from different laboratories that prostaglandin inhibitors impair healing of the burn wound when applied topically but improve wound healing when given parenterally. The present study further suggested that the improvement in wound healing in this model was not mediated by improved dermal perfusion.

Administration, Topical↗
PubMedDate not supplied

Evaluation of the effect of topical steroids on human scar contracture using a nude mouse model.

Adult nude mice had 1.5 to 1.0 meshed split-thickness human skin applied to an excised area of their back. The animals were then randomized into two groups, one of which had a steroid cream applied to their graft on alternate days. The other group had no ointment applied and served as a control. The wounds were measured on a weekly basis and the rate of wound contracture was found to be identical. Topical steroids would thus appear to offer no benefit in the prevention of scar contracture.

Animals↗