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Biomedical subjects

A Gilhar

Publications and source records attributed to A Gilhar.

At least 19 recordsLinked to original sources
PubMed1992

Response of aged versus young skin to intradermal administration of interferon gamma.

BACKGROUND: Interferon gamma (IFN-gamma) induces the interaction of intercellular adhesion molecule-1 (ICAM-1) and lymphocyte function-associated antigen type 1 expression, and of HLA-DR antigens by keratinocytes. OBJECTIVE: The aim of the present study was to determine the potential ability of aged versus young skin to respond to intradermal administration of IFN-gamma, as an in vivo immunologic stimulus. METHODS: For 3 consecutive days elderly and young volunteers were injected with 10 micrograms of recombinant IFN-gamma diluted in 0.1 ml of sterile water. On day 5, punch biopsy specimens were obtained from the injected sites. Histologic and immunohistochemical stainings were performed on all sections. RESULTS: ICAM-1 was expressed by keratinocytes in both aged and young skin. An impairment was manifested mainly by the reduced accumulation of mononuclear cells throughout the dermis, the absence of HLA-DR expression by keratinocytes in 7 of 10 elderly volunteers, and the absence of an effect on the Langerhans cell population. CONCLUSION: This observation shows a diminished immune response in aged skin.

Adult↗
PubMed1992

Failure of passive transfer of serum from patients with alopecia areata and alopecia universalis to inhibit hair growth in transplants of human scalp skin grafted on to nude mice.

We have previously demonstrated regrowth of hair in scalp skin grafts taken from patients with alopecia areata (AA) and alopecia universalis (AU) following engraftment on to nude mice. This present study was to determine whether serum from patients with AA and AU, has a role in the process of hair loss and the role of antibodies and complement. Forty mice were grafted with transplants obtained from seven patients. One group of the grafted mice was given patients' serum and another group normal serum. The mice were treated topically with cyclosporin (CyA), or olive oil. Hair growth was noted in most grafts and intravenous injections of serum did not prevent or inhibit this process. Immunofluorescence studies before grafting showed deposition of immunoglobulins and complement in hair follicles in both normal and affected scalp skin, but a more striking deposition was noted in the affected skin. Deposition of immunoreactants after grafting was observed only after the injection of serum from the patients but not with normal serum. Thus the sera from patients with AA or AU, when injected into nude mice with hair transplants from the scalp skin of patients with these disorders, does not alter the hair growth despite deposition of immunoreactants around the hair follicles.

Alopecia↗
PubMed1992

Ia expression in keratinocytes following ultraviolet radiation.

Injections of murine gamma interferon (IFN-gamma) into BALB/c nude mice induced Ia expression by keratinocytes. The aim of the present study was to use this murine model to determine the effect of ultraviolet radiation (UV) or cyclosporine A (CyA) on Ia expression by keratinocytes. Two sets of experiments were performed. In the first, mice were injected intraperitoneally with IFN-gamma for 6 days. The mice were divided into three groups. One group, with one ear protected by electrical tape, was exposed to UVB radiation for 15 days starting 4 days before the injection. The second group received subcutaneous injections of CyA simultaneously with the IFN-gamma and during the 10 days following the IFN-gamma injection. The third group received only IFN-gamma injections. Fifteen days after the IFN-gamma injection all mice were killed and evaluations of Ia positive cells were performed. In the second set of experiments the nude mice were treated with CyA or UVB only 10 days after the last IFN-gamma injections. In both experiments UVB inhibited and down-regulated Ia expression by keratinocytes. This effect on keratinocytes was not observed in the protected ears. Thus it appears that the effect of UVB on keratinocytes is local and not systemic. CyA failed to inhibit or down-regulate Ia expression. This study may shed some light on understanding the mechanism effect of UV radiation in a variety of skin diseases.

Animals↗
PubMed1991

Effect of cyclosporine A on the regulation of Ia antigen keratinocytes expression.

Since many skin diseases characterized by positive Ia keratinocytes show improvement with cyclosporine therapy, the purpose of this study was to determine whether cyclosporine A (CyA) alters the expression of Ia keratinocytes. Nude mice were injected with normal mouse serum (NMS) to induce keratinocyte expression of the Ia antigen. The injected mice were then divided into four groups: one was treated with oral CyA; the second was treated topically with CyA twice a day; the third was treated topically with olive oil; and the fourth was injected with nude mouse serum. The third and fourth groups served as Ia positive and Ia negative controls, respectively. The mice were treated during the first 10 days after the injections. On Day 10, epidermal sheets were analyzed for Ia expression. Analysis was made by an indirect immunoperoxidase staining method using monoclonal antibodies specific for Ia determinants. Quantitation of the number of Langerhans cells was analyzed on epidermal sheets using immunodiagnostic reagents, anti-MHC-Ia, and surface ectoenzyme, ATPase. A significant reduction of Ia-positive keratinocytes was noted in the oral CyA group vs topical and olive oil groups (64.9 +/- 29.9% vs 20.1 +/- 18.7%, respectively, P less than 0.01). In a second set of experiments mice were injected with NMS, but treatment was started only on Day 10 after injections, for 10 days. The results showed that CyA failed to down-regulate Ia expression. Topical and systemic CyA did not modify Langerhans cell population. The present study showed that systemic administration of CyA significantly reduced Ia induction by keratinocytes of nude mice that were injected with NMS.

Animals↗
PubMed1991

Dopa reaction test in hair bulbs of fetuses and its application to the prenatal diagnosis of albinism.

No information is available on the amount of tyrosinase normally present in fetuses. A dopa reaction test in hair bulbs from the scalp of normal fetuses obtained after abortion showed that tyrosinase is present in fetuses as early as 17 weeks. Only faint activity was detected in skin specimens other than from the scalp. This assay can serve as a quick and reliable method for the prenatal diagnosis of tyrosinase-negative albinism.

Albinism, Oculocutaneous↗
PubMed1991

Melanocytes and Langerhans cells in aged versus young skin before and after transplantation onto nude mice.

Previous studies have demonstrated decreased numbers of melanocytes and Langerhans cells (LC) in aged skin. In the present study, we employed dopa and indirect immunoperoxidase techniques in epidermal sheets to determine the fate of melanocytes and LC of aged versus young donors after skin transplantations onto nude mice. The detection of positive homologous leucocytic antibody reaction of degeneration (HLA-DR) of LC indicates an age-associated reduction in sun-protected thigh skin in aged versus young subjects (263 +/- 63 versus 589.25 +/- 142.643, p less than 0.001). The mean number of LC four weeks after transplantation remained almost constant. Prior to skin engraftment, a decreased number of melanocytes was found in aged versus young epidermis (160.77 +/- 51.7 versus 255.83 +/- 81.2, respectively, p less than 0.05). A significantly increased number of melanocytes was noted four weeks following engraftment in epidermis from aged (307.44 +/- 174, p less than 0.05) and young human donors (402.16 +/- 139, p less than 0.02). The marked increase in density of dopa-positive melanocytes following engraftment onto nude mice may indicate the existence of circulating factors in nude mice that perhaps both stimulates and enhances proliferation and activity of these cells.

Adult↗
PubMed1991

Aged versus young skin before and after transplantation onto nude mice.

The behaviour of aged skin transplanted onto nude mice was investigated to determine whether the skin maintains its histological features. Split-thickness skin grafts obtained from the unexposed skin on the thighs of healthy aged and young volunteers were grafted onto nude mice. A significant difference between the mean thickness of young versus aged epidermis was noted before transplantation (P less than 0.001). The epidermis of aged and young skin showed an increase in thickness following engraftment with a mean increase in epidermal thickness of 18.8% in the young (P less than 0.01) and 142.5% in aged skin (P less than 0.001). The number of blood vessels in the aged skin was significantly lower than in the young skin, but a remarkable increase was found post-transplantation. These findings indicate that part of the typical histological changes of unexposed aged skin are reversible.

Adult↗
PubMed1991

Topical cyclosporin induces hair growth in human split skin grafted onto nude mice.

Previously we observed that systemic CyA induces hair growth in an experimental model of human scalp skin graft transplanted onto nude mice. In the present study we investigated the role of topical CyA in the murine transplantation model, using human split-thickness skin grafts (HSTSG). Ten mice grafted with 1-mm-thick skin and another 10 mice grafted with 0.4-mm-thick skin were treated topically with CyA in olive oil. Ten other mice, treated with olive oil only, served as a control group. At the end of the study we observed hair growth only on the grafted skin of the CyA-treated group. Four out of 10 grafts showed hair growth in each of the groups. Quantitative analysis of transverse sections of cylindrical punch biopsy specimens of HSTSG before transplantation revealed anagen follicles, including small ones and telogen/catagen follicles, whereas specimens after skin transplantation showed terminal follicles mostly in the anagen phase. The present study provides further support to previous observations regarding the beneficial effect of CyA on hair growth.

Administration, Topical↗
PubMed1990

Topical cyclosporine in male pattern alopecia.

We previously demonstrated a systemic and topical effect of cyclosporine on hair growth in an experimental model composed of human scalp skin transplanted onto nude mice. The aim of this study was to determine whether topical cyclosporine affects male pattern alopecia. For 4 months in a double-blind study, 10 subjects were treated with cyclosporine and three were treated with olive oil. Hair growth was evaluated by photographs and hair counts. Significant hair growth was observed in two of the eight patients who completed the study. In one the hair growth was cosmetically satisfactory. No systemic or cutaneous side effects were noted.

Administration, Topical↗
PubMed1990

Hair growth in human split-thickness skin grafts transplanted onto nude rats: the role of cyclosporin.

To date, there have been no descriptions of hair growth following transplantation of human split-thickness skin grafts (HSTSG) to congenitally athymic (nude) mice or rats. Recently, we noted hair growth in HSTSG from scalp skin (HSTSG-SS) transplanted onto rats treated with ciclosporin (CS). By definition, HSTSG-SS of 0.4 mm had all the anagen hairs cut from the papillae. Two months after engraftment, there was histological evidence of the formation of new papillae. Density of hair correlated with thickness of HSTSG, i.e. there were more hairs/square centimeter in HSTSG-SS of 1 mm thickness than in those of 0.4 mm thickness. New hairs appeared on an average of 1 cm2/week in HSTSG-SS that were 1 mm thick; by 10 weeks, the mean density was 7.9 hairs/cm2. In the thinner grafts, the density was 3.5 hairs/cm2 (p less than 0.025). The rate of growth in the thicker grafts ranged from 0 to 0.25 mm/day, with an average of 0.1 mm/day. At 10 weeks after grafting, the hairs had a mean length of 4.4 mm in the thicker and 1.7 mm in the thinner grafts (p less than 0.001). The average diameter of the hair shafts was 0.05 mm at the various times tested. These observations identify a previously unrecognized process of hair growth and present an in vivo model to study human hair growth process, including the role of CS in hair growth.

Animals↗
PubMed1989

Vitiligo and idiopathic guttate hypomelanosis. Repigmentation of skin following engraftment onto nude mice.

Several diseases are included in the category of hypomelanosis. Their clinical course as well as the pathogenesis are diverse and in many cases poorly understood. The aim of the present study is to use the nude mice model to determine whether the primary defect in various pigmentary skin disorders is inherent to the tissue itself or is secondary to systemic factors. Split-thickness skin grafts obtained from patients with vitiligo, acquired hypomelanosis guttata, and tyrosinase-negative albinism were grafted onto nude mice. Histologic examination and dopa staining were performed prior to and following the engraftment. The dopa staining was performed on the epidermal sheet following separation from the dermis. The depigmented area of the vitiligo became completely pigmented 6 to 10 weeks after skin transplantation. The dopa reaction that was negative prior to skin engraftment became completely positive after the transplantation. The number of melanocytes (expressed per square millimeter of skin surface) 8 weeks after transplantation was 197 +/- 73 mm2. Dopa reaction in acquired hypomelanosis guttata showed reduction of the number of melanocytes in the depigmented macula as compared with the surrounding area (55.25 +/- 18.00 mm2 vs 220 +/- 28.28 mm2. Twenty days after skin transplantation, repigmentation of the area was observed. The number of melanocytes increased significantly (388.75 +/- 213 mm2). The grafted skin obtained from patients with tyrosinase-negative albinism showed persistence of the depigmentation after skin transplantation. Dopa reaction was negative prior to and 8 weeks after transplantation. The results of the present study suggest that systemic factors may play a role in the pathogenesis of vitiligo and acquired hypomelanosis guttata.

Adult↗
PubMed1989

Skin hyperreactivity response (pathergy) in Behçet's disease.

Behçet's disease is very difficult to diagnose because its clinical signs overlap with those of other systemic diseases. Thus there is a clear need for nonclinical diagnostic criteria for Behçet's disease. The nonspecific cutaneous hyperreactivity response, pathergy, may serve as an important diagnostic indicator. A test for pathergy may also clarify the role of an immune complex mechanism in the pathogenesis of Behçet's disease. In our study of 11 patients with Behçet's disease, deposition of immunoglobulins or complement was not found 4 hours after histamine or saline injection. In contrast, 24 hours after histamine or saline injection, 10 of 11 patients responded positively both clinically and histologically during the active stage of their disease. Vasculitis was noted in only two patients. Thus in most patients no evidence of an immune complex mechanism was observed. We conclude that any nonspecific intracutaneous injection is a good clinical tool for the diagnosis of Behçet's disease.

Adolescent↗
PubMed1989

The pathogenesis of lichen planus.

The histological features of lichen planus (LP) are characterized by typical epidermal changes with dermal lymphocytes that are mostly Ia positive T cells. In order to find out whether the primary event of LP is damage to basal keratinocytes or a delayed hypersensitivity reaction in which an as yet unidentified antigen activates T lymphocytes that destroy keratinocytes, we transplanted skin obtained from six patients with LP. Two millimetre punch and split thickness of grafts were obtained from involved and uninvolved areas from each patient and grafted onto nude mice. Biopsies were taken from the grafts at 14 and 21 days after transplantation for histological and immunofluorescence studies and after 6 weeks for Dopa incubation for melanocyte populations. A complete disappearance of the pathological changes of LP was found 21 days following grafting. An increased number of melanocytes was noted. This indicates that the pathogenesis of LP may not be due to an inherent change in the epidermal cells, but rather to the migration of cellular elements of the immune system.

Adult↗
PubMed1989

Effect of ultraviolet radiation on Ia expression by keratinocytes.

Many skin diseases, such as graft-versus-host disease (GVHD), are marked by lymphocyte infiltrates in the skin. Severity of these diseases is often correlated with the induced expression of class II antigens (human, HLA-DR,; murine, Ia) by the keratinocytes. This suggests that HLA-DR-expressing keratinocytes may be involved in the pathogenesis of these diseases. Since some of these diseases are effectively treated with ultraviolet radiation (UVR), this study was conducted to determine whether UVR alters the keratinocyte expression of class II antigens. To test this hypothesis, 2 models of experimentally induced keratinocyte Ia expression were employed. First, athymic nude mice with one ear protected by electrical tape were exposed to UVR (450 J/m2/day on 4 consecutive days). They were then given an i.v. injection of normal mouse serum (NMS) to induce keratinocyte Ia expression. Keratinocytes in the UVR-exposed skin of these animals were not induced to express Ia; however, Ia-expressing keratinocytes were observed in the epidermis of shielded skin sites. Likewise, it was determined that UVR was capable of downregulating keratinocyte expression of Ia when administered to nude mice 7 d after receiving an injection of NMS. Second, employing a clinically relevant model, we found that Ia expression by keratinocytes in mice undergoing experimentally induced GVHD was abrogated by UVR treatment. This appeared to be a direct effect of the UVR, since keratinocytes in shielded skin sites and mucosal cells in the intestinal epithelium of animals with GVHD were shown to express Ia. These data provide compelling evidence for our hypothesis that decreased HLA-DR expression by keratinocytes in diseased skin treated with UVR is a mechanism by which UVR exerts its therapeutic effect.

Animals↗
PubMed1989

Topical cyclosporin A in alopecia areata.

We conducted a trial of topical application of 10% cyclosporin A in an oil preparation in 10 patients with alopecia areata and alopecia universalis. After 12 months of therapy, no beneficial response was observed in any of the 10 patients.

Administration, Cutaneous↗