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Biomedical subjects

D Salomon

Publications and source records attributed to D Salomon.

At least 55 records · Page 3Linked to original sources

Influence of metoclopramide on the pharmacokinetics of 8-methoxypsoralen.

BACKGROUND: Previous studies have shown important inter- and intraindividual variations in bioavailability of 8-methoxypsoralen (8-MOP) under the influence of factors that are not yet known with certainty. However, they seem to be independent of age, sex and concomitant retinoid administration for RePUVA whereas the influence of diet remains controversial. OBJECTIVE: The purpose of this study was to investigate a possible effect of metoclopramide on the bioavailability of 8-MOP since these drugs are frequently combined to prevent nausea, a common side effect of systemic 8-MOP. METHODS: After a standard breakfast and the ingestion of 8-MOP plasma kinetics of 8-MOP were assessed in 6 healthy volunteers at 0, 1, 1.30, 1.45, 2, 2.15, 2.30, 3 and 4 h after drug ingestion. This procedure was repeated 3 weeks later by associating metoclopramide with 8-MOP. Plasma determinations of 8-MOP were performed using high-pressure liquid chromatography. RESULTS: Time and peak value of maximum plasma 8-MOP concentrations (Tmax, Cmax) ranged from 1 to 3 h and from 124 to 540 ng/ml, respectively. Individual values of the area under the curve of time-related 8-MOP concentration were between 284 and 1,158 ng-h/ml. Concomitant intake of 8-MOP with metoclopramide did not significantly influence these 3 pharmacokinetic values. CONCLUSIONS: Our results confirm the important interindividual variability of the pharmacokinetics of 8-MOP. Associating 8-MOP with metoclopramide does not alter the pharmacokinetic values of 8-MOP and should not require any change in PUVA treatment.

Administration, Oral↗

Epiluminescent light microscopy of melanocytic lesions after dermoepidermal split.

BACKGROUND: In vivo epiluminescent light microscopy (ELM) of pigmented skin lesions reveals numerous elementary structures. Among them, the pigment network (PN), black dots (BD) and brown globules (BG) constitute important semiologic features. Based on histological extrapolations, it has been postulated that PN should reflect the presence of melanin in the epidermis and its honeycomb aspect should result from the dermoepidermal architecture. OBJECTIVE: To demonstrate this directly by analyzing separately by ELM the epidermal and dermal sides of melanocytic lesions. METHODS: We split the epidermis from the dermis of 10 pigmented lesions (6 lentigos, 4 nevocytic nevi) by incubation with dispase. ELM images were done in vivo before excision, then ex vivo on the whole specimen and separately on the split epidermis and dermis. Epidermal and dermal specimens were finally controlled by histology. RESULTS: PN was observed only on the epidermal side of the split. Its organization was remarkably conserved after the procedure as compared with prior in vivo images. In contrast, pigmentation observed on dermal sides of the splits showed no organized pattern and corresponded to melanophages. BG were found on the dermal side and BD on the epidermal side of the split lesions, which confirms previous hypotheses. CONCLUSION: By subtracting the dermal pigmentation and vessels from the image, the split technique has thus established the epidermal origin of the PN and given a more detailed ELM analysis of network components.

Culture Techniques↗

In vivo modulation of connexins 43 and 26 of human epidermis by topical retinoic acid treatment.

After 14 weeks of topical application of 0.1% all-trans-retinoic acid to the napes of volunteers, we observed a 2.5-fold increase in the thickness of epidermis, owing to an increase (p < 0.001) in the number and size of keratinocytes and the induction of keratin 6. These changes in the differentiation of epidermal keratinocytes were paralleled by an increase in the amount of Cx43, a connexin that is normally expressed in human epidermis, and by the massive induction of Cx26, which is barely detectable in normal interfollicular epidermis, as judged at both the transcript (Northern blotting) and the protein level (immunolabeling). In contrast, retinoic acid treatment did not alter the morphology and connexin pattern of hair follicles or of sebaceous and sweat glands, and did not induce the expression of other connexins (C32, Cx37, Cx40) in either skin adnexae or epidermis. These observations suggest that the expression of two distinct connexins by interfollicular keratinocytes is related to selective changes in the differentiation program of epidermis that are induced by retinoic acid.

Administration, Topical↗

Evaluation of pathologic criteria for acute renal allograft rejection: reproducibility, sensitivity, and clinical correlation.

This study was designed to evaluate the pathologic criteria used for acute renal allograft rejection that were developed by a panel of renal pathologists participating in the Cooperative Clinical Trials in Transplantation, a National Institutes of Health-supported, multicenter research group. The panel defined three categories of acute rejection. (1) Type I: mononuclear infiltrate in > or =5% of cortex, a total of at least three tubules with tubulitis in 10 consecutive high-power fields from the most severely affected areas, and at least two of the three following features: edema, activated lymphocytes, or tubular injury. (2) Type II: arterial, or arteriolar, endothelialitis with or without the preceding features. (3) Type III: arterial fibrinoid necrosis or transmural inflammation with or without thrombosis, parenchymal necrosis, or hemorrhage. Using these criteria, and without any knowledge of the clinical course or original diagnosis, a rotating panel of three pathologists agreed with the original study pathologist's diagnosis of the presence or absence of rejection in 259 of the 286 biopsies (91%) used for this analysis (kappa = 0.80). The sensitivity to establish the diagnosis of rejection was 91% for a single core and 99% for two cores. To validate the diagnostic criteria, the thresholds for number of tubules with tubulitis and the percent infiltrate were varied, and the pathologic diagnosis was compared with the clinical course. The greatest agreement occurred with a threshold of > or =1 tubule with tubulitis and > or =5% cortex with interstitial infiltrate (91%). Clinically severe rejection episodes were correlated with the type of rejection (type I, odds ratio [OR] 6.2; type II, OR 37.9). Type II rejection was more likely to be clinically severe than type I (OR 6.1). Analysis of other individual pathologic features revealed a correlation with clinical severity for endothelialitis (OR 13.2), interstitial hemorrhage (OR 13.2), and the presence of glomerulitis (OR 3.7) (all P < 0.05). The extent of tubulitis or of the interstitial infiltrate did not correlate with severity (P > 0.05). It is concluded that these criteria are simple, reproducible, and clinically relevant. These data should lead to further refinement of the diagnostic systems for renal allograft rejection.

Acute Disease↗

[Postoperative infection with Mycobacterium chelonae].

A 70-year-old patient developed Mycobacterium chelonae infection at a donor vein graft site following cardiac bypass surgery. The infection presented as fibrinous, necrotic ulcerations in the scar area. Mycobacterium chelonae and mycobacterium fortuitum are atypical mycobacteria and have been described previously causing infections after injections or surgical procedures. Infection of donor vein graft site is a rare complication after cardiac surgery. As mycobacterium chelonae cannot be cultivated on normal culture media, delayed wound healing might be disinterpretated as a primary wound healing disorder. Treatment of atypical myobacteriosis includes antibiotics, local heat therapy and surgical excision. Clarithromycin is the antibiotic of choice. We obtained complete healing after two months of Clarithromycin treatment, combined with heat therapy.

Aged↗

Ichthyosiform dermatosis with superficial blister formation and peeling: evidence for a desmosomal anomaly and altered epidermal vitamin A metabolism.

We describe a man with generalized congenital ichthyosiform dermatosis, severe cheilitis, and palmar and plantar hyperkeratosis with superficial blistering. Low-dose acitretin therapy induced areas of peeling skin, similar to that seen in the peeling skin syndrome. Histologically, the skin was moderately hyperkeratotic and the palmar blisters were subcorneal. Electron microscopy revealed that the splitting occurred within the desmosomal plaque. Ultrastructural and biochemical investigations indicated epidermal hypervitaminosis A, probably related to alteration of epidermal retinoic acid metabolism. This disease is proposed as a hitherto unreported variant of the peeling skin syndrome.

Adolescent↗

Suppression of tumorigenicity by plakoglobin: an augmenting effect of N-cadherin.

Plakoglobin is a major component of the submembranal plaque of adherens junctions and desmosomes in mammalian cells. It is closely related to the Drosophila segment polarity gene armadillo which has a role in the transduction of transmembrane signals that regulate cell fate. Like its close homologue beta-catenin, plakoglobin can associate with the product of the tumor suppressor gene APC that is linked to human colon cancer. We have studied the effect of plakoglobin overexpression, and the cooperation between plakoglobin and N-cadherin, on the morphology and tumorigenic ability of cells either lacking, or expressing cadherin and alpha- and beta-catenin. Overexpression of plakoglobin in SV40-transformed 3T3 (SVT2) cells suppressed the tumorigenicity of the cells in syngeneic mice. Transfection with N-cadherin conferred an epithelial phenotype on the cell culture, but had no significant effect on the tumorigenicity of the cells. Cotransfection of plakoglobin and N-cadherin into SVT2 cells, however, was considerably more effective in tumor suppression than plakoglobin overexpression alone. Finally, transfection of plakoglobin into a human renal carcinoma cell line that expresses neither cadherins nor plakoglobin, or alpha-and beta-catenin, resulted in a dose-dependent suppression of tumor formation by these cells in nude mice. Plakoglobin, in these cells, did not exhibit junctional localization and was diffusely distributed in the cytoplasm, with a significant amount of the protein also localized in the nucleus. The results suggest that plakoglobin can efficiently suppress the tumorigenicity of cells in the presence of, or independently of the cadherin-catenin complex.

3T3 Cells↗

Livedo-like dermatitis (Nicolau's syndrome): a review of three cases.

We report 3 patients with typical features of livedo-like dermatitis. Emergency vasoactive therapy was administered to 2 of these patients, in whom the lesions healed completely. Although spontaneous resolution cannot be ruled out, we think that early recognition of this entity leading to rapid vasoactive treatment may limit the extent of thrombotic complications and the resulting tissue necrosis.

Aged↗

Endogeneously regulated site-specific differentiation of human palmar skin keratinocytes in organotypic cocultures and in nude mouse transplants.

Palmar and plantar epidermis is characterized by specific features such as the development of a striking lucidum, a very thick stratum corneum, prominent rete ridges and the unique expression of keratin K9. Using organotypic cocultures of keratinocytes and fibroblasts, we investigated to which extent the specific phenotype of palmar keratinocytes is maintained in vitro and under systemic host influences after transplantation onto nude mice. In vitro, palmar keratinocytes developed a thick epithelium with a prominent, although parakeratotic stratum corneum showing no significant differences in proliferation and differentiation in coculture with either palmar or nonpalmoplantar fibroblasts. All differentiation markers including keratohyaline and membrane coating granules as well as keratin K9 were also found, but at reduced levels and with slightly altered localization. In transplants, substantial normalization towards the palmar phenotype occurred. In 3-week-old grafts, a homeostatic state was reached, as illustrated by a constant thickness of the stratum Malpighii, presence of keratin K10 throughout the entire suprabasal compartment, increased numbers of K9- and filaggrin-positive cells, and reduction of keratins K16 and K17. At the ultrastructural level, numerous membrane coating granules and an enlargement of keratohyaline granules were seen accordingly, and immunofluorescence showed intense continuous lining of the dermo-epidermal junction by laminin, type IV collagen and integrin alpha 6. The high percentage of bromodesoxyuridine-positive cells, mainly in the basal compartment, underlined the hyproproliferative state, comparable to palmoplantar epidermis. In conclusion, (i) palmar keratinocytes can preserve the potential to express their specific phenotype upon transfer to culture conditions, and (ii) this intrinsic property is not significantly modulated by the type of cocultured fibroblasts. This suggests that fibroblasts act primarily by sustaining keratinocyte proliferation which is permissive for the fully differentiated phenotype.

Adolescent↗

[Ulcers of the tongue, pityriasis lichenoides and primary parvovirus B19 infection].

INTRODUCTION: We report a case of parapsoriasis en gouttes (or pityriasis lichenoides) which presents two peculiarities. First, the patient had lingual ulcerations and second, the eruption appeared during a seroconversion for Parvovirus B19. OBSERVATION: A 25 old woman presented a first episode of characteristic parapsoriasis en gouttes associated with purpuric palmoplantar lesions and lingual ulcerations, reaching deep muscular in histology. DISCUSSION: This observation of parapsoriasis en gouttes, peculiar because of lingual ulcerations, is mostly interesting because of its association with a primo-infection to Parvovirus B19. The receptor of the virus is localised on endothelial cells and that could explain purpuric lesions and ulcerations observed.

Adult↗

Zebrafish cyclin D1 is differentially expressed during early embryogenesis.

We have isolated and determined the nucleotide sequence of a cDNA containing the complete coding region of cyclin D1 from embryonic zebrafish cDNA library. The cyclin D1 gene is a single copy gene within the zebrafish genome, which undergoes an alternative polyadenylation process. The initial expression of cyclin D1 transcript occurs at the presumed onset of G1 phase in the developing zebrafish embryo.

Amino Acid Sequence↗

Coexpression of TGF alpha, epidermal growth factor receptor, and P-glycoprotein in normal and benign diseased breast tissues.

Twenty-four normal or benign breast tissues were examined for the expression of transforming growth factor-alpha (TGF alpha), epidermal growth factor receptor (EGFR), and P-glycoprotein, the product of the mdr-1 gene. Specific staining for all three proteins was observed in the majority of the samples. P-glycoprotein staining was present in most (88%), and confined to the lumenal surface of the ductal epithelium. Membranous EGFR expression was observed in epithelial cells in 92% of the specimens and 42% displayed both myoepithelial and epithelial cell staining. TGF alpha staining was intense and uniformly distributed through the cytoplasm (96%). Coexpression of EGFR, TGF alpha, and P-glycoprotein in normal human breast tissues suggests a role for each of those proteins in normal breast physiology. An interaction may be present in normal breast tissue between the EGF receptor pathway and P-glycoprotein.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Topography of mammalian connexins in human skin.

We have explored the expression of gap junction proteins in normal human skin by immunostaining cryostat sections (indirect immunofluorescence) or lyophilized epidermis (Western blotting) with antibodies against four mammalian connexins Cx26, Cx32, Cx40, Cx43; and by hybridizing total epidermal RNA (Northern blotting) with cRNA probes for Cx26, Cx32, and Cx43. We found that epidermal keratinocytes express Cx43 but not Cx26, Cx32, or Cx40. This expression was minimal in the basal layer, much higher in the spinous layer, reduced in the granular layer, and absent in the stratum corneum. Immunostaining for Cx43 was also observed in sebaceous glands, hairs, and eccrine sweat ducts. The two latter epidermal adnexae were also markedly labeled by antibodies against Cx26, a gap junction protein that was undetectable by immunofluorescence in interfollicular keratinocytes. Immunoblots of polyacrylamide gel electrophoresis-separated epidermal proteins and hybridization of epidermal RNA confirmed the presence of Cx43 in epidermis. These observations indicate that 1) Cx43 and Cx26 are components of human keratinocyte gap junctions; 2) these two proteins are differentially expressed in the interfollicular epidermis and the skin adnexae; 3) in interfollicular epidermis, Cx43 is a predominant gap junction protein, mostly expressed by the differentiating spinous cells; 4) Cx43 distribution is in accordance with the extensive dye coupling previously observed in this epidermal compartment.

Animals↗