Search PubMed⌕ Search

Biomedical subjects

E Bell

Publications and source records attributed to E Bell.

At least 91 records · Page 5Linked to original sources

A new method for studying epidermalization in vitro.

A new method for studying epidermalization in vitro is described. It consists of inserting a punch biopsy that serves as a source of epidermis into dermal equivalent freshly made up, with fibroblasts mixed in a collagen matrix. Fibroblasts cling to collagen fibrils and contract the matrix, leading in 3 days to a resistant dermal equivalent holding the punch biopsy firmly in place. At day 5, a culture medium favouring epidermal growth was used and a fringe of a new epidermis appeared around the punch, the area of which grew linearly with time. This new epidermis showed a pattern of differentiation similar to epidermis in vivo, with cuboidal basal cells, keratohyalin granules, membrane coating granules and the expression of the 65-67 kd keratin subset. The method seems to combine the advantages of the explant technique and of classical keratinocyte cultures, providing the researcher with a large quantity of differentiated epidermis, the pharmacologist with simple and quantitative system in which to study modifications of growth and differentiation of epidermis, and the plastic surgeon with a possible material for skin grafting.

Biopsy↗

AIDS: an overview.

Explore the source record for details and available documents.

Acquired Immunodeficiency Syndrome↗

Psoriatic fibroblasts induce hyperproliferation of normal keratinocytes in a skin equivalent model in vitro.

A skin equivalent model has been used to fabricate tissues with psoriatic and normal cells. Psoriatic fibroblasts can induce hyperproliferative activity in normal keratinocytes. The psoriatic epidermis from lesions continues to proliferate at high rates for at least 15 days in this model, and normal fibroblasts are unable to suppress this hyperproliferation. The primary defect in psoriatic skin may reside in the dermal fibroblast.

Adult↗

Pseudomonas dermatitis associated with a swimming pool.

One hundred forty-seven (66%) of 224 scouts and chaperons were interviewed after a weekend visit to a dude ranch in upstate New York. One hundred seventeen (80%) complained of papular rashes or eye and ear inflammation. Onset of illness occurred within 24 to 48 hours of arrival at the ranch. After controlling for participation in other available activities, only swimming was found to be associated with illness. Pseudomonas aeruginosa serotype 0 11 grew from a culture of pool water and from 17 cultures of skin, eye, and ear lesions in visitors to the ranch. Follow-up was obtained for 76 of the affected persons for whom initial information was available. Mean duration of illness was 14.5 days (range, one to 40+ days). The recurrence rate was 24%.

Adult↗

Nuclear mutation leads to an accelerated turnover of chloroplast-encoded 48 kd and 34.5 kd polypeptides in thylakoids lacking photosystem II.

We have studied the synthesis and accumulation of a chloroplast-encoded 48 kd chla-reaction center protein and the 34.5 kd ;atrazine binding' protein in a nuclear maize mutant which fails to assemble photosystem II reaction centers. The failure of these polypeptides to accumulation in mutant thylakoids is not due to direct nuclear control over their synthesis but is rather due to their specific, accelerated turnover from the thylakoid membrane. The accelerated turnover of these polypeptides in mutant thylakoids is largely independent of illumination conditions, as accelerated turnover occurs in the dark as well as in the light. In contrast to wild type, the 48 kd and 34.5 kd polypeptides are preferentially associated with stroma, rather than grana, lamellae in mutant membranes, suggesting that turnover occurs before these polypeptides become enriched in the grana. The nucleus thus plays a role in the stabilization of these chloroplast-encoded photosystem II reaction center polypeptides.

Journal Article↗

Regulation of proliferation of bovine aortic endothelial cells, smooth muscle cells, and adventitial fibroblasts in collagen lattices.

We compared the proliferation of bovine aortic cells grown in collagen lattices. Smooth muscle cells continued to divide for 2 weeks while adventitial fibroblasts ceased to divide after 4-5 days. Endothelial cells did not proliferate within an untreated collagen lattice; however, if the lattice was covered with culture medium, endothelial cells populated its surface and proliferated to form a monolayer. We also found that both smooth muscle cells and endothelial cells, like fibroblasts, are able to contract a collagen lattice to a small fraction of its original volume, although endothelial cells are able to do so only if the lattice is covered with culture medium.

Animals↗

Association between urinary zinc excretion and lymphocyte dysfunction in patients with lung cancer.

Patients with bronchogenic carcinoma often have low serum zinc concentrations and sometimes have markedly elevated renal zinc losses. Since normal zinc metabolism is critical for the proper function of T lymphocytes and natural killer cells, the effect of zinc status on T cell phytohemagglutinin response and peripheral blood lymphocyte natural killer cell activity was studied in patients with lung cancer. Mean (+/- SEM) serum zinc concentration in 75 patients with cancer was 67.4 +/- 2.2 micrograms/dl versus 96.0 +/- 8.0 micrograms/dl for normal subjects. Patients with low serum zinc levels (less than 70 micrograms/dl) had significantly higher urine zinc excretion than patients with normal serum zinc levels (1,385 +/- 240 micrograms per 24 hours versus 392 +/- 107 micrograms per 24 hours) (p less than 0.001). This pattern of zinc concentrations (i.e., low serum zinc in combination with high urine zinc) is typical of patients with mild zinc deficiency, and suggests that a mild chronic zinc deficiency state was present in some of these patients. When lymphocyte data were analyzed according to serum zinc concentrations and urinary zinc excretion, low serum zinc concentration and high urine zinc excretion both correlated with depressed T cell phytohemagglutinin response (p less than 0.005 and p less than 0.001, respectively). For instance, mean maximal phytohemagglutinin response in patients with urinary zinc excretion of more than 700 micrograms per 24 hours was 22,132 +/- 3,201 cpm (n = 14) compared with 68,130 +/- 6,850 cpm for patients with normal zinc excretion (n = 7). Peripheral blood lymphocyte natural killer cell activity did not correlate with either serum or urine zinc values. Oral zinc sulfate (220 mg, three times daily for six weeks) was then administered to patients with hyperzincuria (mean = 992 micrograms per 24 hours). Zinc-supplemented patients had normalization of T cell phytohemagglutinin response after zinc therapy, whereas control patients demonstrated continued T cell dysfunction. Natural killer cell activity did not change in either group during the study period. These data suggest that a mild subclinical zinc deficiency state may exist in some patients with lung cancer and may be an important cause of abnormal T cell function. Furthermore, zinc supplementation may be useful to improve lymphocyte function in selected patients. Whether zinc supplementation would alter the course of the disease or the patient's prognosis is presently unknown.

Adenocarcinoma↗

Reconstruction of a thyroid gland equivalent from cells and matrix materials.

A living thyroid gland equivalent has been fabricated with a cultivated strain of rat thyroid cells (FRTL), dermal or thyroid fibroblasts, and matrix materials. The mixture becomes tissuelike in vitro by virtue of interactions between fibroblasts and collagen. Initially in vitro the thyroid cells are uniformly distributed as single cells and a small number of clusters containing less than 10 cells. When implanted into thyrodectomized hosts the thyroid cells in the tissue lattice become organized into follicles containing a colloidlike material. The follicles were found in clusters in sizes up to 0.3 mm. The clusters are vascularized. It is thought that they arise within clones rather than by an aggregation process. Using an antithyroglobulin antibody it was shown that both thyroid cells and the colloidlike material within follicles reacted positively. Development of follicles was strictly dependent on whether hosts were thyroidectomized. In nonthyroidectomized hosts no follicles were observed. We conclude that an organotypic structure can develop in vivo from a "gland-equivalent" fabricated with adult cells and matrix materials combined in vitro, and that cells cultivated for years in vitro retain the capacity to express differentiated functions in a reconstituted organ equivalent in vivo.

Animals↗

Collagen biosynthesis by cells in a tissue equivalent matrix in vitro.

Collagen biosynthesis by fibroblasts and subsequent processing and polymerization have been studied in conventional monolayer cultures and in a new model system in vitro in which cells organize into a tissue like structure. While the bulk of the newly made collagen becomes tightly and selectively bound to the matrix of the tissue equivalent model, in monolayer cultures most of the collagen passes into the culture medium. Collagen biosynthesis appears to be regulated differently in cells of the tissue equivalent model as compared with monolayered cells. In the former there is a 6- to 8-fold decrease in collagen output even though overall protein synthesis per unit of DNA is twice as great as in monolayered cells. Cells grown in tissue lattices exhibit much higher collagenolytic activity than cells in monolayer suggesting the model may also be of special use for studying collagen turnover and matrix remodeling.

Cell Line↗

The contractility of fibroblasts in a collagen lattice is reduced by corticosteroids.

Normal human and rat skin fibroblasts, incorporated into a three-dimensional collagen lattice, were assayed for their ability to contract collagen fibrils. This capacity is inhibited in a dose-dependent fashion by both dexamethasone and hydrocortisone. The inhibition is reversed when the corticosteroids are removed from the culture medium, but while the effect of hydrocortisone is almost entirely reversible, that of dexamethasone is not.

Adrenal Cortex Hormones↗

The living skin-equivalent as a structural and immunological model in skin grafting.

The living skin equivalent is a tissue formed when self-assembled collagen fibrils are contracted by fibroblasts. The rate and extent of volume contraction is proportional to the number of cells incorporated into the lattice. The fibroblasts are biochemically active in the lattice, synthesizing collagen and adding it to the matrix. This compacted lattice provides a substrate allowing attachment of keratinocytes and the formation of a multilayered keratinized epidermis with a basement lamella. When a skin equivalent grafted to a recipient animal is wounded, it is capable of wound contraction and repair. Because of the simplified character of the skin equivalent it may offer a useful model for studying wound healing. During the initial healing of the grafted skin equivalent, fibroblasts from the skin equivalent move freely into the surrounding tissue. Karyotyping of fibroblasts grown from skin surrounding the skin equivalent graft shows that fibroblasts from the graft migrate at least 6-9 mm from the graft edge. At 3-6 mm from the graft edge about 50% of the fibroblasts present are of donor origin. Fibroblasts also migrate from allogenic skin grafts before these grafts are rejected. At 3-6 mm from the scar left by the rejected graft 36% of the fibroblasts are of donor origin 2 months after grafting. The skin equivalent model provides a well-defined system for studying transplantation reactions. Results obtained on persistence of allografted fibroblasts support our theory that in the rat, the fibroblast is antigenically neutral.

Animals↗

Acceptance of allogeneic fibroblasts in skin equivalent transplants.

Living skin equivalents (SE) were prepared by combining cultured fibroblasts with a collagen matrix and overlaying this lattice with keratinocytes. SEs prepared using allogeneic female rat fibroblasts or xenogeneic rabbit or human fibroblasts and keratinocytes isogeneic to the graft recipient were transplanted to recipient male rats. Biopsies of some of these SE grafts were examined histologically at intervals ranging from 5 days to 2 months. Biopsies of other grafts were done, and fibroblasts grown from them were karyotyped to determine the percentage of donor fibroblasts remaining in the graft. SEs containing xenogeneic fibroblasts were rejected. Allografted fibroblasts in SEs were accepted by recipient rats after a transient mononuclear cell response. A second SE allograft from the same donor strain did not provoke rejection either in the original allograft or in the challenge allograft. A secondary graft of allogeneic skin did not provoke rejection in the original SE graft, although the skin graft was rejected. Grafting the recipient first with allogeneic skin and then with the SE allograft led to rejection of the skin but not of the SE graft, ruling out the possibility that suppressor T cells were responsible for SE allograft acceptance. Allografted fibroblasts in SEs do not provoke a rejection response, even in presensitized animals, do not render the recipient tolerant to allogeneic skin, and do not act as targets when active rejection is taking place. We propose that cells bearing class I antigens may be acceptable graft constitutents if incorporated in a tissue equivalent excluding cells with class II antigens.

Animals↗

Structural integration of skin equivalents grafted to Lewis and Sprague-Dawley rats.

Bilayered skin equivalents, composed of a sheet of epidermal cells overlying a collagen lattice populated with fibroblasts, quickly become structurally integrated with the surrounding host skin after grafting to Lewis rats. Three days after transplantation, the skin equivalent lies on a bed of host granulation tissue and is loosely attached to the adjoining host dermis. Blood vessels begin to invade the collagen lattice by 5 days after grafting. By the 7th day a fully keratinized, hypertrophic epidermis covers the surface of the graft and blood vessels penetrate the lattice to the base of the epidermis. Vascularization of the graft is accompanied by activation and proliferation of the fibroblasts and by a condensation of the collagen matrix. During the 2nd week after grafting, the collagen fibrils become organized into thin fibers that show a basketweave pattern of birefringence when examined using polarized light. By 1 month the structure of the skin equivalent has become stabilized. The fibroblasts now resemble the quiescent fibrocytes of normal, resting dermis and the epidermis remains moderately hypertrophic. One to two years after grafting to Sprague-Dawley rats, the skin equivalents do not appear hypertrophic. The graft lacks secondary derivatives such as hair follicles and sweat glands, presumably because the stem cells are lost during the isolation of the epidermal cells. Grafts that are prepared using epidermal cells overlying a collagen gel without fibroblasts give rise to raised, linear scars within 2 weeks.

Animals↗

Fibroblasts in isogeneic skin equivalents persist for long periods after grafting.

We have fabricated skin equivalents by combining fibroblasts from female Fischer rats with collagen to form a lattice and overlaying the lattice with a suspension of epidermal cells. The epidermal cells attach and form a sheet which differentiates. These skin equivalents were then grafted to male Fischer rats in order to follow the fate of the fibroblasts after implantation. Biopsies of the skin equivalent were taken between 9 days and 13 months after grafting and examined histologically or placed in tissue culture to permit karyotyping of the resident fibroblasts. Approximately 82% of the fibroblasts from the graft biopsied at 9 days were female, with this proportion decreasing sharply to 50% at 2 weeks and 60-64% at 1 month. At 1 month, this initial sharp drop is followed by a slow, linear decline which continues through the 13th month when 42% of the fibroblasts are female. We conclude that fibroblasts of the grafted skin equivalent become permanent residents of the skin of the host rat.

Animals↗