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Biomedical subjects

E Burke

Publications and source records attributed to E Burke.

At least 19 recordsLinked to original sources
PubMed2001

The Heartmate II: design and development of a fully sealed axial flow left ventricular assist system.

Our group is developing the control and power transmission components required to implement a permanent and fully sealed left ventricular assist system (LVAS). Starting with the percutaneously powered HeartMate II blood pump, our development efforts are focused in the following areas: a complete redesign of the transcutaneous energy transmission system (TETS) to include a rectification network and autonomous voltage regulation within the secondary coil, a hermetically sealed electronics package containing a miniaturized implementation of the existing redundant drive and control electronics with several power-input options, an implanted rechargeable lithium ion battery pack capable of providing up to 1 h of untethered operation, implantable electrical connectors that allow components to be connected after placement in the body or to be replaced if needed, and a radio telemetry subsystem to transmit diagnostic information and to permit remote adjustment of selected parameters.

Electric Power Supplies↗
PubMed2000

Profilin is required for optimal actin-dependent transcription of respiratory syncytial virus genome RNA.

Transcription of human respiratory syncytial virus (RSV) genome RNA exhibited an obligatory need for the host cytoskeletal protein actin. Optimal transcription, however, required the participation of another cellular protein that was characterized as profilin by a number of criteria. The amino acid sequence of the protein, purified on the basis of its transcription-optimizing activity in vitro, exactly matched that of profilin. RSV transcription was inhibited 60 to 80% by antiprofilin antibody or poly-L-proline, molecules that specifically bind profilin. Native profilin, purified from extracts of lung epithelial cells by affinity binding to a poly-L-proline matrix, stimulated the actin-saturated RSV transcription by 2.5- to 3-fold. Recombinant profilin, expressed in bacteria, stimulated viral transcription as effectively as the native protein and was also inhibited by poly-L-proline. Profilin alone, in the absence of actin, did not activate viral transcription. It is estimated that at optimal levels of transcription, every molecule of viral genomic RNA associates with approximately the following number of protein molecules: 30 molecules of L, 120 molecules of phosphoprotein P, and 60 molecules each of actin and profilin. Together, these results demonstrated for the first time a cardinal role for profilin, an actin-modulatory protein, in the transcription of a paramyxovirus RNA genome.

Actins↗
PubMed2000

Has the mammography quality standards act affected the mammography quality in North Carolina?

OBJECTIVE: The United States Food and Drug Administration implemented federal regulations governing mammography under the Mammography Quality Standards Act (MQSA) of 1992. During 1995, its first year in implementation, we examined the impact of the MQSA on the quality of mammography in North Carolina. MATERIALS AND METHODS: All mammography facilities were inspected during 1993-1994, and again in 1995. Both inspections evaluated mean glandular radiation dose, phantom image evaluation, darkroom fog, and developer temperature. Two mammography health specialists employed by the North Carolina Division of Radiation Protection performed all inspections and collected and codified data. RESULTS: The percentage of facilities that met quality standards increased from the first inspection to the second inspection. Phantom scores passing rate was 31.6% versus 78.2%; darkroom fog passing rate was 74.3% versus 88.5%; and temperature difference passing rate was 62.4% versus 86.9%. CONCLUSION: In 1995, the first year that the MQSA was in effect, there was a significant improvement in the quality of mammography in North Carolina. This improvement probably resulted from facilities' compliance with federal regulations.

Mammography↗
PubMed1999

Intravenous immunoglobulin reduces anti-HLA alloreactivity and shortens waiting time to cardiac transplantation in highly sensitized left ventricular assist device recipients.

BACKGROUND: Recipients of left ventricular assist devices (LVADs) develop prominent B-cell hyperreactivity. We investigated the influence of anti-HLA antibodies on waiting time to cardiac transplantation in LVAD recipients and compared the effects of 2 immunomodulatory regimens on anti-HLA serum reactivity. METHODS AND RESULTS: Fifty-five previously nonsensitized LVAD recipients of a TCI device implanted between 1990 and 1996 were studied. Patients with anti-HLA antibodies received monthly courses of either intravenous immunoglobulin (IVIg) or plasmapheresis, in conjunction with cyclophosphamide. The effects of these regimens on anti-HLA alloreactivity and waiting time to transplantation were then determined by Kaplan-Meier log-rank statistics, nonparametric Wilcoxon rank-sum test, and Student's t test. Prolongation in transplant waiting time was related to serum IgG anti-HLA class I alloreactivity. Infusion of IVIg (2 g/kg) caused a mean reduction of 33% in anti-HLA class I alloreactivity within 1 week. Waiting time to transplantation was significantly reduced by IVIg therapy and subsequently approximated that in nonsensitized patients. Side effects of IVIg (2 g/kg) were minimal and related primarily to immune complex disease. Although plasmapheresis caused a similar reduction in alloreactivity to IVIg, this effect was achieved after longer treatment. Moreover, plasmapheresis was associated with an unacceptably high frequency of infectious complications. In patients resistant to low-dose (2 g/kg) IVIg therapy, high-dose (3 g/kg) IVIg was effective in reducing alloreactivity but was associated with a high incidence of reversible renal insufficiency. CONCLUSIONS: These results indicate that IVIg is an effective and safe modality for sensitized recipients awaiting cardiac transplantation, reducing serum anti-HLA alloreactivity and shortening the duration to transplantation. The therapeutic and safety profile of IVIg would appear to be superior to plasmapheresis.

Graft Rejection↗
PubMed1999

Structural and functional characterization of an epitope in the conserved C-terminal region of HIV-1 gp120.

Through an integrated study of the reactivity of a monoclonal antibody, 803-15.6, with synthetic peptides and native recombinant HIV-1 envelope glycoprotein gp120, we have obtained structure-functional information on a region of rgp120 not yet elucidated by X-ray crystallography. mAb 803-15.6 binds with high affinity and broad cross-clade specificity to the conserved C-terminal region (amino acids 502-516) of HIV-1 rgp120. Phage display selection from a random peptide library identified the core binding motif as AXXKXRH, homologous to residues 502-508. Using quantitative binding analyses, the affinity of mAb 803-15.6 for native, monomeric recombinant gp120HXB2 (rgp120) was found to be similar to that for the synthetic gp120 peptide (502-516). Circular dichroism studies indicate that the synthetic peptide largely has a random coil conformation in solution. The results therefore suggest that the 803-15.6 epitope is fully accessible on rgp120 and that this region of rgp120 is as flexible as the synthetic peptide. Residues 502-504 are on the edge of a putative gp41 binding site that has been postulated to change conformation on CD4 binding. However, the affinity of mAb 803-15.6 for rgp120 is not affected by binding of CD4 and vice-versa. These results suggest either that the 502-504 region does not change conformation upon CD4 binding, or that recombinant gp120 does not undergo the same changes as occur in the native viral gp120-gp41 oligomer. The detailed characterization of the 803-15.6 epitope may be useful for further study of the role of the C5 region of gp120 in the viral attachment and fusion process.

Amino Acid Sequence↗
PubMed1998

Role of cellular actin in the gene expression and morphogenesis of human respiratory syncytial virus.

Cytoskeletal protein actin and nonactin cellular proteins were essential for human respiratory syncytial virus (RSV) gene expression. In vitro, specific antibodies against actin inhibited RSV transcription, whereas antibodies against other cytoskeletal proteins had little or no effect. Affinity purified cellular actin or bacterially expressed recombinant actin activated RSV transcription. However, optimal transcription required additional cellular protein(s) that appeared to function as accessory factor(s) for actin. In the absence of actin, these proteins did not activate viral transcription. Purified viral nucleocapsids contained actin, but no cytokeratin, tubulin, or vimentin. Cytochalasin D or DNasel--agents that destabilize actin polymers--had little effect on RSV transcription. RSV infection itself seemed to alter the structure of the cellular actin filaments. Treatment of infected cells with cytochalasin D produced a more severe disruption of the filaments and drastically reduced the production of infectious virus particles but still had little effect on intracellular synthesis of viral macromolecules. Thus actin seems to serve a dual role in RSV life cycle: its monomeric form as well as polymeric form activate viral transcription, while only the microfilament form may take part in viral morphogenesis and/or budding.

Actin Cytoskeleton↗
PubMed1998

Intrahepatic biliary enteric bypass provides effective palliation in selected patients with malignant obstruction at the hepatic duct confluence.

BACKGROUND: Palliating the effects of biliary obstruction is a major goal of therapy in patients with cancer at the hepatic duct confluence. This study was undertaken to evaluate the effectiveness of intrahepatic biliary-enteric bypass to either the segment III duct or the right sectoral hepatic ducts in patients with unresectable hilar cholangiocarcinoma or gallbladder carcinoma. METHODS: From December 1991 to October 1996, 55 consecutive bypass procedures were prospectively evaluated in patients with unresectable hilar cholangiocarcinoma or gallbladder cancer. Patients were divided into three groups based on the primary tumor and the type of bypass performed: group 1A, cholangiocarcinoma/segment III bypass (n = 20); group 1B, cholangiocarcinoma/right sectoral hepatic duct bypass (n = 14); group 2, gallbladder cancer/segment III bypass (n = 21). RESULTS: Mean hospital stay (14+/-2 days) and mean blood loss (629+/-84 mL) were similar among the three groups. Perioperative death occurred in 6 patients (11%): 0 in group 1A, 3 each in groups 1B and 2. All survivors had relief of jaundice and pruritus after bypass. Complications occurred in 25 patients (45%). Preoperative transhepatic biliary drainage, performed in 14 patients prior to referral, was associated with a higher incidence of contaminated bile, greater operative blood loss, and postoperative biliary leak that was less likely to resolve spontaneously. Median survival in patients with cholangiocarcinoma (groups 1A and 1B) was 52 weeks and was unaffected by the type of bypass performed. By contrast, median survival in patients with gallbladder cancer (group 3) was 20 weeks; all but 3 died within 32 weeks of surgery. In patients with cholangiocarcinoma, the 1-year bypass patency was 80% in group 1A (segment III bypass) and 60% in group 1B (right sectoral hepatic duct bypass). Overall, there were 9 late bypass failures (18%) requiring reintervention. CONCLUSIONS: Intrahepatic biliary-enteric bypass effectively relieves symptoms due to malignant hilar obstruction. In patients with cholangiocarcinoma, segment III bypass provides excellent palliation with relatively few late complications and can be performed with minimal morbidity and mortality. Bypass to the right sectoral hepatic ducts, on the other hand, is associated with significant procedure-related morbidity and mortality and more late complications. Patients with gallbladder cancer, because of their poor survival, are probably better palliated by percutaneous biliary stenting.

Anastomosis, Surgical↗
PubMed1997

Large sample validations of three general predictors of pilot training success.

This article addresses one of the perennial problems of pilot selection research: obtaining an adequate sample size for reliable statistical analysis of predictive validity. Results from three studies involving the same computerized tests of instrument comprehension and psychomotor ability were combined in a meta-analysis to determine whether the validities of these tests generalized across three contexts. These were Royal Air Force and Turkish Air Force fixed-wing pilot training and British Army Air Corps rotary-wing pilot training. In this article, we discuss the adequacy of samples for estimating the validity of the tests, and the persistence of predictive validity to later stages of training as shown by British Army Air Corps data. Reference is also made to data from a fourth independent study of Qantas pilot training.

Australia↗
PubMed1996

Immunization with soluble BDC 2.5 T cell receptor-immunoglobulin chimeric protein:antibody specificity and protection of nonobese diabetic mice against adoptive transfer of diabetes by maternal immunization.

The BDC 2.5 T cell clone is specific for pancreatic beta-cell antigen presented by I-Ag7, and greatly accelerates diabetes when injected into 10-21-d-old nonobese diabetic (NOD) mice. The BDC 2.5 T cell receptor (TCR) has been solubilized as a TCR-IgG1 chimeric protein. All NOD mice immunized against BDC 2.5 TCR-IgG1 produced antibodies recognizing TCR C alpha/C beta epitopes that were inaccessible on the T cell surface. 56% of the mice produced antibodies against the BDC 2.5 clonotype that specifically blocked antigen activation of BDC 2.5 cells. We have used the adoptive transfer model of diabetes to demonstrate that maternal immunization with soluble TCR protects young mice from diabetes induced by the BDC 2.5 T cell clone.

Adoptive Transfer↗