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1.
Dermatol Ther (Heidelb) ; 4(1): 115-24, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24865468

ABSTRACT

INTRODUCTION: Psoriasis results in expenses to patients from many cost sources. Psoriasis treatments may result in considerable time and traveling costs, yet many studies fail to account for these costs. The objective of this study was to evaluate the multidimensional economic burden of psoriasis to patients. METHODS: The study was based on 232 Finnish patients with psoriasis or psoriatic arthritis visiting a tertiary level dermatological clinic during a 1-year study period between October 1, 2009 and September 30, 2010. The data were based on a patient questionnaire, clinical data from the medical records and reimbursement data from the Finnish Social Insurance Institution. Item costs were based on true costs charged from the patients and all time cost estimates were based on the Human Capital Approach method. RESULTS: 199 patients with psoriasis and 33 with psoriatic arthritis were included in the study. Total costs were higher for patients receiving traditional systemic medications or phototherapy than those not receiving such treatment. Travel costs and travel time costs accounted for more than 60% of the costs of phototherapy. Skin care at home was time consuming and thus caused significant burden to patients. The majority of the visit costs arose from hospital visits and only a small proportion were attributed to visiting primary health care providers. CONCLUSION: Visit charges and other patient co-payments were estimated to play a minor role in the total cost of psoriasis incurred by patients, while travel costs and lost time comprised the majority of the costs, which should not be omitted in future studies regarding costs of treatments.

2.
Clin Exp Allergy ; 42(10): 1472-8, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22994344

ABSTRACT

BACKGROUND: During infancy, a disturbed cytokine balance leads to an atopic immune response. Many risk factors have been associated with the development of atopy. These include parental smoking, elevated cord blood IgE, early exposure to pets and family history of atopy, but the knowledge of their impact on cytokine balance is limited. OBJECTIVE: To assess the cytokines induced by mitogen in peripheral blood mononuclear cells (PBMC) of infants at 3 months and 12 months of age and their potential association with fatty acid (FA) intervention, parental atopy, atopic dermatitis and parental smoking. METHODS: Infants from an intervention study using black currant seed oil (BCSO, n = 34) or placebo (n = 34) were included. PBMC samples were taken at the age of 3 and 12 months. Signs of atopic dermatitis and parental smoking were registered. PBMC were isolated from heparinized blood samples, stimulated with ConcanavalinA mitogen and the cytokine responses were detected at 72 h of stimulation by Luminex technology. RESULTS: Children of smoking parents had elevated levels of IL-4 (P = 0.0004), IL-5 (P = 0.0002), IFN-γ (P = 0.039) and TNF (P = 0.0003) at 12 months of age. Children who had atopic dermatitis by the age of 3 months showed elevated levels of IL-5 at 3 months (P = 0.0027) and 12 months of age (P = 0.022). The production of TNF at the age of 3 months was higher (P = 0.010) and the production of IL-12 at the age of 12 months was lower (P = 0.025) in infants whose parents were atopic. BCSO intervention did not have any effect on any cytokine production or mRNA expression. CONCLUSION: Children of smoking parents had highly significantly elevated levels of Th2-type cytokines IL-4, IL-5 and pro-inflammatory cytokine TNF. The detrimental effects of parental smoking on the child's immune function should lead us to pay more attention to supporting parents to stop smoking.


Subject(s)
Cytokines/biosynthesis , Parents , Smoking/adverse effects , Th2 Cells/immunology , Adult , Cytokines/immunology , Dermatitis, Atopic/immunology , Female , Humans , Hypersensitivity, Immediate/immunology , Infant , Inflammation/immunology , Leukocytes, Mononuclear , Male
3.
Clin Exp Allergy ; 40(8): 1247-55, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20545710

ABSTRACT

BACKGROUND: The present increased incidence of atopic diseases has been associated with an altered intake of essential fatty acids (EFAs). The composition of blackcurrant seed oil (BCSO) corresponds to the recommended dietary intake of EFAs, and as a dietary supplement could, in small doses, modify the imbalance of EFAs in an efficient way. OBJECTIVE: To assess the effect of dietary supplementation with BCSO on the prevalence of atopy at 12 months of age. METHODS: Three hundred and thirteen pregnant mothers were randomly assigned to receive BCSO (151) or olive oil as placebo (162). The first doses were administered at 8th-16th weeks of pregnancy and were continued until the cessation of breastfeeding, followed by supplementation to the infants until the age of 2 years. Atopic dermatitis and its severity (SCORAD index) were evaluated, serum total IgE was measured and skin tests were performed at the age of 3, 12 and 24 months. RESULTS: Parental atopy was common (81.7%) among study subjects, making them infants with increased atopy risk. There was a significantly lower prevalence of atopic dermatitis in the BCSO group than in the olive oil group at the age of 12 months (33.0% vs. 47.3%, P=0.035). SCORAD was also lower in the BCSO group than in the olive oil group at 12 months of age (P=0.035). No significant differences in the prevalence of atopic dermatitis were observed between the groups at the age of 24 months (P=0.18). CONCLUSION: Dietary supplementation with BCSO was well tolerated and it transiently reduced the prevalence of atopic dermatitis. It could therefore be one potential tool in the prevention of atopic symptoms when used at an early stage of life. (Registration number SRCTN14869647, http://www.controlled-trials.com)


Subject(s)
Dermatitis, Atopic/prevention & control , Linolenic Acids/therapeutic use , Plant Oils/therapeutic use , Prenatal Exposure Delayed Effects/immunology , Dietary Supplements , Double-Blind Method , Female , Humans , Immunoglobulin E/blood , Immunoglobulin E/immunology , Infant , Infant, Newborn , Male , Pregnancy , Skin Tests
4.
Int Immunopharmacol ; 2(2-3): 263-75, 2002 Feb.
Article in English | MEDLINE | ID: mdl-11811930

ABSTRACT

Recent studies on the immunosuppressive effects of ultraviolet radiation (UVR) and the related resistance to infections in rodents and humans are presented. The waveband dependency of trans-to-cis isomerisation of urocanic acid in the stratum corneum and the role of DNA damage in UVR-induced erythema and immunosuppression were investigated to further elucidate the underlying mechanisms. Furthermore, human experimental studies on UVR-induced immunomodulation were performed. It appeared that the doses needed to suppress various immune parameters in humans (e.g. NK activity, contact hypersensitivity) were higher than those needed in experiments in rodents. Still, extrapolation of experimental animal data to the human situation showed that UVR may impair the resistance to different systemic infections at relevant outdoor doses. In observational human studies we aimed to substantiate the relevance of UVR for infections in humans. It was shown that sunny season was associated with a slightly retarded but clinically non-relevant antibody response to hepatitis B vaccination. Furthermore, sunny season appeared to be associated with a small decline in the number of CD4+ T-helper cells in a cohort of HIV-infected persons and a higher recurrence of herpes simplex and herpes zoster in a cohort of renal transplant recipients. However, in a study among young children a higher exposure to solar UVR was associated with a lower occurrence of upper respiratory tract symptoms. As disentangling the effects of UVR from other relevant factors is often impossible in observational studies, concise quantitative risk estimations for the human situation cannot be given at present.


Subject(s)
Bacterial Infections/immunology , Immunity, Innate/immunology , Immunity, Innate/radiation effects , Ultraviolet Rays/adverse effects , Virus Diseases/immunology , Animals , Bacterial Infections/epidemiology , Bacterial Infections/microbiology , Disease Models, Animal , Humans , Immunosuppression Therapy , Risk Assessment , Virus Diseases/epidemiology , Virus Diseases/virology
6.
J Invest Dermatol ; 115(4): 687-93, 2000 Oct.
Article in English | MEDLINE | ID: mdl-10998144

ABSTRACT

We have assessed the ability of xeroderma pigmentosum and normal keratinocytes grown out from skin biopsies to undergo apoptosis after irradiation with ultraviolet B. Keratinocytes have been studied from xeroderma pigmentosum complementation groups A (three biopsies), C (three biopsies), D (one biopsy), xeroderma pigmentosum variant (two biopsies), and Cockayne syndrome (one biopsy). The three xeroderma pigmentosum group A and the xeroderma pigmentosum group D samples were at least six times more sensitive than normal cells to ultraviolet B-induced apoptosis. The xeroderma pigmentosum variant samples showed intermediate susceptibility. Xeroderma pigmentosum group C samples proved heterogeneous: one showed high sensitivity to apoptosis, whereas two showed near normal susceptibility. The Cockayne syndrome sample showed the high susceptibility of xeroderma pigmentosum groups A and D only at a higher fluence. These results suggest that the relationships between repair deficiency, apoptosis, and susceptibility to skin cancer are not straightforward. Ultraviolet B-induced skin cancer is also thought to be due in part to ultraviolet B-induced impairment of immune responses. The release of the inflammatory cytokines interleukin-6 and tumor necrosis factor-alpha from cultured xeroderma pigmentosum keratinocytes tended to occur at lower fluences than in normals, but was less extensive, and was more readily inhibited at higher fluences of ultraviolet B.


Subject(s)
Keratinocytes/cytology , Ultraviolet Rays , Xeroderma Pigmentosum/pathology , Apoptosis/radiation effects , Cells, Cultured , Cytokines/metabolism , Enzyme-Linked Immunosorbent Assay , Fibroblasts/radiation effects , Humans , In Situ Nick-End Labeling , Infant, Newborn , Interleukin-6/metabolism , Keratinocytes/radiation effects , Male , Tumor Necrosis Factor-alpha/metabolism
7.
J Leukoc Biol ; 65(5): 573-82, 1999 May.
Article in English | MEDLINE | ID: mdl-10331484

ABSTRACT

We examined systemic effects of whole-body UVB irradiation on human peripheral blood phagocytes. We found that 24 h after a single erythemal dose of UVB radiation two phagocyte functions, adhesion and phagocytosis, were reduced by 50%. This functional suppression was accompanied by a significant decrease in the expression of complement receptors (CR1 and CR3) and IgG Fc receptors (FcRII and FcRIII). The greatest reduction (47%) was observed in CR3, which is important for both adhesion and phagocytosis. A kinetic analysis showed that both CR1 and CR3 levels started to decrease 15 min after the UVB exposure, reaching the lowest levels at 4.5- and 24-h time points, respectively. The down-modulation of CRs after whole-body UVB exposure was not due to a defective receptor synthesis or translocation from internal stores to plasma membrane because the maximal CR levels in stimulated cells were not affected by UVB. No change in the serum soluble ICAM-1 was detected after UVB, which rules out CD1 1b epitope masking by sICAM-1. UVB did not release low-receptor-density myeloid progenitor cells from storage pools into circulation. Interleukin 10, a mediator of UVB-induced immunosuppression, was unable to modulate CR expression in vitro. When seven suberythemal whole-body UVB exposures were given repeatedly within 2 weeks, a significant decrease in CR expression was seen, which was greatest after three irradiations. Our data suggest that an exposure to UVB has systemic effects in humans which, possibly due to the down-modulation of preexisting cell-surface receptors, suppress some important functions of circulating phagocytic cells.


Subject(s)
Immunosuppression Therapy/adverse effects , Neutrophils/radiation effects , Ultraviolet Rays/adverse effects , Whole-Body Irradiation/adverse effects , Adult , Cell Adhesion/immunology , Cell Adhesion/radiation effects , Female , Hematopoietic Stem Cells/radiation effects , Humans , Interleukin-10/pharmacology , Macrophage-1 Antigen/biosynthesis , Male , Neutrophils/immunology , Phagocytosis/immunology , Phagocytosis/radiation effects , Receptors, Complement 3b/biosynthesis , Receptors, IgG/biosynthesis , Recombinant Proteins/pharmacology
8.
J Am Acad Dermatol ; 40(5 Pt 1): 694-6, 1999 May.
Article in English | MEDLINE | ID: mdl-10321595

ABSTRACT

BACKGROUND: Long-term oral 8-methoxypsoralen (8-MOP) and UVA (PUVA) therapy increases the risk of nonmelanoma skin cancer and possibly also of cutaneous malignant melanoma. Topical application of 8-MOP PUVA induces malignant tumors in rodent skin, but little is known about its carcinogenicity in human skin. OBJECTIVE: Our purpose was to investigate the carcinogenicity of 8-MOP bath PUVA in humans. METHODS: This was a cohort study of 158 patients with psoriasis, for whom 8-MOP bath PUVA had been initiated during 1979 to 1992. The average number of 8-MOP bath PUVA treatments was 36 (range, 6 to 204) and the mean cumulative UVA dose was 92 J/cm2 (range, 3 to 884 J/cm2) by the end of 1995. The patients were not treated with any other forms of PUVA. Cancer incidence subsequent to 8-MOP bath PUVA up to the end of 1995 was determined by linking the cohort with the records of the Finnish Cancer Registry. The standardized incidence ratios (SIR) were calculated for skin cancer and some common internal cancers, using the expected numbers of cases based on the regional cancer incidence rates. RESULTS: There was one case of basal cell carcinoma, but no cases of other types of skin cancer. A total of 6 noncutaneous cancers were observed (SIR, 1.3; 95% confidence interval, 0.5 to 2.8). CONCLUSION: No association between cutaneous cancer and 8-MOP bath PUVA was found, but the statistical power of this study alone is not adequate to warrant definite conclusions. The results can be used in a meta-analysis as soon as other studies on the carcinogenicity of 8-MOP bath PUVA are published.


Subject(s)
Baths , Methoxsalen/therapeutic use , PUVA Therapy , Photosensitizing Agents/therapeutic use , Psoriasis/drug therapy , Skin Neoplasms/etiology , Administration, Cutaneous , Adolescent , Adult , Aged , Aged, 80 and over , Carcinoma, Basal Cell/etiology , Child , Cohort Studies , Confidence Intervals , Female , Finland , Follow-Up Studies , Humans , Incidence , Male , Medical Record Linkage , Melanoma/etiology , Methoxsalen/administration & dosage , Methoxsalen/adverse effects , Middle Aged , Photosensitizing Agents/administration & dosage , Photosensitizing Agents/adverse effects , Radiation Dosage , Registries , Risk Factors
9.
Cancer Res ; 57(11): 2281-9, 1997 Jun 01.
Article in English | MEDLINE | ID: mdl-9187133

ABSTRACT

CD44 is a family of molecules involved in cell-cell and cell-matrix interactions. Various isoforms of CD44 arise by insertion of one or more of the variant exons into the common backbone shared by all forms of CD44. In this work, we studied the expression of CD44 and exon v6-containing CD44 isoforms (CD44v6) in several nonmalignant and malignant conditions and the possibilities for regulating the expression of CD44v6. In primary squamocellular carcinomas of the head and neck, CD44 and CD44v6 were down-regulated in poorly differentiated tumors, whereas these molecules were uniformly expressed in the normal squamocellular epithelium, in proliferating skin diseases, and in nonmalignant tumors. When CD44v6 expression of original tumors and that of squamocellular carcinoma cell lines derived from them were compared, no CD44v6 up-regulation could be observed on in vitro growing cells. Moreover, several regulators were unable to up-regulate CD44v6 expression on cultured cell lines in vitro. When the same cell lines formed tumors after s.c. injection into severe combined immunodeficient mice, some of them up-regulated their CD44v6 expression. These data suggest that cell lines at certain differentiation stages can be induced to express CD44v6. Our results further indicate that CD44v6 positivity cannot be used as a universal indicator of tumor metastasis. Instead, the down-regulation of CD44v6 in squamocellular tumors is a sign of malignant transformation of the epithelium.


Subject(s)
Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/metabolism , Hyaluronan Receptors/genetics , Hyaluronan Receptors/metabolism , Isomerism , Adult , Aged , Animals , Down-Regulation , Epithelium/metabolism , Exons , Female , Fluorescent Antibody Technique, Indirect , Gene Expression Regulation, Neoplastic/radiation effects , Humans , Hyaluronan Receptors/immunology , Immunohistochemistry , Male , Mice , Mice, SCID , Middle Aged , Skin Diseases/genetics , Skin Diseases/metabolism , Tumor Cells, Cultured , Ultraviolet Rays , Up-Regulation
10.
Photochem Photobiol ; 65(5): 862-5, 1997 May.
Article in English | MEDLINE | ID: mdl-9155258

ABSTRACT

To investigate the relationship between erythemal sensitivity of the skin to UV radiation and epidermal urocanic acid (UCA) concentration, 45 healthy volunteers of anamnestic skin phototypes (ASP) 1-IV were studied. In 16 of the subjects, we analyzed UCA photoisomerization after graded UVB exposures. The median and mean total UCA concentration in unirradiated skin was 22.4 and 35.3 nmol/cm2, and no statistically significant difference in total UCA concentrations was detectable either between ASP I through II and III through IV or between the phototested skin type (PSP) groups 1 through 2 and 3 through 4. The relative amount of the cis-isomer varied between 3 and 35%, with median and mean values of 7 and 12%, respectively. No statistically significant difference in absolute or relative cis-UCA concentrations was detectable between ASP I through II and III through IV, but a significantly lower absolute (P < 0.009) and relative (P < 0.002) cis-UCA concentration in unirradiated skin was recorded in PSP groups 1 through 2, compared to types 3 through 4. In all tested subjects, an erythemally weighted dose of 1 mJ/cm2 sufficed to cause trans- to cis-UCA isomerization. When comparing photosensitive (skin phototype I) and phototolerant (phototypes III and IV) individuals, who were irradiated with a reference 5 mJ/cm2 UV dose or with fractions of 0.1-1.0 of their individual minimal erythema dose values, no skin phototype-dependent difference in ability to photoisomerize was discernible.


Subject(s)
Skin/metabolism , Urocanic Acid/metabolism , White People , Adult , Aged , Female , Humans , Isomerism , Male , Middle Aged , Photochemistry , Radiation Tolerance , Ultraviolet Rays , Urocanic Acid/analysis
11.
Acta Derm Venereol ; 72(3): 231-3, 1992.
Article in English | MEDLINE | ID: mdl-1357870

ABSTRACT

A noninvasive Finn Chamber sampling method and HPLC analysis were used to determine epidermal urocanic acid (UCA) concentrations of psoriasis patients during 4 weeks of heliotherapy on the Spanish Canary Islands and a follow-up period of 8 weeks. During heliotherapy the epidermal cis-UCA concentration increased from a mean initial value of 0.2 nmol/cm2 to a mean final value of 2.9 nmol/cm2. The total UCA concentration decreased during the first week of heliotherapy from an initial value of 5.5 nmol/cm2 to a nadir of 2.0 nmol/cm2. Thereafter, a steady increase was recorded in the total UCA level, with a maximum of 10.2 nmol/cm2 in week 2 of the post-treatment follow-up period. Suberythemal sun exposures caused near-maximal UCA isomerization, and during heliotherapy the cis isomer constituted 63.7-74.3% of the total UCA concentration. Clinical response of psoriasis to heliotherapy, however, seemed to be independent of UCA isomer levels.


Subject(s)
Heliotherapy , Psoriasis/therapy , Skin/radiation effects , Urocanic Acid/radiation effects , Adult , Follow-Up Studies , Humans , Middle Aged , Psoriasis/metabolism , Skin/metabolism , Urocanic Acid/metabolism
14.
J Am Acad Dermatol ; 18(5 Pt 1): 1053-9, 1988 May.
Article in English | MEDLINE | ID: mdl-2968374

ABSTRACT

Successful results have been reported for bath-psoralens plus ultraviolet A (PUVA) treatment of psoriasis with the use of either a low-sensitizing psoralen (methoxsalen) or a high-sensitizing psoralen (trioxsalen), but no evidence has been presented that phototoxicity would be a prerequisite for antipsoriatic activity of these treatments. To study therapeutic-to-phototoxic ratios, bath-PUVA was applied to psoriasis patients with the use of either a 0.2 mg/L solution of trioxsalen or a 0.4 mg/L solution of methoxsalen. The average minimal phototoxic ultraviolet A (UVA) dose (MPD) obtained after 15 minutes' bathing was 0.86 joule/cm2 for trioxsalen and 9.76 joules/cm2 for methoxsalen. In the first part of the study phototoxically equipotent treatment schedules were used, compensating the much lower phototoxic potential of methoxsalen by using about 10 times larger UVA doses compared to the doses used with trioxsalen. A healing rate of 71% +/- 25% was recorded for trioxsalen and 63% +/- 34% for methoxsalen treatment (mean +/- SD). Both PUVA treatments decreased epidermal Langerhans cell counts to 10% to 20% of the control value. In the second part of the study, the much lower phototoxic potential of methoxsalen was not compensated for. Instead, methoxsalen bath-PUVA was carried out with the use of UVA doses physically similar to those used in the trioxsalen therapy series. Surprisingly enough, even this very suberythemal methoxsalen therapy caused a significant healing effect (51% +/- 10%). Langerhans cell depletion in methoxsalen-bathed areas (reduction to 53% of the control value) was much less than that caused in trioxsalen-bathed areas (reduction to 11% of the control value).(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Erythema/pathology , Langerhans Cells/enzymology , PUVA Therapy/methods , Psoriasis/drug therapy , Adenosine Triphosphatases/metabolism , Adolescent , Adult , Dose-Response Relationship, Drug , Erythema/chemically induced , Female , HLA-DR Antigens/analysis , Humans , Langerhans Cells/immunology , Male , Methoxsalen/therapeutic use , Middle Aged , Psoriasis/pathology , Trioxsalen/therapeutic use
16.
Acta Physiol Scand ; 131(4): 583-7, 1987 Dec.
Article in English | MEDLINE | ID: mdl-2831696

ABSTRACT

Murine fibroblasts in culture were labelled with either [14C]arachidonic acid, [14C]dihomo-gamma-linolenic acid or [14C]eicosapentaenoic acid. All these [14C]fatty acids were effectively incorporated into the fibroblasts and the bulk of the radioactivity was recovered in various phospholipids. The major radiolabelled phospholipids were phosphatidylethanolamine, phosphatidylcholine and the phosphatidylinositol + phosphatidylserine fraction. Significant amounts of radiolabel were found also in the triacylglycerols: even as much as 30% of the total of the incorporated dihomo-gamma-linolenic acid was recovered in the triacylglycerols. The present study suggests that arachidonic acid, dihomo-gamma-linolenic acid and eicosapentaenoic acid are effectively taken up and esterified into different lipid fractions of murine fibroblasts and that also the triacylglycerols are significantly involved in the incorporation, storage, and release of the eicosanoid precursor fatty acids.


Subject(s)
Arachidonic Acids/metabolism , Eicosapentaenoic Acid/metabolism , Fibroblasts/metabolism , Linolenic Acids/metabolism , Animals , Cells, Cultured , Mice
17.
Photodermatol ; 4(4): 176-81, 1987 Aug.
Article in English | MEDLINE | ID: mdl-2448759

ABSTRACT

HLA-DR expression on human keratinocytes (KC) was induced in vivo by intradermal injection of purified protein derivative of tuberculin (PPD). Neither preceding nor subsequent exposure of the PPD injection site to a dose of approximately 2 MED of UVB radiation abolished KC HLA-DR, though subsequent irradiation caused a slight diminution in the intensity of the antigen expression. By contrast, epidermal Langerhans cell (LC) HLA-DR and T6 expressions in normal epidermis were greatly reduced by an identical dose of UVB. Pemphigus antigen on the surface of KC was not affected by irradiation or PPD injection.


Subject(s)
Epidermis/radiation effects , HLA-D Antigens/radiation effects , HLA-DR Antigens/radiation effects , Keratins/radiation effects , Langerhans Cells/radiation effects , Ultraviolet Rays , Adult , Epidermal Cells , Epidermis/immunology , Female , Fluorescent Antibody Technique , Humans , Langerhans Cells/immunology , Male , Pemphigus/immunology
18.
J Immunol ; 136(4): 1227-30, 1986 Feb 15.
Article in English | MEDLINE | ID: mdl-3511144

ABSTRACT

Recent studies have demonstrated that antibodies from about half of patients with pemphigus foliaceus (PF) bind to a 160 kd polypeptide ("PF antigen") in sodium dodecyl sulfate (SDS) extracts of normal human epidermis. Desmoglein (DG) I, a glycoprotein enriched in desmosomal cores, is approximately the same m.w. as PF antigen. To demonstrate that PF autoantibodies bind to DG I, we used a monoclonal IgG antibody (MmDGI-1) that was raised against bovine muzzle desmosomal cores, and that specifically binds DG I. Double immunofluorescence labeling was performed on the same section of normal human skin with PF antibodies, detected by fluorescein-conjugated goat anti-human IgG, and MmDGI-1, detected by rhodamine-conjugated goat anti-mouse IgG. The pattern of reactivity with both antibodies was identical. Immunoblotting studies on proteins extracted from normal human epidermis and separated by SDS-polyacrylamide gel electrophoresis demonstrated that PF antibodies and MmDGI-1 bound co-migrating polypeptide bands of approximate m.w. 160,000. To confirm that these were identical polypeptides, we performed immunoblots of these epidermal extracts that were separated by two-dimensional gel electrophoreses (isoelectric focusing followed by SDS-PAGE). PF antibodies and MmDGI-1 bound identical spots with pI approximately 5.4 to 5.7 and m.w. approximately 160,000. These studies demonstrate that autoantibodies from certain patients with PF, a disorder of cell adhesion, bind to DG I, a desmosomal core glycoprotein.


Subject(s)
Antibodies, Monoclonal/physiology , Autoantibodies/physiology , Binding Sites, Antibody , Cytoskeletal Proteins , Glycoproteins/metabolism , Pemphigus/immunology , Proteins/metabolism , Antibodies, Monoclonal/analysis , Antibody Specificity , Autoantibodies/analysis , Collodion , Desmoglein 1 , Desmogleins , Desmoplakins , Desmosomes/immunology , Desmosomes/metabolism , Electrophoresis, Polyacrylamide Gel , Epidermis/analysis , Epidermis/immunology , Fluorescent Antibody Technique , Glycoproteins/immunology , Humans , Paper , Proteins/immunology
19.
Photodermatol ; 2(6): 339-46, 1985 Dec.
Article in English | MEDLINE | ID: mdl-2937025

ABSTRACT

Healthy human volunteers were irradiated with graded doses of UVA and UVB radiation on the volar aspect of their forearms. The UVA doses ranged from 8 to 100 J/cm2, and the UVB doses from 37 to 416 mJ/cm2, corresponding to 5 to 52 mJ/cm2 of erythemally effective (300 nm) radiation (1/4-3 X MED). 7 days after irradiation, punch biopsy specimens were obtained from UVA and UVB irradiated spots. Epidermal sheets were stained for Langerhans cells (LC) using 3 different histochemical methods, viz: ATPase activity and immunoperoxidase staining with monoclonal antibodies against T6 and Ia antigens. A slightly higher control LC count was obtained with anti-T6 staining (848 cells/mm2) than with anti-Ia or ATPase staining (728 and 721 cells/mm2 respectively). No significant change in LC count was detected with any of the staining methods after UVA doses of up to 100 J/cm2. In contrast, UVB irradiation caused a dose-dependent decrease in the LC counts. The decrease was quite similar whether measured by anti-T6 or anti-Ia staining. With ATPase staining, the decrease in LC numbers was somewhat more pronounced at low to medium UVB doses, but at the dose of 416 mJ/cm2 (52 mJ of erythemally effective UVB, corresponding to approx. 3 X MED), the residual LC count as determined with any of the 3 histochemical methods was within the range of 23-30% of the control LC count. We conclude that the activity of the membrane-bound enzyme, ATPase, is more sensitive to abrogation by moderate UVB doses than the immunological reactivity of the 2 surface antigens, T6 and Ia.


Subject(s)
Adenosine Triphosphatases/analysis , Antibodies, Monoclonal/immunology , Histocompatibility Antigens Class II/analysis , Langerhans Cells/radiation effects , Ultraviolet Rays/adverse effects , Adult , Cell Count , Erythema/etiology , Female , Humans , Langerhans Cells/enzymology , Langerhans Cells/immunology , Male
20.
Dermatologica ; 171(4): 220-5, 1985.
Article in English | MEDLINE | ID: mdl-3865844

ABSTRACT

Peripheral blood natural killer (NK) cell activity was screened in patients with non-malignant disorders of the skin who took oral etretinate or 13-cis-retinoic acid for up to 11 months. Compared to pretreatment values, the basic NK activity rose during the first 2 months of treatment, but thereafter returned to starting values. Interferon reactivity (IFN-alpha, IFN-gamma) was essentially unaltered by the treatment. It is concluded that moderate oral retinoid doses cause a mild, transient stimulation of this natural immune surveillance system in man.


Subject(s)
Etretinate/therapeutic use , Killer Cells, Natural/drug effects , Skin Diseases/drug therapy , Tretinoin/therapeutic use , Administration, Oral , Adult , Aged , Etretinate/administration & dosage , Female , Humans , Isotretinoin , Male , Middle Aged , Skin Diseases/immunology , Stimulation, Chemical , Tretinoin/administration & dosage
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