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Biomedical subjects

F Wojnarowska

Publications and source records attributed to F Wojnarowska.

At least 73 records · Page 4Linked to original sources
PubMed2001

Distribution of transforming growth factor-beta isoforms TGF-beta 1, TGF-beta 2 and TGF-beta 3 and vascular endothelial growth factor in vulvar lichen sclerosus.

OBJECTIVE: To study the distribution of transforming growth factor beta (TGF-beta) isoforms TGF-beta 1, TGF-beta 2 and TGF-beta 3 and vascular endothelial growth factor (VEGF) in vulvar lichen sclerosus. STUDY DESIGN: Biopsies were obtained from 10 patients with vulvar lichen sclerosus, snap frozen and stained with polyclonal antibodies to TGF-beta 1, TGF-beta 2, TGF-beta 3 and VEGF. Control tissues used were uninvolved thigh tissue from two of the lichen sclerosus patients and normal vulvar tissue obtained from eight patients during gynecologic procedures. Two specimens of morphea were also examined. RESULTS: Weak TGF-beta 1 staining was demonstrated in the epidermis of all the lichen sclerosus, morphea, thigh and five of the eight normal vulvar specimens. Slight increase in TGF-beta 1 staining was seen in the upper and middermis in 6 of the 10 lichen sclerosus specimens and in the morphea specimens as compared to the control tissue, and this staining was localized within cells. TGF-beta 2 staining was present throughout the epidermis in all the normal thigh, normal vulva, lichen sclerosus and morphea specimens. TGF-beta 2 staining was increased within cells in the upper and middermis of the lichen sclerosus and morphea specimens. TGF-beta 3 staining occurred in the basal half of the epidermis of all the control, lichen sclerosus and morphea specimens, and only slight upper dermal staining of a few individual cells was seen in 3 of the 10 lichen sclerosus specimens. VEGF staining was similar in the normal tissues, lichen sclerosus and morphea. CONCLUSION: These results suggest that TGF-beta may.

Biopsy↗
PubMed2000

A variant within the DNA repair gene XRCC3 is associated with the development of melanoma skin cancer.

Exposure to UV radiation is a major risk factor for the development of malignant melanoma. DNA damage caused by UV radiation is thought to play a major role in carcinogenesis induction. Multiprotein pathways involved in repairing UV-DNA damage are the base excision, the nucleotide excision, and the homologous double-stranded DNA repair pathways. This study used a sequence-specific primer PCR (PCR-SSP) genotyping method to investigate the association between polymorphisms in DNA repair genes from these pathways with the development of malignant melanoma. The patient cohort was comprised of 125 individuals with malignant melanoma with lesions or staging suggesting a high risk of relapse or metastatic disease. The control population consisted of 211 individuals. We found the presence of a T allele in exon 7 (position 18067) of the XRCC3 gene was significantly associated with melanoma development (P = 0.004; odds ratio, 2.36; relative risk, 1.74). This gene codes for a protein involved in the homologous pathway of double-stranded DNA repair, thought to repair chromosomal fragmentation, translocations, and deletions. These results may provide further insights into the pathogenesis and the mechanism of UV-radiation induced carcinogenesis as well as having a role in prevention.

Adult↗
PubMed2000

p53 codon 72 polymorphism and susceptibility to skin cancer after renal transplantation.

BACKGROUND: Infection with human papillomavirus (HPV) is an important risk factor for the development of skin cancer after renal transplantation. It has recently been suggested that degradation of the tumor suppressor gene p53 is an important mechanism for human papillomavirus-induced carcinogenesis. A common genomic polymorphism occurs at codon 72 of the p53 gene, and in vitro the codon 72Arg variant appears to be particularly susceptible to degradation. METHODS: To test the hypothesis that this polymorphism predisposes to the development of human papillomavirus-associated tumors, we studied p53 codon 72 genotype in 222 long-term survivors of renal transplantation, of whom 55 had developed at least one skin tumor. RESULTS: No differences in allele or genotype frequency were detected between individuals who had or had not developed skin tumors after transplantation, or any subgroup thereof. CONCLUSIONS: The p53 codon 72Arginine allele does not confer susceptibility to the development of skin tumors after renal transplantation.

Alleles↗
PubMed2000

The shed ectodomain of collagen XVII/BP180 is targeted by autoantibodies in different blistering skin diseases.

Collagen XVII/BP180, an epidermal adhesion molecule, exists as a full-length transmembrane protein and as a soluble 120-kd ectodomain that is shed from the keratinocyte surface by furin-mediated proteolysis. Despite a number of studies on autoantibody targets in blistering skin diseases, it has remained unclear whether the physiologically shed ectodomain of collagen XVII plays a role as an autoantigen. Here we isolated the authentic, soluble form of human collagen XVII and showed that it is an autoantigen recognized by IgG and IgA autoantibodies in different blistering skin diseases and is, in some cases, the preferential target. The ectodomain was isolated from the epidermis, keratinocyte media, amniotic fluid, and pemphigoid blister fluid, and autoantibodies affinity-purified with this ectodomain bound to the proximal surface of the epidermis in normal skin but not in collagen XVII-deficient skin. The antibody reactivity was not dependent on the native conformation or the N-glycosylation of the soluble ectodomain, but was abolished by collagenase treatment. Sera of 81 patients with a clinically active blistering skin disease were reacted with full-length collagen XVII, the authentic soluble ectodomain, and recombinant fragments. In bullous and cicatricial pemphigoid, IgG reactive with full-length collagen XVII also recognized the soluble ectodomain. In linear IgA dermatosis and chronic bullous dermatosis of childhood, IgA targeted the soluble ectodomain more efficiently than the full-length protein. The use of recombinant fragments demonstrated that epitopes were present in several noncollagenous and collagenous subdomains of the molecule, and that a significant portion of the sera targeted Col15 domain, a hitherto unrecognized epitope region.

Adolescent↗
PubMed2000

Keratin expression in the normal nail unit: markers of regional differentiation.

Differentiation within the nail unit was examined using a range of antikeratin monoclonal antibodies including the recently described antibody LHTric-1, specific to the acidic hair-type keratin Ha1. Keratinocytes of the nail matrix, nail bed and the digit pulp were characterized by different patterns of keratin expression. Nail matrix was the sole site of expression of Ha1, which colocalized in suprabasal matrix epidermis with epidermal keratins K1 and K10. Small amounts of K17 were found at the apex of the matrix in some cases. K6 and K16 were found where the epidermal surface folds forwards to become the ventral aspect of the proximal nail fold. The nail bed was distinguished by the absence of hair-type keratin Ha1 and the absence of markers of cornified epidermis and mucosal differentiation K1/K10 and K4/K13, respectively, while K6, K16 and K17 were detected. The basal keratin conformation marker, LH6, was expressed suprabasally throughout the nail bed. This complement of keratins exists in the nail bed in the absence of notable proliferative activity, and suggests a state of minimally developed differentiation which may be afforded by the physical or biological properties of the overlying nail. Keratins, K6, K16 and K17 were all found in the digit pulp in limited amounts, possibly in association with the epidermal component of the eccrine duct. The simple epithelial keratins, K7, K8 and K18, were found in small amounts in the specimens from younger individuals, mainly in epibasal cells of the apex of the matrix and in putative Merkel cells.

Cell Differentiation↗
PubMed2000

Lichen sclerosus premenarche: autoimmunity and immunogenetics.

Lichen sclerosus is among the most frequently seen paediatric vulval disorders. In adults a strong association between lichen sclerosus and autoimmune diseases, and also with HLA class II locus DQ7, has been well demonstrated in women and a weaker association in men. These associations have not previously been studied in children, although in other autoimmune diseases, the HLA associations have been strongest in children. We performed HLA tissue typing and looked for autoimmune associations in a group of 30 children with vulval lichen sclerosus. HLA DQ7 was present in 66% of female children with lichen sclerosus compared with 31% in controls. Previous studies reported DQ7 in 51% of adult female patients and 45% of male patients. Sixteen per cent of the children were homozygous for DQ7 as opposed to 5% of controls. In the childhood group, only 4% had another autoimmune disease, but 56% of their parents or grandparents did. Age differences make comparison difficult, but the family history of autoimmunity appears to be strong in the early-onset group, in addition to the stronger association with DQ7.

Adolescent↗
PubMed2000

Do plasminogen activators play a role in lichen sclerosus?

The histological changes of lichen sclerosus suggest that significant remodelling of the extracellular matrix is occurring. As the proteases of the plasminogen activator system have been implicated in tissue remodelling, cell migration and tumour invasion, we performed an immunohistochemical study to look for evidence of alteration in the expression of plasminogen/plasmin, urokinase-type plasminogen activator, tissue-type plasminogen activator and alpha2-antiplasmin in biopsies of clinically typical vulval lichen sclerosus obtained from 11 untreated adult women. Normal vulva obtained from gynaecological procedures and samples of the patients' uninvolved thigh tissue were used as controls. No significant difference was seen in the staining pattern between the lichen sclerosus tissue and control tissue. However, although we found no immunohistochemical evidence that the plasminogen activator system is involved in the pathogenesis of vulval lichen sclerosus, it may be that other proteases are involved.

Adult↗
PubMed2000

Mixed immunobullous disease: is this linear IgA disease?

We report five patients who demonstrated clinical, histological and direct immunofluorescence (IF) features typical of linear IgA disease (LAD), but who also displayed IgG anti-basement membrane zone (BMZ) antibodies on indirect IF. The presence of circulating IgG anti-BMZ antibodies is often said to exclude the diagnosis of LAD. Unable to confidently classify these patients, we reviewed their clinical progress for unifying features. This revealed an almost universal benefit from dapsone therapy. We therefore propose that when strong linear IgA deposition is observed at the BMZ, a first line trial of dapsone is indicated, irrespective of the presence of circulating IgG. The class of antibody fixed in vivo appears to influence the clinical picture more than the class of circulating antibody.

Adolescent↗
PubMed2000

Aetiological factors in vulvar dermatitis.

AIM: To determine aetiological factors in vulvar dermatitis. BACKGROUND: Dermatitis of the vulva is a common clinical diagnosis in the specialized vulva clinic, although the exact prevalence is unknown. Aetiological factors are poorly understood in particular the incidence of atopy and seborrhoeic dermatitis. Other factors implicated are iron deficiency and exogenous causes such as contact irritants and allergens. METHODS: During a 1-year period, 38 patients with an initial clinical diagnosis of vulvar dermatitis were questioned, examined and investigated with full blood count, serum ferritin, bacterial swab where indicated and punch biopsy. After three patients had been excluded with other diagnoses, prick testing and patch testing were carried out. RESULTS: Of the 35 patients with vulvar dermatitis, 34 (97%) had either an atopic background and/or seborrhoeic dermatitis. Iron deficiency occurred in seven patients (20%) and relevant positive patch tests in nine patients (26%). Twenty patients had biopsies and all had confirmatory histology. CONCLUSION: This study suggests that the main aetiological factor in vulvar dermatitis is an endogenous predisposition. Iron deficiency may also contribute, while contact with irritants and allergens may explain the localization and frequently complicates and exacerbates the picture. Secondary sensitization to multiple substances is common.

Adult↗
PubMed2000

Genital lichen sclerosus associated with morphoea or systemic sclerosis: clinical and HLA characteristics.

Although patients with both morphoea and lichen sclerosus have been reported previously, in the majority of these reports the lichen sclerosus has been extragenital. We report nine patients in whom genital lichen sclerosus coexisted with scleroderma spectrum disorders including seven with morphoea, one with morphoea and lichen planus, and one with systemic sclerosis. The clinical features, associated autoimmune disease, autoantibodies and HLA type are reported. Antibodies to Borrelia burgdorferi were not detected in any of the patients. The coexistence of these diseases raises a number of intriguing questions about the relationship between them.

Aged↗
PubMed2000

Glutathione S-transferase polymorphisms and skin cancer after renal transplantation.

BACKGROUND: Susceptibility to skin cancer after transplantation is multifactorial, and risk factors include skin type, sun exposure, and level of immunosuppression. A major mechanism of carcinogenesis is ultraviolet radiation-induced free radical damage, and genetically determined ability to metabolize free radicals may also predispose to skin cancer. The glutathione S-transferase enzymes play a major role in limiting the toxic effects of reactive oxygen species, and this study was designed to determine whether polymorphisms in these enzymes are associated with skin cancers in renal transplant recipients. METHODS: Two hundred twenty-two long-term survivors of renal transplantation were examined for polymorphisms in the GSTM1, GSTT1, and GSTP1 genes, using a unified polymerase chain reaction with sequence specific primers (PCR-SSP) genotyping method. RESULTS: The GSTP1*C allele was associated with the development of squamous cell carcinomas (SCCs; P = 0.01). No associations of the GSTM1 null genotype or the GSTT1 null genotype were identified, and the development of basal cell carcinomas was not associated with any GST polymorphism studied. CONCLUSIONS: These results indicate that genetic variation in enzymes involved in free radical metabolism in the skin are associated with the development of skin cancer. While all renal transplant recipients should be advised to protect themselves from the sun, the identification of transplant patients with a genetic predisposition to skin tumors may permit the targeting of preventative and early intervention strategies to high-risk individuals.

Alleles↗
PubMed2000

Alterations in distribution of tenascin, fibronectin and fibrinogen in vulval lichen sclerosus.

BACKGROUND: The pathophysiology of lichen sclerosus remains uncertain. The clinical features, including increased fragility and scarring, and the histology suggest that significant reorganisation of the extracellular matrix is occurring. Tenascin, fibrinogen and fibronectin are extracellular matrix components that play a significant role in tissue remodelling, for example during wound repair. AIM: To examine the distribution of tenascin, fibrinogen and fibronectin in vulval lichen sclerosus. MATERIALS AND METHODS: Immunohistochemical staining was performed to study the distribution of tenascin, fibronectin and fibrinogen in 16 specimens of untreated vulval lichen sclerosus and 1 specimen of extragenital lichen sclerosus. Haematoxylin and eosin staining of the specimens was also performed to identify the position of the pale staining homogenous zone/zone of sclerosis and the inflammatory infiltrate below this. The control tissues studied included biopsies taken from the uninvolved thigh of 13 of the lichen sclerosus patients and 6 samples of normal vulva tissue obtained during gynaecological procedures from women of similar age to the lichen sclerosus women. RESULTS: All the lichen sclerosus specimens demonstrated increased immunostaining of tenascin in the upper dermis and comparing this with the haematoxylin and eosin staining this corresponded to the zone of sclerosis with relatively little tenascin staining associated with the inflammatory band. In 14 out of the 16 vulval lichen sclerosus specimens and the extragenital lichen sclerosus specimen fibrinogen immunostaining was increased in the upper dermis which corresponded--in haematoxylin and eosin staining --to the zone of sclerosis. There was also slightly increased fibrinogen staining in the mid dermis which corresponded to the inflammatory band. Fibronectin staining was reduced in the upper dermis of 12 of the vulval lichen sclerosus specimens and the extragenital lichen sclerosus specimen which corresponded to the zone of sclerosis. However, in 14 of the vulval lichen sclerosus specimens and the extragenital lichen sclerosus specimen, fibronectin was slightly increased in the mid and deeper dermis which corresponded to the zone of inflammatory cells and the area below this. There was also increased fibronectin staining around blood vessel walls both in the mid dermis and within the zone of sclerosis. CONCLUSION: The distribution of tenascin, fibrinogen and fibronectin is altered in lichen sclerosus and the alteration in these extracellular matrix components may be relevant to the initiation of scarring in lichen sclerosus and the associated increased skin fragility.

Extracellular Matrix Proteins↗
PubMed1999

Lichen sclerosus.

Lichen sclerosis is a chronic inflammatory skin disease that causes substantial discomfort and morbidity, most commonly in adult women, but also in men and children. Any skin site may be affected (and, rarely, the oral mucosa) but lichen sclerosus is most common in the anogenital area, where it causes intractable itching and soreness. In children, the disorder may be confused with changes seen in sexual abuse. Progression to destructive scarring is common. There is increased risk of developing vulval cancer, and there are links with penile cancer. Patients should be kept under long-term review. Lichen sclerosus can occur without symptoms, and the exact prevalence is uncertain. It occurs most commonly in women at times of low sex hormone output. The underlying cause is unknown, but there seems to be a genetic susceptibility and a link with autoimmune mechanisms. The wart virus and the spirochaete borrelia have been suggested but not substantiated as infective triggers. The Koebner phenomenon is known to occur (lichen sclerosus occurs in skin already scarred or damaged), so trauma, injury, and sexual abuse have been suggested as possible triggers of symptoms in genetically predisposed people. The treatment of choice for anogenital lichen sclerosus is potent topical corticosteroid ointment for a limited time. Circumcision may be indicated in men, and surgery may be considered in women, to relieve effects of scarring or to treat coexisting carcinoma. Current research aims to identify a treatable cause of lichen sclerosus, to identify patients at risk of scarring and of malignant disorders, and to find target pathways for therapeutic intervention.

Carcinoma, Squamous Cell↗
PubMed1999

Lichen sclerosus in adult men: a study of HLA associations and susceptibility to autoimmune disease.

Lichen sclerosus is a skin disorder of unknown prevalence affecting both men and women, and several studies have established HLA associations in women with this disease. Autoimmune disease associations in the form of a personal and/or family history of autoimmune disease have also been shown to be related to lichen sclerosus. In this study, we examined 58 men (mean age 38 years) with lichen sclerosus, 39 of whom had histologically proven disease. HLA tissue typing by phototyping was performed on these patients and contrasted with that of 602 control subjects. There was no difference in antigen frequencies of the HLA class I loci. The patient group was found to have an increased frequency of several HLA antigens of the class II loci: DR11, 13 of 58 (22%) patients vs. 75 of 602 (13%) control subjects (P = 0.05); DR12, five of 58 (9%) patients vs. 16 of 602 (3%) control subjects (P = 0.04); DQ7, 26 of 58 (45%) patients vs. 189 of 602 (31%) control subjects (P = 0.05). There were few autoimmune disease associations: two of 58 (3%) patients had a personal history of a different autoimmune disease, two patients were found to have abnormal thyroid function and six of 58 (10%) had a first-degree relative with an autoimmune disease. There was no difference in the frequency of the autoimmune haplotype HLA A1, B8, DR3/17, DQ2 compared with the control population. HLA DQ7 has now been shown to occur more frequently in both male and female patients with lichen sclerosus, which may reflect the immunopathogenesis of the disease. Autoimmune disease associations, however, are less common in men with lichen sclerosus.

Adult↗