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Biomedical subjects

S Jablonska

Publications and source records attributed to S Jablonska.

At least 19 recordsLinked to original sources
PubMed1992

Autocrine growth limitation of human papillomavirus type 16-harboring keratinocytes by constitutively released tumor necrosis factor-alpha.

TNF-alpha is known to exert antitumor and antiviral effects and to participate in the regulation of the immune response. In our study we demonstrate that human rTNF-alpha specifically blocks growth of SK-v keratinocyte cell line harboring and expressing human papillomavirus type 16 (HPV16) sequences. This inhibitory effect was shown by [3H]TdR incorporation and cell counting. Binding experiments with 125I-TNF-alpha showed that SK-v cells express about 10,000 single class TNF-alpha R per cell with affinity constant of about 0.7 nM. Binding of 125I-TNF-alpha could be inhibited by htr-9 mAb recognizing a 55/60-kDa type I TNF-alpha R but not by utr-1 mAb recognizing 75/80-kDa type II TNF-alpha R or irrelevant mAb specific for HPV16E7 protein. Addition of anti-TNF-alpha antibodies to SK-v cell culture resulted in significant (p < 0.05), dose-dependent stimulation of their proliferation. SK-v cells constitutively expressed TNF-alpha mRNA, and SK-v CM contained TNF-alpha, as demonstrated by Northern blot analysis, a specific ELISA, Western blot analysis, and a bioassay with TNF-alpha-sensitive L-M cells. HPLC gel filtration of SK-v cell CM showed that the factor cytotoxic for L-M cells coeluted with immunoreactive TNF-alpha. These results demonstrate that HPV16-harboring SK-v cells constitutively express and release immunoreactive and biologically active TNF-alpha that in turn may exert an autocrine growth inhibitory effect. This phenomenon could represent one of the self-limiting mechanisms controling growth of HPV-induced neoplasia.

Cell Division↗
PubMed1992

Adhesion of peripheral blood mononuclear cells to vascular endothelium in patients with systemic sclerosis (scleroderma).

OBJECTIVE: Perivascular infiltrates in skin, subcutaneous tissue, and internal organs are a characteristic feature of early systemic sclerosis (SSc). We studied the first step of migration of peripheral blood mononuclear cells (PBMC) through the vessel wall to the extravascular space, i.e., adhesion of PBMC to endothelial cells (EC), in patients with various forms of SSc (limited scleroderma, diffuse scleroderma, and the transitional form). METHODS: Radioisotope-labeled patient PBMC were coincubated with umbilical cord EC in vitro, and the percentage adhesion was measured. RESULTS: Adhesion of PBMC to EC was markedly decreased, while adhesion of isolated active rosette-forming cells (ARFC) was significantly increased, in SSc patients compared with healthy controls. Decreased adhesion of PBMC to EC was found to correlate with a diminished percentage of ARFC in the peripheral blood. Preincubation of PBMC from healthy donors with interleukin-2 (IL-2) enhanced their adhesion to EC, while preincubation of PBMC from SSc patients with this cytokine resulted in a decrease in adhesion in 10 of 14 individuals. IL-1, interferon-gamma, and transforming growth factor beta had no significant effect on adhesion of SSc patient PBMC to EC. Differences in adhesion of PBMC to EC among the SSc subgroups were not significant. CONCLUSION: Our findings suggest that in SSc, activation of subpopulations of PBMC leads to their enhanced adhesion to vascular endothelium in vivo and to migration of these cells to the extravascular space, resulting in the elimination from the peripheral blood of those PBMC with high ability to adhere to EC.

Adult↗
PubMed1992

Epidermodysplasia verruciformis as a model of human papillomavirus-induced genetic cancers: the role of local immunosurveillance.

Epidermodysplasia verruciformis (EV) presents a genetically determined, unusual susceptibility to infection with EV-specific human papillomaviruses (HPVs) related to abrogation of immunosurveillance exclusively against these viruses. The cutaneous viral carcinogenesis depends upon potentially oncogenic HPVs, the cocarcinogenic effect of ultraviolet irradiation, and genetic host factors, presumably a defect of anti-oncogenes or alleles of major histocompatibility complex and tumor necrosis factor locus involved in antigen presentation.

Epidermodysplasia Verruciformis↗
PubMed1992

Human papillomavirus (HPV) types specific of epidermodysplasia verruciformis detected in warts induced by HPV3 or HPV3-related types in immunosuppressed patients.

Epidermodysplasia verruciformis (EV) is characterized by an abnormal genetic predisposition to infection with specific types of human papillomavirus (HPV). Specific defects of the cell-mediated immunity and/or of the control of HPV infection in keratinocytes are assumed to be involved in the development of the disease. As a model to test this hypothesis, we have studied the prevalence of EV-specific HPV in skin warts of 56 immunosuppressed patients. All main types of cutaneous HPV (HPV1, 2, 3, 4, 10, and 28) responsible for skin warts in the general population were detected by blot hybridization. EV-specific HPV (HPV5, 20, and 23) were detected in three patients. Four additional patients were found infected with HPV49, first characterized in the course of this study, and found to be related to EV HPV. A most important finding was that HPV5, 20, 23, and 49 were always codetected with HPV3 or the related types HPV10 and 28. None of the specimens showed the typical clinical morphology of EV lesions. In none of these specimens was the specific cytopathic effect of EV recognized; instead that of HPV3 and related types was seen. No evidence for productive EV HPV DNA replication was obtained for the three specimens that could be further analyzed by in situ hybridization. Our data suggest that HPV3 infection favors infection with EV HPV in immunosuppressed patients but that the full expression of EV HPV is usually restricted as in the general population.

Adult↗
PubMed1992

Morphea with high titer of fibronectin antibodies.

A 20-year-old man with a 9-year history of unusual subcutaneous morphea with nodular lesions in a circular arrangement and wooden-hard symmetrical induration of the arms, had high titers of fibronectin antibodies. A possible role of fibronectin and antifibronectin antibodies in the pathogenesis of scleroderma is discussed.

Adult↗
PubMed1992

A distinct stratum corneum antigen in psoriasis and its reactions with stratum corneum autoantibodies.

Stratum corneum antibodies are ubiquitous and can be detected by various immunological methods. Of these, the ones detected by hemagglutination undergo changes in antibody titers and have been implicated in psoriasis. The purpose of our study was to examine if differences exist in the activities of the antigens isolated from psoriatic scales in comparison to normal callus. Stratum corneum antigens were prepared by trypsin-phenol-water extraction. The water phase, which contains the stratum corneum antigen, was used to sensitize the red blood cells in the hemagglutination assay. The antibody activity in human sera was determined before and after absorption with antigens isolated from callus, psoriatic scales, and cell envelopes. We found notable differences in the antigens obtained from callus and psoriatic scales. These include higher antibody titers to the antigens of the scales, the presence of unique antigenic determinants on psoriatic scales and the localization of the antigen on cell envelopes. These immunological differences were corroborated by the marked biochemical differences of certain amino acids, most notably glycine and proline, and these differences were unique to psoriatic scales as they were not shared with other hyperproliferative disorders.

Amino Acids↗
PubMed1992

Antitumor action of retinoids: inhibition of tumor cell line-induced angiogenesis and prevention of tumors in mice.

Acitretin was shown to inhibit angiogenic response to the tumorigenic SKV cell line bearing HPV16 genome and to sarcoma L-1 cell line, both in vitro and in vivo systems. The lowered angiogenic response to tumor cells was independent of duration and timing of the application of acitretin to animals. Acitretin, but not etretinate, was also found to be effective in the prevention of sarcoma tumors in mice.

Acitretin↗
PubMed1991

Constitutive release of IL6 by human papillomavirus type 16 (HPV16)-harboring keratinocytes: a mechanism augmenting the NK-cell-mediated lysis of HPV-bearing neoplastic cells.

In the present study we demonstrate that the cultured human keratinocyte cell line (SK-v cells) harboring and expressing integrated human papillomavirus type 16 (HPV16) DNA sequences constitutively releases IL6, which is known as a pleiotropic immunoregulatory cytokine of potential antitumor properties. The presence of IL6 activity in SK-v cell-conditioned media (SK-v CM) was demonstrated by tritiated thymidine incorporation into IL6-dependent B9 murine plasmacytoma cells. The effect on B9 cells was specific since it could be inhibited by anti-IL6 neutralizing antibodies but not by a normal control serum. IL6 did not affect SK-v cell growth; however, it significantly augmented NK cell activity of human peripheral blood lymphocytes against both K562 erytholeukemic and SK-v cells as assessed by 51Cr release assay. SK-v CM displayed NK cell-augmenting activity that copurified with IL6 activity in both size exclusion and anion-exchange HPLC. Furthermore, SK-v cell-derived NK cell stimulatory activity could be neutralized with anti-IL6 antibodies. These results suggest that HPV-harboring neoplastic cells can release IL6 which may indirectly mediate tumor death by augmentation of NK cell activity.

Cytotoxicity, Immunologic↗
PubMed1991

Topical treatment of multiple actinic keratoses of the face with arotinoid methyl sulfone (Ro 14-9706) cream versus tretinoin cream: a double-blind, comparative study.

In a double-blind, randomized, within-patient comparative study, the efficacy and tolerability of Ro 14-9706 (an arotinoid methyl sulfone) in the treatment of actinic keratoses was compared with that of tretinoin (all-trans-retinoic acid). A total of 25 patients with more than three lesions on each side of the face completed the study. All patients applied each agent twice daily for 16 weeks as a 0.05% cream to opposite sides of the face. The number of actinic keratoses in each treatment area was counted before treatment and at weekly intervals. The mean percent decrease in the number of actinic keratoses was 37.8% for areas treated with Ro 14-9706 and 30.3% for areas treated with tretinoin. Each of these decreases was significantly different from baseline (p less than 0.01), but not from each other. Ro 14-9706 was better tolerated; local inflammation was slight or absent in most patients, whereas tretinoin caused severe erythema in 50% and severe scaling in 23% of patients.

Administration, Cutaneous↗
PubMed1991

IgA pemphigus foliaceus with a clinical presentation of pemphigus herpetiformis.

A patient with clinical features of herpetiform pemphigus of the foliaceus type had histologic findings consistent with pemphigus. Intercellular IgA deposits in a pattern like that of IgG in pemphigus were present. Circulating pemphigus-type IgA-class antibodies reacted first only with guinea pig and later in the disease also with monkey esophagus sections. IgG-class pemphigus antibodies were blocked by the IgA-class antibodies of this patient. In addition, the IgA-class pemphigus antibodies in this patient were blocked by the IgG-class pemphigus antibodies in tests on guinea pig and monkey esophagus. This indicates that the IgA-class antibodies in this patient were directed either to the same antigen as the IgG-class pemphigus foliaceus antibodies or to one that is close enough to it to give steric hindrance. The skin lesions responded poorly to systemic corticosteroid therapy. Dapsone therapy initially produced dramatic improvement, but the condition flared to the point that plasmapheresis, in addition to high doses of corticosteroids and cyclophosphamide, had to be used to control it.

Acantholysis↗
PubMed1991

TGF beta-1 and TNF alpha expression in the epidermis of patients with epidermodysplasia verruciformis.

In epidermodysplasia verruciformis (EV), the infection with specific human papillomaviruses (HPV) might be under control of the local immunosurveillance mechanisms related to cytokines produced by epidermal cells. We have investigated by in situ hybridization the expression of mRNA coding for TGF beta-1 and TNF alpha in the skin of patients with EV (n = 4) as compared to the skin lesions of patients with other premalignant (actinic keratosis; n = 5) or malignant (squamous cell carcinoma; n = 4) skin lesions, and to the skin of healthy individuals (n = 5). The expression of TGF beta-1 and TNF alpha mRNA was higher in the epidermis of EV patients as compared to the control skin from healthy individuals. The increased expression of mRNA for both cytokines was confirmed by northern blot analysis of RNA isolated from the skin lesions of the patient with EV. No specific signals for TGF beta-1 and TNF alpha were detected in actinic keratosis, and in cases of squamous cell carcinomas only single neoplastic cells were positive for TGF beta-1. It is conceivable that in EV TGF beta-1 and TNF alpha can be involved in the regulation of the growth and differentiation of HPV-infected keratinocytes and in the persistence of HPV-induced skin lesions.

Adult↗
PubMed1991

Efficacy and safety of CD 271 alcoholic gels in the topical treatment of acne vulgaris.

CD 271, a naphthoic acid, is a powerful modulator of epidermal differentiation. This double-blind, randomized study compared the efficacy and safety of two concentrations (0.03% w/w and 0.1% w/w) of CD 271 alcoholic gel, with 0.025% w/w tretinoin gel in 72 male patients with acne vulgaris over a period of 12 weeks. Efficacy was measured by counting facial inflammatory and non-inflammatory lesions and by grading the severity of the acne at each visit. Skin tolerance was assessed with subjective symptoms, such as burning and pruritus, as well as clinical assessment of erythema, dryness and scaling on the treated areas. The alcoholic 0.1% CD 271 gel was as effective as 0.025% tretinoin gel in reducing total comedone counts (83% reduction for both products after 12 weeks' treatment). The reduction in the number of inflammatory lesions and the total number of acne lesions were significantly greater with 0.1% CD 271 gel than with tretinoin gel (69% and 79% for 0.1% CD 271, 50% and 73% for tretinoin gel, respectively, P less than 0.05). All three treatments were well tolerated and there were no changes in any major blood parameters. No CD 271 could be detected in blood plasma at the end of the study (detection limit = 1 ng/ml).

Acne Vulgaris↗
PubMed1991

Studies on criteria of the European Academy of Dermatology and Venerology for the classification of cutaneous lupus erythematosus. I. Selection of clinical groups and study factors.

A group of 140 cases of various forms of lupus erythematosus (LE) were examined for 24 variables, including the 11 criteria of the American Rheumatism Association (ARA) for the classification of systemic lupus erythematosus (SLE), and 13 additional criteria suggested by the European Academy of Dermatology and Venerology (EADV) for studies of cutaneous LE with or without systemic involvement. The EADV study factors included skin histopathology and immunopathology, complement and IgG levels, and other laboratory tests, as well as selected clinical findings, most notably the papulosquamous and/or annular lesions that characterize subacute cutaneous LE (SCLE). The patients examined included 50 SLE, 35 SCLE, 30 discoid LE (DLE), 25 disseminated DLE (DDLE), and 17 polymorphous light eruption (PMLE) cases. Preliminary analyses of the data reveal the following: (1) The SCLE cases differed significantly from SLE, DLE, and DDLE in 10 of 11 ARA criteria (all but photosensitivity). (2) The frequencies of positive findings in SCLE also differed significantly for 11 of 13 EADV study factors. (3) While no significant differences appeared in the frequency of photosensitivity between the five study groups, photo-testing revealed significant increases in the frequency of persistence of the photo reactions for 10 days and their Koebnerization in the SCLE cases. (4) The presence of SS-A (Ro)/SS-B (La) antibodies had some predictive value for the appearance of systemic involvement in SCLE, as seen by the increased frequencies of five or more ARA criteria, although highly significant differences from SLE occurred in the absence of renal involvement and lower frequency of ANA and LE band test.(ABSTRACT TRUNCATED AT 250 WORDS)

Dermatology↗
PubMed1991

Prognosis and treatment of advanced squamous cell carcinoma secondary to epidermodysplasia verruciformis: a worldwide analysis of 11 patients.

Data were collected from three medical centers in the USA, Poland, and Japan regarding 11 patients with advanced squamous cell carcinoma (SCC) secondary to epidermodysplasia verruciformis (EV). Analysis was conducted regarding primary tumor location, age at onset of EV, age at diagnosis of SCC, treatment of SCC, history of local tumor recurrence, presence of metastases, and age at death. Three of 11 patients developed both lymph node and visceral metastases and the mean patient age at death was 44 years (N = 6) with no patient to date living past 54 years. Mean patient survival time following metastases was 1.7 years (N = 2). Human papilloma virus typing of nine patients was performed. Current controversies regarding the treatment of patients with advanced SCC in the setting of EV are reviewed.

Adolescent↗
PubMed1991

Ultrastructural changes of the skin induced by human leukocyte elastase and cathepsin G.

Human neutrophil elastase and cathepsin G at a concentration of 10(-6) M were found to attack various substrates when normal skin biopsy specimens were incubated at 37 degrees C for 1 h with either of these enzymes. Elastase damaged primarily hemidesmosomes, leading to the epidermal cleavage from the dermis, whereas cathepsin G damaged the membrane structures. Both these neutral proteinases were highly specific to basal lamina of blood vessels. This indicates that neutrophil elastase and neutrophil cathepsin G may play different roles in various skin diseases related to enhanced activity and infiltration of neutrophils.

Cathepsin G↗