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Biomedical subjects

E Bell

Publications and source records attributed to E Bell.

At least 37 records · Page 2Linked to original sources

New Trends at Immunology Todayellipsis.

'It is not the strongest of the species that survives, nor the most intelligent; it is the one that is most adaptable to change.'Charles Robert Darwin (1809-1882)

Journal Article↗

Integration tutorials and seminars: examining the integration of academic and fieldwork learning by student occupational therapists.

This paper, the second of two companion papers, describes a collaborative research study conducted by academic and fieldwork educators of an undergraduate educational programme in occupational therapy. The study examined the perception of student occupational therapists' ability to integrate and apply academic and theoretical knowledge in fieldwork education sites following the introduction of Integration Tutorials and Seminars to the curriculum. The literature review supports the need to develop educational strategies to improve this integration process. The qualitative research design consisted of guided interviews with preceptors and students during two consecutive fieldwork education experiences. Inductive data analysis revealed three themes that contribute to understanding students' ability to integrate academic learning during their fieldwork education: the fieldwork learning environment; preceptor influence on student learning; and the student learning process over time. The discussion section raises implications for academic and fieldwork education approaches.

Adult↗

Homeotic transformation of branchial arch identity after Hoxa2 overexpression.

Overexpression of Hoxa2 in the chick first branchial arch leads to a transformation of first arch cartilages, such as Meckel's and the quadrate, into second arch elements, such as the tongue skeleton. These duplicated elements are fused to the original in a similar manner to that seen in the Hoxa2 knockout, where the reverse transformation of second to first arch morphology is observed. This confirms the role of Hoxa2 as a selector gene specifying second arch fate. When first arch neural crest alone is targeted, first arch elements are lost, but the Hoxa2-expressing crest is unable to develop into second arch elements. This is not due to Hoxa2 preventing differentiation of cartilages. Upregulation of a second arch marker in the first arch, and homeotic transformation of cartilage elements is only produced after global Hoxa2 overexpression in the crest and the surrounding tissue. Thus, although the neural crest appears to contain some patterning information, it needs to read cues from the environment to form a coordinated pattern. Hoxa2 appears to exert its effect during differentiation of the cartilage elements in the branchial arches, rather than during crest migration, implying that pattern is determined quite late in development.

Animals↗

Homeotic transformation of rhombomere identity after localized Hoxb1 misexpression.

Segmentation of the hindbrain and branchial region is a conserved feature of head development, involving the nested expression of Hox genes. Although it is presumed that vertebrate Hox genes function as segment identifiers, responsible for mediating registration between elements of diverse embryonic origin, this assumption has remained untested. To assess this, retroviral misexpression was combined with orthotopic grafting in chick embryos to generate a mismatch in Hox coding between a specific rhombomere and its corresponding branchial arch. Rhombomere-restricted misexpression of a single gene, Hoxb1, resulted in the homeotic transformation of the rhombomere, revealed by reorganization of motor axon projections.

Animals↗

Expression of GATA-2 in the developing avian rhombencephalon.

Here we describe the expression pattern of GATA-2 in the developing chick hindbrain. We found that during the early period of neurogenesis this gene specifically labels a particular neuronal subtype, the contralateral vestibular-acoustic neurons of rhombomere 4, and that expression of this gene in these cells is transient. We also found that GATA-2 labels a broader territory of the ventral neural tube at later stages. As well as this hindbrain expression, we also describe expression of GATA-2 in the otic vesicle, oculomotor nucleus, third nerve and metanephros.

Animals↗

Specification of distinct motor neuron identities by the singular activities of individual Hox genes.

Hox genes have been implicated in specifying positional values along the anteroposterior axis of the caudal central nervous system, but their nested and overlapping expression has complicated the understanding of how they confer specific neural identity. We have employed a direct gain-of-function approach using retroviral vectors to misexpress Hoxa2 and Hoxb1 outside of the normal Hox expression domains, thereby avoiding complications resulting from possible interactions with endogenous Hox genes. Misexpression of either Hoxa2 or Hoxb1 in the anteriormost hindbrain (rhombomere1, r1) leads to the generation of motor neurons in this territory, even though it is normally devoid of this cell type. These ectopic neurons have the specific identity of branchiomotor neurons and, in the case of Hoxb1-induced cells, their axons leave the hindbrain either by fasciculating with the resident cranial motor axons at isthmic (trochlear) or r2 (trigeminal) levels of the axis or via novel ectopic exit points in r1. Next, we have attempted to identify the precise branchiomotor subtypes that are generated after misexpression and our results suggest that the ectopic motor neurons generated following Hoxa2 misexpression are trigeminal-like, while those generated following Hoxb1 misexpression are facial-like. Our data demonstrate, therefore, that at least to a certain extent and for certain cell types, the singular activities of individual Hox genes (compared to a combinatorial mode of action, for example) are sufficient to impose on neuronal precursor cells the competence to generate distinctly specified cell types. Moreover, as these particular motor neuron subtypes are normally generated in the most anterior domains of Hoxa2 and Hoxb1 expression, respectively, our data support the idea that the main site of individual Hox gene action is in the anteriormost subdomain of their expression, consistent with the phenomenon of posterior dominance.

Animals↗

Use of an automated anesthesia information system to determine reference limits for vital signs during cesarean section.

INTRODUCTION: We evaluated whether automated anesthesia information systems can be used to calculate reference limits (population-based "normal values") for vital signs. We considered four populations of women undergoing cesarean section: healthy under spinal anesthesia, healthy under general anesthesia, pre-eclamptic/eclamptic under spinal anesthesia, and pre-eclamptic/eclamptic under general anesthesia. METHODS: Reference limits were calculated for each of the study populations by determination of percentiles for: minimum heart rate, maximum heart rate, minimum arterial oxyhemoglobin saturation (SaO2), minimum mean arterial pressure (MAP), maximum MAP, decrease in MAP, and increase in MAP. RESULTS: There was one adverse anesthetic outcome among the 1,300 women in the study; the woman sustained a post-dural puncture headache. The 5th percentiles of SaO2 were at least 95% saturation under spinal versus 90% under general. Under spinal anesthesia, 95th percentiles for decreases in MAP from baseline were 63 mmHg for healthy and 75 mmHg for pre-eclamptic/eclamptic women. Under general anesthesia, the 95th percentiles for maximum MAP were 161 and 177 mmHg, respectively. Two women of the 1,300 patients experienced simultaneously a minimum SaO2 < 92% and minimum MAP < 50 mmHg. DISCUSSION: Automated anesthesia information systems can be used to determine reference limits for vital signs during anesthesia. Reference limits may play a role in malpractice cases when an expert claims that care by an anesthesiologist was sub-standard as shown by vital signs that were not maintained within the normal range during the critical portions of an anesthetic. Automated anesthesia information systems may enhance expert witnesses' clinical judgment.

Adult↗

Advantage of the presence of living dermal fibroblasts within in vitro reconstructed skin for grafting in humans.

Methods for serial cultivation of human keratinocytes can provide large quantities of epidermal cells, which have the potential of restoring the vital barrier function of the epidermis in extensive skin defects such as burns. To investigate the value of combining an epidermis with a dermal component, fibroblasts originated from the superficial dermis were used to seed a collagen lattice as described by E. Bell (dermal equivalent). Beginning in 1981, we grafted 18 patients (burns and giant nevi) using 35 grafts 10 x 10 cm in size. In the course of this work, the original technique was modified and improved as experience was gained. We began by using small skin biopsy samples as a source of keratinocytes cultured on a dermal equivalent before grafting in a one-step procedure, but this gave poor cosmetic results, because of a nonhomogeneous epidermalization. We then chose to cover the graft bed using a two-step procedure. The first step consisted of grafting a dermal equivalent to provide a dermal fibroblast-seeded substrate for subsequent in vivo epidermalization by cultured epidermal sheets. Whatever the epidermalization technique used, a living dermal equivalent applied to the graft bed was found to reduce pain, to provide good hemostasis, and to improve the mechanical and cosmetic properties of the graft. A normal undulating dermal-epidermal junction reappeared by 3 to 4 months after grafting and elastic fibers were detectable 6 to 9 months after grafting. As a result of the biosynthesis of these products, the suppleness (e.g., elasticity) of the grafts was closer to that of normal skin than the cicatricial skin usually obtained with epidermal sheets grafted without the presence of living dermal cells. This rapid improvement of the mechanical properties of the graft could be attributed to the presence of fibroblasts cultured from the dermis and seeded into the collagen matrix.

Adult↗

Characterization of the interaction between the Staphylococcus aureus clumping factor (ClfA) and fibrinogen.

The ability of Staphylococcus aureus to adhere to adsorbed fibrinogen and fibrin is believed to be an important step in the initiation of biomaterial and wound-associated infections. In this study, we show that the binding site in fibrinogen for the recently identified S. aureus fibrinogen-binding protein clumping factor (ClfA) is within the C-terminus of the fibrinogen gamma chain. S. aureus Newman cells expressing ClfA adhered to microtitre wells coated with recombinant fibrinogen purified from BHK cells, but did not adhere to wells coated with a purified recombinant fibrinogen variant where the 4 C-terminal residues of the gamma chain were replaced by 20 unrelated residues. In addition, a synthetic peptide corresponding to the 17 C-terminal amino acids of the fibrinogen gamma chain effectively inhibited adherence of ClfA-expressing cells to fibrinogen. In western ligand blots, a recombinant truncated ClfA protein called Clf33 (residues 221-550) recognized intact recombinant fibrinogen gamma chains, but failed to recognize recombinant fibrinogen gamma chains where the 4 C-terminal amino acids were altered by deletion or substitution. Previous studies have shown that the C-terminal domain of fibrinogen gamma chains contains a binding site for the integrin alphaIIb beta3 (glycoprotein gpIIb/IIIa) receptor on platelets [Kloczewiak, M., Timmons, S., Bednarek, M. A., Sakon, M. & Hawiger, J. (1989) Biochemistry 28, 2915-1919; Farrell, D. H., Thiagarajan, P., Chung, D. W. & Davie, E. W. (1992) Proc. Natl. Acad. Sci. USA 89, 10729-10732; Hettasch, J. M., Bolyard, M. G. & Lord, S. T. (1992) Thromb. Haemostasis 68, 701-706]. We now show that Clf33 inhibits ADP-induced, fibrinogen-dependent platelet aggregation in a concentration-dependent manner and inhibits adhesion of platelets to immobilized fibrinogen under fluid shear stress, indicating that the binding sites for the platelet integrin and the staphylococcal adhesin overlap. The interaction between Clf33 and fibrinogen was further characterized using the BIAcore biosensor. When soluble Clf33 was allowed to bind to immobilized fibrinogen, a Kd of 0.51 +/- 0.19 microM was experimentally determined using equilibrium binding data. It was also shown that the synthetic C-terminal gamma-chain peptide effectively inhibited this interaction.

Adenosine Diphosphate↗

Jasmonate is essential for insect defense in Arabidopsis.

The signaling pathways that allow plants to mount defenses against chewing insects are known to be complex. To investigate the role of jasmonate in wound signaling in Arabidopsis and to test whether parallel or redundant pathways exist for insect defense, we have studied a mutant (fad3-2 fad7-2 fad8) that is deficient in the jasmonate precursor linolenic acid. Mutant plants contained negligible levels of jasmonate and showed extremely high mortality ( approximately 80%) from attack by larvae of a common saprophagous fungal gnat, Bradysia impatiens (Diptera: Sciaridae), even though neighboring wild-type plants were largely unaffected. Application of exogenous methyl jasmonate substantially protected the mutant plants and reduced mortality to approximately 12%. These experiments precisely define the role of jasmonate as being essential for the induction of biologically effective defense in this plant-insect interaction. The transcripts of three wound-responsive genes were shown not to be induced by wounding of mutant plants but the same transcripts could be induced by application of methyl jasmonate. By contrast, measurements of transcript levels for a gene encoding glutathione S-transferase demonstrated that wound induction of this gene is independent of jasmonate synthesis. These results indicate that the mutant will be a good genetic model for testing the practical effectiveness of candidate defense genes.

Journal Article↗