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Biomedical subjects

A Gilhar

Publications and source records attributed to A Gilhar.

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

The effect of topical cyclosporin on the immediate shedding of human scalp hair grafted onto nude mice.

Considerable evidence now exists that cyclosporin (CyA) has a stimulatory effect on hair growth. Previously, we demonstrated the systemic effect of CyA on hair growth using an experimental model of human scalp skin graft transplanted onto nude mice and rats. In the present study we used this model to investigate the effect of topical CyA on human hair growth. One group of 15 mice was treated with topical CyA in olive oil, and a second group of 10 mice with olive oil only. The numbers of grafts with hair and the number of hairs per graft in the different groups were compared. A statistically significant delay in hair shedding appeared from day 24 onwards in the CyA treated group. This pilot study supports the possibility that CyA may be effective in the treatment of alopecia.

Administration, Cutaneous↗
PubMed1987

Hair growth in scalp grafts from patients with alopecia areata and alopecia universalis grafted onto nude mice.

A basic question in both mild and severe forms of alopecia areata (AA) relates to whether the disease is inherent to the affected tissue or secondary to circulating factors. This question has been addressed by grafting 2-mm grafts of scalp from affected areas of seven patients with AA or alopecia universalis (AU) onto congenitally athymic (nude) mice. Hair growth in these grafts has been compared with that of 2-mm grafts from hair-bearing skin remnants from two individuals undergoing elective plastic surgical procedures. Because cyclosporine seems to directly affect hair growth, a group of grafted mice was treated with this agent. By day 48, hair growth was present in many surviving grafts. Cyclosporine affected hair growth; this was most prominent by day 78 when the number of hairs per graft and the mean length of hair had increased significantly over untreated groups. Grafts from patients with AU had more hairs per graft and had greater hair length than did similar grafts from patients with AA. These experiments show that hair growth ability in situ is likely normal in AA and AU, and that the factors causative to this disease in situ are mediated humorally. Furthermore, cyclosporine seems to directly influence hair growth in this model system.

Alopecia↗
PubMed1986

Description of and treatment to inhibit the rejection of human split-thickness skin grafts by congenitally athymic (nude) rats.

Gradual rejection of topically engrafted human split-thickness skin grafts (HSTSG) occurred in greater than 90% of congenitally athymic (nude) rats between 21 and 42 days of grafting. Engraftment and rejection of HSTSG is accompanied by a partial restoration of some cell-mediated immune components, the mixed lymphocyte response and lysis of human target cells. Histologic features of the rejection process were those seen in a host-versus-graft reaction. Immunofluorescent analysis of skin undergoing rejection demonstrated IgG at the basement membrane zone in most grafts. Nude rats rejecting HSTSG had circulating IgG which bound to the basement membrane zone and blood vessels of human skin. Nude rats treated with cyclosporine injections for 21 days had an enhanced survival of HSTSG, 120 or more days.

Animals↗
PubMed1985

The development of a rat/human skin flap served by a defined and accessible vasculature on a congenitally athymic (nude) rat.

Experience in microvascular surgery on rats and availability of athymic (nude) rats led us to believe that a long-term functional rat/human skin sandwich flap could be generated on a defined and experimentally accessible vasculature on nude rats. Such a system has been developed and validated. Microvasculature has been assessed. The volume of blood to the flap ranges from 1 to 2 ml/min, collateral circulation to the flap exists, but is negligible, and there is little change in the capillary blood flow as the flap ages. The flap can be utilized to study absorption of compounds from a half-cell diffusion chamber or from direct deposition on the skin, and can be utilized to study various parameters of percutaneous absorption, e.g., the effect of hydration on the stratum corneum. Transdermal flux can be determined. Altering the microcirculation directly affects the percutaneous absorption of compounds that are rapidly absorbed. The absorption of benzoic acid through an experimentally vasoconstricted area (iontophoresis of phenylephrine) significantly alters the time to peak absorption, with values being 14 times that of the control site. The system has been utilized to assess metabolic activity of skin in situ using [3H]adenine arabinoside and studying the appearance of its major metabolite, [3H]Ara-H, in flap blood, as well as the back diffusion of this compound into the donor chamber. Recently the human/rat skin sandwich flap component has been developed. With this system, it has been demonstrated that benzoic acid, when applied to the human skin component of the flap has an absorption profile which is quite different from that when benzoic acid is applied to rat skin, peak flux occurred 2 hr after application. This contrasts with 10 min to peak flux when the same experiment is carried out on the rat/rat skin sandwich flap. To our knowledge, the human/rat skin sandwich flap is the first example of a viable, functional human organ that is chronically maintained by a biologic support system which has the added distinction of being on an independent but accessible vasculature. The validation experiments strongly suggest that this system will be important in gaining insights into the more sophisticated in vivo components of skin, relative to toxicology and pharmacology.

Animals↗