Effect of gel re-organization and tensional forces on alpha2beta1 integrin levels in dermal fibroblasts.
Mechanical forces are known to play an important role in regulating cell function in a wide range of biological systems. This is of particular relevance to dermal fibroblast function, given that the skin is known to be held under an intrinsic natural tension. To understand more about the generation of force by dermal fibroblasts and their ability to respond to changes in it, we have studied the role of the beta1 integrin receptors expressed by dermal fibroblasts in their ability to generate tensional forces within a collagen type I matrix and the effect of altered tensional force on integrin expression by dermal fibroblasts. Using a purpose-built culture force monitor, function-blocking antibodies directed towards the beta1 receptors dramatically reduced the tensional forces generated by dermal fibroblasts in a 3D collagen I matrix. However, the specific involvement of alpha1 or alpha2 subunits could not be demonstrated. Analysis of cellular response demonstrated that cells isolated from contracting collagen gels expressed fourfold higher levels of alpha2 mRNA than cells isolated from fully restrained gels. The levels of beta1 messenger RNA were relatively unaffected by reductions in force. Cells exposed to single reductions in force, however, did not exhibit alterations in either alpha1 or beta1 mRNA levels. We propose, therefore that alpha2beta1 integrin receptor levels in dermal fibroblasts are not altered in response to single reductions of gel tension, but do change following a continual change in force and associated matrix re-organization (+info)
p21(WAF1/Cip1) functions as a suppressor of malignant skin tumor formation and a determinant of keratinocyte stem-cell potential.
p21(WAF1/Cip1) is one of the best characterized downstream targets of p53, and the growth suppressing function of this cyclin-dependent kinase inhibitor is well established. However, whether p21 exerts a tumor-suppressing function of its own remains to be established. We report here that, similarly to loss of p53, disruption of the p21(WAF1/Cip1) gene results in a markedly increased susceptibility to chemically induced skin carcinoma formation, whereas the number of papillomas is reduced. Previous evidence indicates that malignant versus benign keratinocyte tumor formation is likely to involve distinct target-cell populations with a different commitment to differentiation. In parallel with the increased susceptibility to carcinoma formation, loss of p21(WAF1/Cip1) was found to promote keratinocyte subpopulations with increased growth/differentiation potential, including clonal growth capability, reversible commitment to differentiation, and capability to generate all types of terminally differentiated keratinocytes present in vivo, not only in the interfollicular epidermis but also in hair follicles. Thus, these findings have revealed a function of p21 as a suppressor of malignant but not benign skin-tumor formation and a determinant of the growth/differentiation potential of keratinocyte subpopulations. (+info)
Detection of gastric slow wave propagation from the cutaneous electrogastrogram.
The gastric slow wave is originated in the proximal stomach and propagates distally toward the pylorus. It determines the maximum frequency and propagation of gastric contractions. The aim of this study was to detect the propagation of the gastric slow wave from the surface electrogastrogram (EGG). The study was performed in 11 healthy subjects of normal weight. Gastric myoelectrical activity was recorded for 1 h in the fasting state with the use of a specially designed multichannel recording device that was composed of four identical amplifiers with cutoff frequencies of 1.8 and 16.0 cycles/min. Four active electrodes were placed on the abdomen along the gastric axis and were connected to a common reference electrode placed near the xiphoid process, yielding four-channel bipolar EGG signals. Cross-covariance analysis was performed to compute the time lag among the four channels. There was a time lag in EGG waveform between channels 1 and 4 (9.6 +/- 1.1 s); the average time during which the time lag was observed (>/=3 s) was 89.9 +/- 9.0%. There was a significant difference in the time lag among different adjacent channels (P < 0.04); the time lag observed between channels 3 and 4 was significantly smaller than that between channels 1 and 2 (P < 0.03). No correlation was found between the body mass index and the time lag between channels 1 and 4 (r = -0.31, P = 0.3). It was concluded that, with a multichannel recording device with identical multiamplifiers and an appropriate arrangement of abdominal electrodes, the propagation of the gastric slow wave could be identified from the EGG in healthy subjects. This method may be used to detect the coupling of the gastric slow wave noninvasively. (+info)
The diving physiology of bottlenose dolphins (Tursiops truncatus). III. Thermoregulation at depth.
During diving, marine mammals initiate a series of cardiovascular changes that include bradycardia and decreased peripheral circulation. Because heat transfer from thermal windows located in peripheral sites of these mammals depends on blood flow, such adjustments may limit their thermoregulatory capabilities during submergence. Here, we demonstrate how the thermoregulatory responses of bottlenose dolphins (Tursiops truncatus) are coordinated with the diving response. Heart rate, skin temperature and heat transfer from the dorsal fin and flank were measured while dolphins rested on the water surface, stationed 5-50 m under water and floated at the surface immediately following a dive. The results showed that heat flow ranged from 42.9+/-7.3 to 126.2+/-23.1 W m(-)(2) and varied with anatomical site and diving activity. Upon submergence, heat flow declined by 35 % from the dorsal fin and by 24 % from the flank. An immediate increase in heat flow to levels exceeding pre-dive values occurred at both sites upon resurfacing. Changes in heart rate during diving paralleled the thermoregulatory responses. Mean pre-dive heart rate (102.0+/-2.6 beats min(-)(1), N=26) decreased by 63.4 % during dives to 50 m and immediately returned to near resting levels upon resurfacing. These studies indicate that heat dissipation by dolphins is attenuated during diving. Rather than challenge the diving response, heat transfer is delayed until post-dive periods when the need for oxygen conservation is reduced. (+info)
Human epidermal growth factor: isolation and chemical and biological properties.
A polypeptide hormone has been isolated from human urine, human epidermal growth factor. It was assayed by its ability to compete with 125I-labeled mouse-derived epidermal growth factor in binding to human foreskin fibroblasts. The biological effects of the human polypeptide are similar to those previously described for the mouse hormone. These include the stimulation of the growth in vitro of human foreskin fibroblasts and corneal epithelial cells in organ culture, and the in vivo induction of precocious eyelid opening in the newborn mouse. The amino acid compositions of the two polypeptides differ, although certain similarities are present. The estimated molecular weight of the human polypeptide, 5300-5500, is slightly lower than that of the mouse hormone. Both polypeptides apparently compete for the same site on the cell membrane; and antibodies to the mouse polypeptide crossreact to some extent with the human hormone. (+info)
Possible role of aldosterone and T(3) in development of amiloride-blockable SCC across frog skin in vivo.
There are inconsistencies between the in vitro and in vivo effects of thyroid hormone and aldosterone (Aldo) on the development of an amiloride-blockable short-circuit current (SCC) across bullfrog skin [Takada, M., H. Yai, and K. Takayama-Arita. Am. J. Physiol. 268 (Cell Physiol. 37): C218-C226, 1995]. To address this issue, tadpoles were raised in Aldo + T(3). An amiloride-blockable SCC developed across the skin before forelimbs appeared. Noise analysis of the characteristics (single-channel current, blocking and unblocking rate coefficients, and apparent dissociation constant) of this amiloride-blockable Na(+) channel showed that it really was of the adult type. A similar SCC developed at stage XIX in the skin of tadpoles raised with Aldo alone. These results strongly support our hypothesis that the crucial hormone in the development of this SCC is Aldo but that a suppression mechanism attenuates its effect on SCC development until it is removed by the increase in the serum concentration of thyroid hormone (which starts at stages XVIII-XIX in vivo). (+info)
Evaluation of skin viscoelasticity and anisotropy by measurement of speed of shear wave propagation with viscoelasticity skin analyzer.
Skin viscoelasticity was evaluated by a fast, noninvasive assay based on the measurement of the speed of elastic shear wave propagation in the skin by a new portable and user-friendly viscoelasticity skin analyzer. The range of speed of elastic shear wave propagation measured by viscoelasticity skin analyzer allows the evaluation of the stiffness of a wide spectrum of artificial materials as well as the viscoelasticity of skin of laboratory animals and human subjects. The directional nature of the measurement enables to monitor the anisotropy of the materials tested. The speed of elastic shear wave propagation was shown to have a positive correlation with the stiffness of the material tested. In symmetric contralateral areas of intact skin in rabbit ears, similar viscoelasticity and anisotropy were observed. Twenty-four hours after the induction of local edema by croton oil, skin stiffness and anisotropy were significantly increased. In healthy human subjects of both sexes significant variations in skin stiffness and anisotropy were observed in three different skin areas along the forearms, but the speed of elastic shear wave propagation was similar in the symmetric contralateral areas. Age (17-65 y) seemed to have a limited effect on the viscoelasticity of the forearm skin. Hydrating creams decreased the stiffness of the forearm skin for only approximately 3 h. The stiffness and anisotropy of the skin of the breasts in female volunteers (20-86 y) increased with age, but the speed of elastic shear wave propagation was similar in symmetric contralateral areas in the same individuals. Based on these results, we propose the application of the viscoelasticity skin analyzer in experimental and clinical practice for quantitative evaluation of skin condition. (+info)
Fetal epidermal differentiation and barrier development In vivo is accelerated by nuclear hormone receptor activators.
Nuclear receptors which interact with the retinoid X receptor are involved in the regulation of epidermal differentiation and development. We have recently shown that activators of the peroxisome proliferator-activated receptor and of the farnesoid X-activated receptor accelerate epidermal barrier maturation in fetal rat skin in vitro. In this study we asked whether cutaneous development in utero was affected by peroxisome proliferator-activated receptor or farnesoid X-activated receptor activators, or by an activator of another retinoid X receptor partner, liver X receptor. Activators of the peroxisome proliferator-activated receptor (clofibrate or linoleic acid), farnesoid X-activated receptor (farnesol or juvenile hormone III), or liver X receptor (22R-hydroxycholesterol), were injected into the amniotic fluid of fetal rats on gestational day 17. Fetal epidermal barrier function and morphology was assessed on day 19. Whereas vehicle-treated fetal rats displayed no measurable barrier (transepidermal water loss > 10 mg per cm2 per h), a measurable barrier was induced by the intra-amniotic administration of all activators tested (transepidermal water loss range 4.0-8.5 mg per cm2 per h). By light microscopy, control pups lacked a well-defined stratum corneum, whereas a distinct stratum corneum and a thickened stratum granulosum were present in treated pups. By electron microscopy, the extracellular spaces of the stratum corneum in control pups revealed a paucity of mature lamellar unit structures, whereas these structures filled the stratum corneum interstices in treated pups. Additionally, protein and mRNA levels of loricrin and filaggrin, two structural proteins of stratum corneum, were increased in treated epidermis, as were the activities of two lipid catabolic enzymes critical to stratum corneum function, beta-glucocerebrosidase and steroid sulfatase. Finally, peroxisome proliferator-activated receptor-alpha and -delta and liver X receptor-alpha and -beta mRNAs were detected in fetal epidermis by reverse transcriptase-polymerase chain reaction and northern analyses. The presence of these receptors and the ability of their activators to stimulate epidermal barrier and stratum corneum development suggest a physiologic role for peroxisome proliferator-activated receptor and liver X receptor and their endogenous ligands in the regulation of cutaneous development. (+info)