Epidermolysis bullosa-specific module of the Infants and Toddlers Dermatology Quality of Life (InToDermQoL) questionnaire.

BACKGROUND: Epidermolysis bullosa (EB) may have severe impact on different aspects of patients' life. Until now there was no EB-specific quality of life (QoL) instrument for young children. OBJECTIVE: To create EB-specific proxy module of the Infants and Toddlers Dermatology Quality of Life (InToDermQoL) questionnaire. METHODS: Focus groups with parents of children with EB were organized. Parents of EB children were interviewed by the project staff with regard to their perception of QoL issues of the skin disease of their children. RESULTS: Focus groups with parents of EB children in Ukraine and Romania were organized. Parents represented eight boys and 12 girls from 3 months to 4 years old with different EB types and disease severity. Based on the analysis of focus groups' results, two EB specific items that were not mentioned by parents of children with other skin diseases and therefore were not included to the dermatology-specific InToDermQoL questionnaire were developed: 'problems with defecation' and 'problems with shoes'. These problems were mentioned by 55% of all parents and 11.76% of parents that represented EB children older than 1 year, respectively. CONCLUSION: We want to invite other centres and EB related organizations to join our project starting from the pilot test. There are many different reasons why QoL measurement is important in dermatology clinical practice and our goal is practical use of the instrument in children with EB.

Primary squamous cell carcinoma of the endometrium: case history, pathologic findings, and discussion.

Primary squamous cell carcinoma of the endometrium (PSCCE) is an exceedingly rare tumor. Rarely are cytological criteria discussed. We report our experience in the cytological diagnosis of a case. A postmenopausal, 64-yr-old woman suffered from pyometria. An endometrial Pap smear displayed some malignant squamous cells. Curettage of the cervix and the uterine cavity only recovered some fragments of atypical squamous epithelium whose origin could not be precisely identified. A hysterectomy with bilateral adnexectomy was decided upon. Pathological study evidenced a primary squamous cell carcinoma in the uterine cavity while the cervix was tumor-free and the lymph nodes were devoid of metastases (pT1, pN0, pM0). The patient died 46 mo PO with multiple pulmonary and renal metastases. The histological feature of PSCCE is identical to that of any tumor of a similar nature, whatever the site, especially the cervix. Confirmation of the primary endometrial nature is only possible on the hysterectomy specimen.

Peritubular capillary basement membrane reduplication in allografts and native kidney disease: a clinicopathologic study of 278 consecutive renal specimens.

BACKGROUND: An association has been found between transplant glomerulopathy (TG) and reduplication of peritubular capillary basement membranes (PTCR). Although such an association is of practical and theoretical importance, only one prospective study has tried to confirm it. METHODS: We examined 278 consecutive renal specimens (from 135 transplants and 143 native kidneys) for ultrastructural evidence of PTCR. In addition to renal allografts with TG, we also examined grafts with acute rejection, recurrent glomerulonephritis, chronic allograft nephropathy and stable grafts ("protocol biopsies"). Native kidney specimens included a wide range of glomerulopathies as well as cases of thrombotic microangiopathy, malignant hypertension, acute interstitial nephritis, and acute tubular necrosis. RESULTS: We found PTCR in 14 of 15 cases of TG, in 7 transplant biopsy specimens without TG, and in 13 of 143 native kidney biopsy specimens. These 13 included cases of malignant hypertension, thrombotic microangiopathy, lupus nephritis, Henoch-Schonlein nephritis, crescentic glomerulonephritis, and cocaine-related acute renal failure. Mild PTCR in allografts without TG did not predict renal failure or significant proteinuria after follow-up periods of between 3 months and 1 year. CONCLUSIONS: We conclude that in transplants, there is a strong association between well-developed PTCR and TG, while the significance of mild PTCR and its predictive value in the absence of TG is unclear. PTCR also occurs in certain native kidney diseases, though the association is not as strong as that for TG. We suggest that repeated endothelial injury, including immunologic injury, may be the cause of this lesion both in allografts and native kidneys.

Interstitial cells from the atrial and ventricular sides of the bovine mitral valve respond differently to denuding endocardial injury.

The mitral valve has atrial and ventricular sides, each lined by endocardial cells. The valve stroma contains alpha smooth muscle actin positive interstitial cells, collagen, glycosaminoglycans, and elastic tissue. To eliminate the effect of endocardium on wound repair in bovine mitral valve organ culture, the endocardium was removed from both sides of the valve. At 6 days, organ cultures of these preparations revealed surface cells on the ventricular side but not in the atrial side. Ventricular surface cells were negative for Factor VIII-related antigen, and positive for alpha smooth muscle actin. Immunoperoxidase staining for proliferating cell nuclear antigen/cyclin, a marker for cell proliferation, revealed a positive labeling index of (mean +/- standard deviation) 0.08 +/- 0.16% for interstitial cells from the atrial side and 0.14 +/- 0.19% for ventricular side interstitial cells in uncultured preparations (not significant), and 0.44 +/- 0.69% for atrial side interstitial cells and 2.25 +/- 1.64% for ventricular side interstitial cells in the cultured preparations (significant, P < 0.0006). The results suggest that in organ culture, interstitial cells from the ventricular side of the mitral valve respond to a denuding endocardial injury by proliferating and migrating onto the adjacent surface whereas interstitial cells from the atrial side do not. This difference in the response to injury of interstitial cells from the atrial and ventricular sides of the valve may reflect differences in phenotype or may be due to effects of extracellular matrix on interstitial cell behavior. The latter is possible because of differences in the extracellular matrix of the atrial and ventricular sides of the valve.

Bovine mitral valve organ culture: role of interstitial cells in repair of valvular injury.

The atrial and ventricular surfaces of the mitral valve are lined by endothelial cells termed endocardial cells, while the valve stroma contains interstitial cells. Bovine mitral valve organ cultures were immunoperoxidase-stained for Factor VIII RAg, alpha smooth muscle actin, and PCNA/cyclin in order to identify the cell types involved in mitral valve wound repair. Factor VIII RAg is a well-characterized endothelial cell marker, alpha smooth muscle actin is an indicator of smooth muscle differentiation and PCNA/cyclin is a marker for S phase. Bovine mitral valve endocardium was Factor VIII RAg positive and remained positive after culturing for 6 days (n = 7). Mitral valve interstitial cells were Factor VIII RAg negative and positive for alpha smooth muscle actin. By 6 days in culture, the lateral edges of the preparations, where the tissue was originally dissected from the mitral valve leaflet, were covered by multiple layers of cells. These cells were Factor VIII RAg negative (n = 7), and hence not endocardial, but were alpha smooth muscle actin positive like interstitial cells. Interstitial cells subjacent to the lateral edges were negative for PCNA/cyclin in uncultured preparations (n = 5), but positive in 12 out of 15 specimens cultured for 6 days. The results suggest that mitral valve interstitial cells are responsible for the repair process seen in the lateral edges of mitral valve organ cultures.

Changes in cell-substratum adhesion and nuclear-cytoskeletal anchorage during cytodifferentiation of BeWo choriocarcinoma cells.

Changes in the substratum anchorage of cells and nuclei were examined during methotrexate (MTX)-induced cytodifferentiation of BeWo human choriocarcinoma cells. During this process cytotrophoblast-like cells (CTLs) transform into giant mono- and multinucleated syncytiotrophoblast-like cells (STLs). Cells treated with MTX for 24 h exhibited significantly faster rates of substratum detachment by EDTA, trypsin-EDTA, EDTA-glycine, and DMSO than did uninduced controls. The decrease in cell-substratum adhesiveness occurred prior to the onset of morphological transformation. By 48 h, when morphological transformation was first observed, there had occurred a marked change in nuclear-cytoskeletal anchorage to the substratum, as evidenced by a difference in sensitivity of Triton-extracted STL and CTL monolayers to detachment by KI. STL monolayers were completely detached within 5 min of exposure to 0.3 M KI, while CTL monolayers remained firmly attached to the substratum for at least 3 h. KI-extracted residues were examined by electron microscopy and found to consist of nuclear shells attached to intermediate filaments. When cytoskeletal residues and KI-extracted proteins of STL and CTL cells were compared by two-dimensional polyacrylamide gel electrophoresis (PAGE), qualitative and quantitative differences were seen in a number of minor components. Thus the sensitivity of STL nuclear-cytoskeletal monolayers to removal by KI, an effective actin depolymerizing agent, may involve changes in the organization, stability, or interactions of actin with other components of the cytoskeletal framework.