PubMed Health⌕ Search

Biomedical subjects

D Salomon

Publications and source records attributed to D Salomon.

At least 37 records · Page 2Linked to original sources

Trends in mortality from sporadic Creutzfeldt-Jakob disease in France 1992-7.

This study examined trends in mortality from sporadic Creutzfeldt-Jakob disease in France for 1992-7 by age, genotype at the codon 129 of the prion protein gene, and geographical area. Case ascertainment was based on notifications by neurologists, neuropathologists, and laboratories; 324 deaths from definite or probable Creutzfeldt-Jakob disease were registered during the study period. The yearly number of deaths increased significantly between 1992 and 1997. The rise was higher for older age groups. It was also higher in those who were homozygous for valine compared with other genotypes. Eighteen departments (geographical administrative areas) out of 95 showed a significant increase in the number of deaths from sporadic Creutzfeldt-Jakob disease. Intensive epidemiological surveillance is a likely explanation for the apparent increase in the number of sporadic cases of Creutzfeldt-Jakob disease over the 1992-7 period, particularly in older age groups and in departments with low mortality rate at the beginning of the study period. Intensive surveillance may also have led to a better identification of atypical valine homozygous cases.

Aged↗

Human melanocytes grown in epidermal equivalents transfer their melanin to follicular outer root sheath keratinocytes.

Because outer root sheath (ORS) cells are valuable substitutes for interfollicular epidermal keratinocytes, we wanted to determine whether epidermal equivalents generated from ORS cells and containing cultured melanocytes can serve as an in vitro model for skin pigmentation. In such epidermal equivalents prepared with ORS cells and melanocytes from donors of phototypes II, III and VI, a stratified epithelium resembling normal epidermis developed within 14 days, as documented by histological, ultrastructural (e.g. basement membrane-like structure, keratohyalin granules, keratinosomes) and immunohistochemical (e.g. keratins, integrins, gp80, involucrin, filaggrin) criteria. The melanocytes were localized in the basal layer and accounted for 10% of the total cell number. Heavily pigmented melanocytes from black donors contained regular melanosomes in all stages of maturation, whereas melanocytes derived from white donors contained predominantly melanosomes of stages I and II. Melanosome-laden dendrites were readily detected extending from the heavily pigmented melanocytes, while they were less conspicuous in melanocytes from white donors. The extent of melanosome transfer was independent of the racial origin of the ORS cells. Melanosomes could also be transferred "through racial barriers". Melanosomes, mainly of stages III and IV, were detected in the ORS cells, being distributed either as single or compound melanosomes, again irrespective of the racial origin of the ORS cells. In conclusion, pigmented epidermal equivalents generated from ORS cells offer practical advantages over other in vitro pigmentation models: (1) the ORS cells are easily and repeatedly available from any donor regardless of age; (2) primary cultures of ORS cells are free of contaminating melanocytes, a bias if using interfollicular epidermal keratinocytes; (3) a high degree of epidermal differentiation is maintained for 3 weeks in fully defined medium, enabling labelling and stimulation experiments to be performed and compounds interfering with melanin pigmentation to be tested.

Biological Transport↗

Research potential of a unique xenograft model of human proliferative breast disease.

A workshop on the 'Research potential of a unique xenograft model of human proliferative breast disease' was held at the Karmanos Cancer Institute, Wayne State University, Detroit, Michigan, in November of 1998. The accumulated information and current experimental findings on the MCF10AT model of preneoplastic, proliferative breast disease were reviewed. Discussions focused on the relevance of the model to clinical breast cancer and on the most profitable lines of further research to strengthen its utility.

Animals↗

IgG autoantibodies from a lichen planus pemphigoides patient recognize the NC16A domain of the bullous pemphigoid antigen 180.

Lichen planus pemphigoides (LPP) most likely encompasses a heterogeneous group of subepidermal autoimmune blistering disorders occurring in association with lichen planus. We describe the case of a 49-year-old patient with features characteristic of LPP. Direct immunofluorescence microscopy studies demonstrated linear deposits of C3 along the cutaneous basement membrane, while circulating IgG autoantibodies directed against the epidermal side of skin separated by 1 M NaCl were detected. The patient's serum contained IgG autoantibodies immunoblotting a recombinant form of bullous pemphigoid antigen 180 (BP180), but not the COOH-terminus of BP230. By using deletion mutants, it was found that IgG reactivity was restricted to the NC16A domain of BP180, the region harboring the major antigenic sites targeted by IgG autoantibodies from patients with the bullous pemphigoid group of disorders. Our findings provide support to the idea that a subset of patients with LPP have a distinct form of bullous pemphigoid associated with lichen planus.

Animals↗

Incidence of transient acantholytic dermatosis (Grover's disease) in a hospital setting.

BACKGROUND: Grovers's disease may be triggered by bed rest. METHODS: We have prospectively analyzed, over a 30-month period, all cases of transient acantholytic dermatosis (TAD) diagnosed in the context of a dermatological consultation for inpatients of a community hospital. RESULTS: A total of 28 cases of TAD were diagnosed within a total of 3,750 patients examined (0.8%). The mean age of patients with TAD was 66.7 years, and the male-to-female ratio was 1.8. In 83% of cases the length of hospitalization preceding TAD was 66.7 years, and the male-to-female ratio was 1.8. In 83% of cases the length of hospitalization preceding TAD exceeded 2 weeks, and in all cases there was an association with strict bed rest. No association with malignant disease or other specific pathologies was observed. CONCLUSION: Our results suggest that TAD, which is frequent in elderly patients within a hospital setting, is not paraneoplastic and favor the hypothesis of a sweat-related pathogenesis.

Acantholysis↗

Inhibition of toxic epidermal necrolysis by blockade of CD95 with human intravenous immunoglobulin.

Toxic epidermal necrolysis (TEN, Lyell's syndrome) is a severe adverse drug reaction in which keratinocytes die and large sections of epidermis separate from the dermis. Keratinocytes normally express the death receptor Fas (CD95); those from TEN patients were found to express lytically active Fas ligand (FasL). Antibodies present in pooled human intravenous immunoglobulins (IVIG) blocked Fas-mediated keratinocyte death in vitro. In a pilot study, 10 consecutive individuals with clinically and histologically confirmed TEN were treated with IVIG; disease progression was rapidly reversed and the outcome was favorable in all cases. Thus, Fas-FasL interactions are directly involved in the epidermal necrolysis of TEN, and IVIG may be an effective treatment.

Adolescent↗

Differential nuclear translocation and transactivation potential of beta-catenin and plakoglobin.

beta-Catenin and plakoglobin are homologous proteins that function in cell adhesion by linking cadherins to the cytoskeleton and in signaling by transactivation together with lymphoid-enhancing binding/T cell (LEF/TCF) transcription factors. Here we compared the nuclear translocation and transactivation abilities of beta-catenin and plakoglobin in mammalian cells. Overexpression of each of the two proteins in MDCK cells resulted in nuclear translocation and formation of nuclear aggregates. The beta-catenin-containing nuclear structures also contained LEF-1 and vinculin, while plakoglobin was inefficient in recruiting these molecules, suggesting that its interaction with LEF-1 and vinculin is significantly weaker. Moreover, transfection of LEF-1 translocated endogenous beta-catenin, but not plakoglobin to the nucleus. Chimeras consisting of Gal4 DNA-binding domain and the transactivation domains of either plakoglobin or beta-catenin were equally potent in transactivating a Gal4-responsive reporter, whereas activation of LEF-1- responsive transcription was significantly higher with beta-catenin. Overexpression of wild-type plakoglobin or mutant beta-catenin lacking the transactivation domain induced accumulation of the endogenous beta-catenin in the nucleus and LEF-1-responsive transactivation. It is further shown that the constitutive beta-catenin-dependent transactivation in SW480 colon carcinoma cells and its nuclear localization can be inhibited by overexpressing N-cadherin or alpha-catenin. The results indicate that (a) plakoglobin and beta-catenin differ in their nuclear translocation and complexing with LEF-1 and vinculin; (b) LEF-1-dependent transactivation is preferentially driven by beta-catenin; and (c) the cytoplasmic partners of beta-catenin, cadherin and alpha-catenin, can sequester it to the cytoplasm and inhibit its transcriptional activity.

3T3 Cells↗

Pulse methylprednisolone therapy for severe alopecia areata: an open prospective study of 45 patients.

BACKGROUND: Oral corticosteroids may be effective in the treatment of severe alopecia areata (AA), but the side effects of prolonged therapy limit their use. The benefit of a single intravenous pulse of methylprednisolone has not been evaluated in patients with ongoing hair loss of less than 12 months' duration. OBJECTIVE: Our purpose was to determine the effectiveness of an intravenous pulse of methylprednisolone at 1, 3, 6, and 12 months in patients with active severe AA of less than 12 months' duration. METHODS: Forty-five patients were included in this open study. All had rapid and extensive hair loss for less than 1 year (first occurrence or relapse), with the bald area exceeding 30% of the scalp. There were 20 multifocal, 10 ophiasic, 9 universalis, and 6 totalis cases. Intravenous methylprednisolone, 250 mg, was administered twice a day on 3 successive days. Follow-up for at least 12 months (up to 29 months) was performed. The percentage of pretreatment bald area covered by hair regrowth at 1,3,6, and 12 months was measured. RESULTS: No major side effects were observed. Patients with multifocal AA (n = 20) showed the best response rate, with 9, 12, 13, and 12 showing 100% or 50% to 100% regrowth at 1, 3, 6, and 12 months, respectively. Relapse occurred at 3 months in 1 patient, at 6 months in 2, and at 12 months in 4. A second pulse was tried in 2 patients with relapse with 100% regrowth that was stable at 12 and 28 months. In patients with ophiasic AA (n = 10), no total regrowth was observed; 6 had no response, 4 showed 20% to 70% regrowth at 1 month with relapse at 3 and 6 months. A second series of pulses was given to the 4 initial responders 3 to 13 months after the first series; the response rate to this second treatment was better than the first. In patients with universalis and totalis AA (n = 15), no total regrowth was observed initially; 8 patients had no response, and 3 showed 50% to 90% regrowth at I month, with subsequent improvement at 3 and 6 months. In 4 patients who did not show an initial response, a significant (90% to 100%) delayed regrowth was observed between 9 and 16 months after the pulse therapy. CONCLUSION: A single series of intravenous pulse of methylprednisolone appears to be well tolerated and effective in patients with rapidly progressing extensive multifocal AA, but not those with ophiasic and universalis AA.

Adolescent↗

Upregulation of connexin 26 between keratinocytes of psoriatic lesions.

To assess whether the expression of connexins (Cx) by keratinocytes is altered under conditions of abnormal epidermal differentiation, we have compared Cx26, Cx32, Cx37, Cx40, and Cx43 in the epidermis of 11 psoriatic patients who had not been treated for at least 1 mo and of seven healthy individuals. In all samples of fully mature psoriatic plaques, we have observed a massive expression of Cx26, as judged at both the transcript level (northern blot) and the protein level (immunofluorescence). This protein became consistently detected between keratinocytes of the basal and granular layers at the periphery of psoriatic plaques and in all layers of fully developed psoriatic epidermis, except in regions of parakeratosis. None or a minimal amount of Cx26 was observed in both control and nonlesional regions of psoriatic epidermis. Psoriatic plaques also contained Cx43, the prominent gap junction protein in the interfollicular epidermis of normal human skin. The levels of this protein appeared to be slightly higher in psoriatic than in control skin, as judged at both the transcript level (northern blot) and the protein level (immunofluorescence). Three other connexins (Cx32, Cx37, and Cx40), which are not observed in control interfollicular epidermis, were not induced in either nonlesional or lesional regions of psoriatic skin. The data indicate that selective changes in the normal expression of connexins by keratinocytes are associated with the changes in the proliferation and differentiation program that these cells undergo in psoriasis.

Adult↗

Two types of pattern modification detected on the follow-up of benign melanocytic skin lesions by digitized epiluminescence microscopy.

Digital epiluminescence microscopy (DELM) is currently being developed for the diagnosis of pigmented skin lesions (PSL) and the early diagnosis of malignant melanoma. So far there are only few studies documenting if modifications in PSL may be detected by DELM over time. Our purpose was to determine if DELM is an adequate tool for the follow-up of PSL and if any detectable modifications occur within PSL over time. We followed 150 PSL over 2 years in 67 patients using a DELM system. At the end of the follow-up period, the retrieved DELM images were analysed by two observers and evaluated for the presence and type of modifications. Modifications were observed in 69% of the PSL. These modifications were of two types. Type 1 corresponded to an increase in the pigment content of the lesion without modification of either its size or architecture, and was probably related to sun-related seasonal variation. Type 2 included an increase in the size and various variations in the architecture, corresponding to a progression of the lesion. Correlation of the type of modification with the type of PSL, as defined by its epiluminescence microscopy (ELM) patterns, indicated that type 2 modifications were associated with lesions initially showing ELM signs of 'dysplasia', whereas lesions showing only type 1 modifications did not show such patterns. We have documented the feasibility of following up PSL with DELM. The pattern of modification of a PSL over time could be correlated with its nature.

Adolescent↗

Use of Biobrane after laser resurfacing.

BACKGROUND: Laser skin resurfacing has become an ever more popular and effective technique for the treatment of photoaged skin. Often a prolonged postoperative healing period adversely affects patients and physician satisfaction. Erythema and a certain degree of patient discomfort are often believed to be inevitable as they are thought to reflect depth of wounding and consequently the efficacy of wrinkle removal. In addition, a high incidence of irritant contact dermatitis has been observed, complicating recovery. OBJECTIVE: To develop a simplified wound dressing protocol aimed at achieving mild, short-term erythema and minimal side effects following effective rhytidectomy performed by laser resurfacing. METHODS: In a retrospective study from September 1995 to May 1997, 85 patients undergoing laser resurfacing for rhytid removal were placed on a postoperative wound care protocol consisting of immediate postsurgical once-only application, for 6 days, of Biobrane, a biosynthetic semipermeable dressing followed by the topical use of only a 10% cartilage extract in ointment. RESULTS: Thirty-eight full-face/three-quarter face, 26 supralabial, 13 perioral, and eight lower eyelid/crow's feet cosmetic units were treated. The fine and course wrinkles were improved in most patients, comparing favorably with other reported series. In 94% of patients erythema was absent to light pink at 4 weeks. Mild pain necessitating a medication was used in only five patients. Twenty-six patients developed transient hyperpigmentation and three patients developed focal hypopigmentation. Delayed irritant contact dermatitis presented in three patients. No infections developed and no scarring was observed. CONCLUSION: With this wound healing protocol, carbon dioxide laser skin resurfacing can effectively improved facial rhytids with minimal to insignificant erythema or discomfort.

Adult↗

Regulation of beta-catenin levels and localization by overexpression of plakoglobin and inhibition of the ubiquitin-proteasome system.

beta-Catenin and plakoglobin (gamma-catenin) are closely related molecules of the armadillo family of proteins. They are localized at the submembrane plaques of cell-cell adherens junctions where they form independent complexes with classical cadherins and alpha-catenin to establish the link with the actin cytoskeleton. Plakoglobin is also found in a complex with desmosomal cadherins and is involved in anchoring intermediate filaments to desmosomal plaques. In addition to their role in junctional assembly, beta-catenin has been shown to play an essential role in signal transduction by the Wnt pathway that results in its translocation into the nucleus. To study the relationship between plakoglobin expression and the level of beta-catenin, and the localization of these proteins in the same cell, we employed two different tumor cell lines that express N-cadherin, and alpha- and beta-catenin, but no plakoglobin or desmosomal components. Individual clones expressing various levels of plakoglobin were established by stable transfection. Plakoglobin overexpression resulted in a dose-dependent decrease in the level of beta-catenin in each clone. Induction of plakoglobin expression increased the turnover of beta-catenin without affecting RNA levels, suggesting posttranslational regulation of beta-catenin. In plakoglobin overexpressing cells, both beta-catenin and plakoglobin were localized at cell-cell junctions. Stable transfection of mutant plakoglobin molecules showed that deletion of the N-cadherin binding domain, but not the alpha-catenin binding domain, abolished beta-catenin downregulation. Inhibition of the ubiquitin-proteasome pathway in plakoglobin overexpressing cells blocked the decrease in beta-catenin levels and resulted in accumulation of both beta-catenin and plakoglobin in the nucleus. These results suggest that (a) plakoglobin substitutes effectively with beta-catenin for association with N-cadherin in adherens junctions, (b) extrajunctional beta-catenin is rapidly degraded by the proteasome-ubiquitin system but, (c) excess beta-catenin and plakoglobin translocate into the nucleus.

3T3 Cells↗

[Secondary wound healing with reference to anatomic subunits in operations of the mid-facial area].

The healing of wounds by secondary intention is a simple method to close operative defects. The quality of wound healing will depend on the anatomic site on the face as well as on size and depth of the defect. Best functional and cosmetic results are obtained at locations with concave geometry and when the defect lies symmetrically at the interface of two anatomic subunits. Partial reconstruction or guiding sutures can create a symmetric defect in relation to anatomic subunits which will heal by second intention. This simple and efficient operative procedure is illustrated by two case reports.

Basal Cell Carcinoma↗

Epiluminescence videomicroscopy: black dots and brown globules revisited by stripping the stratum corneum.

BACKGROUND: The pattern and distribution of several elementary structures, such as black dots and brown globules, observed by epiluminescence microscopy (ELM) are valuable to the diagnosis of pigmented lesions. Black dots are considered to be focal accumulations of melanin in the stratum corneum, and brown globules are thought to be clusters of nevocytes at the dermoepidermal junction. Because of their distinct locations within the layers of the skin, black dots might be removed by stripping of the stratum corneum whereas brown globules should not. OBJECTIVE: Our purpose was to evaluate the efficacy of ELM features to identify brown globules and black dots and to analyze the relation of these structures within the pigmented network. METHOD: The distribution and number of black dots and brown globules from 27 benign melanocytic lesions were analyzed by videomicroscopy before and after a stripping procedure. Several lesions were observed for months to see whether the pattern before stripping is reconstituted. RESULTS: Before stripping, 549 black dots and 214 brown globules were identified by means of three criteria: color, contour, and size. Ninety-eight percent of black dots were superimposed on the gridlines of the pigmented network. Stripping removed 56% of black dots and only 10% of brown globules. Eighty-two percent of the black dots that could be stripped were superimposed on the gridlines of the pigmented network. On follow-up, both black dots and brown globule-like structures previously removed by stripping were restored at their initial locations within a few months after stripping. CONCLUSION: The close association of black dots with the gridlines of pigmented network should be taken as one criterion to identify black dots. Half the structures identified as black dots by ELM are not localized in the stratum corneum but rather correspond to vertical stacking of pigment within the epidermis. Accumulation of melanosomes in the stratum corneum may take the appearance of brown globules.

Humans↗