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Biomedical subjects

Amos Gilhar

Publications and source records attributed to Amos Gilhar.

14 recordsLinked to original sources
PubMed2006

Fas pulls the trigger on psoriasis.

Fas/FasL signaling is best known for induction of apoptosis. However, there is an alternate pathway of Fas signaling that induces inflammatory cytokines, particularly tumor necrosis factor (TNF)-alpha and interleukin (IL)-8. This pathway is prominent in cells that express high levels of anti-apoptotic molecules such as Bcl-xL. Because TNF-alpha is central to the pathogenesis of psoriasis and psoriatic epidermis has a low apoptotic index with high expression of Bcl-xL, we hypothesized that inflammatory Fas signaling mediates induction of psoriasis by activated lymphocytes. Noninvolved skin from psoriasis patients was grafted to beige-severe combined immunodeficiency mice, and psoriasis was induced by injection of FasL-positive autologous natural killer cells that were activated by IL-2. Induction of psoriasis was inhibited by injection of a blocking anti-Fas (ZB4) or anti-FasL (4A5) antibody on days 3 and 10 after natural killer cell injection. Anti-Fas monoclonal antibody significantly reduced cell proliferation (Ki-67) and epidermal thickness, with inhibition of epidermal expression of TNF-alpha, IL-15, HLA-DR, and ICAM-1. Fas/FasL signaling is an essential early event in the induction of psoriasis by activated lymphocytes and is necessary for induction of key inflammatory cytokines including TNF-alpha and IL-15.

Adoptive Transfer↗
PubMed2005

Alopecia areata: a tissue specific autoimmune disease of the hair follicle.

The goal of this review is to introduce the immunologic community to alopecia areata as a model system for the study of tissue directed autoimmune disease. Alopecia areata is marked by autoimmune assault on the hair follicle resulting in hair loss. It is linked to HLA-DQ3 and evidence suggests it is mediated by T-lymphocytes with a TH1 cytokine profile. Hair follicles are an immune protected site with deficient MHC expression. Evidence is presented suggesting that alopecia areata results from loss of immune privilege with presentation of autoantigens. Alopecia areata is one of the most common human autoimmune conditions, with a lifetime risk of approximately 1.7%. Study of alopecia areata in humans is facilitated by the accessibility of scalp for biopsy. It is possible to transfer the condition with lesional human lymphocytes in a human scalp graft/SCID mouse model. There are also spontaneous animal models which share the features of the human condition. For these reasons, alopecia areata is a powerful model for study of the induction and pathogenesis of tissue directed autoimmune disease.

Alopecia Areata↗
PubMed2005

The effect of interleukin-8 on the viability of injected adipose tissue in nude mice.

Adipose tissue injection as a free graft for the correction of soft-tissue defects is a widespread procedure in plastic surgery. The main problem in achieving long-term soft-tissue augmentation is partial absorption of the injected fat and hence the need for overcorrection and re-injection. The purpose of this study was to improve the viability of the injected fat by the use of interleukin-8. The rationale for the use of interleukin-8 was its abilities to accelerate angiogenesis and attract inflammatory cells and fibroblasts, providing the injected adipocytes more feeding vessels and a well-established graft bed to enhance their viability. Human adipose tissue, obtained by suction-assisted lipectomy, was re-injected into the subcutis in the scalp of nude mice. Interleukin-8 (0.25 ng) was injected subcutaneously to the scalp as a preparation of the recipient site 24 hours before the fat injection and was added to the fat graft itself (25 ng per 1 cc of injected fat). In the control group, pure fat without interleukin-8 was injected and no interleukin-8 was added for the preparation of the recipient site. One cubic centimeter of fat was injected in each animal in both the study and control groups. There were 10 animals in each group. The animals were euthanized 15 weeks after the procedure. Graft weight and volume were measured and histologic evaluation was performed. In addition, triglyceride content and adipose cell sizes were measured as parameters for fat cells viability. Histologic analysis demonstrated significantly less cyst formation in the group treated with interleukin-8. No significant differences were found between the groups with regard to graft weight and volume or the other histologic parameters investigated. No significant differences were demonstrated in adipose cell sizes and their triglyceride content. In conclusion, less cyst formation, indicating improved quality of the injected fat, can be obtained by the addition of interleukin-8. Further studies of various dosages of interleukin-8 and their long-term effect are required before these encouraging results could be applied clinically.

Absorption↗
PubMed2005

Searching for the favorable donor site for fat injection: in vivo study using the nude mice model.

BACKGROUND: The use of suctioned fat grafts for correction of soft tissue defects is a widespread procedure in esthetic and reconstructive surgery. The main disadvantage of this simple and sensible procedure is the unpredictable absorption rate of the fat graft. A lot of research has been performed aiming for enhancement of the take of the fat grafts. OBJECTIVE: Our study was performed to find if there is any favorable donor site for fat harvesting. METHODS: This in vivo experiment using the nude mice model enables the study of the long-term survival of human fat in an animal model. The fat was harvested from three donor areas: the thigh, abdomen, and breast of a 48-year-old woman who came for an elective esthetic procedure. After centrifugation, 1 cc of fat was injected subcutaneously into the scalp of the nude mouse. There were 15 mice in each of the three groups, according to the selected donor sites. The animals were sacrificed 16 weeks after the procedure. The extracted fat was evaluated in terms of weight, volume, and six histologic parameters: integrity, vascularization, cyst formation, fibrosis, necrosis, and inflammation. RESULTS: This study could not find any statistically significant differences between the three investigated donor sites in the evaluated parameters. CONCLUSION: On the basis of this study, there is no favorable area for harvesting fat grafts. The donor site can be chosen according to the preference of the surgeon and the patient.

Adipose Tissue↗
PubMed2005

Enhancing the take of injected adipose tissue by a simple method for concentrating fat cells.

Injection of aspirated fat for the correction of tissue defects is a common procedure in plastic surgery. The reported rates of fat cell survival vary greatly in the medical literature, and different techniques of harvesting, processing, and reinjecting the fat cells are claimed to be responsible for these differences. However, there is no agreement concerning the best way to process the harvested fat before reinjection. The present study was initiated to examine and evaluate the effect of a simple method of isolating the fat particles on the outcome of fat graft survival. In this study, the nude mouse model was used to examine the survival and take of the fat graft concentrated before injection by the cumbersome recommended closed centrifugation technique in comparison with the authors' recommended open method, using an operating room cotton towel as a platform for concentrating the fat cells and separating them from fluids, oil, and debris. One milliliter of concentrated human fat cells preprocessed by towel separation was injected into the nuchal subcutis of 11 nude mice in the study group, and the same amount of fat that was preprocessed by centrifugation was injected into 11 control mice. Injected fat survived in both groups. No significant differences were found regarding fat graft weight and volume, although a tendency for better survival was noticed in the experimental group. Histologic evaluation of the grafts revealed significantly less fibrosis within the study group, meaning that the quality of the fat grafts was better. The authors found this method to be simple, cheap, and friendly to the surgeon in comparison with traditional processing using the centrifuge.

Absorption↗
PubMed2005

Effect of non-steroidal anti-inflammatory drugs on natural killer cell activity in patients with dementia.

BACKGROUND: Alteration of innate and acquired immunity can play a role in the mechanism involved in the development of dementia. Epidemiologic studies indicate that the use of non-steroidal anti-inflammatory drugs can delay the onset or slow progression of Alzheimer disease. OBJECTIVES: To determine whether the use of NSAIDs is associated with natural killer activity alteration in AD and multi-infarct vascular dementia patients, as compared with non-demented elderly and healthy young people. METHODS: In this prospective open study four groups of subjects (AD, VD, non-demented elderly, and healthy young people) were treated with an NSAID drug (rofecoxib 12.5 mg/day or ibuprofen 400 mg twice daily) for 7 days. Natural killer cell cytotoxicity was measured after flow cytometry analysis before and after treatment. RESULTS: Of the 49 subjects studied, 15 had a diagnosis of AD (3 men, 12 women; mean age 83.5 +/- 8.1 years), 15 had a diagnosis of multi-infarct VD (7 men, 8 women; mean age 75.5 +/- 8.4), 13 were non-demented elderly (1 man, 12 women; mean age 80.2 +/- 7.2), and 6 were healthy young volunteers (3 men, 3 women; mean age 36.8 +/- 4.4). While all examined subjects showed decreased NK cell cytotoxicity after treatment, this decrease was most prominent and statistically significant in elderly patients suffering from vascular dementia--from an average of 30.5 +/- 11.8% before treatment to 22.5 +/- 16% after treatment (P = 0.04). The decrease in NK cell cytotoxicity was only moderate and not statistically significant in all other elderly and young subjects. Young healthy volunteers exhibited a significantly higher total NK cytotoxicity before and after treatment compared to all age groups (P < 0.001). CONCLUSION: These findings suggest that NSAIDs decrease NK activity in vascular dementia patients. Our findings also suggest that natural killer activity alteration cannot explain the ability of anti-inflammatory drugs to delay the onset or slow the progression of AD.

Adult↗
PubMed2004

Aging of human epidermis: reversal of aging changes correlates with reversal of keratinocyte fas expression and apoptosis.

The goal of this study was to determine the role of Fas-mediated apoptosis in human epidermal aging. Epidermal Fas expression and apoptosis are increased in aged human skin. Aging changes of human epidermis, including decreased epidermal thickness and proliferation, are reversed following grafting of human skin to SCID (severe combined immunodeficiency) mice. Skin from aged participants (n = 14; mean 70.7 years), and young participants (n = 14; mean 23.4 years) was grafted to beige SCID mice, and epidermal thickness, proliferation (Ki-67 expression), apoptosis (TUNEL [Tdt-mediated dUTP nick end labeling] reaction below granular layer), and expression of Fas and FasL were determined by histology and immunochemical staining. Aged skin was associated with thinning of the epidermis, decreased epidermal proliferation, a significant increase in apoptosis below the granular layer, and epidermal Fas expression. Engraftment significantly reversed these aging changes, including apoptosis, and Fas expression. Correlation of reversal of aging changes, with decreased epidermal Fas expression and apoptosis, supports a role for Fas-mediated apoptosis in aging of human epidermis.

Adolescent↗
PubMed2003

Transfer of alopecia areata in the human scalp graft/Prkdc(scid) (SCID) mouse system is characterized by a TH1 response.

Alopecia areata is an autoimmune condition directed at hair follicles, which results in loss of hair. We have previously demonstrated that it is possible to transfer hair loss, along with the immunohistologic findings of alopecia areata, to human scalp grafts on Prkdc(scid) (SCID) mice by injection of autologous activated lesional T-cells. This study examines the cytokine profile of T-cells and follicular epithelium following transfer of hair loss. Two consistent findings significantly (P < 0.01) associated with hair loss were production of interferon-gamma-inducible protein-10 kDa (IP-10) by follicular epithelium (13/13), and production of INF-gamma by infiltrating T-cells (10/12). Noninjected control grafts regrew hair, and were generally negative for IP-10 (positive 2/9), and INF-gamma (positive 2/9), but expressed of IL-10 on the follicular epithelium (7/9). These data support an INF-gamma TH1 pathogenesis for hair loss in alopecia areata.

Alopecia Areata↗
PubMed2003

Alopecia areata: autoimmunity--the evidence is compelling.

There is strong evidence indicating that alopecia areata is a tissue-specific, autoimmune disease. Hair loss is associated with a perifollicular lymphocytic infiltrate made up primarily of CD4+ cells, along with a CD8+ intrafollicular infiltrate. Evidence of immune activation includes expression of HLA-DR; HLA-A,B,C; and ICAM-1 on the follicular epithelium. It is likely that the follicular expression of HLA-DR and ICAM-1 is induced by interferon-gamma produced by T cells. Antibodies to follicular epithelium are often present, but their significance is not known. Lesional scalp from alopecia areata patients grafted onto nude mice regrows hair coincident with a loss of infiltrating lymphocytes from the graft. Hair loss can be transferred to human scalp explants on SCID mice by injection of lesional T cells. It is necessary to activate the T cells by culture with follicular autoantigens. Melanocyte-associated antigens are also capable of activating T cells to induce hair loss, suggesting that they are capable of functioning as autoantigens for alopecia areata. Parallel evidence in rodent models of spontaneous alopecia areata also strongly supports a role for T cells in the pathogenesis of this condition.

Alopecia Areata↗
PubMed2002

Mediation of alopecia areata by cooperation between CD4+ and CD8+ T lymphocytes: transfer to human scalp explants on Prkdc(scid) mice.

OBJECTIVE: To determine the role of CD4+ and CD8+ T lymphocytes in the pathogenesis of alopecia areata. DESIGN: Relapse of alopecia areata was induced in autologous human scalp grafts on Prkdc(scid) mice by injection of activated T lymphocytes derived from lesional skin. CD4+ and CD8+ T cells were separated by magnetic beads before injection. SETTING: University-based dermatology practice. PARTICIPANTS: Eleven patients with either alopecia totalis or severe alopecia areata. MAIN OUTCOME MEASURES: Hair regrowth, hair loss, and immunohistochemical findings of scalp explants. INTERVENTION: Transfer of scalp T cells to autologous lesional scalp explants on Prkdc(scid) mice. RESULTS: Injection of unseparated T cells and mixed CD4+ plus CD8+ T cells resulted in significant hair loss (P<.01) in 5 of 5 experiments. However, injection of purified CD4+ or CD8+ T cells alone did not result in reproducible hair loss. CD4+ and CD8+ T cells induced follicular expression of intercellular adhesion molecule 1 (CD54), HLA-DR, and HLA-A, HLA-B, and HLA-C after injection into scalp grafts. CONCLUSIONS: CD4+ and CD8+ T cells have a role in the pathogenesis of alopecia areata. It is hypothesized that CD8+ T cells act as the effector cells, with CD4+ T cell help. It is now necessary to look for HLA-A, HLA-B, and HLA-C associations with alopecia areata. Therapeutic manipulations that interfere with CD8+ activity should be examined.

Adult↗
PubMed2002

Psoriasis is mediated by a cutaneous defect triggered by activated immunocytes: induction of psoriasis by cells with natural killer receptors.

This study was performed to ask whether psoriasis is a unique pathologic response of epidermis of psoriatic patients, or cells with natural killer receptors can induce psoriatic changes in skin from nonpsoriatic donors. Human nonlesional skin from five psoriatics, as well as from seven nonpsoriatics was grafted on to beige-SCID mice. Lymphocyte lines with natural killer activity, and mixed natural killer, natural killer T cell phenotype, were generated by culture of peripheral blood mononuclear cells from both psoriatic, and normal donors, in 100 U interleukin-2 per ml for 14 d. Natural killer cells were injected into the human skin grafts, and the grafts were harvested after 4 wk. Injection of natural killer cells from psoriatic donors into autologous nonlesional psoriatic skin resulted in classic psoriasis histology with a significant increase in epidermal thickness, and proliferation, as well as expression of epidermal human leukocyte antigen DR, intercellular adhesion molecule-1, CD1d, and K-16. Superantigen stimulation was not necessary. In contrast, injection of natural killer cells from normal donors into autologous normal skin did not induce the histology of psoriasis, but that of psoriasiform dermatitis. This is a nonspecific reaction pattern. These grafts also exhibited a significant increase in epidermal thickness, and proliferation. Differences from psoriasis included mild epidermal edema (spongiosis), hypergranulosis, irregular elongation of rete ridges, and lack of thinning of the suprapapillary plate. Injection of allogeneic natural killer cells into grafts also resulted in psoriasiform dermatitis, regardless of the source of natural killer cells, or skin. Psoriasis induction by cells with natural killer receptors appears to be dependent upon the source of skin. This suggests that psoriasis results from a cutaneous defect that is triggered by an autoimmune activation.

Animals↗
PubMedDate not supplied

Long-term fat preservation.

The injection of autologous free fat obtained by suction-assisted lipectomy for the correction of soft tissue defects is a common procedure in plastic surgery. However, unpredictable partial absorption of the injected fat often necessitates repeated harvesting and injection. Fat preservation for future re-injection is indicated to avoid repeated fat harvesting procedures. A previous study has shown that fat obtained by suction can be preserved by freezing for at least 2 weeks. The purpose of the present study was to investigate the effect of freezing autologous free fat for 7 months on the take of the fat graft. Human fat obtained by suction-assisted lipectomy was centrifuged and stored in a domestic refrigerator at -18 degrees C for 7 months. After thawing, the fat was injected into the scalp of 10 nude mice, which served as the study group. In the control group (n = 10), fresh fat was injected. Fifteen weeks later, the fat grafts were dissected out. Volumes, weights, and histological parameters were compared between the groups. The injected fat survived in both the study and the control groups but the histological parameters were significantly inferior in the frozen fat. The weight of the frozen fat was also significantly less compared with the fresh fat. The volume of the frozen fat was inferior but not significantly. Based on this in vivo experiment, it is suggested to refrain from using fat that has been frozen for 7 months or longer. The longest period and the optimal conditions for fat preservation should be further investigated.

Adipose Tissue↗
PubMedDate not supplied

The effect of lidocaine and adrenaline on the viability of injected adipose tissue--an experimental study in nude mice.

Adipose tissue injection as a free graft for the correction of soft tissue defects is a widespread procedure in plastic surgery. The main problem in achieving long-term soft tissue augmentation is partial absorption of the injected fat, and hence the need for over-correction and re-injections. Lidocaine, used for local anesthesia, has been suspected as an inhibitor of growth of adipocytes in culture and slowing down glucose transport and lipolysis in adipocytes. In addition, reduced blood supply by local application of epinephrine was accused of having a negative effect on the graft. The purpose of this study was to examine the effect of local anesthesia, administered to the fat donor site, on the take of the injected fat. Human adipose tissue, obtained by suction-assisted lipectomy, was injected subcutaneously into the scalp of nude mice. Local anesthesia of the fat donor site consisted of a solution with 600 mg of lidocaine (0.06%) and epinephrine 1:1000000. In a control group, normal saline with no local anesthesia or epinephrine was administered to the donor site. One cc of fat was injected after centrifugation into each animal scalp. There were 10 animals in each group. The animals were sacrificed 15 weeks after the procedure. Graft weight and volume were measured, and histologic evaluation was performed. No significant differences were demonstrated between the groups in regard with the grafts' weight and volume and the histologic parameters investigated. In conclusion, local anesthesia solution, consisting of lidocaine and epinephrine, does not alter the take of fat grafts, and has no influence on the adipocytes viability.

Adipose Tissue↗