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Biomedical subjects

S Jablonska

Publications and source records attributed to S Jablonska.

At least 109 records · Page 6Linked to original sources
PubMed1994

Cancer combination chemotherapy with retinoids: experimental rationale.

Retinoids, cytokines as well as 1,25-dihydroxyvitamin D3 and its analogs are all classes of compounds with pleiotropic actions. They inhibit proliferation in human transformed epithelial cell lines and induce differentiation in human transformed hemopoietic cell lines. In a murine model of tumor cell-induced angiogenesis all three classes of compounds inhibit the formation of new blood vessels, necessary for supplying the growing tumor with oxygen and nutrients. Combinations of compounds from the three different classes lead to higher efficacy than the compounds administered as single agents. The effects of combinations vary depending on the individual representatives of the three classes and on the particular test models used. Additive, synergistic and potentiating effects have been observed. The results obtained in experimental systems raise hope that combination therapy might be useful in the treatment of certain human neoplastic diseases.

Animals↗
PubMed1993

Inhibition of tumor cell-induced angiogenesis by retinoids, 1,25-dihydroxyvitamin D3 and their combination.

Tumor-induced angiogenesis (TIA), i.e., the ability of transformed cells to stimulate new blood vessel formation is an important factor contributing to tumor growth and invasiveness. The antiangiogenic effect of the retinoids, all-trans retinoic acid, 13-cis retinoic and 9-cis retinoic acid, of 1,25-dihydroxyvitamin D3, and of their combinations were studied using an experimental system in vivo. TIA was induced in immunosuppressed mice by intradermal injection of the two human transformed keratinocyte lines, Skv-e2, harboring DNA of human papillomavirus (HPV) type 16, and HeLa, harboring HPV18 DNA. The three retinoids and 1,25-dihydroxyvitamin D3, when administered systemically to mice, before the angiogenesis assay significantly decreased TIA. Their combination led to a synergistic inhibition of TIA. These results provide the basis for the use of combination of retinoids and 1,25-dihydroxyvitamin D3 in treatment of neoplastic diseases.

Animals↗
PubMed1993

NK-cell activity in patients with HPV16-associated anogenital tumors: defective recognition of HPV16-harboring keratinocytes and restricted unresponsiveness to immunostimulatory cytokines.

Peripheral blood mononuclear cells (PBMC) from patients with active HPV16-associated pre-malignant and malignant anogenital lesions display a significantly decreased NK-cell activity against HPV16-harboring SKv keratinocytes (NK/SKv) while their cytotoxicity against erythroleukemic K562 cells (NK/K562) remains unaffected. A similar defect can also be seen in some healthy individuals displaying no symptoms of HPV infection (low responders). Analysis with specific Leu IIa monoclonal antibodies (MAbs) has revealed that all patients as well as weakly responding control subjects had normal numbers of circulating CD16+ NK cells. However, PBMC from patients with active disease and weakly responding controls displayed a significantly decreased ability to bind SKv cells. Binding of K562 was in the normal range. In patients in whom the lesions were successfully removed or regressed spontaneously (patients with no lesions), NK/SKv activity did not differ from that of normally responding healthy subjects and the ability of their PBMC to bind SKv cells was unaffected. To determine whether an abrogated NK/SKv cytotoxicity may be corrected by NK-cell stimulatory cytokines. PBMC were pre-incubated overnight with IL-2 and interferon-alpha. Both cytokines stimulated NK/K562 activity in all tested groups. Significant stimulation of NK/SKv activity was observed in PBMC from normal and weakly responding controls as well as patients with no lesions. No increase could be seen in patients with active disease. Evaluations of NK-cell activity before and after surgical removal or spontaneous regression of the lesions showed normalization of primarily depressed NK/SKv activity. Malignant progression was associated with a significant drop in SKv cell killing. Our results suggest that abrogation of NK-cell activity against HPV16-harboring targets in patients with HPV16-associated anogenital neoplasia is associated with restricted inability to recognize the disease-specific target cells, and may depend on persistence of the lesions.

Anus Neoplasms↗
PubMed1993

Erythema annulare-like acantholytic dermatosis (EAAD): nonbullous pemphigus or a new entity?

This article describes a case of unusual annular erythema-like dermatosis, with histological features of pemphigus foliaceus (subcorneal acantholysis) and IgG antibodies in circulation and bound in vivo to the keratinocyte surface. The reactivity of the antibodies, restricted to human squamous epithelium, was unique, differing from that of all known forms of pemphigus. This also was confirmed by immunoprecipitation. The problem is that these circulating antibodies could be missed if not determined on human substrate. It is to be established whether such cases present a new type of pemphigus or a unknown dermatosis with an autoimmune response of a pemphigus type.

Acantholysis↗
PubMed1993

Preliminary, dermatologic first step criteria for lupus erythematosus and second step criteria for systemic lupus erythematosus.

BACKGROUND: Comparisons of cases of systemic lupus erythematosus (SLE) with cases of rheumatoid arthritis and other rheumatologic disorders affords the basis of the 1982 revised criteria of the American Rheumatism Association (ARA) for classifying SLE cases. We address three questions: Do comparisons of LE cases with non-LE cases that have suggestive skin lesions yield criteria for use in dermatology clinics for primary classification of cases with photo distributions of skin lesions? Do comparisons of SLE with cutaneous LE cases yield the same or similar criteria to the revised ARA criteria for SLE? How should subacute cutaneous LE cases be evaluated for signs of significant systemic involvement? METHODS: Discriminant analyses on 168 cases with skin lesions suggestive of LE were performed using data based on the ARA criteria for SLE and study factors for cutaneous LE suggested by the European Academy of Dermatology and Venereology. RESULTS: These yielded two sets of criteria: (1) The 11 preliminary, dermatologic first step criteria (10 plus 1 for discoid lesions and histology) serve to classify cases as LE or non-LE. (2) The 11 preliminary, dermatologic second step criteria classify LE cases as cutaneous LE or systemic LE. Interestingly, 5 of 11 of these second step criteria differ from the 11 ARA criteria for systemic LE. These second step criteria afford a useful means of distinguishing between subacute cutaneous LE cases with or without significant systemic involvement. CONCLUSIONS: The study factors included in both the first and the second step criteria fall into three groups, notably clinical criteria, laboratory criteria, and "added study factors." The latter factors distinguish between the groups compared (LE vs. non-LE and cutaneous vs. systemic LE) but not as well as the study factors included as "criteria."

Humans↗
PubMed1993

Childhood condyloma acuminatum: association with genital and cutaneous human papillomaviruses.

We studied 25 children, age 7 months to 12 years 6 months, with anogenital warts, and their parents. In most children the warts were localized in the anal area, in 3 of 18 girls perianally and on the vulva, and in 4 girls exclusively on the vulva. Southern blot hybridization studies disclosed an association of condylomata with human papillomaviruses (HPV) 6 and 11 in 74% and HPV 2 in 17.4% of patients. The clinical features were similar in warts induced by genital and cutaneous HPVs. Even the HPV 2-associated warts in the vulva of two girls were typical of condyloma acuminatum. In all children with HPV 2-induced condylomata, cutaneous common warts coexisted, also induced by HPV 2. However, three mothers had cutaneous warts, and the children's condylomata were associated with HPV 6. Thus, the mere presence of skin warts in family members does not rule out other sources of infection. Sexual abuse was suspected in four girls and two boys, but was not confirmed in any. Nonsexual transmission could occur by persons with the lesions taking care of children. Perinatal transmission also appears to be an important route of infection in small babies. Infection in utero was probable in one girl in whom anal warts appeared in the first week of life and whose mother had cervical condylomata during pregnancy. This study provides further confirmation of possible nonsexual transmission of genital HPVs and the not infrequent association of childhood condylomata with HPV 2.

Anus Neoplasms↗
PubMed1993

Sporadic cases of Heck disease in two Polish girls: association with human papillomavirus type 13.

Two sporadic cases of Heck disease in Polish girls were associated with human papillomavirus 13. No other children and nobody from their surroundings had similar lesions. The course of the disease was chronic in both patients. The lesions regressed spontaneously in one girl within several years after some of the papules were excised. The second girl's warts persist after eight years.

Child↗
PubMed1993

Genetic heterogeneity of oncogenic human papillomavirus type 5 (HPV5) and phylogeny of HPV5 variants associated with epidermodysplasia verruciformis.

Variants of oncogenic human papillomavirus type 5 (HPV5), specifically associated with epidermodysplasia verruciformis, were recognized on the basis of the genetic heterogeneity of the E6 open reading frame (ORF). To further evaluate the genetic heterogeneity of HPV5, we sequenced the long control region (LCR), the E7 ORF, and the terminal parts of the E2 ORF of five previously characterized HPV5 variants and compared the data with the published HPV5a1 and HPV5b sequences. Alignment of the variants showed 140 (7.6%) variable nucleotides of 1,854 sequenced. Nucleotide substitution rates varied from 3.6% in the E7 ORF to 11% in the E6 ORF. By sequencing the variable region encompassing the LCR 3' part and the E6 ORF of isolates from six additional epidermodysplasia verruciformis patients, we identified three new variants and three already known variants, indicating the stability of HPV5 variants. This stability was further demonstrated by the identity of isolates obtained years later from benign and malignant lesions of three patients. Phylogenetic analysis of the 10 HPV5 variants distributed them into three groups, tentatively defining subtypes a, b, and c. The phylogenetic grouping shows no geographical dependence, a fact that may be related to the host restriction that characterizes HPV5 infections. No differences in the enhancer potential of the LCR or in the transactivating properties of the E2 protein assayed in vitro were observed among HPV5 variants. Whether HPV5 variants possess distinct biological properties in vivo remains to be determined.

Base Sequence↗
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↗