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Biomedical subjects

A Etzioni

Publications and source records attributed to A Etzioni.

At least 91 records · Page 5Linked to original sources
PubMed1994

Effect of antiinsulin-like growth factor 1 on epidermal proliferation of human skin transplanted onto nude mice treated with growth hormone.

Recently it has been demonstrated that long-term administration of GH leads to increase of skin thickness. The aim of the present study was to determine whether this effect of GH is mediated by insulin growth factor 1 (IGF-1), which enhances epidermal proliferation. In order to address this question, human split-thickness grafts obtained from aged skin were grafted onto nude mice. One group of mice was treated systemically with GH, whereas a second group was treated with intradermal graft injections of anti-IGF-1 in addition to GH. A third group received distilled water and served as a control group. Histological and autoradiographic analyses were performed before and after engraftment. The GH-treated mice showed a significant increase in epidermal proliferation measured by epidermal thickness (analysis of variance with repeated measurements, P < 0.01) and labeled index (analysis of variance, P < 0.01) as compared to the control group. The intradermal injections of anti-IGF-1 reduced significantly the proliferative stimulatory effect of GH (P < 0.01). The present study emphasizes the role of IGF-1 in the increased skin thickness observed after GH administration and provides a useful model for determining the effect of various compounds, including GH, on human skin.

Aged↗
PubMed1994

Adhesion molecule deficiencies and their clinical significance.

Adhesion molecules play a major role in the recruitment of neutrophils to the site of inflammation. Currently, two congenital hereditary Leukocyte Adhesion Deficiency (LAD) syndromes are recognized. LAD I is due to the absence of the beta subunit of the integrin molecule, while LAD II is caused by a deficiency of Sialy1 Lewis X, the neutrophil ligand for selectins. Clinically, both syndromes are characterized by recurrent bacterial infections, more severe in LAD I. Developmental abnormalities (growth and mental retardation) constitute a prominent feature of LAD II and may be attributed to a general defect found in fucose metabolism in LAD II. Neutrophil motility was found to be defective in both syndromes. Using activated umbilical endothelial cells, we showed that LAD I neutrophil do not bind to cells expressing ICAM-1, while LAD II cells do not bind to endothelial cells expressing E- or P-selectin. Skin window technique showed a marked decrease in margination in both syndromes. Using intravital microscopy we were able to show that the basic defect in LAD II is in the "rolling" phase, while in LAD I, firm adhesion and transmigration are defective. Studies of these two rare conditions emphasized the important in vivo roles of adhesion molecules in host defense mechanism.

Animals↗
PubMed1994

Core values in health care reform: a communitarian approach.

Controlling health care costs should allow the nation to provide more health services and higher quality care to more people. The authors are concerned, however, that many of the reform efforts will unwittingly undermine the culture of care in their pursuit of savings and access. This article is a plea to maintain the core moral values and the social and institutional commitments that are essential in the delivery of care, so that the health care community is not turned into a health industry. The authors' communitarian approach aims to preserve the balance between individual rights and social responsibilities, the moral integrity of a caring society, and the unique character of mutual trust between patients and health care personnel. They advocate an orientation toward preventing disease and promoting health, an imperative of reforming the violent, reckless, and costly aspects of American society, and a moral justification for cutting administrative waste, defensive medicine, and excessive profits rather than rationing beneficial and humane health services.

Child↗
PubMed1994

Prescription for health care reform.

In a concise critical look at Clinton's proposal the author provides direction signs, caveats, and guiding principles for a durable reform. In opposing the Oregon health care system as discriminatory, the author cautions against rationing as a means of reducing health care costs.

Evaluation Studies as Topic↗
PubMed1993

Response of grafts from patients with alopecia areata transplanted onto nude mice, to administration of interferon-gamma.

A variety of evidence has pointed to immunological involvement in the pathogenesis of alopecia areata (AA). The aim of the present study was to determine whether differential expression of HLA-DR and intracellular adhesion molecules-1 (ICAM-1) occurs in hair structures of patients with longstanding AA, following stimulation with interferon-gamma (IFN-gamma). IFN-gamma was injected i.v. to nude mice grafted with transplants obtained from affected areas of seven patients and of normal individuals. All mice were injected with IFN-gamma or phosphate-buffered saline (PBS) alone for 3 consecutive days. Immunohistochemical studies were performed in specimens of grafts in order to detect the change in adhesion molecules, HLA-DR antigen, and Langerhans cells. ICAM-1 and HLA-DR induction was found to be similar in grafts from AA patients and normal skin grafts in the IFN-gamma injected mice. However, more intraepithelial Langerhans cells were observed in the AA patients' grafts treated with IFN-gamma than in those treated with PBS and in normal grafts treated with IFN-gamma. This study suggests an important role of Langerhans cells in this issue.

Adult↗
PubMed1993

In vivo behavior of neutrophils from two patients with distinct inherited leukocyte adhesion deficiency syndromes.

The selectins and the beta 2-integrins (CD11/CD18) mediate distinct adhesive interactions between neutrophils and endothelial cells. Selectins are believed to initiate binding by mediating neutrophil rolling, whereas beta 2-integrins are required for subsequent activation-induced firm sticking and emigration. In vitro evidence suggests that two endothelial cell selectins, P- and E-selectin, can mediate rolling by binding to the carbohydrate ligand sialyl-Lewisx (sLex) on neutrophil surface glycoconjugates. To test the relative contribution of selectins and beta 2-integrins in vivo we used intravital microscopy to study the behavior of neutrophils from two patients with distinct inherited leukocyte adhesion deficiency syndromes. Neutrophils from a patient suffering from CD18 deficiency showed normal rolling behavior but were incapable of sticking or emigrating upon chemotactic stimulation. Neutrophils from a second patient with a newly described adhesion deficiency had normal CD18 but did not express sLex. These neutrophils rolled poorly and also failed to stick in venules under shear force. Under static conditions, however, chemoattractant-induced sticking and emigration could be observed. This demonstrates that both selectin-carbohydrate-mediated initiation of adhesion and subsequent activation-induced beta 2-integrin engagement are essential for the normal function of human neutrophils in vivo.

Animals↗
PubMed1993

Vitiliginous vs pigmented skin response to intradermal administration of interferon gamma.

BACKGROUND AND DESIGN: Decreased sensitization and elicitation of contact allergens in vitiliginous skin has been described. This may be related to altered epidermal Langerhans cell migration with bound hapten to dermis and draining lymph nodes. The aim of the present study was to detect the potential ability of vitiliginous skin to respond to an in vivo immunologic stimulus such as intradermal injections of interferon gamma (IFN-gamma). Vitiliginous and normal pigmented skin of each patient was injected intradermally with 10 micrograms of recombinant IFN-gamma diluted in 0.1 mL of sterile water for 3 consecutive days. On day 5, punch biopsy specimens were obtained from the injected sites. Histologic and immunohistochemical staining was performed on all sections. The cryostat sections were stained with adenosine triphosphatase as well as with the indirect immunoperoxidase technique employing murine monoclonal antibodies to HLA-DR, ICAM-1, CD1, CD11a, and CD18. RESULTS: HLA-DR and ICAM-1 expression by epidermal cells, combined with perivascular accumulation of mononuclear cells with CD11a and CD18 expression, was observed in all sites injected with IFN-gamma. However, absence of an effect on the epidermal Langerhans cell population was noted only on the vitiliginous skin. CONCLUSION: The reactivity of depigmented and pigmented skin was found to be different after IFN-gamma administration, with fewer CD1-positive cells in the depigmented skin. As adenosine triphosphatase staining also showed fewer positive cells, it may be concluded that no effect on the migration of epidermal Langerhans cells was noted in the involved skin. This may shed light on the immunologic aberration seen in vitiliginous skin.

Adenosine Triphosphatases↗
PubMed1993

The role of cyclosporine on Ia antigen expression on gut epithelium in nude mice.

Increased expression of class II antigens (HLA-DR, human:Ia murine) on epithelial cells (EC) such as keratinocytes and gut EC suggests a role of the epithelium in the inflammatory response. It has been shown that injection of normal mouse serum (NMS) into nude mice caused an induction of Ia antigen by keratinocytes of the nude mice. The aim of the present study was to determine whether such induction could be observed in gut EC and whether it can be inhibited by cyclosporine A (CyA). Forty nude mice were divided into 4 groups of 10 each, designated A-D. Group A was injected with 0.1 ml of NMS; groups B and C were also injected with NMS and treated with oral CyA for 10 days. The dosage in group B was 30 g/ml and in group C 60 g/ml of drinking water. Group D was injected with serum of nude mice and served as a control group. Biopsies of small intestine and colon were obtained from each mouse and analyzed by indirect immunoperoxidase to identify Ia expression. Small intestine and colon EC were induced to express Ia antigen in most of the mice in groups A and B. A striking reduction in Ia expression was noted in group C. The differences between groups A and C concerning Ia expression on small intestine and colon EC were statistically significant. Our results demonstrate that the nude mouse may serve as a model for the study of Ia expression on gut EC, and that CyA can suppress the expression of Ia antigen also in the gut.

Animals↗
PubMed1992

Rambam-Hasharon syndrome of psychomotor retardation, short stature, defective neutrophil motility, and Bombay phenotype.

We describe 2 Arab patients, both offspring of unrelated consanguineous matings, with unusual facial appearance, severe mental retardation, microcephaly, cortical atrophy, seizures, hypotonia, dwarfism, and recurrent infections with neutrophilia. Neutrophil motility was markedly decreased but the opsonophagocytic activity was normal. Both patients lack the red blood cell (RBC) H antigen and manifest the Bombay (hh) phenotype. Familial endocardial fibroelastosis and familial tetralogy of Fallot segregated independently in one family. The occurrence of the same syndrome in 2 unrelated families suggests that the various aspects of the disorder are the pleiotropic effects of a single mutation. Homozygosity-by-descent for a deletion involving contiguous genes may explain the findings in this syndrome. Alternatively, a mutation which involves an ubiquitous GDP fucose donor rather than the enzyme (alpha 2-L-fucosyltransferase) or its substrate (glcNAc) may account for the pleiotropic manifestations in this syndrome.

ABO Blood-Group System↗
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

High dose intravenous gamma-globulin in intractable epilepsy of childhood.

Eight children aged between 1.3 and 13 years suffering from epilepsy refractory to conventional anticonvulsive therapy were treated with high dose intravenous gamma globulin (200 mg/kg, 3 times per week, repeated after 3 weeks). Immunological studies after therapy showed normal results. In four children, clinical and EEG findings markedly improved. In one other case a partial response was noted. No improvement was observed in the remaining three cases. We confirm that although the mechanism is still obscure, high doses of i.v. gammaglobulin may have a beneficial effect in a significant number of children with intractable epilepsy.

Adolescent↗