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Biomedical subjects

L Sigurdson

Publications and source records attributed to L Sigurdson.

6 recordsLinked to original sources

Does cartilage down-regulate growth factor expression in tracheal epithelium?

BACKGROUND: Maintaining tracheal integrity and restoring normal physiologic function after injury is complex. Some of the critical events in this process are deposition of a provisional extracellular matrix, tissue remodeling, and angiogenesis. These events are coordinated with epithelial migration and proliferation to restore the mucosal barrier. The ability of respiratory epithelial cells (REC) to migrate and proliferate and restore denuded areas of the large conducting airway after injury is poor. OBJECTIVE: To test the hypotheses that (1) the cartilaginous framework, underlying the extracellular matrix (submucosa) and epithelium, decreases the migratory ability of REC when compared with REC on the same provisional extracellular matrix (type I collagen) alone, and (2) this phenomenon is associated with a change in expression of transforming growth factor (TGF)-alpha and TGF-beta, both of which have been demonstrated in cutaneous models to be important in epithelial migration and proliferation. DESIGN: We developed a culture system that reconstitutes the tracheal lumen in vitro, consisting of dissociated chondrocytes cultured in a manner to form cartilage, submucosa (type I collagen), and REC (termed a "composite culture"). Control cultures consisted of epithelial cells grown on type I collagen alone. Control and composite cultures were evaluated morphologically using scanning electron and light microscopy. Expression of TGF-alpha and TGF-beta was determined in day 14 cultured epithelial cells from control and composite cultures by semiquantitative polymerase chain reaction. RESULTS: Epithelial cells from composite cultures did not spread and were less squamoid in morphological appearance than epithelial cells on type I collagen alone. Expression of both growth factors was reduced in epithelial cells from composite cultures compared with those on type I collagen. CONCLUSIONS: Cartilage modulates TGF-alpha and TGF-beta expression in REC, and may contribute to regulation of REC proliferation and differentiation.

Animals↗

The sartorius muscle: anatomic considerations for reconstructive surgeons.

To evaluate the sartorius muscle as an alternative donor site for functional transfer, the neurovascular anatomy of the muscle was studied in 42 human sartorius muscle specimens (22 fresh and 20 preserved). Eleven adult fresh cadavers were injected with a mixture of lead oxide, gelatin and water (200 ml/kg) through the common carotid and femoral arteries. The sartorius muscle with its neurovascular pedicles was dissected, and radiographed. The sartorius muscle was also dissected out in 10 preserved cadavers. The neurovascular anatomy was thus analyzed in 42 sartorius muscles. The results show that each nerve supplying the sartorius muscle is accompanied by one vascular pedicle, forming a neurovascular hilum. Within the muscle, most of the nerves and vessels divide early, and their branches run parallel to each other and to the muscle fibers. Many of the vessels anastomose with each other to form an intricate vascular network. We conclude that it is possible to subdivide the muscle into functional units to harvest a segmental muscle flap with a neurovascular pedicle for transfer.

Adult↗

Isolation and characterization of basal cells from human upper respiratory epithelium.

Cellular pathways of normal and reparative differentiation of upper airway epithelium are not well understood. Of the three main cell types, basal and secretory cells are known to divide, while ciliated cells are considered terminally differentiated. Several investigations support the role of the basal cell as a progenitor cell type, but others suggest that the secretory cell can regenerate a complete mucocilliary epithelium. Thus, lineage relationships within renewing adult epithelia are still unclear. Understanding the pathways involved in upper airway epithelial cell differentiation is critical for studying injury and repair mechanisms and for developing clinical strategies for tracheal reconstruction. We undertook the current studies to determine the integrin profile of isolated human upper airway basal cells. Respiratory epithelial cells (REC) were isolated by elastase digestion, stained with FITC-labeled Griffonia simplicifolia isolectin B4 (GSI-B4), and sorted by flow cytometry. Approximately 80% of the lectin-positive cells were basal cells, as determined by morphology and cytokeratin staining. These cells expressed integrins alpha 1, alpha 2, alpha 3, alpha 5, alpha v beta 5, beta 1, beta 3, and alpha 6 beta 4, by immunohistochemistry. This is the first report to identify the integrin profile of isolated human upper airway basal cells. These basal cells could be maintained on type I collagen for at least 7 days, where they became partially confluent and retained expression of cytokeratins 5 and 14. Availability of pure populations of basal cells should permit investigations of their role in both normal and maladaptive repair of adult upper airway epithelium.

Adult↗

Thyroxine 5'-deiodinase in hamster and rat brown adipose tissue: effect of cold and diet.

Thyroxine 5'-deiodinase (type II) is present in a microsomal fraction of brown adipose tissue (BAT) of Syrian hamsters. Cold exposure increased specific activity in homogenates after a lag period of approximately 2 h to reach a maximum by 1-3 days. Total activity increased 80 times in cold-acclimated hamsters. During deacclimation, a rapid decrease occurred again after a lag period of approximately 2 h. The increase did not parallel increases in protein or in thermogenic state of mitochondria (mitochondrial GDP binding), which occurred more slowly. Changes in serum 3,5,3'-triiodothyronine concentration paralleled changes in BAT 5'-deiodinase during both acclimation to cold and deacclimation. The cold-induced increase in BAT 5'-deiodinase activity occurred more slowly but was much larger in hamsters than in rats. Eating a palatable diet increased BAT protein content and thermogenic activity in both hamsters and rats but did not alter total 5'-deiodinase activity in either species. We conclude that the trophic response of brown adipose tissue to cold in both hamsters and rats is accompanied by an enhanced endogenous production of triiodothyronine that may play a role in control of tissue growth. The trophic response to a palatable diet differs in that enhanced endogenous production of triiodothyronine is not an obligatory accompaniment. Specific stimulation of 5'-deiodinase by cold might modify thermogenesis in tissues other than BAT by providing triiodothyronine and be of greater significance in hamsters than in rats.

Acclimatization↗

Thyroxine 5'-deiodinase in brown adipose tissue of myopathic hamsters.

Myopathic Syrian hamsters (BIO 14.6) have less brown adipose tissue (BAT) than normal. The trophic response of this tissue to cold is smaller than normal and trophic responses to diet and to photoperiod are absent. The objective was to find out whether activity of thyroxine 5'-deiodinase in their BAT was increased normally in response to cold and thus whether a defect in endogenous production of 3,5,3'-triiodothyronine might underlie the attenuated trophic response. The effect of feeding a high-fat diet on activity of 5'-deiodinase was also studied. Cold acclimation increased thyroxine 5'-deiodinase activity in BAT of the myopathic hamster, but the total remained smaller than normal because of the smaller size. The cold-induced increase in concentration of mitochondrial uncoupling protein was also smaller than normal. The level of serum 3,5,3'-triiodothyronine was low in myopathic hamsters and remained lower than normal when they were cold-exposed or cold acclimated. Feeding the high-fat diet to myopathic hamsters resulted in a greater than normal suppression of thyroxine 5'-deiodinase activity than in normal hamsters; the normal increases in protein content and in concentration of mitochondrial uncoupling protein were absent. We conclude that the defective trophic response of BAT of the myopathic hamster is not secondary to defective regulation of its thyroxine 5'-deiodinase activity because this activity does not appear to be obligatorily linked to hypertrophy of BAT. The low level of serum 3,5,3'-triiodothyronine in the myopathic hamster may be secondary to reduced capacity for peripheral thyroxine deiodination in its BAT.

Acclimatization↗

Immunoregulatory factors from a human macrophage-like cell line. II. A human T-cell lymphokine-induced suppressor factor for lymphocyte proliferation.

It has been demonstrated that the human histiocytic lymphoma-derived cell line U937, which has monocytoid characteristics, responds to a concanavalin A-induced T-cell-derived suppressor supernatant (T-SFS) with the release of a factor markedly suppressing mitogen-stimulated proliferation of normal peripheral blood lymphocytes. The suppressor material is not dialyzable, appears within 2 hr of exposure of U937 cells to the T-SFS, persists for at least 24 hr, and has a Mr of approximately 40,000 by gel chromatography. The suppressor factor does not affect the proliferation of continuous T- and B-lymphoid cell lines, distinguishing it from the inhibitor of DNA synthesis also released by U937, but appears to be specific for a stage of activation of normal lymphocytes that is independent of (a) utilization of interleukin-2 and (b) inhibition of production of interleukin-2.

B-Lymphocytes↗