Biomedical subjects
Publications and source records attributed to P M Lewis.
Traumatic brain injury accounts for up to half of trauma related fatalities. This review describes current management practices including pre-hospital care, surgical interventions and various treatment modalities for intracranial hypertension. The lack of class I evidence for the majority of interventions is highlighted.
In 1993 we published a paper stating that wet construction cement is a poorly recognised cause of full-thickness burns [Injury 24 (1993) 615]. Ten years since publication we re-evaluated cement burns to ascertain if there had been any changes in awareness and incidence. All cement related burns assessed at this unit were reviewed over a three and a half year period. Postal questionnaires were sent to all those affected. Cement burns accounted for 2.2% of referrals to the Burns Unit during this studied period as compared to 1% during the original study. Fifty-one percent of patients stated they were unaware of the risk of cement burns and took no precautions. Eighty-six percent of the burns involved the lower limb. Fifty-three percent of burns affected professional users. Fifty percent had full-thickness involvement with 21% requiring operation. Eighty-eight percent of patients did not notice any warnings on the cement bag or delivery docket and 95% felt warnings should be larger and more obvious. This study has shown that cement burns may have resulted from shortcomings in the information and warnings provided to customers by cement manufacturers.
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Sonic hedgehog (Shh) signaling from the posterior zone of polarizing activity (ZPA) is the primary determinant of anterior-posterior polarity in the vertebrate limb field. An active signal is produced by an autoprocessing reaction that covalently links cholesterol to the N-terminal signaling moiety (N-Shh(p)), tethering N-Shh(p) to the cell membrane. We have addressed the role played by this lipophilic modification in Shh-mediated patterning of mouse digits. Both the distribution and activity of N-Shh(p) indicate that N-Shh(p) acts directly over a few hundred microns. In contrast, N-Shh, a form that lacks cholesterol, retains similar biological activity to N-Shh(p), but signaling is posteriorly restricted. Thus, cholesterol modification is essential for the normal range of signaling. It also appears to be necessary for appropriate modulation of signaling by the Shh receptor, Ptc1.
BACKGROUND: The skin is responsible for forming a variety of epidermal structures that differ amongst vertebrates. In each case the specific structure (for example scale, feather or hair) arises from an epidermal placode as a result of epithelial-mesenchymal interactions with the underlying dermal mesenchyme. Expression of members of the Wnt, Hedgehog and bone morphogenetic protein families (Wnt10b, Sonic hedgehog (Shh) and Bmp2/Bmp4, respectively) in the epidermis correlates with the initiation of hair follicle formation. Further, their expression continues into either the epidermally derived hair matrix which forms the hair itself, or the dermal papilla which is responsible for induction of the hair matrix. To address the role of Shh in the hair follicle, we have examined Shh null mutant mice. RESULTS: We found that follicle development in the Shh mutant embryo arrested after the initial epidermal-dermal interactions that lead to the formation of a dermal papilla anlage and ingrowth of the epidermis. Wnt10b, Bmp2 and Bmp4 continued to be expressed at this time, however. When grafted to nude mice (which lack T cells), Shh mutant skin gave rise to large abnormal follicles containing a small dermal papilla. Although these follicles showed high rates of proliferation and some differentiation of hair matrix cells into hair-shaft-like material, no hair was formed. CONCLUSIONS: Shh signaling is not required for initiating hair follicle development. Shh signaling is essential, however, for controlling ingrowth and morphogenesis of the hair follicle.
The mammalian lung, like many other organs, develops by branching morphogenesis of an epithelium [1]. Development initiates with evagination of two ventral buds of foregut endoderm into the underlying splanchnic mesoderm. As the buds extend, they send out lateral branches at precise, invariant positions, establishing the primary airways and the lobes of each lung. Dichotomous branching leads to further extension of the airways. Grafting studies have demonstrated the importance of bronchial mesenchyme in inducing epithelial branching, but the significance of epithelial signaling has largely been unstudied. The morphogen Sonic hedgehog (Shh) is widely expressed in the foregut endoderm and is specifically upregulated in the distal epithelium of the lung where branching is occurring [2]. Ectopic expression of Shh disrupts branching and increases proliferation, suggesting that local Shh signaling regulates lung development [2]. We report here that Shh is essential for development of the respiratory system. In Shh null mutants, we found that the trachea and esophagus do not separate properly and the lungs form a rudimentary sac due to failure of branching and growth after formation of the primary lung buds. Interestingly, normal proximo-distal differentiation of the airway epithelium occurred, indicating that Shh is not needed for differentiation events. In addition, the transcription of several mesenchymally expressed downstream targets of Shh is abolished. These results highlight the importance of epithelially derived Shh in regulating branching morphogenesis of the lung.
The receptor tyrosine kinase Dtk/Tyro 3/Sky/rse/brt/tif is a member of a new subfamily of receptors that also includes Axl/Ufo/Ark and Eyk/Mer. These receptors are characterized by the presence of two immunoglobulin-like loops and two fibronectin type III repeats in their extracellular domains. The structure of the murine Dtk gene has been determined. The gene consists of 21 exons that are distributed over 21 kb of genomic DNA. An isoform of Dtk is generated by differential splicing of exons from the 5' region of the gene. The overall genomic structure of Dtk is virtually identical to that determined for the human UFO gene. This particular genomic organization is likely to have been duplicated and closely maintained throughout evolution.
Using the polymerase chain reaction with degenerate oligonucleotides derived from conserved motifs within the catalytic kinase domain of protein tyrosine kinases, and RNA extracted from embryonic stem cells, sequences that encode a segment of the kinase domain of several potentially novel receptor tyrosine kinases (RTKs) have been identified. One of these was selected for further study because in Northern analysis it hybridized to RNA from multipotential hematopoietic cell lines, but not from lines representative of lineage-committed cells. A cDNA for this receptor, designated developmental tyrosine kinase (DTK), was isolated and encodes a protein with structural similarities to AXL. Together these receptors form a new class of RTK. DTK is expressed in a number of human leukemic cell lines, and in the blasts of 6 of 11 patients with acute myeloid leukemia (AML) analyzed. The structure of DTK suggests that it may function as a cell adhesion molecule, and mediate cell-to-cell or cell-matrix interactions between hematopoietic cells and their respective microenvironments.
Analysis of receptor tyrosine kinases expressed during mouse embryonic stem cell differentiation resulted in the cloning of a receptor designated developmental tyrosine kinase (DTK). The 850 amino acid mature receptor protein comprises an extracellular domain with two immunoglobulin-like motifs and two fibronectin type III modules, a 25 amino acid transmembrane domain and a cytoplasmic region with a catalytic kinase domain. In embryonic stem cells growing in the presence of leukemia inhibitory factor DTK is abundantly expressed and this level of expression is maintained in differentiating embryonic stem cells and cystic embryoid bodies. In mid-gestational embryos (E14.5), DTK RNA is expressed in many tissues including brain, eye, thymus, lung, heart, gut, liver, testis and limbs. In contrast, expression of DTK in adult mice becomes restricted to brain, portions of the gastrointestinal tract, bladder, testis and ovary. There is enrichment of transcripts encoding DTK in purified fetal liver hematopoietic stem cells, when compared with unfractionated fetal liver. The DTK gene maps to mouse chromosome 2, band F.
A cDNA encoding the human homologue of the murine DTK receptor tyrosine kinase has been isolated from a human brain library. The DTK cDNA encodes a mature protein of 850 amino acids with similar structural features to those of the murine receptor. The extracellular domain contains two immunoglobulin-like motifs and two fibronectin type III modules; features which define a new class of receptor tyrosine kinase. The human DTK gene has been mapped by fluorescent in situ hybridization to chromosome 15q15, and a DTK-related gene identified at chromosome 15q24. In fetal tissues, transcripts for DTK were detected in brain, kidney, lung and heart. Prominent expression was observed in the embryonal carcinoma cell line NT2/D1. Expression of the gene is up-regulated in adult tissues with high levels of expression in many regions of the adult brain. DTK is also abundantly expressed in adult kidney, testis, and ovary.
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Every nursing administrator needs a credible performance appraisal system. By using psychometric methods and computer technology, the process of developing such a system can be more efficient and demonstrably successful. This article raises issues that relate to changing the performance appraisal system and gives a clear, step-by-step description of how computerized, statistical procedures were applied in improving nursing performance appraisal.
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