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1.
Adult Naval Medical Research Institute (NMRI) mice, after prenatal exposure to retinoic acid (RA), were treated with a standard two-stage skin carcinogenesis regime to characterize hyperplastic epidermal foci that precede the appearance of cutaneous papillomas, and to investigate the in vivo long-term action of RA on adult mouse skin treated with DMBA (7,12 dimethyl benz[a]anthracene) and TPA (12-O-tetradecanoylphorbol 13-acetate). The results demonstrate that RA administered to pregnant mice had a long-term inhibitory action on the cell differentiation and development of hyperplastic lesions occurring prior to cancer on the adult skin of their offspring as well as a stimulatory effect on cell proliferation of these hyperplastic lesions.  相似文献   

2.
Reasons for performing study: Abnormal epidermal stem cell regulation may contribute to the pathogenesis of equine chronic laminitis. Objective: To analyse the involvement of p63, a regulator of epidermal stem cell proliferative potential, in chronic laminitis. Methods: Epidermal tissues from skin, coronet and lamellae of the dorsal foot were harvested from 5 horses with chronic laminitis and 5 control horses. Tissues were analysed using histopathology, immunofluorescence microscopy and quantitative immunoblotting Results: Hoof lamellae of laminitic horses had a lower frequency of p63 positive cells than control lamellae, particularly in the distal region. Quantitative immunoblotting confirmed reduced p63 expression in the laminitic distal lamellar region. The decreased p63 expression in laminitic epidermal lamellae was most apparent in the abaxial region adjacent to the hoof wall and highly associated with the formation of terminally differentiated, dysplastic and hyperkeratotic epidermis in this region, whereas lamellae from control horses maintained high p63 expression throughout the axial‐abaxial axis. Conclusions: Expression of p63 in equine skin resembles that reported in other species, including man and rodents, suggesting that p63 can serve as a marker for the proliferative potential of equine epidermal stem cells. p63 expression was significantly lower in the chronic laminitic hoof than in that of control horses, suggesting laminitic hoof epithelium has more limited proliferative potential with a shift towards differentiation. This may reflect reduced activity of epidermal stem cells in laminitic hoof. It is proposed that p63 contributes to the maintenance of hoof lamellae and that misregulation of p63 expression may lead to epidermal dysplasia during lamellar wedge formation. Potential relevance: This study suggests that loss of epidermal stem cells contributes to the pathogenesis of equine laminitis. Autologous transplantation of p63‐positive epidermal stem cells from unaffected regions may have regenerative therapeutic potential for laminitic horses.  相似文献   

3.
The purpose of this study was to evaluate the effect of protein malnutrition on the skin epidermis of mice. A low protein diet induced thinning of the skin epidermis, a decrease of cell proliferative activity in epidermal cells and a decrease of stratum corneum hydration. Dityrosine was immunostained in the cytoplasm of epidermal cells in the low protein diet group. Plasma advanced oxidation protein product (AOPP) levels were significantly more increased in the low protein diet group than in the control diet group. These results suggest that protein malnutrition adversely affects the structure and water barrier and reservoir functions of the skin epidermis, and these pathological changes are associated with the expressions of protein oxidation markers, dityrosine and AOPP.  相似文献   

4.
The purpose of this study was to measure the thickness of canine epidermis at various anatomical sites according to localization of cornified envelopes (involucrin and filaggrin), keratins (keratin 10, 5), and their mRNA expression. This was done in the skin of five breeds of dogs including seven poodles, six golden retrievers, six Shih Tzus, four pugs, and four Labrador retrievers. Epidermal thickness of the stratum corneum and nucleated epidermal layer was significantly different. The greatest thickness was observed in the digital web area and the thinnest epidermis was in the axilla. Epidermal thickness was also significantly different between the breeds (p < 0.05). Immunohistochemical staining scores revealed significant decreases of involucrin, filaggrin, and keratin 10 in the ventral and weight-bearing sites, and a relative increase of keratin 5 (p < 0.05). q-PCR analysis showed that their the levels of mRNA were positively correlated with expression of the corresponding proteins in skin samples (p < 0.05). The present study is the first to report the relationship between epidermal gene expression and histologic morphology of the skin in normal dogs. Further studies will be essential to fully understand the pathogenesis of skin barrier dysfunctions in canines.  相似文献   

5.
It is known that topical all-trans-retinoic acid (RA) modulates growth and differentiation of skin and its cutaneous appendages. To examine whether a pre-natal exposure to a potentially non-teratogenic dosage of all-trans-RA had any effect on vibrissal follicle development, the histologic and immunohistochemical responses to RA during its morphogenesis in NMRI mouse were investigated. After a single oral dose of 30 mg/kg body weight of all-trans-RA on day 11.5 of gestation, no fetal malformations were detected and the histological features and the distribution of keratin (K) proteins in comparable stages of vibrissal development were similar for the untreated, vehicle-treated and RA-treated mice. The absence of teratogenic response and of adverse effects on the vibrissae under the experimental conditions indicates that this protocol may be useful for investigation of the effects of pre-natal exposure to RA on the post-natal development of experimental tumours in the mouse skin.  相似文献   

6.
Basic Concepts of the Bovine Teat Canal   总被引：4，自引：0，他引：4  
The bovine teat canal is highly specialized in its unique function of preventing both leakage of milk and entry of bacteria and thereby plays a major role in the defence of the udder against mastitis. The teat canal is a longitudinally folded cylinder-shaped body opening, covered with approximately the same type of epithelia as the normal skin and surrounded with a net-like integrated musculoelastic system facilitating its opening and closure. During milking, dead, flattened, enucleated squamae (cellular detritus) are sloughed from the teat canal surface and are continually replaced by inner cells differentiating outwards. The epidermis is characterized by a polarized pattern of epithelial growth and differentiation, with a single layer of proliferating keratinocytes and multiple overlying differentiated layers. Morphologically, the cells transit from the basal layers on the basement membrane of the dermis through stratum corneum before they finally end up as the keratin of the teat canal. The majority of the epidermal protein synthesizing machinery is devoted to making keratin. This is reflected in the fact that keratins are the major structural proteins, constituting up to 85% of a fully differentiated keratinocyte. Epidermal keratin is a 40-70 kDa alpha-helical coiled-coil dimer of the intermediate filament family that, among other marker proteins, characterizes each stage of keratinocyte differentiation. Studies of skin fragility disorders show that the primary role of keratins in epidermal cells is to reinforce them so that they do not lyse upon physical pressure and to provide cells with subtly different properties of resistance and plasticity to equip the epithelial cells for the physical stress of each particular body site. Epithelial cell specialization for function also depends, however, on the lipid composition and organization and on the epidermal architecture. Epidermal architecture depends on epidermal turnover time, which in turn depends on cell number as well as the proliferative condition. Both in vitro and in vivo studies have implicated calcium as a major modulator of epidermal differentiation. Calcium is a factor known to enhance differentiation and promote expression of the differentiation-specific keratin genes. In animals and humans, both topical and systemic retinoids produce acanthosis, hypergranulosis and a relative (but not absolute) decrease in the thickness of the stratum corneum. Despite a high degree of epithelial specialization, we expect a somewhat similar immunological functional importance in the teat canal epithelia as in other stratified squamous keratinized type epithelia.  相似文献   

7.
Epidermal growth factor was injected intracamerally into the anterior chamber of the right eye of 9 cats. The central portion of the cornea in 8 of the 9 cats that had been cryoinjured. Effect of epidermal growth factor on the repair of endothelial cells in cats was evaluated by endothelial specular microscopy. Endothelial cell density and corneal thickness were studied quantitatively, as a measure of endothelial cell function. The repair process also was evaluated qualitatively by studying morphologic changes, developing as a result of reendothelialization and return to normal function. Seemingly, differences between rate of healing of cryoinjured eyes injected with epidermal growth factor and that in nontreated eyes were not significant (P = 0.86). The endothelial repair process was characterized by enlargement and migration of adjacent noninjured cells.  相似文献   

8.
Muscle growth of male obese (ob/ob) and lean mice at 2, 3, 5 and 8 wk were analyzed on the basis of weights of gastrocnemius, plantaris and soleus muscles from each hind leg. The carcasses (prepared by removing skin, viscera, head, feet and tail) were analyzed for fat content so that the effect of phenotype on the relationship between muscle weight and fat-free carcass weight could be assessed. For each age group the obese mice had less muscle relative to fat-free carcass weight than lean mice, with the difference being significant at 3 wk (P less than .05) and 8 wk (P less than .025). The proliferative activity of muscle satellite cells in 2- and 3-wk-old obese and lean mice was measured on isolated muscle fibers by autoradiography. Muscle fiber diameter and number of nuclei/unit length were unaffected by phenotype, but the proportion of muscle nuclei showing proliferative activity was lower (P less than .01) in obese than in lean mice at 2 wk (1.05 vs 1.93%, respectively) and 3 wk of age (.23 vs .59%, respectively). These results are consistent with the suggestion that muscle growth is limited by satellite-cell proliferative activity, although direct evidence for a cause and effect relationship is not provided.  相似文献   

9.
Epidermal growth factor (EGF) receptors were detected in plasma membrane preparations of equine hoof wall laminar tissue at concentrations comparable to that of equine liver. Scatchard analysis of the equilibrium binding data suggested the presence of two classes of EGF binding sites in most of the controls (plasma membranes from clinically normal horses); a high-affinity class and a more numerous low-affinity class. The dissociation constant of the low-affinity class of EGF-specific receptors (KD = 1 x 10(-9)M) is in reasonable agreement with other values established for the EGF receptor. The variability between individual estimates for the KD of the high-affinity receptor class precluded an accurate estimate for those sites. A possible explanation is discussed. The high-affinity binding sites were uniformly absent in plasma membranes prepared from horses affected by chronic laminitis. Autoradiographic analysis localised the EGF receptors primarily to the secondary epidermal laminae, with an apparent greater density over the proliferative basal keratinocytes. Little label was associated with the dermal or the keratinised primary epidermal laminae. Tissue from horses with chronic laminitis had EGF receptors located uniformly over the hyperplastic epidermal keratinocytes. These data suggest that an EGF-mediated response may be involved in the hyperproliferative response that is characteristic of chronic laminitis.  相似文献   

10.
Abstract We investigated in vivo the histological and immunohistochemical responses of mouse hair pelage follicle morphogenesis to prenatal exposure to a potentially nonteratogenic dose of all- trans -retinoic acid (RA), as a basis studying the preventive effect of RA on adult mouse skin carcinogenesis. In pregnant mice, a single oral dose of RA at 30 mg kg−1 body weight given on day 11.5 of gestation caused no RA-induced changes in the morphology or temporal expression patterns of keratins during pelage hair follicle morphogenesis. The only differential effect of RA was a statistically significant increase in the number of BrdU-positive nuclei in hair bulbs from RA exposed fetuses compared with nonexposed mice. The absence of adverse RA effects suggests that this experimental design may represent a valuable protocol for use in studies on the in vivo effects of this retinoid on different skin diseases.  相似文献   

11.
In the present study, a porcine model for controlled skin expansion was investigated to improve our understanding of epidermal and vascular responses following stretching. The model is of outstanding importance not only for the clinical use of tissue expansion but provides interesting data for skin physiology and oncology, too. Thirteen out of 15 animals, who underwent silicone tissue expander implantation showed good clinical results. In all of them, skin biopsies were taken at the end of a controlled tissue expansion procedure (final expander volumes 350 or 500 ccm): one tissue specimen was obtained from the centre of the expanded skin area and a second from the neighbouring but nonexpanded skin. The tissue specimens were immediately frozen in liquid nitrogen and processed to 4 microns thick acetone-fixed frozen sections. Lectin histochemistry and immunohistology were performed using the following techniques: direct and indirect immunofluorescence technique (DIFT, IIFT), immunoperoxidase technique (POX) with either 3,3'-diamino-benzidine (DAB) or 3-amino-9-ethyl-carbazole (AEC). The histochemical findings were supplemented by measurements of the number of vital epidermal cell layers, the epidermal thickness (microns), and the papillary vascular count per visual field. There was a significant diminuation of the vascular count (mean +/- S.D. = 55.0% +/- 12.5%; U-test: p less than 5%). By immunohistochemistry, a loss of the basal cell reactivity for the following antibodies was noted: ACAM (against calmodulin), K 8.12 (against keratins 13 +/- 16) and A51-B/H4 (against keratins 8, 14, 18). There was a remarkable increase of filaggrin expression in the uppermost spinal cell layers in expanded skin, which was most pronounced in those specimens with the shortest interval to the last fluid injection into the expander. We gained no evidence for alterations of the expression of suprabasal epidermal keratins, lectin binding sites (UEA I, PNA, ConA, WGA), and vascular lectin- and immunoreactivity due to tissue expansion. The subdermal capsule, which had formed around the silicone expander, was strongly vimentin-reactive. In conclusion, controlled tissue expansion is capable to change the basal cell phenotype--a feature which is shared with a number of conditions with increased proliferative activity and with the epidermis covering different skin tumours. The regular expression of suprabasal keratins and epidermal lectin binding sites provides evidence for a normal epidermal cell differentiation. Furthermore, the porcine skin is a reliable model for studying physiology and pathophysiology of human skin.  相似文献   

12.
以S180腹水瘤小鼠为动物模型，应用11.00、14.67和22.00J/cm^2 3种剂量氦氖激光照射荷瘤鼠哈德腺，同时联合应用化疗药物环磷酰胺，对S180荷瘤鼠脾脏淋巴细胞IL-2诱生活性和淋巴细胞增殖反应的影响作了系统地研究。结果表明：CYT/氦氖激光照射联合应用组IL-2诱生活性和淋巴细胞增殖反应均明显高于CYT对照组。CYT可对荷瘤体产生某种程度的免疫抑制效应，而氦氖激光照射则可在某种程度上改善这一效应。  相似文献   

13.
Echinacea purpurea (EP) and Echinacea angustifolia (EA) are ones of the most important world's herbs with immunotropic activity. They were traditional medicinal plants used by North American Indians for the treatment of various illnesses. Now they are cultivated in many countries and are used mainly to treat respiratory tract infections. Rhodiola rosea (RR) and Rhodiola quadrifida (RQ) are medicinal plants originated from Asia and used traditionally as adaptogens, antidepressants, and anti-inflammatory remedies. We previously reported, that extracts of underground parts of RR and RQ exhibited immunotropic activity. We have demonstrated in pigs that in vitro RR or RQ supplementation of blood lymphocyte cultures stimulated T cell proliferative response to Con A in lower, and inhibited it in higher Rhodiola extract concentrations. The aim of this work was to evaluate the in vivo effect of these herbal remedies on the in vitro proliferative response of mouse splenic lymphocytes to another T-cell mitogen- Phaseolus vulgaris haemagglutinin (PHA). We have found significant stimulation of proliferative response, in comparison to the controls, in mice fed lower doses of tested remedies, and inhibition, no effect or lower stimulation, in mice fed higher doses of these drugs.  相似文献   

14.
In the present study, the detrimental effect of β-emission on pig skin was evaluated. Skin injury was modeled in mini-pigs by exposing the animals to 50 and 100 Gy of β-emission delivered by 166Ho patches. Clinicopathological and immunohistochemical changes in exposed skin were monitored for 18 weeks after β-irradiation. Radiation induced desquamation at 2~4 weeks and gradual repair of this damage was evident 6 weeks after irradiation. Changes in basal cell density and skin depth corresponded to clinically relevant changes. Skin thickness began to decrease 1 week after irradiation, and the skin was thinnest 4 weeks after irradiation. Skin thickness increased transiently during recovery from irradiation-induced skin injury, which was evident 6~8 weeks after irradiation. Epidermal expression of nuclear factor-kappa B (NF-κB) differed significantly between the untreated and irradiated areas. One week after irradiation, cyclooxygenase-2 (COX-2) expression was mostly limited to the basal cell layer and scattered among these cells. High levels of COX-2 expression were detected throughout the full depth of the skin 4 weeks after irradiation. These findings suggest that NF-κB and COX-2 play roles in epidermal cell regeneration following β-irradiation of mini-pig skin.  相似文献   

15.
表皮生长因子 (EGF)是表皮生长因子家族成员之一 ,在哺乳动物生殖过程中具有重要的调节作用。在哺乳动物卵巢内有 EGF的表达并调节卵巢的功能活动 ;EGF可促进哺乳动物卵泡发育 ,加速卵母细胞的成熟 ;EGF可促进卵母细胞受精和受精卵发育的能力 ,促进胚泡腔的形成 ;EGF在许多哺乳动物的子宫内均有表达 ,并参与胚胎着床过程的调节。 EGF可能以自分泌或旁分泌的形式参与卵泡发育、卵母细胞成熟、子宫内膜增殖、早期胚胎发育及胚胎着床等过程的调节。文章对 EGF在雌性哺乳动物卵泡发育、卵母细胞成熟、早期胚胎发育、囊胚腔扩展、胚胎着床等过程中的作用进行了概述  相似文献   

16.
Embryos of Clinus dorsalis absorb nutrients from the embiyotrophe, secreted by the follicular epithelium. Autoradiographic studies revealed that the principal areas of nutrient absorption are the embryonic gut and epidermis. A histological and electron microscopic study of embryonic structure revealed an extensively hypertrophied gut with numerous flngerlike villi projecting into the gut lumen. A brushborder of microvilli is, furthermore, characteristic of the columnar gut epithelium. Epidermal surface area is increased apically on individual epidermal cells, particularly on the ventral pericardial surface. Micro ridges further increase epidermal surface area. Epidermal surface area is reduced and a mucous layer is secreted prior to parturition.  相似文献   

17.
Phenotypic analysis for a cell line of canine epidermal keratinocytes   总被引：1，自引：0，他引：1  
Epidermal keratinocytes have the potential to produce inflammatory mediators that are considered to play an important role in skin diseases such as atopic dermatitis (AD). Thus, cell lines of canine epidermal keratinocytes are useful for studying the biological reactivity of keratinocytes in vitro. However, there has been no report on properly analyzing the phenotype of canine keratinocyte cell lines. In this work, we performed phenotypic analysis of CPEK, which was derived from the epidermis of an adult dog in order to examine the phenotypic similarity with epidermal keratinocytes. The present findings indicated that CPEK cells expressed markers for epidermal keratinocytes including cytokeratin 14, alpha6 integrin and PCNA. Our findings demonstrated that CPEK could be a useful cell line for investigating the central role of epidermal keratinocytes in the pathogenesis of AD in vitro.  相似文献   

18.
为观察中药地翁颗粒在体外对小鼠脾淋巴细胞功能的影响,设置高（100mg/L）、中（10mg/L）、低（1mg/L）3个剂量组,采用3 H法进行刀豆蛋白A（ConA）、脂多糖（LPS）诱导脾淋巴细胞增殖试验,ELISA方法检测ConA或金黄色葡萄球菌Cown株灭活菌体（SAC）刺激的脾淋巴细胞上清液IL-2、IL-6、IL-10、IL-12、IFN-γ和TNF-α的含量。结果显示,在安全浓度范围内,地翁颗粒能够明显促进T淋巴细胞和B淋巴细胞增殖;能够促进ConA刺激的淋巴细胞分泌INF-γ;能够促进SAC刺激的淋巴细胞分泌IL-12、INF-γ和IL-6,并抑制IL-10的分泌。结果表明,地翁颗粒能够有效调节小鼠脾淋巴细胞的功能,促进细胞免疫。  相似文献   

19.
We developed a strictly controlled serum-free culture system and tested the effects of adipogenic and antiadipogenic agents on the proliferation and(or) adipose conversion of porcine stromal-vascular cells. To avoid any interference with serum components, stromal-vascular cells were isolated, plated, and grown in absence of serum. In these culture conditions, a very limited growth phase and the absence of cell confluence were observed. However, when compared with continuous culture in serum-containing medium, the serum-free conditions were significantly more adipogenic as assessed by increased lipid content and increased enzymatic activities for lipoprotein lipase, glycerol 3-phosphate dehydrogenase, and malic enzyme. In serum-free medium, physiological concentrations of insulin or IGF-I were sufficient to significantly increase the percentage of lipid-containing cells, whereas triiodothyronine (T3) and GH had no effect. Insulin, IGF-I, and, more moderately, T3 also accelerated the lipid filling in the lipid-containing cells. In the presence of insulin, stimulation by T3 or hydrocortisone alone had no effect on glycerol 3-phosphate dehydrogenase activity, whereas their concomitant addition significantly increased it. Chronic exposure to tumor necrosis factor-alpha dose-dependently stimulated cell proliferation but clearly inhibited differentiation. Epidermal growth factor, another known antiadipogenic agent, also significantly increased the proliferation of stromal-vascular cells, but, surprisingly, this was not correlated with inhibition of adipocyte differentiation. Indeed, epidermal growth factor treatment did not decrease lipid filling and significantly improved lipoprotein lipase and malic enzyme activities. Taken together, the results obtained in these strictly controlled serum-free culture conditions point out functions for insulin, IGF-I, hydrocortisone, and T3 during early and(or) later steps of porcine adipose conversion. In addition, this study reports a positive activity of epidermal growth factor on porcine adipocyte differentiation that is in clear contrast with previous works performed with rodent cells.  相似文献   

20.
Bovine mammary tissue obtained from midpregnant Holstein heifers by surgical biopsy was transplanted subcutaneously to ovariectomized athymic nude mice (n = 5 heifers). After 3 weeks recovery, mice were either sham operated or sialoadenectomized (submandibular salivary glands removed). After an additional week, mice were injected with saline or 17 beta-estradiol + progesterone (1 microgram + 1 mg/day) for 2 days. In addition, half of the sialoadenectomized mice were injected with epidermal growth factor (5 micrograms/day). Grafted tissue was removed and rate of deoxyribonucleic acid (DNA) synthesis estimated by incorporation of 3H thymidine. Estradiol + progesterone increased the incorporation of 3H thymidine from 77 +/- 20 dpm/micrograms DNA to 472 +/- 53 dpm/micrograms DNA. In sialoadenectomized mice, DNA synthesis was increased from 88 +/- 16 dpm/micrograms DNA (saline treated) to 360 +/- 29 dpm/micrograms DNA (estradiol + progesterone treated). In sialoadenectomized mice treated with epidermal growth factor, DNA synthesis in estradiol + progesterone treated mice was 529 +/- 36 dpm/micrograms DNA, compared to 112 +/- 30 dpm/micrograms DNA in sialoadenectomized mice treated with epidermal growth factor. These data indicate that sialoadenectomy of athymic nude mice decreased the ability of transplanted bovine mammary tissue to increase DNA synthesis in response to estradiol and progesterone. This inhibition was removed by epidermal growth factor treatment. These data suggest a physiological role of epidermal growth factor in regulating development and hormone responsiveness of bovine mammary tissue.  相似文献   

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