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Biomedical subjects

S Majewski

Publications and source records attributed to S Majewski.

At least 37 records · Page 2Linked to original sources
PubMed1999

Serum levels of soluble TNF alpha receptor type I and the severity of systemic sclerosis.

Several abnormalities of cytokines have been shown to occur in systemic scleroderma; however their correlation with clinical parameters is controversial. Since serum concentrations of cytokine receptors have been shown to correlate with inflammatory processes, including systemic sclerosis, the aim of our study was to compare serum concentrations of TNF alpha receptor type 1 with the concentrations of soluble intercellular adhesion molecule-1 (sICAM-1), soluble interleukin-2 receptor (sIL-2R) and aminoterminal propeptide of procollagen type III (PIII NP). The findings were correlated with the clinical parameters and antibody patterns, and with the disease severity. Serum samples were studied with the use of enzyme-linked immunosorbent assay (ELISA) or radioimmunoassay (RIA) for sTNF alpha R1, sICAM-1, sIL-2R and PIII NP. The series comprised 36 patients with systemic scleroderma: 13 with diffuse variety and 23 with limited variety, and 7 with Raynaud's disease. Healthy volunteers (n = 25) were chosen from doctors and/or other laboratory staff. Increased levels of sTNF alpha-receptor type 1 were found in 77% of patients with diffuse variety and in only 30% of patients with limited form. Increased serum concentrations in patients with diffuse scleroderma and limited variety were found for sICAM-1 54% and 65%, for sIL-2R 46% and 15%, and for PIIINP 77% and 50%, respectively. There were significant correlations between serum levels of sTNF alpha-receptor type 1 and PIIINP (r = 0.653, p < 0.0001), and sTNF alpha-receptor type 1 and sIL-2R (r = 0.625, p < 0.0001), but not between sTNF alpha-receptor type 1 and sICAM-1 (r = 0.127, p < 0.526). Clinical analysis revealed that serum concentrations of sTNF alpha-RI seem to correlate best with the severity of the disease and, as the only parameter, correlated with lung involvement. The study showed that, in addition to recognized parameters of scleroderma severity (IL-2R, PIIINP), a new important marker appears to be sTNF alpha-receptor type 1.

Adult↗
PubMed1998

Expression of vascular endothelial growth factor (VEGF) in various compartments of the human hair follicle.

Hair follicle vascularization appears to be closely related to the processes involved in hair cycle regulation, in which growth factors, cytokines and other bioactive molecules are involved. In particular, vascular endothelial growth factor (VEGF), essential for angiogenesis and vascular permeability, may be responsible for maintaining proper vasculature around the hair follicle during the anagen growth phase. The aim of our study was to compare the in vitro angiogenic capacity, i.e. the steady-state expression of the VEGF gene, of different cultured cell types derived from normal human hair follicles, corresponding to different follicular compartments. Human dermal papilla cells (DPC), fibrous sheath fibroblasts, dermal fibroblasts, and follicular and interfollicular keratinocytes were cultured and studied in vitro for VEGF expression at the mRNA level using RT-PCR, and for VEGF protein synthesis by radioimmunoprecipitation and immunocytochemistry. In vivo examination for VEGF expression in human terminal hair follicles was performed using immunohistochemical methods. In the present report the expression of four different VEGF molecular isoforms, differing in their angiogenic capacity, are described in different cultured follicular cell types for the first time. Cultured follicular cells strongly expressed mRNA of four VEGF molecular species identified as the 121-, 145-, 165- and 189-amino acid splice variants, the most prominent being the 121-amino acid molecule. DPC, and also other mesenchymal cells such as fibrous sheath fibroblasts and dermal fibroblasts, in vivo and in vitro strongly expressed VEGF mRNA and synthesized a 46-kDa VEGF protein, whereas follicular and interfollicular keratinocytes in vitro expressed lower levels of VEGF mRNA and proteins than mesenchymal cells. As the highest expression of VEGF was found in DPC, we suggest that DPC are mainly responsible for angiogenic processes possibly related to the human hair cycle.

Cells, Cultured↗
PubMed1998

Psoriasis: A possible reservoir for human papillomavirus type 5, the virus associated with skin carcinomas of epidermodysplasia verruciformis.

Recent polymerase chain reaction data have shown that most human papillomavirus (HPV) genotypes associated with epidermodysplasia verruciformis (EV) are widespread; however, HPV5 associated with EV skin carcinomas has only rarely been detected in non-EV patients. To identify the reservoir of this virus, we examined 335 sera from different groups of patients for the presence of HPV5 antibodies by an enzyme-linked immunosorbent assay test based on HPV5 virus-like particles. The prevalence of antibodies reacting with HPV5 virus-like particles was found to be significantly higher in psoriatic patients (24.5%) than in other groups (2-5%), including patients with atopic dermatitis and renal transplant recipients. Analysis of scrapings of lesional and uninvolved skin by a nested polymerase chain reaction method, using degenerate EV HPV primers, disclosed HPV DNA in 91.7% of 48 psoriatic skin samples and 35.5% of 31 atopic dermatitis specimens. Eleven EV HPV genotypes, most frequently HPV5 and HPV36, and a putative novel genotype (PsoX1) were identified in psoriasis. Five EV HPV genotypes and two putative novel genotypes (ADX1 and ADX2) were detected in atopic dermatitis patients. HPV5 was not found in atopic dermatitis patients. Using type specific primers, HPV5, HPV36, and HPV1 were found in 89.4%, 84.2%, and 42.1% of specimens from psoriatic patients, whereas HPV36 was detected in 22.5% of specimens from atopic dermatitis patients. HPV16 was never detected. On the whole, 27 HPV5 and 13 HPV36 DNA variants were disclosed after sequencing amplification products. Our data confirm that EV HPV are widespread and point to psoriasis as a reservoir for HPV5. Whether HPV5 is involved in the pathogenesis of psoriasis remains to be determined.

Adult↗
PubMed1998

A possible vertical transmission of human papillomavirus genotypes associated with epidermodysplasia verruciformis.

Epidermodysplasia verruciformis (EV) is characterized by an abnormal genetic susceptibility to a group of related human papillomavirus (HPV) genotypes, including the oncogenic HPV5 and HPV8. The mode of transmission of these viruses remains unknown. In view of the rare incidence of EV, we had a unique opportunity to perform a virologic study of the amniotic fluid and placenta from an EV patient infected with HPV5, HPV8, several other EV HPV, and HPV3. The child was born by cesarean section and the amniotic fluid specimen was taken prior to rupture of membranes. Analysis of the amniotic fluid and placenta specimens by a nested polymerase chain reaction method, using degenerate EV HPV primers or type-specific HPV primers, disclosed the presence of the variants of EV HPV5, HPV8, HPV24, and HPV36, and of HPV3 detected in the skin lesions of the patient. HPV5, HPV8, HPV24, and HPV3 were also detected in the placenta. No viral sequences were detected in peripheral blood mononuclear cells collected 2 y and 6 mo before cesarean section, rendering an hematogenous transmission unlikely. The same HPV variants were also detected in cervical scrapes taken from the patient, which may suggest an ascending infection of the placenta. This first report of the detection of EV HPV in amniotic fluid, placenta, and cervical scrapes from an EV patient renders vertical transmission of EV HPV likely.

Adult↗
PubMed1997

Skin autografts in epidermodysplasia verruciformis: human papillomavirus-associated cutaneous changes need over 20 years for malignant conversion.

Epidermodysplasia verruciformis (EV) is regarded as a model for cutaneous oncogenesis associated with specific human papillomaviruses (HPVs). Because genital HPV-associated carcinogenesis is a very long-lasting process requiring 20-30 years and epidemiological studies of this type for HPV-associated skin cancers are impossible in such a rare disease as EV, we observed for up to 20 years EV patients having surgery for carcinomas with consecutive autografts from uninvolved and non-sun-exposed skin. We noticed the appearance of premalignant and malignant changes around the grafts, whereas within the grafted skin, only benign macular lesions started to develop several years after transplantation. Thus, skin HPV-associated carcinogenesis appears to be a very slow process comparable to the genital carcinogenesis associated with high risk HPVs.

Adult↗
PubMed1997

Serum levels of soluble tumor-necrosis-factor receptors in patients with benign and malignant HPV-associated anogenital lesions.

The levels of type-I and type-II soluble TNF-alpha receptors (sTNF-Rs) were evaluated in sera from patients with various human-papillomavirus-(HPV)-associated benign and malignant anogenital lesions using specific enzyme-linked immunobiological assays. In patients with benign HPV6/11-associated condylomata acuminata, the levels of sTNF-RI were significantly increased, while sTNF-RII were in normal range. Both types of sTNF-Rs were in normal range in patients with benign HPV16-associated grade-I/II and grade-III cervical intra-epithelial neoplasia. However, their levels were significantly increased in patients with HPV16/18-associated squamous cervical cancer and anogenital Bowen's carcinoma. Sera from patients with condylomata acuminata and anogenital carcinomas displayed significantly increased TNF-alpha-inhibitory activity, as revealed by L929 cell-cytotoxicity assay. Increased serum TNF-alpha-inhibitory activity correlated with higher levels of sTNF-Rs. Furthermore, this inhibitory activity could be specifically abrogated by htr9 and utr1 monoclonal antibodies recognizing TNF-RI and TNF-RII respectively. Our results strongly suggest that serum sTNF-Rs may protect tumor cells from cytotoxic/cytostatic effects of locally released TNF-alpha, and that elevated levels of circulating sTNF-Rs may facilitate the growth of HPV-associated anogenital lesions.

Adolescent↗
PubMed1997

Human papillomavirus-associated tumors of the skin and mucosa.

This review discusses diseases of the lower genital tract in which the presence of human papillomavirus (HPV) DNA is well documented. We discuss epidemiologic, clinical, and experimental data supporting a causative role for HPV in mucosal malignancies, with emphasis on the role of viral and host factors in their pathogenesis. Of special interest is the recently discovered association of cutaneous tumors with HPVs, previously known only for tumors in epidermodysplasia verruciformis (EV). The frequent detection of EV-specific or EV-related HPVs in immunosuppressed persons and in cutaneous tumors in the general population supports the importance of EV as a model of cutaneous oncogenesis. We also discuss recent serologic findings based on enzyme-linked immunosorbent assay results with the use of viruslike particles. This is important both for detection of present or past HPV infection and for epidemiologic and immunologic studies. Novel therapeutic modalities for HPV tumors and prospects for prophylactic and therapeutic vaccination are presented.

Anus Neoplasms↗
PubMed1996

Preliminary results for positron emission mammography: real-time functional breast imaging in a conventional mammography gantry.

In order to optimally integrate radiotracer breast imaging within the breast clinic, anatomy and pathology should be easily correlated with functional nuclear medicine breast images. As a first step in the development of a hybrid functional/anatomic breast imaging platform with biopsy capability, a conventional X-ray mammography gantry was modified to image the compressed breast with positron emitters. Phantom studies with the positron emission mammography (PEM) device showed that a 1-cc hot spot could be detected within 5 min. A preliminary clinical trial demonstrated in vivo visualization of primary breast cancer within 4 min. For sites where positron-emitting radionuclides are available, PEM promises to achieve low-cost directed functional examination of breast abnormalities, with the potential for achieving X-ray correlation and image-guided biopsy.

Breast↗
PubMed1996

Progressive growth of human papillomavirus type 16-transformed keratinocytes is associated with an increased release of soluble tumour necrosis factor (TNF) receptor.

Analysis of conditioned media generated by weakly and highly tumorigenic SKv-1 keratinocyte lines harbouring integrated human papillomavirus type 16 (HPV16) DNA sequences revealed a factor inhibiting TNF-alpha and TNF-beta cytotoxic activity. This inhibitory activity was specifically blocked by htr-9 monoclonal antibody (MAb) recognising 55/60 kDa type I TNF receptor suggesting that it is related to a soluble form of this particular receptor (sTNF-RI). The presence of sTNF-RI was confirmed by Western blot analysis of SKv-1 cell-conditioned medium showing a band of 31.5 kDa as well as by the specific enzyme-linked immunobiological assay (ELIBA). Release of sTNF-RI was a result of shedding because Northern blot analysis showed that SKv-1 cells expressed a full-length TNF-RI mRNA, and radioimmunoprecipitation of TNF-RI from [32S]cysteine-labelled cell extracts demonstrated the presence of normal 55 kDa molecule. Evaluation by ELIBA showed that highly tumorigenic SKv-12 cells released significantly more sTNF-RI than their weakly tumorigenic SKv-11 parental cells. Furthermore, human recombinant as well as SKv cell-derived sTNF-RI stimulated proliferation of weakly tumorigenic SKv-11 cells. This suggests that a progressive growth of some neoplastic cells may be, at least partially, a result of an increased spontaneous release of sTNF-RI that enables the cells to escape from local TNF-alpha-mediated growth inhibition.

Carcinoma in Situ↗
PubMed1996

Interleukin-12 inhibits angiogenesis induced by human tumor cell lines in vivo.

Tumor cell-induced angiogenesis, i.e., new blood vessel formation within tumor tissue, is an essential requirement for the growth of solid neoplasms. Interleukin-12 (IL-12) inhibits growth of a variety of experimental tumors in vivo. We tested whether antitumor activity of IL-12 is related to the inhibition of angiogenesis induced by tumor cell lines. Angiogenesis was induced in x-ray immunosuppressed Balb/c mice by intradermal injection of the following human tumor cells: T47D, originating from mammary carcinoma; A431, derived from vulval carcinoma; and Skv, established from bowenoid papulosis, Systemic treatment of the mice with murine IL-12 significantly decreased angiogenesis induced by human tumor cells in a time-and dose-dependent manner. Preincubation of human cells in vitro with IL-12 did not inhibit tumor cell-induced angiogenesis, suggesting that the antiangiogenic capacity of IL-12 is restricted to in vivo conditions. Treatment of the mice with rat antibody against murine interferon-gamma (IFN-gamma) resulted in counteracting the antiangiogenic effect of murine IL-12. Furthermore, human IFN-gamma inhibited the angiogenic activity of human tumor cell lines. This indicates that IFN-gamma is a mediator of the antiangiogenic effect of IL-12. The results show that the mechanism of antitumor action of IL-12 may depend not only on the immunostimulatory activity of this cytokine but also on its effect on tumor cell-induced angiogenesis. IL-12 should be considered as a potential candidate for the treatment of angiogenesis-dependent malignancies.

Animals↗