Search PubMed⌕ Search

Biomedical subjects

E Frenk

Publications and source records attributed to E Frenk.

At least 37 records · Page 2Linked to original sources
PubMed1995

Antifungal principles of Baccharis pedunculata.

Four compounds including a flavone, an acetylenic lactone, a prenylated coumarin, and a 3-methyl ether flavone were isolated from the dichloromethane leaf extract of Baccharis pedunculata (Mill.) Cabr. (Asteraceae). The latter three compounds were identified to be responsible for the antifungal activity against some human pathogenic and phytopathogenic fungi. The most active compound, lachnophyllum lactone, an acetylenic lactone, showed a very high toxicity (LD50 2 micrograms/ml) against human keratinocytes.

Antifungal Agents↗
PubMed1995

Linkage disequilibrium mapping of the gene for Hermansky-Pudlak syndrome to chromosome 10q23.1-q23.3.

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by the triad of tyrosinase-positive oculocutaneous albinism, bleeding diathesis due to storage-pool deficiency of platelets, and a lysosomal ceroid storage disease. The disorder is particularly frequent in Puerto Rico and in an isolated village in the Swiss Alps. We have used a linkage disequilibrium mapping approach to localize the HPS gene in both of these groups to a 0.6 centiMorgan interval in chromosome segment 10q23.1-q23.3. These results indicate that the Puerto Rican and Swiss forms of HPS are either allelic or that they result from mutations in very closely linked genes in this region. This region of distal chromosome 10q is syntenic to the region of mouse chromosome 19 that includes 'pale ear' (ep) and 'ruby-eye' (ru), which must be considered as potential murine homologues to human HPS.

Albinism, Oculocutaneous↗
PubMed1995

Oxidative defense in cultured human skin fibroblasts and keratinocytes from sun-exposed and non-exposed skin.

Skin fibroblasts and keratinocytes cultivated from chronically light-exposed skin sites have higher levels of the protective protein ferritin than cells derived from unexposed areas of the body, suggesting an adaptive response of cells exposed to chronic external insults. In the same line, ferritin levels were always found to be 2- to 7-fold higher in epidermal keratinocytes than in the underlying dermal fibroblasts of the same person thus providing the keratinocyte with continuous protection by the higher cellular ferritin content. The activation of ferritin by oxidative stress including UVA radiation could represent an important cellular defense mechanism that operates in human skin. Following low fluences of UVA radiation (2-4 x 10(5) J/m2), ferritin levels increased by 20-30% in normal adult skin fibroblasts and showed a subsequent decrease at higher UVA fluences. In contrast, skin keratinocytes were not perturbed by UVA radiation exposure except for very high fluences (1.25 x 10(6) J/m2) where slight decreases in cellular ferritin were noted in 7 of the 12 cell lines. Fibroblasts derived from light-exposed skin sites that possessed higher levels of cellular ferritin were highly protected against UVA-induced membrane damage as measured by lactate dehydrogenase release compared with fibroblasts from nonexposed body sites with lower levels of ferritin. It is clear from our results that ferritin plays an important role in protection at the cellular level in human skin cells, but the role of this putative protective protein in vivo remains to be defined.

Adaptation, Physiological↗
PubMed1995

Two genes contribute to different extents to the heme oxygenase enzyme activity measured in cultured human skin fibroblasts and keratinocytes: implications for protection against oxidant stress.

Activation of expression of the heme oxygenase (HO) gene appears to be involved in a cellular defense system in mammalian cells. We now demonstrate that while HO-1 mRNA levels are strongly inducible in dermal fibroblasts they are barely inducible in human epidermal keratinocytes following oxidative stress (UVA radiation and hydrogen peroxide). Paralleling this result was the observation that HO-2 mRNA levels were low in dermal fibroblasts but were high in epidermal keratinocytes. In neither case was the HO-2 gene inducible. The expression of the two HO genes led to enzymatic activity in both types of skin cells with an approximately 2.5-fold higher level of enzymatic activity present in keratinocytes compared with fibroblasts derived from the same biopsy. In addition, ferritin levels, which have been found to be augmented via the HO-dependent release of iron from endogenous heme sources, were two- to three-fold higher in keratinocytes compared with matching fibroblasts. This higher ferritin pool would result in an enhancement of cellular iron sequestering capacity that may confer increased resistance to oxidative stress. Indeed, keratinocytes showed less UVA radiation-dependent cell membrane damage than fibroblasts. These results are consistent with the hypothesis that HO expression in human epidermis and dermis is related to cellular defense mechanisms that operate in human skin.

Cells, Cultured↗
PubMed1995

Modification of late epidermal differentiation in photoaged skin treated with topical retinoic acid cream.

BACKGROUND: Retinoic acid (RA) cream treatment alters epidermal proliferation and differentiation in photoaged skin. OBJECTIVE: To study the changes in the expression of markers of epidermal differentiation in photoaged skin following RA cream treatment. METHODS: Ten subjects with photoaged skin were examined before treatment and at regular intervals during 12 months of once daily application of 0.05% tretinoin cream over the left forearm. Paraffin-embedded biopsy sections from the forearm were stained with loricrin, filaggrin, involucrin and cornifin antisera in addition to hematoxylin and eosin. The various layers were measured using a calibrated optical micrometer. RESULTS: The thickness of the epidermis increased rapidly, reaching a substantial increase after 1 month of retinoid cream application and retaining it during the following 12 months. The stratum granulosum achieved a transient but substantial increase after 1 and 3 months. Except involucrin, the ratio between the layers expressing the various markers of epidermal differentiation and the epidermis significantly increased following tretinoin cream treatment. CONCLUSION: RA cream treatment not only increases the thickness of the epidermis but also the programming of late terminal epidermal differentiation, as expressed by the markers studied. Thus, RA appears to affect both proliferation and differentiation of keratinocytes in vivo.

Administration, Topical↗
PubMed1995

Angiosarcoma of the scalp. A case with a particularly aggressive evolution.

A 80-year-old woman presented with a spontaneously bleeding wound on her scalp. The diagnosis of angiosarcoma was made based on histopathological examination of the second biopsy 1 month later. At that time, a large hematoma was present on the scalp and forehead with two bleeding erosions and numerous small blue-black nodules as well as a right cervical lymphadenopathy. The patient was treated by wide-field electron-beam radiotherapy, which showed no effect. The particularly aggressive evolution of this angiosarcoma led to death within less than 2 months.

Aged↗
PubMed1995

[Skin changes in endocrine disorders (with the exception of diabetes)].

Endocrinologic disorders occasionally manifest themselves by cutaneous abnormalities. In some instances, these alterations are the most prominent complaints of the patient. It is then important that the physician is able to recognize them as the manifestation of the endocrinologic disease. In this review, we describe the main cutaneous lesions occurring in endocrinopathy, like troubles of the skin pigmentation [melasma, acanthosis nigricans, Addison's disease, Cushing's syndrome, vitiligo], generalized or pretibial myxedema, acne and androgen excess, hirsutism. Where known, we try to approach the physiopathologic mechanisms that account for cutaneous changes. Additionally, some treatments are discussed.

Acne Vulgaris↗
PubMed1994

Antifungal tests in phytochemical investigations: comparison of bioautographic methods using phytopathogenic and human pathogenic fungi.

The detection limits in two bioautographic assays have been determined for a series of antifungal compounds, including clinically used antimycotics, fungicidal agrochemicals, and various classes of secondary plant metabolites. Target organisms were the filamentous fungus Cladosporium cucumerinum and the yeast Candida albicans. For clinical agents and agrochemicals, the detection limits in the two assays reflected to a certain extent their known spectrum of activity. Most of the plant-derived compounds tested showed a positive response in both assays, but with detection limits varying by a factor up to tenfold. For screening purposes, it is thus advisable to use both tests, as some activities would otherwise go undetected. The MIC values of these substances were determined in order to verify a possible correlation with the detection limit in the bioautographic assays.

Antifungal Agents↗
PubMed1994

Candida colonization and subsequent infections in critically ill surgical patients.

OBJECTIVE: The authors determined the role of Candida colonization in the development of subsequent infection in critically ill patients. DESIGN: A 6-month prospective cohort study was given to patients admitted to the surgical and neonatal intensive care units in a 1600-bed university medical center. METHODS: Patients having predetermined criteria for significant Candida colonization revealed by routine microbiologic surveillance cultures at different body sites were eligible for the study. Risk factors for Candida infection were recorded. A Candida colonization index was determined daily as the ratio of the number of distinct body sites (dbs) colonized with identical strains over the total number of dbs tested; a mean of 5.3 dbs per patient was obtained. All isolates (n = 322) sequentially recovered were characterized by genotyping using contour-clamped homogeneous electrical field gel electrophoresis that allowed strain delineation among Candida species. RESULTS: Twenty-nine patients met the criteria for inclusion; all were at high risk for Candida infection; 11 patients (38%) developed severe infections (8 candidemia); the remaining 18 patients were heavily colonized, but never required intravenous antifungal therapy. Among the potential risk factors for candida infection, three discriminated the colonized from the infected patients--i.e., length of previous antibiotic therapy (p < 0.02), severity of illness assessed by APACHE II score (p < 0.01), and the intensity of Candida spp colonization (p < 0.01). By logistic regression analysis, the latter two who were the independent factors that predicted subsequent candidal infection. Candida colonization always preceded infection with genotypically identical Candida spp strain. The proposed colonization indexes reached threshold values a mean of 6 days before Candida infection and demonstrated high positive predictive values (66 to 100%). CONCLUSIONS: The intensity of Candida colonization assessed by systematic screening helps predicting subsequent infections with identical strains in critically ill patients. Accurately identifying high-risk patients with Candida colonization offers opportunity for intervention strategies.

Adult↗
PubMed1994

Abnormal keratin 1 and 10 cytoskeleton in cultured keratinocytes from epidermolytic hyperkeratosis caused by keratin 10 mutations.

Epidermolytic hyperkeratosis is caused by mutations of the differentiation-specific keratins K1 and K10. These mutations produce a weakened cytoskeleton that is prone to collapse resulting in cell fragility and lysis. In this study we have analyzed cultured keratinocytes from EHK patients bearing 10R-to-H and 15L-to-S mutations within the 1A segment of the K10 rod domain. Keratinocytes were grown submerged in serum-free medium and induced to differentiate by growing to confluence and increasing the Ca++ concentration in the medium. Cultures were either harvested for mRNA sequence analysis or subjected to immunofluorescence microscopy. Differentiating keratinocytes from these patients were found to express these K10 mutations in their mRNA. Moreover, these cells could be distinguished from normal keratinocytes by their aberrant morphology. EHK keratinocytes frequently exhibited a collapsed perinuclear network of K1/K10 filaments and sometimes peripheral granules of K1 and K10 aggregates, reminiscent of the cells of the suprabasal layers in these patients. This report documents the expression of mutant keratin 10 in cultured EHK keratinocytes.

Base Sequence↗
PubMed1994

Cellular sensitivity to oxidative stress in the photosensitivity dermatitis/actinic reticuloid syndrome.

Skin fibroblasts from certain patients with the photosensitivity dermatitis/actinic reticuloid syndrome show enhanced sensitivity to ultraviolet radiation compared to normal fibroblasts. To probe further the link between oxidative damage and this disease, we have obtained a more extensive set of cell lines from patients with a severe form of the disease and examined their sensitivity towards oxidative stress by measuring cell survival following UVA radiation (330-450 nm) or hydrogen peroxide treatment (0.1-2.4 mM). The activation of the stress gene, heme oxygenase, has also been assessed by measuring the accumulation of mRNA after hydrogen peroxide treatment. Our studies have confirmed that a slight ultraviolet sensitivity is a characteristic of photosensitivity dermatitis/actinic reticuloid syndrome cell strains and we further demonstrate that these cell lines are particularly sensitive to hydrogen peroxide with up to a three- to fourfold increased sensitivity as compared to normal controls. We also show that certain ataxia telangiectasia strains that are especially sensitive to hydrogen peroxide are also slightly sensitive to ultraviolet radiation. Hydrogen peroxide induces accumulation of mRNA for the oxidant-inducible stress protein, heme oxygenase, with similar kinetics (maximum mRNA accumulation 2-4 h following treatment) and with a similar range of magnitudes in both normal (6.6-20.6 times mRNA increase over basal levels) and photosensitivity dermatitis/actinic reticuloid (2.9-12.8 times) skin cells. Because cells from photosensitivity dermatitis/actinic reticuloid patients show increased sensitivity towards oxidative stress but show no significant change in oxidant activation of the heme oxygenase gene, we propose that the defect involves a late stage of processing of oxidative damage rather than a compromised free radical scavenging system.

Adolescent↗
PubMed1994

An epidemic outbreak of papular and follicular contact dermatitis to tocopheryl linoleate in cosmetics. Swiss Contact Dermatitis Research Group.

BACKGROUND: In Spring 1992, an epidemic outbreak of papular and follicular rashes caused by a new line of cosmetics occurred throughout Switzerland. OBJECTIVE: Epidemiological and clinical data were collected in order to identify the offending agent and to specify the pathophysiological mechanisms. METHODS: The data concerning 263 patients seen by dermatologists plus 642 additional cases directly reported by consumers to the manufacturer were analyzed. Seventy-seven patients were patch-tested, 26 extensively, and 15 performed a repeated open application test for a duration of 4 weeks. Control patch and use tests were performed in 73 and 25 patients, respectively. The results were analyzed statistically. In addition, 12 skin biopsies were performed for histological examination. Biochemical studies on the cosmetics (final products and offending ingredient) supplemented the clinical studies. RESULTS: The lesions were mainly papular and follicular, widely distributed, with pronounced pruritus, which was aggravated by sweating or heat exposure, and were long lasting. In a few cases, the papules were located on intensely erythematous, well-defined plaques, suggesting irritation rather than allergy. Both immediate and delayed onsets of the lesions were observed. Skin biopsies showed signs of folliculitis and perifolliculitis with little alteration of the interfollicular epidermis. Patch and use testing disclosed vitamin E linoleate (a mixture of tocopheryl esters, mainly tocopheryl linoleate) as the offending agent. An in vitro time-dependent formation of oxidative products under storage or oxidation-stimulating conditions was observed. CONCLUSION: Though vitamin E esters have been widely and safely used for decades in dermatological preparations and in cosmetics, vitamin E linoleate was the cause of about 1,000 cases of unusual papular mainly follicular contact dermatitis. Oxidized vitamin E derivatives could act in vivo as haptens and/or irritants, possibly with synergistic effects.

Adolescent↗
PubMed1994

Hydroa vacciniforme.

Hydroa vacciniforme is a rare chronic photodermatosis with onset in childhood. It is characterized by recurrent vesicles healing with scars. We report a typical case of a young, 8-year-old boy showing favorable evolution under treatment with chloroquine and a topical sunscreen.

Child↗
PubMed1994

Ultraviolet A-induced cellular membrane damage in the photosensitivity dermatitis/actinic reticuloid syndrome.

Abnormal photosensitivity of skin in the photosensitivity dermatitis/actinic reticuloid syndrome (PD/AR) correlating to an abnormal photosensitivity of dermal fibroblasts from these patients has been established previously. Cultured human skin fibroblasts from normal infant and adult donors, foreskin tissue and patients with PD/AR were assayed for oxidative stress induced membrane damage following ultraviolet A (UVA) radiation (340-450 nm) and hydrogen peroxide treatment by measurement of lactate dehydrogenase release. Skin fibroblasts from PD/AR patients were, in general, 2- and 4-fold more sensitive than normal controls regarding membrane-induced damage to UVA radiation and hydrogen peroxide treatment, respectively. Cells from one patient where biopsies were taken during full disease flair and 2 years later, following disease remission by immunosuppressive therapy, showed the same cellular sensitivity. In addition, fibroblasts from foreskin tissue were resistant to UVA radiation as measured by lactate dehydrogenase release, suggesting that this frequently used source of cell culture does not provide the best control group for comparison with photosensitive disease states. All these results suggest that the target for the cellular sensitivity seen in cells from PD/AR patients is the membrane.

Adolescent↗
PubMed1994

[Generalized granuloma annulare].

The generalized or atypical granuloma annulare represents 8.5-15 p. 100 of all cases of granuloma annulare (GA). It differs from the localized GA variant by its morphology, its localization, a later age of onset, its protracted course, a poor response to therapy and its facultative association to diabetes mellitus. We present a typical case of generalized GA associated with eczematous dermatitis.

Aged↗