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E Fuchs

Publications and source records attributed to E Fuchs.

412 records · Page 23Linked to original sources

Binding sites of atrial natriuretic peptide in tree shrew adrenal gland.

Adrenal gland binding sites for atrial natriuretic peptide-(99-126) (ANP) were quantitated in tree shrew (Tupaia belangeri) by incubation of adrenal sections with (3-[125I]-iodotyrosyl28) atrial natriuretic peptide-(99-126), followed by autoradiography with computerized microdensitometry. In the adrenal glands, there are three types of ANP binding sites. One is located in the zona glomerulosa (BMax 84 +/- 6 fmol/mg protein; Kd 122 +/- 9 pM); the second in the zona fasciculata and reticularis (BMax 29 +/- 2 fmol/mg protein; Kd 153 +/- 6 pM) and the third in the adrenal medulla (BMax 179 +/- 1 fmol/mg protein; Kd 70 +/- 2 pM). Besides the influence of ANP on the regulation of adrenocortical mineralcorticoid and glucocorticoid secretion our findings raise the possibility for a local site of action of atrial natriuretic peptide in the regulation of adrenomedullary catecholamines in the tree shrew, primates and man.

Adrenal Glands↗

Gender-specific alterations of cerebral metabolites with aging and cortisol treatment.

Excess availability of the adrenocortical glucocorticoid hormone cortisol has been correlated with structural brain changes and a decline of cognitive functions during aging. Pertinent studies need to consider gender as a potential confound because of sexual dimorphism in the regulation of hypothalamus-pituitary-adrenal axis activity. In vivo localized proton magnetic resonance spectroscopy of male and female tree shrews revealed similar concentrations of cerebral metabolites in young adult animals but gender-specific alterations with aging as well as in response to cortisol treatment. In comparison with adult tree shrews, aged males had reduced concentrations of N-acetylaspartate (-33%; P<0.01) and total creatine (-34%; P< 0.01). These findings are in line with the occurrence of neuronal loss. In contrast, aged females exhibited increased concentrations of choline-containing compounds (+27%; P<0.05) which--together with a tendency for increased creatine (+24%) and myo-inositol (+14%)--is indicative of glial proliferation. After chronic administration of cortisol (4 mg/day for 28 days), male but not female tree shrews showed a specific reduction of the choline-containing compounds (-29%; P< 0.05). The observed sex differences with age are likely to result from differences in the regulation of stress-related hormones which is further supported by the gender-specific responses to cortisol.

Aging↗

Age-related levels of urinary free cortisol in the tree shrew.

There are still controversies concerning the effect of aging on the basal glucocorticoid concentration in mammals, including humans. Some studies reported an elevated glucocorticoid concentration in older subjects, while other reports showed no increases with age. These discrepancies may be caused by different experimental designs, gender differences, or varying sampling time points. The bulk of animal studies reporting increases of glucocorticoids with age were performed in rats. The present study was designed to investigate the impact of age on adrenocortical activity in a non-rodent mammalian species, tree shrews (Tupaia belangeri). We analyzed the basal urinary free cortisol concentration in the morning urine of male tree shrews in different age groups. Immediately after birth, a large variation in basal urinary free cortisol concentration (10-818 pg/micromol crea) has been observed. Between 21-40 day of age, the urinary cortisol concentration was low (32.7 +/- 5.6 pg/micromol crea) and increased steadily during puberty until adulthood (201-500 days; 161.8 +/- 15.1 pg/micromol crea). Thereafter, no further rise in basal urinary free cortisol concentration was found with increasing age and after reaching senescence (7-8 years).

Adrenal Cortex↗

Primate-like amyloid-beta sequence but no cerebral amyloidosis in aged tree shrews.

A central pathological feature of Alzheimer's disease is the profuse deposition of amyloid-beta protein (Abeta) in the brain parenchyma and vessel walls. Abeta also forms deposits in the brains of a variety of mammals, including all aged non-human primates studied to date. The sequence of Abeta in these animals is identical to that in humans. No Abeta deposits have been found in the brains of wild-type rats and mice, suggesting that the three amino acid differences between their Abeta and that of amyloid-bearing mammals impedes the fibrillogenicity of Abeta. Analysis of the primary sequence of the beta-amyloid precursor protein in tree shrews revealed a 98% similarity and 97% identity with the human protein. Furthermore, the predicted amino acid sequence of Abeta in tree shrews is identical to that in humans. However, immunohistochemical analysis failed to reveal beta-amyloid deposits in the neural parenchyma or vasculature of eight aged (7-8 years) tree shrews (Tupaia belangeri). The lack of correlation between the Abeta sequence and amyloid formation suggests that other factors contribute to cerebral amyloid deposition in aged animals.

Aging↗

Beauty is skin deep: the fascinating biology of the epidermis and its appendages.

A number of fascinating questions remain unaddressed in the realm of skin biology. We still know very little about the mechanisms that set up the patterning of hair follicles over the surface ectoderm, or about the precise signalling pathways involved in mesenchymal-epithelial interactions during hair development and differentiation. Studies over the past 10 years have implicated both the notch and sonic hedgehog pathways in these processes (Chen et al., 1997; Chiang et al., 1999; Crowe et al., 1998; Kopan and Weintraub, 1993; Nohno et al., 1995; Oro and Scott, 1998; Powell et al., 1998; St. Jacques et al., 1998). Furthermore, we know that members of the fibroblast growth factor and bone morphogenic protein families are also involved in mesenchymal-epithelial cues required for follicle morphogenesis, hair cycling, and/or follicle differentiation (Hebert et al., 1994; Jung et al., 1998; Kratochwil et al., 1996; Noramly and Morgan, 1998; Rosenquist and Martin, 1996; Song et al., 1996). However, it is not clear precisely how these pathways and factors are involved and how they might also interact with the wnt pathway in regulating hair follicle patterning and morphogenesis. These areas are currently centers of activity in the field, and answers will undoubtedly emerge with the flurry of new experiments presently being conducted. Another important issue is the residence of stem cells within the skin. While it is clear that the epidermis contains a population of cells with extraordinary proliferative capacity (Jones and Watt, 1993; Jones et al., 1995), their precise location in most body regions of the skin remains unclear. Similarly, while the bulge hypothesis has received considerable attention and support as the residence of the hair follicle stem cells (Cotsarelis et al., 1989; Lavker et al., 1993), the outer root sheath and the matrix of the follicle have also been postulated as potential homes for these critical cells (Oliver and Jahoda, 1988; Rochat et al., 1994). An equally challenging issue for the future is the extent to which skin stem cells might retain pluripotency, able to choose between an epidermal or hair follicle cell fate. Our recent studies implicating a Wnt pathway provide a starting point for exploration. I have discussed a number of recent insights that have surfaced concerning transcriptional regulation in the epidermis. Additionally, besides Lef1/beta-catenin, there are a number of transcription factors that have been identified that are likely to regulate key aspects of hair follicle differentiation and gene expression. The most interesting of these include a member, Whn, of the winged-helix transcription factors, recently been shown to be the defect underlying the nude mouse phenotype (Nehls et al., 1994; Segre et al., 1995) and the zinc finger transcription factor responsible for the hairless phenotype in mice and in humans (Ahmad et al., 1998; Cachon-Gonzalez et al., 1994). A major area for future study will be to elucidate the upstream and/or downstream targets of Lef1/beta-catenin, hairless, and whn. Let me close by returning to the issues of structure and function in the skin and to the underlying genetic basis of skin disorders. It is surprising that despite nearly 20 years of molecular genetics and its application to skin biology, we still know very little about the molecules and pathways involved in the acquisition of the epidermal barrier, the very purpose of the epidermis. Biochemical studies have given us clues as to the most important lipids involved (for review, see Proksch et al., 1993), and recent studies suggest that barrier function may in part be regulated through action of the steroid hormone superfamily of receptors (Attar et al., 1997; Hardman et al., 1998). A major research effort is now needed to begin to decipher the transcriptional regulation and the complex pathways involved in lipid synthesis and packaging. (ABSTRACT TRUNCATED)

Animals↗

Insects as inhalant allergens.

The importance of insect dust as inhalant allergen (e.g. locust, cockroach, mite, butterfly, bee, fly, etc.) is frequently underestimated as a cause of allergic conjunctivitis, rhinitis and bronchial asthma. The high allergenic potency of insect dust is demonstrated in cases of occupational allergy against locust. This dust is an obligatory sensitizing agent depending upon the degree of exposure and the potency of the allergen irrespective of constitutional factors. No doubts exist any more about the importance of house-dust mite (Dermatophagoides pteronyssinus) as an inhalative allergen. Allergy analysis should be extended also to these insect allergens especially in unclarified cases of perennial and particularly seasonal bronchial asthma or its "equivalents" (atopic rhinitis and conjunctivitis).

Allergens↗

Calcipotriol (MC 903), a synthetic derivative of vitamin D3 stimulates differentiation of squamous carcinoma cell line in the raft culture.

We investigated whether calcipotriol, a synthetic derivative of vitamin D3 has the ability to correct defects in the control of proliferation and differentiation of human squamous carcinoma cells using the raft culture of SCC 13 cell line. Calcipotriol treatment at concentrations of 10(-8)-10(-6) M considerably enhanced terminal differentiation of SCC 13 cells, as shown by the appearance of enucleated-eosinophilic cells as well as granular cells in their upper cell layers. Immunohistochemical staining showed marked increases in the differentiation of marker proteins such as keratin 1, involucrin, or filaggrin expressing cells in their upper layers. The elevated expression at protein level was confirmed by immunoblotting analysis. Furthermore, calcipotriol also stimulated basal cell marker proteins such as keratin 14 and EGF receptor. However, the numbers of basal marker expressing cells within the architecture of SCC 13 raft culture were markedly reduced upon calcipotriol treatment, and their localization was mainly restricted in the innermost cell layer. In addition, calcipotriol stimulated EGF receptor biosynthesis for the first 16 hours post treatment and subsequently inhibited [3H]-thymidine incorporation of SCC 13 cells at 24 hours. In this study, we have clearly demonstrated that the long term application of calcipotriol considerably improves the complex defects in the regulation of proliferation and differentiation of SCC 13 cells, as supported by morphological and biochemical observations. This provides an evidence that calcipotriol can be applied clinically as a potent differentiation inducer in the treatment of human squamous cell carcinoma.

Antineoplastic Agents↗