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D V Belsito

Publications and source records attributed to D V Belsito.

53 records · Page 3Linked to original sources
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↗
PubMed1987

Reversal by lymphokines of the age-related hyporesponsiveness to contact sensitization and reduced Ia expression on Langerhans cells.

Contact sensitivity responses were evaluated in young adult (3-5 months) and aged (16-26 months) BALB/c mice which were systemically treated with interleukin-2 (IL-2), interferon-gamma (IFN-gamma) or saline. Mice older than 16 months of age have deficient numbers of Ia+ Langerhans cells in addition to their well-known impaired T cell functions. They also have an impaired cell-mediated response to contact sensitization with 1-chloro-2,4,6-trinitrobenzene. This hyporesponsiveness in aged mice can be almost completely reversed by IL-2 and is marginally improved by IFN-gamma. Exposure of skin from aged mice to interleukin-2 or interferon-gamma, both in vivo and in vitro, causes increases in the density of Ia+ Langerhans cells to levels approximating those in young mice. Since IFN-gamma causes partial restitution while IL-2 fully restores the contact hypersensitivity in aged animals, we conclude that the hyporesponsiveness in aged mice results both from defective Ia antigen expression on the antigen-presenting Langerhans cells and from deficient T cell function.

Age Factors↗
PubMed1987

Mast cell participation during the elicitation of murine allergic contact hypersensitivity.

In order to evaluate mast cell participation in allergic contact hypersensitivity (ACH), BALB/c mice were sensitized with 0.1% trinitrochlorobenzene (TNCB). Immediately before challenge and at 1, 1.5, 2, 4, 6, 8, 12, 24, and 48 h after challenge with 1% TNCB, groups of animals had ear thickness measured, had blood collected for histamine determinations, and had both ears removed for histologic evaluation of mast cells. The increase in ear swelling was triphasic with peak increases at 1.5 h (14.3 +/- 1.6 X 10(-2) mm; mean +/- SEM), 8 h (19.9 +/- 1.8 X 10(-2) mm), and 24 h (30.2 +/- 2.9 X 10(-2) mm). A triphasic pattern of increased serum histamine was noted at 1-4 h (117% over control levels), at 12 h (131%), and at 48 h (133%). Examination of the tissue specimens from challenged animals showed modest (1+) degranulation of mast cells between 1 and 6 h with extensive (2+) degranulation at 12 h. In addition, hypogranulated mast cells were evident between 1 and 6 h, at 24 h, and at 48 h. There were no statistically significant differences in mast cell numbers at any time. Neither platelets nor other formed elements of the blood contributed to the increased blood histamine levels. These data show that mast cells are activated in a triphasic pattern during ACH, and thus suggest both early and late roles for the mast cell and its products in the evolution of ACH.

Animals↗
PubMed1987

Contact dermatitis to ethyl-cyanoacrylate-containing glue.

3 patients with contact dermatitis to an ethyl cyanoacrylate glue are presented. Although reactions to cyanoacrylate glues are considered rare, more widespread use of these products by nail salons is likely to be associated with an increased incidence of positive reactions. All 3 of our patients came into contact with the glue during "nail wrapping". In this process, ethyl cyanoacrylate or another "instant glue" is used to adhere glue-impregnated silk or linen to the nail plate which is then filed to shape the nail. This procedure creates fine acrylic-containing dust which may facilitate an allergic response. Fine particulate matter may be transferred to other distant cutaneous sites, such as the eyelids, resulting in more widespread cutaneous eruptions. Dermatologists in areas where nail wrapping is becoming more fashionable are advised to be alert to potential cyanoacrylate glue allergies which present as periungual eczema which may be associated with eyelid dermatitis and features of nummular dermatitis particularly over the dorsal hand.

Adhesives↗
PubMed1986

Reversal by lymphokines of the effect of cyclosporin A on contact sensitivity and antibody production in mice.

Cyclosporin A (CsA) treatment of mice during the first 4 days of the sensitization phase prevents induction of contact sensitivity to trinitrochlorobenzene (TNCB). Administration of CsA on the day of ear challenge with TNCB also inhibits the effector phase of this response. Simultaneous treatment of the mice with IL 2-containing murine lymphokine preparations or with recombinant human IL 2 reverses the effect of CsA on the induction of contact sensitivity. Recombinant IL 2 also reverses the inhibition by CsA of the effector phase. Neither phase of the response is restored by murine IFN-gamma. Anti-body production to trinitrophenylated (TNP) Ficoll or TNP-hemocyanin is also strongly inhibited (greater than 75%) by CsA injected on the day of antigen injection. Although lymphokines or endotoxin may strongly enhance these responses, no reversal of the effect of CsA can be obtained. We conclude that inhibition of IL 2 production is of paramount importance for the inhibitory effect of CsA on contact sensitivity, but that additional effects are involved in the inhibition of antibody production to both T-dependent and T-independent antigens.

Animals↗
PubMed1985

Syngeneic mixed lymphocyte reactions to murine Fc receptor-bearing, nonadherent low density lymph node cells and epidermal Langerhans cells.

Both Langerhans cells from BALB/c mouse epidermis and nonadherent, low density (LD) cells, obtained from collagenase-treated minced lymph node, are stimulatory for isolated T cells in syngeneic mixed lymphocyte reaction (SMLR). The method of preparation of LD cells influences whether Fc receptor (FcR) can be detected on them. Fc receptors on nonadherent LD lymph node cells can be detected only if the same procedure is employed as that for Langerhans cell isolation, i.e., Ig-free bovine albumin must be used during gradient centrifugation and EA rosetting must be done overnight at 4 degrees C. Thus, both FcR+ and FcR- LD lymph node cells, as well as FcR+ Langerhans cells, stimulate SMLR. Although Ig+ cells in the LD fraction also stimulate the SMLR, their removal does not affect the stimulating capacity of the LD lymph node fraction.

Animals↗
PubMed1984

Reduced Langerhans' cell Ia antigen and ATPase activity in patients with the acquired immunodeficiency syndrome.

We investigated the possible role of a defect in antigen-presenting cells in the acquired immunodeficiency syndrome (AIDS), by enumeration of Langerhans' cells, the epidermal antigen-presenting cells. These cells were stained for the characteristic markers, surface Ia antigen and surface ATPase activity. A significant reduction was observed in the number of stained cells per square millimeter of body-surface area in 24 patients with AIDS and either opportunistic infections (Ia, 258 +/- 34, and ATPase, 274 +/- 46) or Kaposi's sarcoma (Ia, 378 +/- 100, and ATPase, 530 +/- 26), as compared with 38 appropriate controls (Ia, 721 +/- 13, and ATPase, 693 +/- 12). Examination of six patients with an "AIDS-related complex" revealed significantly reduced numbers of Langerhans' cells per square millimeter; this reduction was more pronounced in staining for Ia antigen (306 +/- 69) than in staining for ATPase activity (517 +/- 101). Given the known role of Ia expression in antigen presentation, we suggest that functional alterations in Langerhans' cells, and perhaps also in antigen-presenting cells in tissues other than skin, may be involved in the pathogenesis of AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1984

The Langerhans cell, as a representative of the accessory cell system, in health and disease.

Cell surface receptors and antigens present on Langerhans' cells (LC) suggest a close relationship between LC and interdigitating cells (IDC) in lymph node sections or lymphoid dendritic cells (LDC) in cell suspensions. One of the reported differences is that Fc receptors (FcR) which are present on LC, are absent on LDC. This difference can at least partly be explained by a laboratory artefact: FcR on murine LC are irreversibly modulated by the Ig that contaminates the bovine albumin commonly used for gradients. Furthermore, the demonstration of FcR on murine LC requires prolonged exposure to EA at 4 degrees C. A significant percentage of nonadherent, low density, Ig- lymph node cells also express such FcR. These cells can stimulate syngeneic mixed lymphocyte reactions as can LC isolated from epidermis. Consideration of LC as cutaneous representatives of the accessory cell system led to an investigation of their numbers in epidermal sheets of patients with acquired immunodeficiency syndrome (AIDS). A marked reduction in Ia+, ATPase+, OKT6+ LC was found as compared to controls, suggesting that accessory cell deficiency may play a role in the extreme immunodeficiency seen in AIDS patients.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Effect of glucocorticoids and gamma radiation on epidermal Langerhans cells.

The effect of 750 rads of gamma radiation on the rate of return of epidermal Langerhans cells (LC) following suppressive doses of topical glucorticoids was studied in guinea pigs. Gamma radiation alone had no effect on the LC as assessed by staining for cell membrane ATPase activity and Ia antigen. It did, however, delay the expected return of Ia but not ATPase surface markers on the LC after perturbation with glucocorticoids. The delayed return of surface Ia antigen is possibly related to a radiation-induced defect in the production of a required lymphokine and/or in intracellular Ia transport. Although our data do not rule out a cytolytic effect of steroids on the LC, they do strongly suggest that, at least in part, glucocorticoids act on the LC by altering cell surface characteristics.

Adenosine Triphosphatases↗
PubMed1984

Effect of combined topical glucocorticoids and ultraviolet B irradiation on epidermal Langerhans cells.

The combined effect of topical glucocorticoids and ultraviolet B (UVB) irradiation on ATPase+ epidermal Langerhans cells in vivo was investigated in the guinea pig model. Glucocorticoids did not significantly enhance the response to UVB radiation, in the dosage range from 90-550 mJ/cm2 of UVB, suggesting that both agents were acting in a similar fashion. The solvent ethanol, however, potentiated the effect of UVB exposure due, at least in part, to increased penetration of the UVB into the epidermis. The recovery of ATPase+ Langerhans cells was significantly slower after high (greater than 165 mJ/cm2) than after more moderate doses (90-145 mJ/cm2) of UVB radiation.

Adenosine Triphosphatases↗
PubMed1982

Effect of glucocorticosteroids on epidermal Langerhans cells.

The effects of topical and systemic administration of various glucocorticoids on the density of epidermal Langerhans cells (LC) were studied in guinea pigs. Glucocorticoids, such as betamethasone dipropionate and valerate, caused a marked decrease in LC demonstrable by staining for cell membrane ATPase activity and Ia antigens. By electronmicroscopy, LC also showed morphologic alterations. The observed decrements in LC density correlated with the concentration and known vasoconstrictive potency of the glucocorticoids administered. The anti-inflammatory action of glucocorticoids in skin disorders may, at least in part, be through their ability to alter epidermal LC, thus interfering with the antigen-presenting functions of these cells.

Adenosine Triphosphatases↗
PubMed1982

The role of tar in Goeckerman therapy.

Seventeen patients with psoriasis were treated with 5% crude coal tar in an absorbent ointment base (Aquaphor) to one half of the body and with the absorbent ointment base alone to the other half. They received twice-daily erythemogenic doses of ultraviolet irradiation (UVR). Both modalities, crude coal tar and absorbent ointment base alone, combined with UVR were equally effective in improving psoriatic plaques. On the basis of this and previous studies, we question the therapeutic role of tar in the Goeckerman regimen.

Adult↗