Search PubMed⌕ Search

Biomedical subjects

S Jablonska

Publications and source records attributed to S Jablonska.

At least 127 records · Page 7Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Beta-carotene in prevention of cutaneous carcinogenesis.

Beta-carotene, administered orally to mice, caused a decrease in angiogenesis evoked by HPV-transformed tumorigenic cell lines (SKv-t, HeLa). It did not affect angiogenesis induced by the non-tumorigenic SKv (not-t) cell line, and increased lymphocyte-induced immune angiogenesis. We suggest that the anti-cancerogenic effect of beta-carotene may be due, at least in part, to its inhibitory effect on formation of new blood vessels within the tumour mass.

Animals↗

Two new human papillomavirus types (HPV54 and 55) characterized from genital tumours illustrate the plurality of genital HPVs.

The genomes of two new human papillomavirus (HPV) types, named HPV54 and HPV55, were cloned from penile lesions of 2 patients. HPV54 was isolated from a verrucous carcinoma (Buschke-Löwenstein tumour) together with full-length HPV6 genomes and HPV6 DNA molecules with a deletion of about 0.3 kb located in the non-coding region. HPV55 was isolated from a condyloma acuminatum. No cross-hybridization was observed between HPV54 DNA and the DNAs of the known cutaneous and genital HPVs by blot hybridization experiments performed under stringent conditions. In contrast, significant cross-hybridization was detected between HPV55 DNA and the DNA of HPV13, associated with benign oral lesions, and, to a lesser extent, with the DNAs of HPV6, 11, and 44, associated with benign genital proliferative lesions. The DNA sequence homology between HPV55 and HPV6, 11, and 13 was estimated at 12%, 12%, and 20%, respectively, by hybridization in liquid phase at saturation, followed by nuclease S1 analysis. The physical maps of HPV54 and 55 were aligned with the genetic maps of HPV16 and 11, respectively, by heteroduplex mapping and partial DNA sequencing. HPV54 is thus only weakly related to the known HPVs, while HPV55 represents an additional HPV6-related HPV type. HPV54 and HPV55 are uncommon genital HPV types since, in a survey of a large series of specimens of benign, pre-malignant or malignant anogenital and orolaryngeal tumours, HPV54 was not detected, and HPV55 was found in another case of condyloma acuminatum.

Adult↗

Natural cell-mediated cytotoxicity against various target cells in patients with epidermodysplasia verruciformis.

Natural cell-mediated cytotoxicity of peripheral blood mononuclear cells was studied in eight patients with epidermodysplasia verruciformis induced by human papillomaviruses specific for epidermodysplasia verruciformis and in five patients with epidermodysplasia verruciformis-induced exclusively by human papillomavirus type 3. Nine patients with various cutaneous warts and 25 age- and sex-matched healthy persons were control subjects. Natural cell-mediated cytotoxicity against both K-562 erythroleukemic and Sk-v cells was in the normal range in patients with epidermodysplasia verruciformis induced by epidermodysplasia verruciformis-specific human papillomaviruses and in patients with cutaneous warts. The lysis of both targets, however, was significantly decreased in patients with the form of epidermodysplasia verruciformis associated with human papillomavirus type 3. Experiments with normal keratinocytes and with keratinocytes isolated from a malignant lesion bearing human papillomavirus type 5 genomes showed that the latter were susceptible to lysis by the peripheral blood mononuclear cells of healthy persons and of patients with cutaneous warts. Lysis of keratinocytes in epidermodysplasia verruciformis, however, was strongly reduced in patients with epidermodysplasia verruciformis induced by specific human papillomaviruses. This reduction was not associated with a decrease in anti-K-562 natural cell-mediated cytotoxicity. Our results suggest that in patients with epidermodysplasia verruciformis induced by disease-specific human papillomaviruses, there is reduced natural cell-mediated cytotoxicity against epidermodysplasia verruciformis keratinocytes.

Adult↗

Condylomata acuminata in children: frequent association with human papillomaviruses responsible for cutaneous warts.

To identify the papillomavirus types associated with condylomata acuminata in children and to evaluate their mode of transmission, we studied 32 children with anogenital warts. External condylomata were found in 12 of their mothers and in 10 of their fathers. Ten mothers, including two without external lesions, had cervical condylomata. Blot hybridization studies disclosed a genital human papillomavirus (HPV) in 14 of 27 children (HPV-6 in 12 and HPV-11 in two) and in 8 of 14 patients (HPV-6 in all). HPV-6 was found in another child by the polymerase chain reaction technique. Infection occurred most likely at birth or from nonsexual contact, but sexual abuse could not be excluded in one 11-year-old girl. Cutaneous HPV-2 was found in seven children and as yet uncharacterized papillomaviruses were found in two children. Three mothers of HPV-2-infected children had common hand warts, and two children had subungual warts. This study shows the frequent nonsexual transmission of genital papillomaviruses in children and the unexpectedly high association of children's condylomata with papillomaviruses responsible for skin warts, possibly transmitted by heteroinoculation or autoinoculation.

Adult↗

Premalignant lesions and cancers of the skin in the general population: evaluation of the role of human papillomaviruses.

To evaluate the role of human papillomaviruses (HPV) in the development of premalignant lesions and cancers of the skin in the general population, 314 biopsies obtained from 227 patients with benign neoplasms, premalignant lesions, and cancers of the skin and from 25 patients with squamous cell carcinoma of the lip were analyzed by Southern blot hybridization. DNA probes specific for various cutaneous and genital HPV types were used in hybridizations conducted under nonstringent or stringent conditions. HPV DNA sequences were only detected in eight specimens obtained from six patients: HPV 34 in one case of periungual Bowen's disease, HPV 36 and an as yet uncharacterized HPV in two cases of actinic keratosis, HPV 20 in one case of basal cell carcinoma, an as yet unrecognized HPV in one case of squamous cell carcinoma, and HPV 16 in one case of squamous cell carcinoma of the lip. None of the specimens of cutaneous horn and keratoacanthoma contained detectable HPV DNA. In contrast, HPV DNA sequences, mostly HPV 16, were detected in 13 of 23 cases of anogenital Bowen's disease and invasive Bowen's carcinoma. HPV DNA sequences were not detected in 90 cutaneous samples further analyzed by the polymerase chain-reaction technique, using amplification primers that contain conserved sequences among the genomes of HPV. These results strongly suggest that the known HPV types play only a minor role, if any, in skin carcinogenesis in the general population.

Aged↗

[The fibrillarin (Scl-34) autoantibody in systemic scleroderma].

Reexamination of ANA positive sera with nucleolare fluorescence staining on HEp-2 cells and hamster liver imprints revealed 3 sera with an uniform characteristic pattern. It is characterized by: 1. Strong clumpy fluorescence of nucleoli in the interphase. 2. Missing nucleoplasma staining (pure nucleolar). 3. Characteristic granular staining of the cytoplasma from the condensed chromosoma in mitosis. 4. Additive fluorescence of a nucleolus-like body. 5. Extremely high antibody titers. 6. Negative immunodiffusion. This nucleolar staining pattern was described by Bernstein et al. as a clumpy nucleolar pattern. It is produced through an antibody to the dense fibrillar component of the nucleolus (fibrillarin). This antigen is a protein of the U3 RNP with a molecular weight 34 kDa. Clinically is the fibrillarin antibody highly specific for systemic scleroderma especially with diffuse skin involvement. We found it in 1% of scleroderma patients. Its pathogenetic importance is not known.

Antibodies, Antinuclear↗

Abrogated NK-cell lysis of human papillomavirus (HPV)-16-bearing keratinocytes in patients with pre-cancerous and cancerous HPV-induced anogenital lesions.

Natural-cell-mediated cytotoxicity against K-562 erythroleukemic cells and human papillomavirus (HPV)-16 harboring Sk-v keratinocytes was tested in 38 age- and sex-matched healthy volunteers and in patients with HPV-induced benign and malignant anogenital lesions: 9 persons with HPV-16-induced bowenoid papulosis (BP), 8 with anogenital carcinomas (5 with HPV-16- or 33-associated squamous-cell carcinomas of Bowen's type and 3 with HPV-6-associated Buschke-Loewenstein verrucous carcinomas) and 12 with HPV-6-induced condylomata acuminata. Both K-562 and Sk-v cells were killed by a non-adherent CD16+ subset of PBMC as revealed by cell fractionation on the basis of their adherence to plastic and by treatment with Leu-IIb monoclonal antibody (MAb) and complement. "Cold" target competitive assays demonstrated that both cell types inhibited lysis of labelled Sk-v cells. In patients with BP and anogenital carcinomas induced by HPV-16 or 33, there was a significant (at least at p less than 0.01) decrease of Sk-v cell lysis as compared with the healthy control group. Anti-K-562 activity was not affected. In patients with anogenital carcinomas the degree of Sk-v lysis was decreased in proportion to the duration of lesions (correlation coefficient-r = -0.79). Neither anti-K-562 nor anti-Sk-v cytotoxicities were significantly affected in patients with condylomata and with HPV-6 associated verrucous carcinomas. Short-term (3 hr) pre-incubation of normal PBMC with sera from patients with BP and HPV-16-associated anogenital carcinomas resulted in significant inhibition of their ability to lyse Sk-v cells. Lysis of K-562 cells remained unaffected. In patients with carcinomas, the suppressive effect of sera was associated with a lowering of the ability of their PBMC to lyse Sk-v cells (r = -0.79). In patients with longer tumor persistence, the suppressive effect of serum was proportionally higher (r = 0.86).

Adult↗

IgA pemphigus foliaceus. Report of two cases and a review of the literature.

The cases of two patients with vesiculobullous lesions were diagnosed clinically and histopathologically as pemphigus foliaceus; unexpectedly, both revealed intercellular IgA, but not IgG, in the upper epidermis by direct immunofluorescence. Such histologic and immunofluorescence findings have been reported in eight other cases. In our cases no circulating IgA or IgG intercellular antibodies could be detected; in four of eight other reported cases IgA antibodies showed intercellular staining like that of pemphigus antibodies. Subcorneal acantholytic lesions occurred in both our cases; of the other cases reported, five had essentially identical histopathologic findings. The clinical and histopathologic features of pemphigus, as well as the recent findings of circulating IgA intercellular antibodies alone or with IgG antibodies, appear to place this disease into the spectrum of pemphigus. The 10 IgA pemphigus cases reported to date fall into one of two groups, the IgA pemphigus foliaceus (including our two cases) and IgA pemphigus of the intraepidermal neutrophilic type, which seems to be less common.

Adult↗

Congenital fascial dystrophy: stiff skin syndrome--a human counterpart of the tight-skin mouse.

Four patients are described with stony-hard induration of the skin and deeper tissues, most pronounced on the buttocks, thighs, and legs, and with limitation of joint mobility and contractures of the lower limbs. Two patients were siblings and one was the product of a consanguineous marriage. The disorder appears to be genetically determined, but the mode of inheritance has not been established. The disease was noticed in the patients' early infancy and was not progressive. Except for functional impairment of the lungs caused by an underdeveloped thorax that resulted from pressure of the thickened thoracic fascia, there was no involvement of the viscera or muscles and no immunologic abnormalities. The most important finding was markedly thickened fascia. This hereditary connective tissue disorder has all the characteristics of the tight-skin mouse.

Adult↗