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Biomedical subjects

V A DeLeo

Publications and source records attributed to V A DeLeo.

At least 19 recordsLinked to original sources
PubMed1992

Photoallergic contact dermatitis. Results of photopatch testing in New York, 1985 to 1990.

BACKGROUND: Over a 6-year period, 187 patients with a history of photosensitivity were photopatch tested using standard techniques. Seventy-six patients were male and 111 were female. Most patients were white (151 patients). Two thirds of the patients were between the ages of 31 and 60 years. OBSERVATION: Testing revealed a total of 63 positive reactions: 14 plain contact, 41 photocontact, and eight combined contact and photocontact in 37 (20%) patients. Careful history taking resulted in a diagnosis of clinically relevant photoallergic contact dermatitis in 54% of these 37 patients or 11% (20) of the total tested. Ten of the relevant responses were due to fragrance ingredients (musk ambrette and 6-methylcoumarin); 18 were due to sunscreen agents (nine to p-aminobenzoic acid and esters, nine to oxybenzone). The fragrance reactions occurred in the early years of the study (1985, 1986, and 1987) while the sunscreen agents accounted for all but two of the 14 positive reactions in the last 3 years of the study (1988, 1989, and 1990). CONCLUSION: These data suggest that the incidence of photoallergy due to fragrances is declining, while reactions to sunscreen agents, in particular oxybenzone, are increasing. This trend may reflect an altered use pattern by the general population for products containing these chemicals.

Adolescent↗
PubMed1992

Present status of eyelid phototherapy. Clinical efficacy and transmittance of ultraviolet and visible radiation through human eyelids.

BACKGROUND: Phototherapy for the eyelid has not previously been recognized as a safe and effective treatment of photoresponsive dermatoses of the eyelid, such as atopic dermatitis, vitiligo, psoriasis, lymphomatoid papulosis, and parapsoriasis. OBJECTIVE: The purpose of this study was to demonstrate the efficacy and safety of this treatment. METHODS: Two cases are presented to demonstrate clinical efficacy. In addition, a retrospective eye evaluation of seven patients receiving a combined total of greater than 1300 eyelid phototherapy treatments was performed. To determine whether potentially harmful UV radiation is significantly transmitted through eyelid skin, an in vitro study was conducted to measure the percentage transmittance of ultraviolet-visible radiation through five excised eyelids. RESULTS: In the two cases presented, remarkable improvement occurred without adverse side effects, suggesting that it is possible to deliver incremental UV dosages to eyelid skin to achieve clearing of skin disease. Retrospective analysis of patients' records revealed no ocular disease from the phototherapy. In vitro eyelid examination produced data that indicated negligible quantities of UV radiation were transmitted through eyelid skin compared with the visible spectrum, in which up to 77% of the radiation was transmitted through the tissue. CONCLUSION: The combined clinical experience and transmittance data suggest that eyelid phototherapy is a safe and effective treatment in selected patients.

Adult↗
PubMed1992

Protein kinase C in normal human epidermal keratinocytes during proliferation and calcium-induced differentiation.

Recent evidence has implicated protein kinase C (PKC) in the etiology of hyperproliferative diseases such as psoriasis and non-melanoma skin cancer. In this study, PKC activity, immunoreactive protein, and phorbol ester-binding kinetics were examined in primary cultures of normal human epidermal keratinocytes (NHEK) in order to elucidate the relationship between PKC and NHEK proliferation and differentiation. NHEK were maintained in a proliferative phase in serum-free low-calcium (0.15 mM) medium, and then were exposed to high calcium (1.6 mM) in order to stimulate growth arrest and differentiation. Staurosporine was inhibitory to Ca(++)-induced differentiation. Scatchard analysis of phorbol binding indicated that exposure to high calcium for 24 h increased the number of binding sites (Bmax) by fivefold. In correlation with the ligand-binding results, PKC activity was extremely low in proliferating (low-calcium) NHEK compared to differentiating cells (high calcium). When assayed after 24, 48, and 72 h, high calcium induced tenfold or greater increases in Ca++/phospholipid-dependent phosphotransferase activity. Immunoblot analysis of NHEK PKC using antibodies directed against the hinge region of PKC alpha/beta also indicated that exposure to high calcium resulted in higher levels of immunoreactive protein. Therefore, PKC in NHEK appears to be upregulated under conditions of Ca(++)-induced growth arrest and differentiation. In addition, NHEK and other human skin cell particulate fractions contain a protein of approximately 116 kDa that is highly immunoreactive to an antibody to PKC alpha/beta, which coelutes from DEAE-sephacel under the same buffer conditions as the 80-kDa PKC.

Adult↗
PubMed1991

Longwave ultraviolet radiation and promotion of skin cancer.

Exposure to solar ultraviolet (UV) radiation is recognized as an important cause of skin cancer. The carcinogenic effects of UV radiation have been attributed almost entirely to wavelengths in the mid-range (UVB, 290-320 nm). However, the development of potent UVB sunscreens has allowed individuals to increase the length of time that they spend sunbathing and, as a consequence, they may be exposed to massive doses of longwave UV radiation (UVA, 320-400 nm). There is now much evidence to suggest that UVA acts to promote tumors that have been initiated by UVB. This review considers possible mechanisms by which UVA promotes tumorigenesis. Evidence is presented which suggests that UVA acts through modulation of protein kinase C.

Animals↗
PubMed1990

Bullous photosensitivity to naproxen: "pseudoporphyria".

Pseudoporphyria is a photo-induced cutaneous bullous disease characterized by distinct clinical, histologic, and most recently, immunofluorescent features. By definition, results of porphyrin studies are normal in this disease. We describe here a woman with naproxen-induced pseudoporphyria, and we review previously reported cases of pseudoporphyria. The increasing frequency of pseudoporphyria is a result of the current popularity of nonsteroidal antiinflammatory drugs. Physicians need to be aware of this reversible skin disorder. Pseudoporphyria must be considered and an appropriate evaluation must be done when an individual who is taking nonsteroidal antiinflammatory drugs develops bullae and increased fragility of exposed skin.

Adult↗
PubMed1990

Induction of protein kinase C activity by ultraviolet radiation.

Exposure to ultraviolet (UV) radiation has been well correlated with skin cancer incidence. Long wave UV radiation (320-400 nm, UVA) is a major component of natural sunlight and cosmetic tanning 'salon' light, and has been shown not only to damage DNA and to act as a complete carcinogen, but also to promote ultraviolet B (280-320 nm, UVB) carcinogenesis. The mechanism by which the latter occurs is unknown, but it is believed to be related to the inflammation and irritation which results from UV exposure. In order to examine the possibility that UVA stimulates the same signalling pathway as do the phorbol esters, a class of much more thoroughly characterized skin tumor promoters, we exposed cells in culture to UVA radiation and measured cellular responses related to protein kinase C (PKC) activation. The data presented here demonstrate that a low, physiologic dose of UVA inhibits epidermal growth factor binding and increases PKC activity in cultured mammalian fibroblasts. The increase in cytosolic activity is not completely translocated to the membrane, and can be partially suppressed by puromycin and cycloheximide but not by actinomycin D. These observations are the first evidence to suggest that a protein which has been strongly linked to chemical tumor promotion may also be a critical mediator for UV-induced promotion. The response of cells to UVA is also unique, in that it does not cause a 12-O-tetradecanoyl phorbol-13-acetate-like rapid redistribution of PKC activity followed by down regulation.

Animals↗
PubMed1990

Reticular erythematous mucinosis syndrome: review of the world literature and report of the syndrome in a prepubertal child.

An 8-year-old boy with reticular erythematous mucinosis syndrome had erythematous plaques on his chest, face, and arms for three years. Sun exposure resulted in pruritus and increased lesions. Histologic examination revealed a perivascular mononuclear cell infiltrate with hematoxylin and eosin staining, positive staining material between the dermal collagen bundles with alcian blue (pH 2.5) staining, and granular basement membrane deposits of IgM with direct immunofluorescence staining. Results of all lupus erythematosus serologies and porphyrin studies were negative. Minimal erythema dose determinations to ultraviolet A and B were normal, and the lesions could not be induced with high doses of irradiation. Topical sunscreens, corticosteroid cream, and systemic beta-carotene produced no therapeutic benefit.

Adolescent↗
PubMed1990

Detection of DNA adducts in skin biopsies of coal tar-treated psoriasis patients: immunofluorescence and 32P postlabeling.

A clinical therapy for psoriasis, a hyperproliferative disease of the skin, utilizes topical application of crude coal tar sometimes followed by UV irradiation (Goeckerman therapy). To investigate the formation of covalent DNA adducts resulting from this therapy, skin biopsies were obtained from treated patients and controls. Indirect immunofluorescence staining with antisera generated against benzo(a)pyrene diol epoxide-modified DNA was used to investigate cell-specific localization of adduct formation. Specific nuclear staining was detected in the epidermal cells of all biopsies from treated patients but not from control biopsies obtained from untreated individuals. 32P postlabeling of DNA isolated from the biopsies was used to determine the spectrum of hydrophobic adducts present. A pattern of multiple adducts was detected in the samples obtained from the treated patients but not from controls.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1990

Allergic contact dermatitis to nickel in children with atopic dermatitis.

We report two atopic boys with allergic contact dermatitis to nickel. Both children had early onset of atopic dermatitis and subsequently presented with infraumbilical dermatitis corresponding to the site of contact with metal snaps. A positive patch test response to 2.5% nickel sulfate in petrolatum was observed in both boys. Allergic contact dermatitis in patients with atopic dermatitis is not uncommon and probably occurs more often than recognized.

Child↗
PubMed1989

Allergic contact dermatitis resulting from sensitivity to citrus peel, geraniol, and citral.

A bartender with hand dermatitis had allergic contact sensitivity to the skin of lemon, lime, and orange but not to their juices. Although most reported cases of citrus peel allergy are due to d-limonene, for our patient, reactions to patch tests for geraniol and citral, two minor components of citrus peel oil, were positive, whereas those for d-limonene were negative. Contact allergy to citrus peel oil should be considered in patients with hand dermatitis who are occupationally exposed to citrus fruits.

Acyclic Monoterpenes↗
PubMed1989

8-Methoxypsoralen-DNA adducts in patients treated with 8-methoxypsoralen and ultraviolet A light.

The combination of 8-methoxypsoralen (8-MOP) plus ultraviolet A light (320-400 nm), termed PUVA, is used in the treatment of psoriasis, a hyperproliferative disease of the skin. This treatment results in the formation of specific 8-MOP adducts with cellular DNA. We have previously developed monoclonal antibodies which recognize these 8-MOP photoadducts. We now report the use of these antibodies in an indirect immunofluorescence technique to study human skin biopsies. Nuclei in 3 of 5 skin biopsies from psoriasis patients undergoing PUVA therapy were positive for adducts. The presence of adducts by immunofluorescence did not correlate with plasma levels of 8-MOP. Enzyme-linked immunosorbent assays, used to determine whether 8-MOP photoadducts could be detected in DNA isolated from the lymphocytes of psoriasis patients after PUVA therapy, were negative.

Antibodies, Monoclonal↗
PubMed1989

Long wave ultraviolet radiation stimulates arachidonic acid release and cyclooxygenase activity in mammalian cells in culture.

Human fibroblasts and mouse C3H 10T1/2 cells in culture were prelabeled with [3H]arachidonic acid and exposed to UVA radiation. Cells released labeled arachidonate metabolites into medium in a dose-dependent fashion (5-20 J cm-2). The time course of release appeared biphasic with peak responses occurring immediately and at 2 h post irradiation. Release of radiolabel was oxygen and calcium ion dependent and was inhibited by the addition of phenylglyoxal, indomethacin, and dibucaine to the medium. High performance liquid chromatographic examination of medium extracts revealed UVA stimulation of cyclooxygenase metabolism of [3H]arachidonic acid and specifically, prostaglandin E2 production by cells in culture. Furthermore, UVA stimulated a dose-dependent release of membrane incorporated [3H]choline from cells in culture. Paper chromatographic analysis of the medium provided evidence that choline release from the membrane was predominantly accompanied by release of phosphorylcholine with some glycerophosphorylcholine suggesting indirectly that the major pathway for UVA-stimulated arachidonic acid release was via phospholipase C and diacylglycerol lipase enzyme systems.

Animals↗
PubMed1988

Detection and quantification of 8-methoxypsoralen-DNA adducts.

8-Methoxypsoralen (8-MOP) is a photoactivated drug used clinically in the treatment of psoriasis and cutaneous T-cell lymphoma (CTCL). We have developed monoclonal antibodies which specifically recognize 8-MOP-modified DNA and do not cross-react with unmodified DNA or free 8-MOP. Highly sensitive, competitive enzyme-linked immunosorbent assays (ELISA) have been developed with both colour and fluorescence endpoint detection for quantification of DNA adducts in biological samples. In addition, immunofluorescence and flow cytometric techniques have been developed to visualize adducts in tissues and cells. These techniques have been validated in keratinocytes treated in culture and in animals treated in vivo with 8-MOP and ultraviolet A (UVA) light. Adduct levels have also been monitored in skin biopsies and lymphocytes of patients with psoriasis and lymphoma.

Animals↗
PubMed1986

The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on phospholipid metabolism of human epidermal keratinocytes in culture.

The tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) stimulated the release of [3H]choline from prelabelled membrane phospholipids of cultured keratinocytes obtained from normal human skin. In contrast, TPA in the concentration range of 10(-12) to 10(-6) g/ml failed to induce deacylation of [3H]arachidonic acid or stimulate [3H]prostaglandin production in prelabelled keratinocytes. In addition, TPA did not induce [3H]choline incorporation into the membrane phospholipids of these cells. The previously reported inability of TPA to stimulate a proliferative response in these cell cultures may be related to the resistance of these cells to TPA-induced alterations of arachidonate metabolism.

Arachidonic Acid↗