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Biomedical subjects

R Dunn

Publications and source records attributed to R Dunn.

At least 19 recordsLinked to original sources
PubMed2003

To thin or not to thin: the use of the anterolateral thigh flap in the reconstruction of intraoral defects.

The anterolateral thigh (ALT) flap has achieved popularity recently for free-flap reconstruction of intraoral defects following excision of squamous cell carcinoma. We have assessed the feasibility of the ALT flap as a free flap for oral lining and the potential use of the thinned ALT flap in a one-stage reconstruction. We used the ALT flap to reconstruct the oral cavity in 18 consecutive patients between December 2000 and December 2001 following intraoral resection of squamous cell carcinoma. Twelve patients underwent reconstruction using a standard ALT flap, four patients received a thinned ALT flap in a one-stage procedure, one patient received a standard ALT flap in combination with a fibula flap and one patient received a combination of a standard ALT flap and vascularised iliac bone. There were no complications in any of the 14 cases in which a standard ALT flap was used. Two of these flaps were thinned subsequently as secondary procedures. Of the four thinned ALT flaps, one flap failed completely and two flaps experienced partial necrosis. In all but one case the donor site was closed directly with minimal donor-site morbidity. The ALT flap is a versatile flap that can be used in combination with other flaps for more complex defects with minimal donor-site morbidity and is a useful alternative in the armamentarium of the head and neck surgeon. Thinning of the flap is best performed as a secondary procedure, should it be required.

Aged↗
PubMed2003

Initial feasibility study of a sprayable hydrogel adhesion barrier system in patients undergoing laparoscopic ovarian surgery.

STUDY OBJECTIVE: To assess the safety and effectiveness of SprayGel as a barrier to reduce the frequency of adhesion formation and reformation after ovarian surgery, and to determine the feasibility of the study design for a larger, multicenter pivotal trial. DESIGN: Prospective, randomized, internally controlled trial (Canadian Task Force classification I). SETTING: Two metropolitan, academic-affiliated, nonprofit hospitals. PATIENTS: Fourteen women. INTERVENTION: Bilateral adnexal surgery. MEASUREMENTS AND MAIN RESULTS: On completion of surgery, one adnexa was randomized to receive optimal surgical treatment plus application of the adhesion barrier, and the contralateral one to receive optimal surgical treatment alone. Patients returned in 3 to 16 weeks for second-look laparoscopy. All initial and second-look procedures were videotaped and reviewed by a blinded surgeon reviewer, and assessed for frequency, extent, and severity of adhesions. The frequency and extent of adhesion formation at second-look laparoscopy were statistically reduced on treatment sides compared with control sides (71% reduction in frequency, p = 0.0488; 69% reduction in extent, p = 0.0494). Adhesion severity score was reduced by 43% on the treatment side. SprayGel was associated with no adverse effects and was applied successfully in all patients. CONCLUSION: This material shows great promise in preventing postoperative adhesion formation in a population of patients greatly in need of such an adjunct. These findings warrant a larger, pivotal, multicenter study to evaluate SprayGel further.

Adhesives↗
PubMed2002

Optimisation of polystyrene resin-supported Pt catalysts in room temperature, solvent-less, oct-l-ene hydrosilylation using methyldichlorosilane.

Six precursor resins with systematic variation of porous parameters were prepared by suspension polymerisation using specific compositions of divinylbenzene, styrene vinylbenzyl chloride (VBC) and 2-ethylhexan-l-ol (a porogen). Surface areas from N(2) sorption and BET analysis were approximately 2-170 m(2)g-(1). The VBC content in each case was 38 mol% and these groups were aminated using the sodium salt of trimethylethylene diamine. Pt was introduced onto each resin at three different loadings (approximately 0.03, approximately 0.2 and approximately 0.4 mmol g-(1)) by appropriate manipulation of K(2)PtCl(6). The matrix of 18 resin-supported Pt complexes was then assessed for catalytic activity in the room temperature, solvent-less, hydrosilylation of oct-l-ene using methyldichlorosilane such that alkene: silane: Pt ratio was fixed at 2:1:1x10(-3). Though all the catalysts showed activity lower than that of homogeneous Speier s catalyst, most were sufficiently active to be potentially valuable heterogeneous catalysts in the laboratory, and indeed the plant. The most lightly loaded resins proved to be the least active. The remainder were recycled 5 times, and the best performers, the most highly loaded species, a further 5 times making 10 consecutive uses in all. A strong dependence on the porous structure of the resins was demonstrated with the activity rising systemically with the surface area. The two highest surface area highest loaded species displayed good activity even when used for the tenth time. The level of concurrent alkene isomerisation observed was very low throughout (<1%) making these heterogeneous species very selective as well as highly active. Overall the derived catalysts are excellent candidates for use in the research laboratory, and with further development could also be valuable in continuous processes.

Alkenes↗
PubMed2001

Soluble CD137 (4-1BB) ligand is released following leukocyte activation and is found in sera of patients with hematological malignancies.

Expression of CD137 ligand (4-1BBL), a member of the TNF family of proteins, has been reported on several types of APCs, various carcinoma cells, and can be induced on activated T cells. In this study, we report that the soluble ligand was released constitutively at low levels from leukocytes and at higher levels following cellular activation. Release from cells was blocked by addition of a metalloproteinase inhibitor which concomitantly caused the accumulation of 4-1BBL on the cell surface. In addition, we show that a soluble form of 4-1BBL was present at high levels in the sera of some patients with various hematological diseases, but only at low levels in healthy donors. Soluble 4-1BBL was active in that it competed with recombinant 4-1BBL for binding to the 4-1BB receptor and was able to costimulate IL-2 and IFN-gamma release from peripheral T cells. These results indicate that the release of soluble 4-1BBL from the cell surface is mediated by one or more sheddases and likely regulates 4-1BB-4-1BBL interactions between cells in vivo. Cleavage of 4-1BBL to an active soluble form would alter both proximal and distal cellular responses, including cell survival and costimulatory or inflammatory responses, that are mediated through the 4-1BB pathway. This, in turn, would likely alter disease progression or outcome.

4-1BB Ligand↗
PubMed2001

Sequencing and two-dimensional structure prediction of a phospholipase A(2) inhibitor from the serum of the common tiger snake (Notechis scutatus).

A phospholipase A(2) inhibitor has been identified in the serum of the common tiger snake (Notechis scutatus). The inhibitor is composed of two chains, an alpha-chain and a beta-chain, that form a non-covalently associated complex capable of inhibiting the enzymatic activity of all phospholipase A(2) enzymes it was tested against. The alpha and beta-chains have been purified to homogeneity, digested and sequenced. From the peptide sequence generated, degenerate PCR primers were designed and used to elucidate the complete cDNA sequence of the chains using 5' and 3' RACE PCR. A total of three alpha-chain isoforms were identified, only one isoform of the beta-chain was detected. The two-dimensional structure of the three alpha-chains and one beta-chain were predicted using five prediction programs (discrimination of secondary structure class; nearest neighbour secondary structure, profile network from Heidelberg; self-optimised prediction method from multiple alignment, SSPAL). For each protein chain a consensus prediction was generated. Results are discussed in relation to the function of the protein, and how they may influence the three-dimensional structure of the inhibitor. Additionally, the sequences of several snake phospholipase A(2) inhibitors were used as the input for a motif prediction algorithm (MEME). The results are discussed in relation to the activity of these proteins.

Alkylation↗
PubMed2001

Multiple roles for Rsp5p-dependent ubiquitination at the internalization step of endocytosis.

Ubiquitination of integral plasma membrane proteins triggers their rapid internalization into the endocytic pathway. The yeast ubiquitin ligase Rsp5p, a homologue of mammalian Nedd4 and Itch, is required for the ubiquitination and subsequent internalization of multiple plasma membrane proteins, including the alpha-factor receptor (Ste2p). Here we demonstrate that Rsp5p plays multiple roles at the internalization step of endocytosis. Temperature-sensitive rsp5 mutant cells were defective in the internalization of alpha-factor by a Ste2p-ubiquitin chimera, a receptor that does not require post-translational ubiquitination. Similarly, a modified version of Ste2p bearing a NPFXD linear peptide sequence as its only internalization signal was not internalized in rsp5 cells. Internalization of these variant receptors was dependent on the catalytic cysteine residue of Rsp5p and on ubiquitin-conjugating enzymes that bind Rsp5p. Thus, a Rsp5p-dependent ubiquitination event is required for internalization mediated by ubiquitin-dependent and -independent endocytosis signals. Constitutive Ste2p-ubiquitin internalization and fluid-phase endocytosis also required active ubiquitination machinery, including Rsp5p. These observations indicate that Rsp5p-dependent ubiquitination of a trans-acting protein component of the endocytosis machinery is required for the internalization step of endocytosis.

Endocytosis↗
PubMed2001

Evaluation of the SprayGel adhesion barrier in the rat cecum abrasion and rabbit uterine horn adhesion models.

OBJECTIVE: To evaluate the efficacy of a new adhesion barrier in the prevention of postoperative adhesion formation. DESIGN: A double-blind controlled study of the efficacy of SprayGel in reducing postoperative adhesion formation in two animal models. SETTING: Animal care facility of a contract testing laboratory. ANIMAL(S): Sixteen Sprague-Dawley male rats were randomly allocated into two groups in the cecum abrasion model. Twenty New Zealand white female rabbits were randomly allocated into two groups in the uterine horn abrasion model. INTERVENTION(S): In the rat model, the cecum was abraded with gauze and the abdominal wall was abraded with a scalpel. Treated animals received SprayGel coating on injured surfaces; control animals received no treatment. In the rabbit model, uterine horns were abraded with a scalpel. Treated animals received SprayGel coating on injured surfaces; control animals received no treatment. MAIN OUTCOME MEASURE(S): Postoperative adhesion formation. RESULT(S): In the rat model, SprayGel was found to significantly reduce the incidence of adhesions, which formed in 7 of 8 control rats compared with 1 of 8 treated rats. In the rabbit model, SprayGel was found to significantly reduce both the extent and severity of adhesions. CONCLUSION(S): Application of SprayGel in two animal models reduced formation of postoperative adhesions. Further investigation in large animal and clinical settings is warranted.

Abdominal Muscles↗
PubMed2001

Valvular density alone cannot account for sites of chronic venous insufficiency and ulceration in the lower extremity.

OBJECTIVE: Class 6 chronic venous stasis is associated with abnormal venous hemodynamics and ulceration. Ulcers primarily occur over bones and tendon prominences but very rarely over muscular compartments. We hypothesized that the anatomical distribution of venous stasis ulcers in the lower extremity is related to a lower density of venous valves. METHODS: The venous vasculature of six normal human legs was cast with resin, and their microvenous valvular anatomy was examined. Skin samples were obtained from the skin overlying the 1) Achilles' tendon, 2) anterior tibia, 3) medial malleolus, 4) lateral malleolus, 5) dorsal surface of the foot, 6) planta pedis, 7) dorsal aspect of the great toe; and from the skin regions overlying the 8) gastrocnemius, 9) tibialis anterior, and 10) peroneus muscles. The valvular and venous densities were determined in a scanning electron microscope, normalized to the size of specimens, and the valvular index was calculated. Analysis of variance with Bonferroni t-test was used to compare the valvular index between the regions. RESULTS: Venous valves were observed in all tissue regions. The diameter of veins with valves ranged from 18 microm to 803 microm. The valvular index for regions overlying bones/tendons (i.e., regions 1-7) was significantly higher versus those overlying muscular regions (i.e., regions 8-10) (p < 0.05). The valvular index was not different (p = 0.51) when regions 1 and 2 (where ulcers almost never occur) were compared to regions 3, 4, 5, 6, and 7 (where ulcers frequently occur); nor were there differences between the vascular indexes of regions overlying muscle. The largest venous valves were observed in the plantar region, and the smallest-sized ones were present in the peroneal region. CONCLUSIONS: This study shows that the density of venous valves is actually higher in regions of the human lower extremity overlying bones and tendons, where venous stasis ulcers are common, than those overlying muscular areas, where ulcers are rarely seen. Thus, valvular quantity alone cannot account for the higher clinical incidence of ulceration. It is likely that muscular pumping and/or valvular quality are important factors in preventing the development of venous stasis and ulceration in the lower extremity.

Aged↗
PubMed2001

Expanding silicone granuloma.

Complications of breast augmentation using silicone implants have been the subject of much discussion. We report a single case of a silicone granuloma, which has exhibited unusual behaviour in that it has grown rapidly and significantly. Whilst silicone granulomata have been reported on many occasions in the past, to our knowledge this is the first report of a rapidly growing example.

Breast Diseases↗
PubMed2001

Domains of the Rsp5 ubiquitin-protein ligase required for receptor-mediated and fluid-phase endocytosis.

Yeast Rsp5p and its mammalian homologue, Nedd4, are hect domain ubiquitin-protein ligases (E3s) required for the ubiquitin-dependent endocytosis of plasma membrane proteins. Because ubiquitination is sufficient to induce internalization, E3-mediated ubiquitination is a key regulatory event in plasma membrane protein endocytosis. Rsp5p is an essential, multidomain protein containing an amino-terminal C2 domain, three WW protein-protein interaction domains, and a carboxy-terminal hect domain that carries E3 activity. In this study, we demonstrate that Rsp5p is peripherally associated with membranes and provide evidence that Rsp5p functions as part of a multimeric protein complex. We define the function of Rsp5p and its domains in the ubiquitin-dependent internalization of the yeast alpha-factor receptor, Ste2p. Temperature-sensitive rsp5 mutants were unable to ubiquitinate or to internalize Ste2p at the nonpermissive temperature. Deletion of the entire C2 domain had no effect on alpha-factor internalization; however, point mutations in any of the three WW domains impaired both receptor ubiquitination and internalization. These observations indicate that the WW domains play a role in the important regulatory event of selecting phosphorylated proteins as endocytic cargo. In addition, mutations in the C2 and WW1 domains had more severe defects on transport of fluid-phase markers to the vacuole than on receptor internalization, suggesting that Rsp5p functions at multiple steps in the endocytic pathway.

Amino Acid Sequence↗
PubMed2001

When health information and fiscal management meet.

HIM professionals have skills that can allow them to contribute to the bottom line in many ways. The author describes areas where HIM expertise can make a difference in evaluating an organization's fiscal performance through analysis of services driven by health information.

Accounts Payable and Receivable↗
PubMed2000

Solvent dependence of dynamic transitions in protein solutions.

A transition as a function of increasing temperature from harmonic to anharmonic dynamics has been observed in globular proteins by using spectroscopic, scattering, and computer simulation techniques. We present here results of a dynamic neutron scattering analysis of the solvent dependence of the picosecond-time scale dynamic transition behavior of solutions of a simple single-subunit enzyme, xylanase. The protein is examined in powder form, in D(2)O, and in four two-component perdeuterated single-phase cryosolvents in which it is active and stable. The scattering profiles of the mixed solvent systems in the absence of protein are also determined. The general features of the dynamic transition behavior of the protein solutions follow those of the solvents. The dynamic transition in all of the mixed cryosolvent-protein systems is much more gradual than in pure D(2)O, consistent with a distribution of energy barriers. The differences between the dynamic behaviors of the various cryosolvent protein solutions themselves are remarkably small. The results are consistent with a picture in which the picosecond-time scale atomic dynamics respond strongly to melting of pure water solvent but are relatively invariant in cryosolvents of differing compositions and melting points.

Calorimetry, Differential Scanning↗