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Biomedical subjects

D V Belsito

Publications and source records attributed to D V Belsito.

At least 19 recordsLinked to original sources
PubMed1995

Synergism between interferon-gamma and cytokines or lipopolysaccharide in the activation of the HIV-LTR in macrophages.

Macrophages (møs) obtained from transgenic mice carrying the HIV long terminal repeat-chloramphenicol acetyl transferase (LTR-CAT) sequence were used to study the influence of various biologic response modifiers (BRMs) on the activation of LTR-directed CAT expression. It was found that LPS or IL-6 alone induced moderate levels of CAT expression, whereas IFN-gamma or TNF-alpha had no significant effect. Co-exposure of møs to IFN-gamma and either LPS, IL-6, or TNF-alpha led to significant synergistic increases in CAT levels. Levels were also synergistically augmented when møs were exposed first to IFN-gamma (priming), washed, and then exposed to either LPS, IL-6, or TNF-alpha. Although IL-6 was synergistic with subsequently added IFN-gamma, the reverse sequence of addition was more effective. LPS and TNF-alpha were inactive when added before IFN-gamma. Initial priming signals were rapid as exposure for 3 h to IFN-gamma was sufficient to prepare the cells for subsequent activation by other BRMs. These results suggest that the duration of latency and progression of HIV infections may be greatly influenced by events such as intercurrent infections that cause IFN-gamma production, thereby priming møs to respond to other cytokines that have been reported to be constitutively elevated during the course of infection with HIV (e.g., IL-6 and/or TNF-alpha).

Animals↗
PubMed1993

Allergic contact dermatitis to topical glucocorticosteroids.

During the past decade, the reported incidence of allergic reactions to topically applied glucocorticosteroids has increased significantly. The two cases reported here typify the presenting symptoms of the glucocorticosteroid-allergic persons. These cases also illustrate the extensive cross-reactivity among the different topical corticosteroids, as well as the potential for systemic contact dermatitis to occur following parenteral exposure. These cases are reviewed in the context of the many other reports in the literature of similar allergic reactions.

Administration, Topical↗
PubMed1992

Allergic contact dermatitis from formaldehyde resins in permanent press clothing: an underdiagnosed cause of generalized dermatitis.

BACKGROUND AND METHODS: Formaldehyde resins have been used to impart wrinkle resistance to clothing fabrics since 1926. After several patients with positive patch tests to formaldehyde resins had been examined, a study was undertaken of the records of all patch tests performed at the University of Louisville Patch Test Clinic and the Allergy Section of the Skin and Cancer Clinic of New York University Medical Center from January 1988 through April 1990 to determine the prevalence of positive patch-test reactions to formaldehyde-based textile resins and the clinical and demographic patterns associated with textile resin allergy. RESULTS: Seventeen patients were identified at the two centers. Twelve were allergic to formaldehyde as well as to formaldehyde textile resins. Several clinical patterns were found, including accentuation of dermatitis in areas of tight clothing, primary occurrence in clothing-covered areas, and a chronic recalcitrant course. Ethylene urea melamine formaldehyde resin was the best screening agent with 14 definite positive reactions and one equivocal reaction. CONCLUSION: Formaldehyde textile resin allergy is more common than has been previously recognized. Patch testing with one or more formaldehyde textile resins is indicated in patients with a particular pattern of dermatitis.

Adult↗
PubMed1991

Immunosuppressive effects of transforming growth factor beta: inhibition of the induction of Ia antigen on Langerhans cells by cytokines and of the contact hypersensitivity response.

Recent reports show that transforming growth factor (TGF)-beta exerts a variety of immunosuppressive activities. The present study focuses on the effects of TGF-beta 1 on expression of Ia antigen by Langerhans cells. Although TGF-beta 1, in concentrations from 0.001 to 100 micrograms/ml, has no effect on constitutive expression of Ia antigen on these cells, the in vitro up-regulation of Ia antigen on the surface of LC by interleukin (IL)-1, tumor necrosis factor-alpha, interferon-gamma, IL-3, and granulocyte/macrophage-colony stimulating factor is inhibited by the concomitant addition of 1 microgram/ml TGF-beta 1. In contrast, TGF-beta 1 has no effect on the up-regulation induced by IL-2 or IL-6. In this report, the activity of TGF-beta closely resembles that of Cyclosporine A (CsA). Similar results are seen in vivo when either TGF-beta 1 (5 micrograms, intraperitoneally [ip], daily on days 0-3) or CsA (1 mg, subcutaneously [sc], twice daily on days 0-3) are given together with IL-2 (500 U, intraperitoneally [ip], twice daily on days 1-3) or interferon-gamma (4,000 U, ip, twice daily on days 1-3). Given the important role of Ia expression in cell-mediated immune reactions, the effect of TGF-beta on contact sensitivity was next investigated. In doses of 5 micrograms, ip, daily on days 6-8, TGF-beta inhibits the expression of contact reactivity in animals sensitized on day 0 and challenged on day 7. In contrast, no effect is observed on the induction of contact sensitivity in mice given TGF-beta 1 on days--1 to 2, sensitized on day 0, and challenged on day 7. The possible importance of antagonism between TGF-beta and other cytokines, especially IFN-gamma, involved in the elicitation of contact hypersensitivity reactions is discussed.

Animals↗
PubMed1991

Effect of triggering epidermal Fc gamma receptors on the interleukin-2- and interleukin-6-induced upregulation of Ia antigen expression by murine epidermal Langerhans cells: the role of prostaglandins and cAMP.

Following incubation of murine epidermis in medium containing either interleukin-2 or interleukin-6, there is significant upregulation in the density of Ia+ epidermal Langerhans cells (to 159% and 175% of control, respectively). This cytokine-induced upregulation is abrogated by either rabbit or human IgG due to triggering of Fc gamma receptors. In contrast, human IgA does not inhibit the effect of interleukin-2 or interleukin-6. Using different isotypes of murine IgG, we have demonstrated that all subclasses are capable of inhibiting the cytokine-induced enhancement of Ia antigen, although IgG1 and IgG2b must be heat aggregated to be effective. The IgG-mediated events are dependent on prostaglandin synthesis because they can be blocked by the cyclooxygenase inhibitor indomethacin, 10 micrograms/ml. The responsible PG appears to be PGD2; in contrast to its known inhibitory effect on macrophages, PGE2 does not inhibit the upregulation of Ia antigen on Langerhans cells. In addition, these IgG-mediated events are dependent upon the generation of cAMP because they can be blocked by the adenylate cyclase inhibitor 2',5'-dideoxyadenosine, 1 mM. Despite the apparently central role of PGD2 and cAMP in this process, triggering of the Fc gamma R by different isotypes of IgG blocks upregulation of Ia via at least two different pathways. The inhibition caused by aggregated IgG1 or IgG2b, which bind to Fc gamma RII on Langerhans cells, is abrogated by para-bromophenacylbromide, an inhibitor of phospholipase A2. In contrast, the inhibition caused by monomeric IgG2a, which binds to Fc gamma RI most likely on keratinocytes, or monomeric IgG3, which probably binds to this same Fc gamma RI, is abrogated by staurosporine, an inhibitor of protein kinase C, as well as by W7, a calmodulin antagonist. Finally, 1,2 dioctanoyl-rac-glycerol, an activator of protein kinase C, mimics the Ig-mediated events. Based on these findings, as well as studies using monoclonal antibodies to the murine Fc gamma receptors I and II, we conclude that, as is the case in murine macrophages, triggering of an epidermal Fc gamma RI, most likely on keratinocytes, results in the generation of cAMP via a Ca(++)-dependent protein kinase C pathway, whereas triggering of an epidermal Fc gamma RII, most likely on Langerhans cells, results in the elevation of cAMP via a phospholipase A2-mediated pathway. In contrast to the situation for macrophages, PGD2 is a vital intermediate in both pathways, perhaps because Langerhans cells have receptors for only this prostaglandin.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Cimetidine-induced augmentation of allergic contact hypersensitivity reactions in mice.

BALB/c mice were treated with cimetidine (100 mg/kg) or saline, intraperitoneally, twice daily, from days 0-2 or days 7-9 after sensitization with 0.1%, 2,4,6-trinitro-1-chlorobenzene (TNCB) on day 0. On day 7, the mice were challenged with 1% TNCB to one ear. Ear swelling responses (as an index of sensitization), serum histamine levels, and biopsy specimens of challenged ears were evaluated in groups of cimetidine- or saline-treated mice at 0, 0.5, 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after challenge. Additional controls included mice injected with saline or cimetidine and challenged with, but not sensitized to, TNCB (irritant controls). Treatment with cimetidine during the induction but not the elicitation of allergic contact hypersensitivity (ACH) produced a significant enhancement of the response throughout the first 48 h. There was no effect of cimetidine on antigen-presenting cells within the epidermis which might account for this enhancement. Similarly, no difference in mast cell morphology or serum histamine levels between cimetidine- and saline-treated groups was observed. Histologically, the cimetidine-treated animals showed a more intense cellular infiltrate, which was most noticeable at 24 to 48 h, at which time numerous subcorneal and perifollicular neutrophilic abscesses were observed. To further investigate the mechanism of action of cimetidine, mice were injected with cyclophosphamide (150 mg/kg) 2 d prior to sensitization. Mice treated with cyclophosphamide alone or in combination with cimetidine showed no additive or synergistic effect upon the ear swelling response. We conclude that enhancement of ACH by cimetidine is independent of any effect on mast cells or antigen-presenting cells, but may relate to a cimetidine-induced inhibition of the induction of T-suppressor cells at the time of sensitization.

Animals↗
PubMed1990

Contact urticaria caused by rubber. Analysis of seven cases.

Prior to 1979, there had been no reports of contact urticaria to rubber products. Since that time, many cases have been reported. At New York University, the first case, secondary to cornstarch allergy, was seen in 1985. Since that time, we have seen an additional six cases, five of them in the last year. Of these six cases, three were attributable to H. brasiliensis and three to the accelerators. Although the use of latex products has increased dramatically within the past 9 years in response to the epidemic of human immunodeficiency virus infections, it is not clear whether increased exposure alone accounts for the sudden increase in the number of patients with contact urticaria. Four of the patients presented here are hospital personnel involved in surgical procedures, in which, for decades, latex gloves have been used. Furthermore, two of our seven patients are paraplegics, who, as a group, have long had frequent exposure to rubber products. Two possibilities seem most likely: either the diagnosis has been missed by physicians for decades, or in response to the worldwide demand for latex products, the manufacture of latex has become altered in such a fashion that more products from which the allergens (accelerators and H. brasiliensis) are easily leached are now reaching the marketplace.

Adult↗
PubMed1989

Enhancement by various cytokines or 2-beta-mercaptoethanol of Ia antigen expression on Langerhans cells in skin from normal aged and young mice. Effect of cyclosporine A.

The number of Ia+ Langerhans cells (LC) in skin from aged (16- to 18-mo old) BALB/c mice is approximately 40% lower than in skin from young (2- to 3-mo old) mice. Overnight incubation at 37 degrees C with a variety of cytokines, including IL-1, IL-2, IL-3, IL-4, IL-6, TNF-alpha, IFN-gamma, and granulocyte/macrophage-CSF, causes a significant increase in the Ia expression on LC and raises the number of Ia+ cells by at least 300/mm2 in skin from both young and old mice. At 1 to 5 x 10(-5) M, 2-ME has a similar effect. The percentage increment in Ia+ cells is much higher for skin from aged mice than from young mice, particularly with IL-3, which appears to reconstitute the number of Ia+ LC in skin from aged mice to that of IL-3 exposed skin from young mice. Under the incubation conditions of our experiments, neither keratinocytes nor Thy-1+ dendritic cells acquire Ia Ag. Addition of 10 micrograms/ml cyclosporine A to the medium abolishes the effect of 2-ME and of all of the cytokines except IL-2 and IL-6. These results demonstrate the presence of a significant population of Ia- LC in the epidermis of both young and aged mice. It is suggested that epidermal production of cytokines may be of importance in the maintenance of constitutive Ia expression on LC. The possible interaction between keratinocytes and LC and the effect of aging on this process are discussed.

Adjuvants, Immunologic↗
PubMed1989

The immunologic basis of patch testing.

During the past decade much has been learned about the cell-mediated immune responses that result in allergic contact dermatitis. The complex interaction between the hapten, the Langerhans cell, the specifically sensitized T cell, and the various soluble mediators of cellular immunity have begun to be delineated. This article reviews the pathophysiology of allergic contact dermatitis. Clinical and physicochemical modulators of this response, such as patient age, the anatomic site of antigenic challenge, and prior treatment with UVB, PUVA, glucocorticoids, or cyclosporine (Cyclosporin A), are stressed. The implications of these findings to the techniques of patch testing are summarized.

Age Factors↗
PubMed1989

The potential role of nutritional factors in the induction of immunologic abnormalities in HIV-positive homosexual men.

The literature is briefly summarized as to how several nutrients affect immune function, susceptibility to infection, and cancer susceptibility or progression. Nutritional deficiencies can impair immunity and so influence susceptibility to infectious agents, including ones that are common and relatively virulent in acquired immune deficiency syndrome (AIDS) patients. A variety of nutrients affect several of the immune functions that are defective in human immunodeficiency virus (HIV)-infected individuals. For example, beta-carotene increased the number of CD4+ cells; vitamin E decreased the number of CD8+ cells and increased the CD4+/CD8+ ratio; vitamin D decreased the CD4+/CD8+ ratio; and iron increased the number of peripheral lymphocytes in humans receiving supplementation. Furthermore, nutritional deficiencies can influence gastrointestinal function, while infectious diseases can influence nutrient requirements by altering the efficiency of absorption and the rate of tissue metabolism. Malnutrition, depressed serum zinc levels, and intestinal nutrient malabsorption have been found in AIDS patients. The above findings suggest that dietary manipulations might diminish the immune defects in HIV infection and enhance resistance to opportunistic infections. However, dietary alterations in immune defects are generally not well quantified and may be small relative to the magnitude of the defects observed in AIDS patients. Because conflicting or adverse effects have been reported for some nutrients, recommendations for dietary supplementation in HIV-infected individuals are premature and possibly hazardous. Further studies are much needed to relate dietary nutrient intakes to clinical outcomes.

HIV Seropositivity↗
PubMed1989

The pathophysiology of allergic contact hypersensitivity.

During the past decade, much has been learned about the pathophysiology of ACH--yet much remains to be determined. Although LC, IL-1, IL-2, IFN-gamma, and the T effector circuits have been extensively studied, it is still not clear whether it is LC- or keratinocyte-derived IL-1 that is crucial in ACH, whether IL-1 acts primarily on T-cells or the APC, whether other cytokines are involved in the circuit (TNF, KTGF?), the exact relationships between T effector, T memory, and other T helper cells, what the functions of mast cells and basophils are in the allergic reaction, and how the regulatory circuits (including prostaglandins and eicosanoids) affect the outcome of ACH. The mechanism of suppression remains even less well understood despite the potential application of this knowledge to the treatment of diseases caused by Type IV hypersensitivity. A better understanding of the ACH mechanism will lead not only to more sophisticated ACH treatment, but also to a better understanding of the cell-mediated events of cutaneous viral replication, organ transplantation, and tumor growth.

Allergens↗
PubMed1988

Relative lack of systemic effects of mometasone furoate on Langerhans cells of mice after topical administration as compared with other glucocorticosteroids.

The effects of topically applied mometasone furoate were compared with those of other glucocorticosteroids, in particular fluocinolone acetonide, in assays of murine epidermal Ia+ Langerhans cell density. No evidence of systemic effects, as determined by a decline in the density of Ia+ LC in distant sites, was detected after local topical applications (5 times a week) of mometasone furoate 0.001% for periods of up to 3 weeks. Other steroids, even in such very low concentrations, and mometasone furoate in higher concentrations, produced systemic effects on Ia+ LC when used for longer than 5 d. The recovery time of Ia+ Langerhans cells is significantly shorter after application of mometasone furoate than after fluocinolone acetonide. However, with both compounds, recovery occurred more rapidly after 3 weeks than after a 1- or 2-week interval of compound administration.

Administration, Topical↗