Biomedical subjects

R D Granstein

Publications and source records attributed to R D Granstein.

100 records · Page 6Linked to original sources

PubMed1981

Drug- and heavy metal--induced hyperpigmentation.

Several categories of chemical and pharmacologic agents can cause alterations in cutaneous pigmentation, although the mechanisms differ and in several instances may be unknown. Fixed drug eruptions appear to have alteration of the basement membrane zone with incontinence of epidermal pigment as the mechanism of hyperpigmentation. Heavy metals produce increased pigmentation in part from deposition of metal particles and in part from an increase in epidermal melanin production. The antimalarials may bind to melanin. The phenothiazines and minocycline produce pigmentation from deposition of the drug. The mechanism, site, and nature of the pigment occurring with antineoplastic agents is not well understood, but the location is most likely predominantly epidermal. Clofazimine (Lamprene) alteration in pigmentation appears to result from deposition of the drug in subcutaneous fat.

Adrenocorticotropic Hormone↗

PubMed1981

Diffuse melanosis secondary to metastatic malignant melanoma. Light and electron microscopic findings.

Tumor-free hyperpigmented skin from a patient with diffuse melanosis secondary to metastatic melanoma was examined by light and electron microscopy. Our findings indicate that the pathogenesis of this diffuse slate blue color is primarily to pigment deposition within perivascular dermal macrophages. We did not find intact melanosomes or individual tumor cell metastases in clinically normal skin, as has been previously reported.

Adult↗

PubMed1980

Primary cutaneous aspergillosis in a premature neonate.

A case of primary cutaneous aspergillosis in a 3-week-old premature infant is reported. The lesion, which presented as a solitary nodule surmounted by three pustules, occurred following the use of elasticized and cloth adhesive tape and was cured by surgical excision. Factors predisposing to this infection included maceration, antibiotic usage, and prematurity.

Aspergillosis↗

PubMedDate not supplied

Genetically restricted antigen presentation for immunological tolerance and suppression.

The activation of some subsets of T cells requires the recognition of antigen in association with self Ia determinants. It is not clear, however, whether this is also necessary for the induction of unresponsiveness and the active suppression of hapten-specific T cells. We have studied the regulation of the delayed-type hypersensitivity (DTH) response in mice. Subcutaneous (s.c.) injection of haptenated syngeneic cells primarily activates T helper cells, while intravenous (i.v.) injection results in unresponsiveness and the activation of T suppressor cells. Presentation of antigen by an I-A-positive antigen-presenting cell (APC) seems to be critical for T helper cell activation. We now show that the activation of first-order T suppressor cells requires the presentation of hapten on an I-J-positive APC. However, i.v. injection of I-J-depleted haptenated cells also results in hepten-specific unresponsiveness. This non-transferable T-cell tolerance requires the presence of an I-A-positive APC and is genetically restricted. These results suggest that distinct modes of antigen presentation and administration are required for immunity, suppression and non-transferable tolerance.

Animals↗

PubMedDate not supplied

Neuropeptides and Langerhans cells.

The immune system and nervous system are intimately related. In addition to neuroendocrine mechanisms, neuropeptides have a variety of effects on immune cells and are responsible at least in part for neurogenic inflammation. The presence of neuropeptides in the skin has been well documented. The influence of neuropeptides on Langerhans cells is the focus of this paper. The physical presence and effects of calcitonin gene-related peptide on Langerhans cells is emphasized. Discussion also includes the putative inflammatory and immunologic roles of vasoactive intestinal peptide, substance P, neurotensin, neuropeptide Y, and somatostatin in the skin.

Animals↗

PubMedDate not supplied

Carcinogenicity of combined ultraviolet B radiation and psoralen plus ultraviolet A irradiation treatment of mice.

Psoralen plus ultraviolet A (PUVA) therapy and UVB phototherapy are frequently used in the treatment of psoriasis and other skin diseases. Both treatments are thought to be carcinogenic, but little is known about their interaction in the induction of skin cancer. Tumors induced in mice treated with both PUVA and UVB, either given sequentially or concurrently, seemed to be more antigenic as a group than tumors treated by PUVA alone, as determined by their lower frequency of growth when transplanted into naive mice. In this study, we treated C3H mice with a subcarcinogenic dose of UVB radiation for 4 weeks, followed by PUVA treatment for 41 weeks (sequential experiment) or with both UVB radiation (minimal carcinogenic dose) and PUVA for 41 weeks (concurrent experiment) and monitored the development of skin cancers. Although a few tumors appeared earlier in the groups treated with both UVB and PUVA in both experiments, no significant differences were observed in the rate of tumor development in mice treated with UVB and PUVA versus those treated with PUVA alone.

Animals↗

PubMedDate not supplied

Ultraviolet radiation effects on immunologic function.

Studies over the past two decades have established that exposure to ultraviolet radiation (UVR) has profound effects on immunity. Most of this work was done in animal models with limited data from human studies. Exposure to UVR inhibits the induction of contact hypersensitivity in mice systemically at high doses and locally at low doses, associated with the appearance of transferable T suppressor cells. In some strains of mice, chronic UVR exposure results in the occurrence of highly immunogenic cutaneous malignancies which are rejected upon transplantation to syngeneic recipients. However, within the primary host the tumor is protected from destruction, at least in part, by the appearance of T suppressor cells. Syngeneic animals exposed to large doses of UVR also permit the growth of these transplanted tumors and this phenomenon also results, at least in part, from the presence of suppressor cells. Interestingly, these suppressor cells appear to recognize UVR-induced regressor tumors as a class within a given mouse strain, suggesting that they recognize shared determinants. The mechanisms of these examples of UVR-induced immunosuppression are not completely clear, but perhaps relate to changes in Langerhans cell function and/or epidermal cell release of cytokines induced by UVR. Exposure to UVR in vitro alters the ability of epidermal cells and Langerhans cells to present some antigens. Keratinocytes alter their secretion of specific cytokines after exposure to UVR and are induced to produce immunosuppressive factors. Immunosuppressed patients also have increased rates of skin cancer, suggesting immunologic involvement in regulation of cutaneous oncogenesis in humans.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Aqueous humor inhibits epidermal cell antigen-presenting function.

Aqueous humor (AH) is a complex biological fluid containing factors that mediate a number of activities that may contribute to immune privilege in the anterior chamber of the eye. To determine whether AH may inhibit dendritic cell antigen-presenting function, we evaluated the ability of AH to alter the ability of freshly obtained epidermal cell (EC) preparations enriched for Langerhans cells (LC) to present tumor-associated antigens (TAA) derived from the S1509a spindle cell tumor for elicitation of a delayed-type hypersensitivity (DTH) reaction in tumor-immune mice. Fresh EC preparations contain 2-5% LC. Exposure of EC to media containing AH for 2 hours prior to TAA-pulsing and injection into a hind footpad of tumor-immune mice resulted in a dose-dependent decrease in the DTH response. Aqueous humor contains transforming growth factor-beta (TGF beta), primarily TGF beta 2 as determined by specific neutralization of activity in the Mv 1 Lu cell assay. However, exposure of EC to TGF beta 2 in this fashion prior to TAA-pulsing had no effect on the degree of hypersensitivity elicited. Furthermore, preincubation of AH with neutralizing antiserum to TGF beta 2 had no effect on the ability of AH to inhibit LC antigen-presenting function. Mixing of AH-exposed non-TAA-pulsed EC with TAA-pulsed EC not exposed to AH prior to footpad challenge did not diminish the DTH response, suggesting that carryover of AH into the footpad was not responsible for the inhibition observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMedDate not supplied

Modulation of antigen-presenting cell function as a potential regulatory mechanism in tumor-host immune reactions.

A growing body of information suggests that immunological defense mechanisms against newly emerging tumors may exist within the skin. In this regard, the recognition and presentation of tumor-associated antigens by cutaneous antigen presenting cells is a prerequisite for the establishment of specific tumor immunity. However, despite the recently demonstrated ability of normal I-A+ epidermal cells (Langerhans cells) to effectively present tumor-associated antigens in vivo, even tumors with recognizable antigenic epitopes can grow progressively in situ. Therefore, regulatory mechanisms within the local microenvironment may exist that control the ability of resident epidermal APC to initiate and to elicit protective immunity against incipient cutaneous neoplasms. This report reviews the role of APC in tumor immunity and the effects of cytokines and ultraviolet radiation (UVR) on tumor antigen presentation by epidermal APC. Our data suggest that these agents can significantly modify the ability of epidermal cells to present tumor-associated antigens and may therefore control the type and effectiveness of tumor immune responses in situ. Furthermore, the induction of primary tumor immunity and the elicitation of secondary immune responses are independently regulated and respond differently to cytokine application.

Antibody Formation↗

PubMedDate not supplied

Delayed wound healing and disorganized neovascularization in transgenic mice expressing the IP-10 chemokine.

IP-10 is a member of the alpha or cysteine-X amino acid-cysteine (CXC) chemokine family of chemotactic cytokines. High levels of IP-10 expression have been detected in a number of chronic human inflammatory conditions, including psoriasis, a common inflammatory disease of the skin. IP-10 has been shown to chemoattract activated T cells, inhibit the proliferation of endothelial cells, and inhibit the growth of tumors in vivo. To determine the capacity of IP-10 to modulate the inflammatory response in vivo, we have created transgenic mice that constitutively express IP-10 from keratinocytes. These mice developed normally and, in general, did not spontaneously recruit leukocytes into the skin or other organs that expressed the transgene. In addition, the transgenic mice had a normal cutaneous contact hypersensitivity cellular immune response. However, IP-10 transgenic mice had an abnormal wound healing response characterized by a more intense inflammatory phase and a prolonged and disorganized granulation phase with impaired blood vessel formation. These results have demonstrated that IP-10 can inhibit the neovascularization associated with a physiological response in vivo and have revealed a novel biologic activity of IP-10 as an inhibitor of wound healing.

Animals↗