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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

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

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↗
PubMed1979

Immunopathology of psoriasis.

Immunofluorescence (IF) studies by the direct and indirect methods demonstrate immunoglobulins and complement bound in vivo in psoriatic scales. The IF pattern is comparable to that of stratum corneum antibodies (SCAb) bound in vitro on specific substrate, as visualized by the indirect IF method. Formation of immune complexes can be responsible for the "squirting papilla" phenomenon, and conversion of the stratum corneum - which is normally an inaccessible antigen - into its reactive form seems to be brought about by proteases of polymorphonuclear leukocytes. Stimulation of protease production by polymorphonuclears appears to be an important factor in the pathogenesis of psoriasis. The stratum corneum of the epidermis is probably the target, and becomes an antigen for SCAb present in the circulation.

Antibodies↗
PubMed1979

Epidermodysplasia verruciformis versus disseminated verrucae planae: is epidermodysplasia verruciformis a generalized infection with wart virus?

Recently it has been shown that epidermodysplasia verruciformis is induced by human papilloma/virus different from the papilloma/virus of warts, and that 2 distinct viruses-designated HPV-3 and HP-4--are responsible for it. Ten cases of epidermodysplasia verruciformis were found to have been caused by HPV-3. Clinically and histologically, as well as in the often depressed cell-mediated immunity they closely resembled long-standing verrucae planae, also caused by HPV-3. Contrariwise, in epidermodysplasia verruciformis caused by HPV-4 there are characteristic red, red-brown, and depigmented, pityriasis versicolor-like plaques, and malignant transformation seems almost inevitable. Cases due to HPV-3 may be abortive or even regressive, or stationary, and hard to distinguish from flat warts. No malignant conversion was seen in patients infected only with HPV-3, whereas it occurred in 2 patients infected with both viruses: HPV-3 and HPV-4. Pigmented plaques are the most important adverse prognostic sign in EV induced by HPV-3.

Animals↗
PubMed1979

Comparative evaluation of skin atrophy in man induced by topical corticoids.

In this in-patient study, mild skin atrophy was observed clinically in 6 out of a total of 22 patients after fluocinolone acetonide and in one patient after flumethasone pivalate ointment applications (P less than 0,05). Investigations were discontinued prematurely on days 14 and 17 in 2 patients because they developed early atrophy due to fluocinolone acetonide applications. Histological findings indicating either moderate or marked skin atrophy were evident in 15 patients after flucinolone acetonide as against one patient after flumethasone pivalate ointment applications (P less than 0.001). In comparison with the controls the mean decrease in epidermal thickness was more marked after fluocinolone acetonide applications, namely 30.5% vs 21.3% after flumethasone pivalate applications. The ultrastructural tissue changes were less marked at the sites to which flumethasone pivalate was applied. In comparison with controls, the percentages of mean decrease in diameters of collagen fibrils measured in six volunteer patients ranged from 5.1% to 27.6% after fluocinolone acetonide and from 0% to 12.3% following flumethasone pivalate ointment applications, This difference was statistically significant (range P less than 0,01 to less than 0.001). This experimental study has demonstrated that flumethasone pivalate displays only a mild atrophogenic effect and it is clinically and histologically significantly less atrophogenic than fluocinolone acetonide. Flumethasone pivalate can therefore be reckoned as a suitable topical corticosteroid especially for the long-term treatment of corticoid-responsive dermatoses.

Administration, Topical↗
PubMed1979

IgA linear dermatosis of childhood (chronic bullous disease of childhood).

Of twenty-seven cases of subepidermal blistering disease of children twelve corresponded clinically, histologically and immunologically to dermatitis herpetiforms of adults, six to bullous pemphigoid, and eight to chronic bullous disease of childhood (CBDC), i.e. IgA linear dermatosis. This latter disease seems to be a distinct entity, different from both dermatitis herpetiformis and bullous pemphigoid, and is characterized immunopathologically by linear IgA deposits at the basement membrane zone. These cases usually do not show intestinal involvement and respond well to combined treatment with sulphones and corticosteroids, whereas sulphones or sulphapyridine alone are, even in very high doses, not sufficient for full control of the disease. CBDC or IgA linear dermatosis of childhood may be regarded as a counterpart of IgA linear dermatosis of adults.

Child↗
PubMed1979

[New developments relating to papillomaviruses].

Molecular hybridization technique and immunofluorescence studies with use of specific immune sera against the purified virions isolated from various types of warts and wart-like lesions of epidermodysplasia verruciformis (EV) made it possible to detect four different types of human papilloma viruses (HPV). The recognition of the viruses is important because of the different morphology of the lesions induced and their various oncogenic potentials. HPV1 is mainly responsible for plantar warts, HPV2 for common (hand) warts, HPV3 has been found both in flat warts and in the variety of EV in which skin lesions are of flat wart type, the course is relatively more benign, and usually malignant transformation is not to be expected. HPV4 was up to now found exclusively in the cases of EV with prevalent red and red-brownish plaques and hyper- and depigmentations similar to those of pityriasis versicolor. In all cases of this variety of EV malignancies occured invariably. In patients with EV, as also in--to a lesser extent--longstanding flat and/or common warts cell mediated immunity was in general lowered, but humoral specific anti-HPV antibodies were usually present. HPV type seems to be of a decisive significance for potential oncogenesis, because in a vast majority of cases EV due to HPV3 no malignancies occured in spite of anergy, whereas malignant transformation has been found in all cases due to HPV4, even in a patient with still preserved, although lowered, CMI.

Adult↗
PubMed1979

Pre-pin-point papules. Changes preceding pin-point lesions of psoriasis.

Skin areas of 10X10 cm were marked out and closely observed during 14 days in 22 patients with active and 18 cases with less active psoriasis. The first changes - minute papules, slightly erythematous, almost flush with the skin (pre-pin-point papules) appeared within this period and transformed after several days into pin-point lesions. Histological examinations performed in 25 pre-pin-point and 10 pin-point papules, as well as cytochemical studies have shown significant differences. In the pre-pin-point papules inflammatory infiltrates were in a great part polymorphonuclear, and the epidermis had no features characteristic of psoriasis. The performed studies have shown that the earliest changes preceding the appearance of spontaneous psoriatic papules are very much like those of provoked Koebner phenomenon.

Female↗
PubMed1979

[IgA linear dermatosis (author's transl)].

Besides the typical forms of dermatitis herpetiformis (DH) and bullous pemphigoid (BP) of adults and children, there are cases combining clinical, histological and electronmicroscopic features of both. Linear continuous IgA deposits along basement membrane zone (BMZ) are a most characteristic finding. They differ from the granular IgA deposits in DH, even if these are also distributed along the BMZ (however, preserving as a rule their granular pattern). IgG circulating anti-BMZ antibodies are absent, whereas in some cases IgA anti-BMZ antibodies may be found. In contrast to DH, there is no gluten-sensitive enteropathy, and the gluten-free diet is ineffective. The recognition of this bullous disease as a distinct entity is of practical significance because these cases respond well to combined treatment with sulfones and corticosteroids, all in small doses. Because of diagnostic importance of linear IgA deposits at BMZ we have proposed the name IgA linear dermatosis. In children a counterpart of IgA linear dermatosis of adults is chronic bullous disease of childhood (CBDC), which we propose to call IgA linear dermatosis of childhood.

Humans↗
PubMed1978

Autoimmunity in psoriasis. A complement immunofluorescence study.

The stratum corneum (SC) antibodies are present in all human sera as seen by indirect immunofluorescent (IF) staining. They appear to bind in vivo to the stratum corneum of psoriatic lesions. They fix complement in vitro in a two step complement IF test system using either anti C4 or anti C3 conjugates as indicators. IF tests with proper controls showed that the SC antigen in psoriatic scales is coated not only with IgG but in a majority of the lesions also with complement. In the present studies in fully developed lesions complement was detectable in 88% of the specimens studies and in about 50% of very fresh linear lesions of unintentional Köbner type. These as well as some previously published observations afford indirect evidence for the participation of SC antibodies and the ensuing fixation of complement in the development of psoriatic lesions.

Antibody Formation↗
PubMed1978

Autoimmunity in psoriasis. Relation of disease activity and forms of psoriasis to immunofluorescence findings.

Immunofluorescence (IF) studies using the test providing information on the reactivity of stratum corneum (SC) antibodies and their in vivo binding have been performed in 193 cases of psoriasis and 89 cases with other dermatoses. It has been shown that: 1. Essentially all fully developed, active psoriatic lesions had IgG deposits in the stratum corneum at the sites of the SC antigen, presumably due to in vivo binding of SC antibodies. 2. In various forms of psoriasis SC antigen sites appeared to be completely or almost completely satured with in vivo deposits of IgG as seen in tests with SC antibodies. 3. In most but not all lesions complement components C3 and/or C4 was found in a comparable pattern in the SC, especially when multiple specimens of single cases were studied. Partial or complete saturation of the SC antigen could be observed by the performance of complement indirect IF tests for SC antibodies in such specimens. 4. In lesions with typical histology of psoriasis the above-mentioned immunologic characteristics appeared to be a constant finding. However, in specimens of recent lesions which had not yet developed typical histology a proportion (2 of 17) were negative both for IgG and complement deposits. In receding lesions weak deposits of IgG were present only in a few specimens and complement deposits were as a rule negative. 5. In a group of 89 control specimens of other dermatoses only occasional cases gave the psoriasiform IF pattern, but about 30% of the specimens gave positive reactions in the SC though these were usually of a different pattern.

Antibody Formation↗
PubMed1978

Characterization of two types of human papillomaviruses in lesions of epidermodysplasia verruciformis.

Human papillomaviruses (HPVs) found in lesions of 11 patients suffering from epidermodysplasia verruciformis were compared to HPV type 1 (HPV-1) and HPV type 2 (HPV-2) previously characterized in plantar and common warts, respectively. Complementary RNAs (cRNAs) to HPV-1, HPV-2, and viruses obtained from two patients with epidermodysplasia verruciformis (J.D. HPV and J.K. HPV) were used in cRNA.DNA filter hybridization experiments. No sequence homology was detected between HPV-1 or HPV-2 DNAs and DNAs obtained from the 11 epidermodysplasia verruciformis HPV isolates. Furthermore, with J.D. and J.K. HPV cRNAs, epidermodysplasia verruciformis HPV DNAs fell into two groups showing little, if any, sequence homology. A lower extent of annealing was observed for the DNAs of some isolates showing a genetic heterogeneity within each of the two groups. Almost no antigenic crossreaction was detected by immunodiffusion and indirect immunofluorescence tests, either between epidermodysplasia verruciformis HPVs and HPV-1 or HPV-2 or between J.D. and J.K. HPVs. Viruses belonging to the same group have common antigenic properties, but antigenic differences were observed when two of the viruses sharing only partial DNA sequence homology were compared. Viruses related to J.D. HPV were preferentially associated with flat wart-like lesions of epidermodysplasia verruciformis and were further found in the lesions of five patients bearing multiple flat warts. Viruses related to J.K. HPV were found in morphologically distinct lesions (red spots) present in some patients with epidermodysplasia verruciformis. Thus, we propose to distinguish two other types of HPVs designated provisionally as HPV type 3 (HPV-3) and HPV type 4 (HPV-4), with J.D. and J.K. HPVs as prototypes, respectively. Malignant conversion of some epidermodysplasia verruciformis lesions is more frequently associated with HPV-4 than with HPV-3 infection.

Adult↗