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Biomedical subjects

E Tschachler

Publications and source records attributed to E Tschachler.

At least 19 recordsLinked to original sources

[Phototype, vitamin D status and bone mineral density among women at risk of osteoporosis].

PURPOSE: The aim of this study was to test the influence of phototype and vitamin D status feature on the bone mineral density (BMD) of the femoral neck in a group of middle-aged women considered at risk of osteoporosis (low levels of vitamin D [25(OH)D3<78 nmol/L] and hyperparathyroidism [parathormone level>36 pg/mL]). METHODS: This two-step study was conducted on 122 French women enrolled in the SUVIMAX (supplémentation en vitamines et minéraux antioxydants: antioxidant vitamin and mineral supplementation) cohort. The impact of various variables on BMD, including age, body mass index (BMI), vitamin D status, alcohol intake, sun exposure intensity and phototype was investigated using regression models. RESULTS: No statistical link was found between BMD and the variables documenting vitamin D status and parathormone levels, nor phototype. Nevertheless, fair phototypes tended to be associated with lower BMD values. However, BMD decreased with age and increased with BMI and physical activity level. CONCLUSIONS: Whatever their phototype, adult women concerned about precarious vitamin D status should undergo a vitamin D supplementation in combination with an adequate calcium intake all year long and a proper sun protection. Moreover, a physical activity maintenance should provide an additional benefit for prevention of osteoporosis.

Bone Density↗

Reference ranges of skin micro-relief according to age in French Caucasian and Japanese women.

BACKGROUND/PURPOSE: The variation of skin surface morphological indicators according to age has not been frequently studied. The aim of this work was to establish French Caucasian and Japanese reference ranges of these indicators according to age. METHODS: Two studies were performed simultaneously in Paris and Sendai on 356 Caucasian and 120 Japanese healthy women aged from 20 to 80 years. Skin replicas were obtained from the volar forearm and analysed by interferometry. This analysis yielded 16 morphological indicators. Reference ranges according to age were established using the statistical methodology defined by Royston. RESULTS/DISCUSSION: Reference ranges were found for 15 out of the 16 parameters for the French women as well as for the Japanese women. The models' truthfulness will have to be confirmed using new samples, larger if possible. Moreover, non-parametric methods will be used in order to compare the results provided by these approaches.

Adult↗

Self-reported skin sensitivity in a general adult population in France: data of the SU.VI.MAX cohort.

OBJECTIVE: This study aimed to examine the frequency of self-assessed facial skin sensitivity and its different patterns, and the relationship with gender and sun sensitivity in a general adult population. METHODS: A standardized 11-item questionnaire investigating reactions experienced during the past year was developed. The questions explored different patterns of skin sensitivity: pattern I (blushing related to vascular reactivity), pattern II (skin reactions to certain environmental conditions), pattern III (skin reactions after substance contact), and for women pattern IV ('breakout of spots' related to menstrual cycle). Additional items were addressed for women and men, including sun sensitivity. The questionnaire was administered to a large middle-aged population involved in the 'Supplément en Vitamines et Minéraux Antioxydants' (SU.VI.MAX) cohort. RESULTS: Sensitive facial skin was reported by 61% of the women (n = 5074) and 32% of the men (n = 3448), and the frequency decreased with age. The frequency of patterns I, II and III was greater for women (78, 72 and 58%, respectively) than for men (56, 48 and 28%) of comparable classes of age. The frequency of pattern IV was reported by 49% of premenopausal women, and skin reactions after shaving by 41% of the men. Sun sensitivity was found to be a major component of skin sensitivity. Factor analysis showed that individuals with fair phototype frequently evoked reactions associated with pattern I, and skin redness and burning sensations were related to certain environmental conditions (pattern II). CONCLUSION: Skin sensitivity is a common concern that declines with age and is relevant for men as well as for women.

Face↗

[Screening and therapy of anal intraepithelial neoplasia (AIN) and anal carcinoma in patients with HIV-infection].

Anal intraepithelial neoplasia (AIN) is a potential precursor of invasive anal carcinoma. Introduction of highly active antiretroviral therapy (HAART) in the treatment of HIV infection substantially reduced the incidence of some diseases associated with opportunistic viral infections. However, the incidence of AIN is reported to increase and HAART seems to have only little impact on the regression or progression of AIN. Paradoxically, improvement of survival in the HAART era results in an increased risk of anal cancer. The incidence of anal carcinoma amongst homosexual men is substantially higher compared to the normal population (35/100.000). This incidence is similar to the incidence of cervical cancer before screening for CIN with cervical cytology. Recent data suggest that the incidence of AIN and anal cancer is even higher among HIV-infected individuals. Both cancer entities share biologic similarities, including the association with human papillomavirus infection (HPV). Screening for CIN with cervical cytology and early treatment has resulted in a significant decline in the incidence of cervical carcinoma. Like cervical cancer, anal carcinoma may be preventable through identification and treatment of its precursors. Future efforts should focus on a screening protocol, training of clinicians in the diagnosis and treatment of AIN and anal carcinoma, and novel approaches to treatment of these lesions. This screening protocol could help to reduce anal cancer in HIV-infection as well as save limited resources in health care system.

Antiretroviral Therapy, Highly Active↗

[Effect of hormonal replacement therapy on cutaneous biophysical properties of menopausal women].

PURPOSE: The aim of this analysis was to study the possible effect of hormonal replacement therapy on some biophysical properties of the skin of menopausal women. SUBJECTS AND METHODS: A study was carried out on 106 menopausal, phototype I to IV women with clinically healthy skin. During the medical evaluation, the menopausal status, duration of the menopause, and, possible use of hormone replacement therapy and its duration were collected. A series of biophysical skin parameters in controlled environmental conditions was assessed on the face: sebum casual level, skin surface pH, skin colour, transepidermal water loss, capacitance, conductance, skin relief and temperature. The same parameters except for sebum were assessed on the forearm. Three sub-samples were defined according to the duration of the menopause and of hormone replacement therapy. RESULTS: The skin colour parameters revealed a greater red intensity value in menopausal women who had been treated for at least one year. In menopausal women who had been treated for at least 5 or 10 years, the biophysical measurements were significantly higher for the parameters evaluating hydration and sebum secretion, associated with higher values for the yellow intensity parameter and the skin relief parameters on the forehead. CONCLUSION: These results support the subjective impression and the clinical evaluation according to which hormonal replacement therapy could modify the development and the severity of some properties associated with skin ageing after the onset of menopause.

Aging↗

Alternative splicing of caspase-8 mRNA during differentiation of human leukocytes.

Caspase-8 is a key initiator of death receptor-induced apoptosis. Here we provide evidence that caspase-8 expression is subject to posttranscriptional regulation in human leukocytes. Resting peripheral blood lymphocytes preferentially use a distant splice donor site at the 3'-end of caspase-8 exon 8 to generate mRNAs with a truncated open reading frame. When lymphocytes were activated, the expression of caspase-8 variants was shifted to caspase-8/a and b which lack the extension of exon 8. The opposite change of the splicing pattern was found in a neutrophil differentiation model. Promyelocytic HL-60 cells mainly expressed caspase-8 mRNAs with the normal exon 8, but the splicing pattern was changed to the distant exon 8 splice site during DMSO-induced differentiation of HL-60 cells. In spite of the presence of these novel mRNAs, the corresponding translation products were not detectable in either cell type. Our findings suggest that leukocyte differentiation and alternative splicing of caspase-8 pre-mRNA are inter-dependent processes.

Alternative Splicing↗

The helical domain of GBP-1 mediates the inhibition of endothelial cell proliferation by inflammatory cytokines.

Inflammatory cytokines (IC) activate endothelial cell adhesiveness for monocytes and inhibit endothelial cell growth. Here we report the identification of the human guanylate binding protein-1 (GBP-1) as the key and specific mediator of the anti-proliferative effect of IC on endothelial cells. GBP-1 expression was induced by IC, downregulated by angiogenic growth factors, and inversely related to cell proliferation both in vitro in microvascular and macrovascular endothelial cells and in vivo in vessel endothelial cells of Kaposi's sarcoma. Experimental modulation of GBP-1 expression demonstrated that GBP-1 mediates selectively the anti-proliferative effect of IC, without affecting endothelial cell adhesiveness for monocytes. GBP-1 anti-proliferative activity did not affect ERK-1/2 activation, occurred in the absence of apoptosis, was found to be independent of the GTPase activity and isoprenylation of the molecule, but was specifically mediated by the C-terminal helical domain of the protein. These results define GBP-1 as an important tool for dissection of the complex activity of IC on endothelial cells, and detection and specific modulation of the IC-activated non-proliferating phenotype of endothelial cells in vascular diseases.

Apoptosis↗

Evidence that caspase-13 is not a human but a bovine gene.

Caspase-13 was reported to be a member of the human caspase family of proteases (Humke, E., et al., J. Biol. Chem. 273, 15702-15707, 1998). By contrast, a recent study (Lin, X., et al., J. Biol. Chem. 275, 39920-39926, 2000) could not confirm caspase-13 expression in human tissues. When we searched the GenBank database we found several expressed sequence tags (ESTs) from bos taurus completely matching the published caspase-13 sequence. Reverse transcription polymerase chain reaction (RT-PCR) analysis revealed that bovine but not human peripheral blood mononuclear cells express caspase-13. From these cells we cloned two bovine caspase-13 splice variants and found that the sequence of the larger variant was identical to the mRNA published by Humke et al. Our findings strongly suggest that the previously published caspase-13 sequence is not of human origin but represents a bovine gene.

Alternative Splicing↗

Targeted expression of bcl-2 to murine basal epidermal keratinocytes results in paradoxical retardation of ultraviolet- and chemical-induced tumorigenesis.

The antiapoptotic protein bcl-2 is found up-regulated in a number of malignant and premalignant skin conditions of keratinocyte origin, but in normal skin, it is expressed at low levels only in interfollicular epidermis. To investigate whether unregulated bcl-2 expression could affect the incidence of epidermal tumors, we have generated a mouse line that over-expresses human bcl-2 in the basal layer of epidermis under the control of the human keratin 14 promoter. These mice were subjected to both UVB photocarcinogenesis and classical two-stage chemical carcinogenesis. Although transgenic bcl-2 in these mice reduces the formation of sunburn cells after short-term UVB irradiation, chronically UVB irradiated K14/bcl-2 mice were protected against tumor development, because transgenic mice developed tumors much later and at a significantly lower frequency than controls. Immunohistochemical analyses of the UVB-induced tumors revealed no significant differences in the degree of inflammatory cell infiltrates. When either K14/bcl-2 mice or F(1) progeny of matings with mice expressing an activated Ha-ras oncogene (K14/bcl-2/ras) were treated with 9,10-dimethyl-1,2-benzanthracene/phorbol 12-myristate 13-acetate, the latency of first papilloma appearance was the same in transgenic mice and controls, but further papillomas developed more slowly in the mutant mice. Moreover, the K14/bcl-2/ras mice developed far fewer albeit larger tumors/mouse than did the ras/+ controls. The rate of conversion to malignant carcinomas, the carcinoma grade, and the frequency of lymph node metastases were not significantly different between mutants and controls. We conclude that, despite its antiapoptotic function, bcl-2, overexpressed in basal epidermal keratinocytes, exerts a paradoxical retardation on the development of skin tumors induced by chemical carcinogens and particularly by UVB.

9,10-Dimethyl-1,2-benzanthracene↗

Analysis of circadian and ultradian rhythms of skin surface properties of face and forearm of healthy women.

Biologic rhythms of cells and organisms are well documented and have been extensively studied at the physiologic and molecular levels. For the skin, many circadian changes have been investigated but few systematic studies comparing skin at different body sites have been reported. In this study we investigated facial and forearm skin circadian rhythms in eight healthy Caucasian women. Noninvasive methods were used to assess skin capacitance, sebum excretion, skin temperature, transepidermal water loss, and skin surface pH on fixed sites of the face and the volar forearm during a 48 h span under standardized environmental conditions. Using the cosinor or ANOVA methods, circadian rhythms could be detected for sebum excretion (face), transepidermal water loss (face and forearm), skin temperature (forearm), pH (face), and capacitance (forearm). No circadian rhythmicity was found for the other biophysical parameters. In addition to the 24 h rhythm component, rhythms with periods of 8 h were found for sebum excretion, of 8 and 12 h for transepidermal water loss (face and forearm), and of 12 h for skin temperature (forearm). Our study confirms that rhythms of skin surface parameters are readily measurable and that these rhythms differ between different sites. Furthermore, we demonstrate for the first time that, for transepidermal water loss (face and forearm), sebum excretion, and skin temperature (forearm), in addition to circadian rhythms, ultradian and/or component rhythms can be detected.

Activity Cycles↗

Topically applied lactic acid increases spontaneous secretion of vascular endothelial growth factor by human reconstructed epidermis.

BACKGROUND: Alpha-hydroxy acids (AHAs) are widely used for the treatment of hyperkeratotic skin disorders and photodamaged skin. OBJECTIVES: To investigate the effect of lactic acid (LA) on the secretion of cytokines by keratinocytes (KCs) of human reconstructed epidermis. METHODS: Creams containing 1.5%, 3% or 5% LA or vehicle controls were topically applied on to human epidermal equivalents (EEs). After 24 h, EEs were analysed for morphology and for the presence of apoptotic cells. Secretion of vascular endothelial growth factor (VEGF), angiogenin (ANG) and interleukin (IL)-8 was measured in the supernatants by enzyme-linked immunosorbent assay. RESULTS: LA led to a concentration-dependent increase in apoptotic cells as determined by cell morphology and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labelling. VEGF secretion was increased 2.5- and 2.8-fold (P < 0.05) over vehicle control after treatment with 1.5% and 3% LA, respectively. No significant increase in VEGF secretion was detected with 5% LA. In contrast to VEGF, secretion of ANG was decreased by LA in a concentration-dependent manner (0.5-fold for 5% LA; P < 0.01). No significant changes in IL-8 secretion were found with any of the concentrations tested. CONCLUSIONS: Our data demonstrate that the topical application of AHAs modulates the secretion of cytokines by KCs. Regulation of KC-derived growth factors and cytokines by AHAs might represent a mechanism contributing to their therapeutic effects in disorders such as photoageing.

Administration, Topical↗

Cutaneous elimination of 2,3,7,8-tetrachlorodibenzo-p-dioxin.

BACKGROUND: After exposure, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is excreted via the faeces, breast milk and epidermal lipids. OBJECTIVES: To determine to what extent TCDD is eliminated via the skin and to evaluate whethe cutaneous elimination can be accelerated by the application of petrolatum. METHODS: In two patients severely intoxicated with TCDD, material obtained from the skin surface and, in one patient, cerumen and the content of epithelial cysts, was analysed for TCDD. RESULTS: The TCDD concentration in the initial blood sample taken was 144 000 pg g(-1) blood fa in patient 1, and 26 000 pg g(-1) blood fat in patient 2. Six months later, when the skin tests were performed, the blood TCDD levels had decreased to 80 900 and 16 100 pg g(-1) blood fat, respectively. In the two samples of pooled cyst contents from patient 1, TCDD levels of 34 400 an 18 600 pg g(-1) fat were found. A cerumen sample contained TCDD at 20 500 pg g(-1) fat. In the material collected from the skin surface we observed a linear increase of the amount of TCD measured per test field with time, indicating a continuous elimination of TCDD via the skin. Th daily amount of TCDD eliminated via the skin was 1.51 pg cm(-2) in patient 1 and 0.57 pg cm(-2) in patient 2. Application of petrolatum led to a twofold increase in the amount of TCDD measured in patient 1, but had no significant effect in patient 2. CONCLUSIONS: In our patients, elimination of TCDD via the skin, most probably through desquamating scales, represented 1-2% of the overall daily TCDD elimination rate, with regard to the body surface and when calculated on the basis of the half-life of TCDD at the time of the skin test. If a more typical overall elimination half-life of 7 years is used as the basis for the calculatio the skin would account for 9% (patient 1) and 15% (patient 2) of the overall elimination. Although we observed an increase in TCDD in material derived from the skin surface of up to 100% after application of petrolatum in patient 1, such an approach appears not to be a feasible means to increase elimination. Owing to the small amount of TCDD measured in skin-surface material, as well as in the cyst contents and cerumen obtained from one patient, contamination of the environment and other persons appears highly unlikely.

Acne Vulgaris↗

Severe 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication: clinical and laboratory effects.

A variety of health effects have been attributed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), but little information is available on the course of a verified high-level TCDD intoxication. In this paper we describe two cases of heavy intoxication with TCDD and present a 2-year follow-up including clinical, biochemical, hematologic, endocrine, and immunologic parameters monitored in two women, 30 and 27 years of age, who suffered from chloracne due to TCDD intoxication of unknown origin. Patient 1, who had the highest TCDD level ever recorded in an individual (144,000 pg/g blood fat), developed severe generalized chloracne, whereas in the second patient, despite heavy intoxication (26,000 pg/g blood fat), only mild facial acne lesions occurred. Both patients initially experienced nonspecific gastrointestinal symptoms. In Patient 1 we observed a moderate elevation of blood lipids, leukocytosis, anemia, and secondary amenorrhoea. The laboratory parameters in Patient 2 were all normal. Despite the high TCDD levels, apart from chloracne, only few clinical and biochemical health effects were observed within the first 2 years after TCDD intoxication.

Acneiform Eruptions↗

Caspase-14: analysis of gene structure and mRNA expression during keratinocyte differentiation.

Caspase-14 is expressed in a tissue-specific manner in mouse skin. Here we determined the complete caspase-14 cDNA sequence of human caspase-14 by rapid amplification of cDNA ends. Sequence comparison with a cosmid clone containing genomic DNA revealed that the human caspase-14 gene comprises seven exons. Facultative utilization of a cryptic splice acceptor site within intron 5 leads to the formation of two mRNA species. In situ hybridization of human skin showed that caspase-14 is expressed in the uppermost layer of living epidermal cells, i.e., the granular layer, in hair follicles and sebaceous glands. In vitro caspase-14 transcription was low in subconfluent cultures but strongly increased when keratinocyte differentiation was simulated by maintaining cells at confluence for several days. This transcriptional upregulation was suppressed in the presence of a high extracellular calcium concentration. Our findings show that caspase-14 is regulated at the level of transcription during keratinocyte differentiation in vitro and in vivo.

Amino Acid Sequence↗