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Biomedical subjects

D Salomon

Publications and source records attributed to D Salomon.

At least 73 records · Page 4Linked to original sources

Topical retinaldehyde on human skin: biologic effects and tolerance.

The present study was designed to explore if *etinaldehyde, a natural metabolite of vitamin A, has any biologic activity and is tolerated by human skin. Biologic activity was shown by the induction of cellular retinoic acid-binding protein type 2 (CRABP 2) mRNA and protein; the rank order for CRABP-2 increase was retinoic acid > retinaldehyde > 9 cis retinoic acid > retinol > beta carotene. In volunteers treated 1-3 months with 0.5, 0.1, and 0.05% retinaldehyde, there was a dose-dependent and significant increase in epidermal thickness, keratin 14 immunoreactivity, and Ki67-positive cells. The area of distribution of involucrin, transglutaminase, and filaggrin immunoreactivity was also increased in a dose-dependent manner, and keratin 4 immunoreactivity was induced in the upper epidermis. In pilot clinical tolerance studies, 229 patients received topical retinaldehyde at different concentrations; the 1% preparation was tolerated by up to 70% of the treated subjects; tolerance of the 0.5% preparation was slightly better, whereas both 0.1 and 0.05% preparations applied on facial skin were well tolerated and allowed prolonged use (up to 3 years) in patients with inflammatory dermatoses. These findings indicate that topical retinaldehyde has biologic activity and is well tolerated on human skin.

Administration, Topical↗

Topical haemotherapy for leg ulcers.

Several growth factors, present in the plasma or delivered by blood cells, are involved in wound healing. We have treated 15 chronic atonic leg ulcers by topical application of autologous heparinized blood under a hydrocolloidal dressing. This 'topical haemotherapy' (THT) was applied every other day. After the first THT, 30% of the fibrinonecrotic material had already been removed. After a mean of 9 THT applications (range: 5-18), granulation tissue covered up to 75% of the surface of the ulcer (range: 30-100%) allowing autologous skin grafting. No local or systemic side-effects occurred during the treatment. THT is feasible and well tolerated; it is an easy and inexpensive treatment of chronic leg ulcers that rapidly induces granulation tissue. Growth factors and proteases produced by the blood cells could play a relevant role in this process.

Administration, Topical↗

The association of the two antimalarials chloroquine and quinacrine for treatment-resistant chronic and subacute cutaneous lupus erythematosus.

Antimalarials are the first line in the treatment of chronic and subacute cutaneous lupus erythematosus (LE). However, some patients show either no or only minor improvement on antimalarial monotherapy. We treated 14 patients (9 with chronic LE and 5 with subacute cutaneous LE) who had poorly responded to chloroquine or hydroxychloroquine with an association of chloroquine and quinacrine. The initial dose was: chloroquine 100 mg 3x/day and quinacrine 65 mg 3x/day. The skin lesions improved significantly or cleared totally in 5 of the 9 patients with chronic LE and in all the 5 patients with subacute cutaneous LE. These findings suggest that a chloroquine-quinacrine combination may sometimes be superior to the usual antimalarial monotherapy, especially for subacute LE. If chloroquine or hydroxychloroquine fails to control chronic or subacute cutaneous LE, chloroquine-quinacrine is worthy to be tried.

Adult↗

Kaposi's sarcoma following allogeneic bone marrow transplantation.

Localised Kaposi's sarcoma (KS) was diagnosed 240 days after allogeneic bone marrow transplantation (BMT) in a severely immunosuppressed HIV negative patient with genetic predisposition. The tumour was of host origin, based on PCR amplification of DNA minisatellites. Treatment with radiotherapy prompted almost complete regression of the lesions. However the patient subsequently died with relapsed acute myelogenous leukaemia. Contrary to the incidence observed after organ allografts, the advent of KS appears to be exceptional after BMT, since only one case has been reported to date, following reinfusion of autologous marrow.

Bone Marrow Transplantation↗

L-tryptophan-induced eosinophilia-myalgia syndrome associated with primary cutaneous malignant fibrous histiocytoma and extraabdominal desmoid tumor.

A 57-year-old woman with L-tryptophan-induced eosinophilia-myalgia syndrome, 23 months after the onset of symptoms, experienced development of a parasternal malignant fibrous histiocytoma on previously scleroderma-like skin areas and, almost concurrently, an extraabdominal desmoid tumor of the left arm muscle fascia. The malignant fibrous histiocytoma was treated by surgical excision without sign of recurrence or metastasis 19 months later. Radiation therapy was performed on the extraabdominal desmoid tumor. We suspect that these two connective tissue tumors in this patient were related to the exposure to contaminated L-tryptophan, which interfered with connective tissue metabolism.

Eosinophilia-Myalgia Syndrome↗

Amplified surface microscopy. Preliminary evaluation of a 400-fold magnification in the surface microscopy of cutaneous melanocytic lesions.

BACKGROUND: Surface microscopy (SM) opened a new dimension in the clinical assessment of cutaneous pigmented lesions. Diagnostic patterns were described to provide guidelines for the preoperative diagnosis of pigmented skin lesions. OBJECTIVE: Our purpose was to explore whether "amplified" surface microscopy (ASM), by increasing magnification up to 400-fold, provides any improvement in the analysis of patterns previously described in cutaneous pigmented lesions. METHODS: A fiber-optic camera, allowing magnification up to 400 times and associated with an imaging system computer, was used for the analysis of 40 melanocytic lesions. Special emphasis was put on the most important features that can be observed in surface microscopy, the so-called pigment network and brown globules. RESULTS: The lines (grids) of the pigment network appeared to be composed of three zones: two darker external lines and one central clearer zone. This pattern, not previously seen with SM, is compatible with the anatomy of pigment accumulation in the epidermal rete ridges. Two types of brown globules could be distinguished: one located in the center of the pigment network holes, the other on the lines of its grids. The "on-the-grid" type was smaller than the "in-the-hole" type; it could be misinterpreted as "black dots" when seen at lower magnification (x10). CONCLUSION: ASM is a tedious procedure that may help in the analysis of the features previously recognized by SM; SM is more accessible for routine use.

Diagnosis, Differential↗

Suppression of vinculin expression by antisense transfection confers changes in cell morphology, motility, and anchorage-dependent growth of 3T3 cells.

The expression of vinculin, a major component of adhesion plaques and cell-cell junctions, is markedly modulated in cells during growth activation, differentiation, motility and cell transformation. The stimulation of quiescent cells by serum factors and the culturing of cells on highly adhesive matrices induce vinculin gene expression, whereas the transformation of fibroblast and epithelial cells often results in decreased vinculin expression (reviewed in Rodríguez Fernández, J. L., B. Geiger, D. Salomon, I. Sabanay, M. Zöller, and A. Ben-Ze'ev. 1992. J. Cell Biol. 119:427). To study the effect of reduced vinculin expression on cell behavior, 3T3 cells were transfected with an antisense vinculin cDNA construct, and clones displaying decreased vinculin levels down to 10-30% of control levels were isolated. These cells showed a round phenotype with smaller and fewer vinculin-positive plaques localized mostly at the cell periphery. In addition, they displayed an increased motility compared to controls, manifested by a faster closure of "wounds" introduced into the monolayer, and by the formation of longer phagokinetic tracks. Moreover, the antisense transfectants acquired a higher cloning efficiency and produced larger colonies in soft agar than the parental counterparts. The results demonstrate that the regulation of vinculin expression in cells can affect, in a major way, cell shape and motility, and that decreased vinculin expression can induce cellular changes reminiscent of those found in transformed cells.

3T3 Cells↗

Pulse of methylprednisolone in alopecia areata.

In an attempt to stop the evolution of recent-onset severe alopecia areata (AA), we tested pulse corticotherapy on 9 patients. Acceptance into the study was based on the following criteria: recent-onset AA (< 1 year), AA in an active state, bald surface > 30% of the scalp, no contraindication to pulse corticotherapy. Each patient was given 250 mg i.v. of methylprednisolone twice a day on 3 successive days. In 8 patients the course of the ongoing episode of AA was stopped. At the 6-month follow-up, a regrowth on 80-100% of the bald surface was observed in 6 patients. One patient did not respond to treatment, and 2 had less than 50% of regrowth. This open study suggests that pulse corticotherapy: (1) can stop the course of severe AA in an active state, (2) is well tolerated without major side effects and (3) does not permit a stable control of AA of more than 1 year duration. This treatment seems to be indicated for severe AA of recent onset.

Adolescent↗

[Bacillary angiomatosis: apropos of a case].

We report a case of bacillary angiomatosis (BA), a recently described opportunistic infection, in a 30-year-old patient with Aids who was referred for a purplish vascular nodule on the forehead, of one-month duration, surrounded by similar smaller papules. For the previous 4 months he had suffered from progressive cachexia with fever, chills, night sweats, arthralgias and bone pain for which no infectious or malignant cause had been discovered after an extensive medical work-up. Histological examination of the skin lesions using Warthin-Starry staining revealed lobular vascular proliferation and protuberant endothelial cells with clumps of small bacilli. These findings were confirmed by electron microscopy. We believe that this is the first case of BA diagnosed in Switzerland and discuss the skin lesions, systemic symptoms and evolution under antibiotic treatment.

Acquired Immunodeficiency Syndrome↗

Overexpression of vinculin suppresses cell motility in BALB/c 3T3 cells.

The content of vinculin, a cytoplasmic protein found in focal contacts and cell-cell junctions, was increased in BALB/c 3T3 cells by gene transfection. The vinculin expressed from the full length chicken cDNA, incorporated into focal contacts and its pattern was identical to that of the endogenous protein. Cells stably expressing vinculin by 20% over the endogenous level had altered locomotory properties. In these cells, the ability to migrate into a wound formed in a confluent monolayer and the locomotion of individual cells were drastically reduced. The results provide direct evidence that cell locomotion can be regulated by modulating vinculin expression.

3T3 Cells↗

Gap junctional communication of primary human keratinocytes: characterization by dual voltage clamp and dye transfer.

We have compared dye coupling in pairs of small (less than 10 microns in diameter) and large (greater than 20 microns in diameter) keratinocytes isolated from normal human epidermis, using Lucifer yellow microinjection. Under control conditions, dye coupling was found in only 1 out of the 25 small pairs tested, whereas it was evident in 75% of the large pairs (n = 52). After a 30-min incubation of the latter pairs in the presence of 10(-6) and 10(-4) M all-transretinoic acid (RA), the percentage of coupling was 53% (n = 15; NS) and 7% (n = 14; P less than 0.001), respectively. The almost complete uncoupling observed after 10(-4) M RA was not reversible even 30 min after return to control medium (n = 8). Dual whole-cell patch-clamp recordings from large keratinocyte pairs showed a macroscopic junctional conductance (gj) of 9 +/- 2 nS (n = 43), which was abolished by heptanol (3.5 mM) in a fully reversible way. Compared to heptanol, 10(-4) M RA abolished keratinocyte gj more slowly and irreversibly (n = 10). By contrast, 10(-6) M RA had no significant effect on gj (n = 8). Single-gap junctional channels were also identified between large keratinocytes. Events histograms of 152 transitions from three experiments revealed three main unitary conductances (gamma j) of 45 +/- 4, 78 +/- 4, and 106 +/- 7 pS. The dye coupling results indicate that junctional communication is markedly different in pairs of small and large cells, which showed the phenotype and keratin markers of basal and suprabasal keratinocytes, respectively. In the latter cell type, coupling is ensured by channels of three sizes and is blocked irreversibly by pharmacologic concentrations of RA.

Alcohols↗

Orbital and palpebral paraffinoma.

Paraffinoma is a well-recognized complication of paraffin injection. We describe a 44-year-old man who had an ethmoidectomy for chronic sinusitis. A communicating fracture of the ethmoid bone into the orbit occurred intraoperatively. The nasal cavity was subsequently packed with gauze containing a petrolatum-based antibiotic ointment. Bilateral, periocular swelling developed 1 week later. Optical and electron microscopic studies revealed a paraffinoma.

Administration, Intranasal↗

Suppression of tumorigenicity in transformed cells after transfection with vinculin cDNA.

Transfection of chicken vinculin cDNA into two tumor cell lines expressing diminished levels of the endogenous protein, brought about a drastic suppression of their tumorigenic ability. The SV-40-transformed Balb/c 3T3 line (SVT2) contains four times less vinculin than the parental 3T3 cells, and the rat adenocarcinoma BSp73ASML has no detectable vinculin. Restoration of vinculin in these cells, up to the levels found in 3T3 cells, resulted in an apparent increase in substrate adhesiveness, a decrease in the ability to grow in soft agar, and suppression of their capacity to develop tumors after injection into syngeneic hosts or nude mice. These results suggest that vinculin, a cytoplasmic component of cell-matrix and cell-cell adhesions, may have a major suppressive effect on the transformed phenotype.

3T3 Cells↗

Extrajunctional distribution of N-cadherin in cultured human endothelial cells.

Human endothelial cells contain prominent Ca(2+)-dependent intercellular adherens-type junctions (AJ), which are associated, at their cytoplasmic surfaces, with actin, vinculin and plakoglobin. The transmembrane adhesion molecules present in these sites are members of the cadherin family, which are recognized by a pancadherin serum, directed against the conserved C terminus of these molecules. Immunoblotting analysis of cultured human endothelial cells using these antibodies revealed three immunoreactive bands with apparent molecular masses of 135, 130 and 120 kDa. Cloning and sequencing of the 135 kDa cadherin from an endothelial cDNA expression library indicated that this molecule is a typical cadherin, essentially identical to N-cadherin. Transfection of cDNA encoding this molecule into CHO cells resulted in the induction of AJ formation and an apparent epithelialization of the cells. Immunofluorescent labeling with antibodies to chicken N-cadherin indicated that the molecule is associated with intercellular junctions in the transfectants. In contrast, cultured human umbilical cord endothelial cells exhibited a largely diffuse N-cadherin labeling over the entire cell surface with only occasional enrichment in cell-cell junctions. Comparison of this pattern with the discrete junctional labeling obtained with the pan-cadherin antibody suggests that different cadherins, co-expressed in the same endothelial cells, may undergo differential surface distribution.

Amino Acid Sequence↗

A chimeric N-cadherin/beta 1-integrin receptor which localizes to both cell-cell and cell-matrix adhesions.

To study the molecular mechanisms involved in formation of cell contacts, we have transfected cultured cells with a chimeric cDNA encoding the cytoplasmic and transmembrane domains of beta 1 integrin and the extracellular region of N-cadherin and determined the subcellular distribution of the chimeric molecule. We show that the chimeric receptor associates preferentially with cell-matrix focal contacts, suggesting that its distribution is directed by its beta 1 integrin segment, presumably via interactions of the cytoplasmic domain with cytoskeletal elements characteristic of focal contacts. Transfected cells which expressed relatively high levels of the cadherin/integrin chimera underwent an apparent epithelialization and contained the molecule both in cell-matrix and cell-cell contacts. Location in cell-cell contacts indicates competence of the cadherin extracellular domain to participate in formation of cell-cell junctions using a foreign cytoplasmic domain. Labeling of these cultures for talin, which is normally associated only with matrix adhesions, revealed specific labeling along the newly formed intercellular junctions. This suggests that the local association of talin with these sites is induced by the cytoplasmic tail of beta 1 integrin receptor presented by the chimeric protein. These results suggest that the formation of adherens-type junctions is driven by the cooperative interactions of the relevant adhesion molecules (cadherins and integrins) both with the respective extracellular ligands and with the cytoskeleton.

3T3 Cells↗