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Biomedical subjects

J Burch

Publications and source records attributed to J Burch.

At least 19 recordsLinked to original sources
PubMed2001

Pro-apoptotic cleavage products of Bcl-xL form cytochrome c-conducting pores in pure lipid membranes.

During apoptotic cell death, cells usually release apoptogenic proteins such as cytochrome c from the mitochondrial intermembrane space. If Bcl-2 family proteins induce such release by increasing outer mitochondrial membrane permeability, then the pro-apoptotic, but not anti-apoptotic activity of these proteins should correlate with their permeabilization of membranes to cytochrome c. Here, we tested this hypothesis using pro-survival full-length Bcl-x(L) and pro-death Bcl-x(L) cleavage products (DeltaN61Bcl-x(L) and DeltaN76Bcl-x(L)). Unlike Bcl-x(L), DeltaN61Bcl-x(L) and DeltaN76Bcl-x(L) caused the release of cytochrome c from mitochondria in vivo and in vitro. Recombinant DeltaN61Bcl-x(L) and DeltaN76Bcl-x(L), as well as Bcl-x(L), cleaved in situ by caspase 3-possessed intrinsic pore-forming activity as demonstrated by their ability to efficiently permeabilize pure lipid vesicles. Furthermore, only DeltaN61Bcl-x(L) and DeltaN76Bcl-x(L), but not Bcl-x(L), formed pores large enough to release cytochrome c and to destabilize planar lipid bilayer membranes through reduction of pore line tension. Because Bcl-x(L) and its C-terminal cleavage products bound similarly to lipid membranes and formed oligomers of the same size, neither lipid affinity nor protein-protein interactions appear to be solely responsible for the increased membrane-perturbing activity elicited by Bcl-x(L) cleavage. Taken together, these data are consistent with the hypothesis that Bax-like proteins oligomerize to form lipid-containing pores in the outer mitochondrial membrane, thereby releasing intermembrane apoptogenic factors into the cytosol.

Animals↗
PubMed2001

The carotid artery as alternative access for endoluminal aortic aneurysm repair.

Endograft treatment of aortic aneurysms has become a common procedure in many centers. However, not all patients are candidates for this new technology, because of their vascular anatomy and device limitations. One common problem is iliofemoral occlusive disease, which when present, even in a moderate degree, may preclude introduction of the large-diameter delivery devices currently in use. We present a case of a high-risk male patient with a thoracic aortic aneurysm and severe occlusive disease of the iliac arteries. An alternative approach for device delivery through the carotid artery was used and the procedure was successful with no neurologic complications. We recommend this technique for highly selected patients with an aneurysm who can undergo tube endograft repair without feasible access through the iliac or femoral arteries.

Aneurysm, False↗
PubMed2001

Stimulation of extracellular signal-regulated kinase by pituitary adenylate cyclase-activating polypeptide in alpha T3-1 gonadotrophs.

The putative hypophysiotropic factor pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates glycoprotein hormone alpha-subunit (alpha GSU) gene transcription and secretion in the clonal gonadotroph alpha T3-1 cell line. The specific signalling pathways regulating these actions of PACAP have not been clearly defined. We have examined the possibility that mitogen activated protein kinases (MAPKs) may play a role in mediating the effects of PACAP on alpha T3-1 gonadotrophs. Treatment of alpha T3-1 cells with PACAP (100 nM) or epidermal growth factor (EGF, 10 nM) for 5 min significantly stimulated extracellular signal-regulated kinase activity (ERK, a component of the MAPK pathway) as determined by an immunocomplex assay. Pre-treatment of alpha T3-1 cells with the specific MAPK kinase (MEK) inhibitor, U0126, blocked PACAP and EGF-induced activation of ERK. Transcriptional stimulation of a human alpha GSU-luciferase reporter construct by PACAP was unaffected by U0126 treatment. However, pre-treatment with U0126 significantly inhibited PACAP stimulation of [(3)H]-thymidine incorporation in alpha T3-1 cells. Thus our results suggest that PACAP stimulates ERK activation in alpha T3-1 cells, and that the functional effect of this ERK activation is increased DNA synthesis and cell proliferation rather then transcriptional activation of the alpha GSU gene.

Animals↗
PubMed2001

Serologic survey for canine coronavirus in wolves from Alaska.

Wolves (Canis lupus) were captured in three areas of Interior Alaska (USA). Four hundred twenty-five sera were tested for evidence of exposure to canine coronavirus by means of an indirect fluorescent antibody procedure. Serum antibody prevalence averaged 70% (167/240) during the spring collection period and 25% (46/185) during the autumn collection period. Prevalence was 0% (0/42) in the autumn pup cohort (age 4-5 mo), and 60% (58/97) in the spring pup cohort (age 9-10 mo). Prevalence was lowest in the Eastern Interior study area. A statistical model indicates that prevalence increased slightly each year in all three study areas. These results indicate that transmission occurs primarily during the winter months, antibody decay is quite rapid, and reexposure during the summer is rare.

Alaska↗
PubMed1999

Murine dendritic cells transfected with human GP100 elicit both antigen-specific CD8(+) and CD4(+) T-cell responses and are more effective than DNA vaccines at generating anti-tumor immunity.

Dendritic cells (DCs) are potent inducers of cytotoxic T lymphocytes (CTLs) when pulsed with an antigenic peptide or tumor lysate. In this report, we have used liposome-mediated gene transfer to examine the ability of plasmid DNA encoding the human melanoma-associated antigen gp100 to elicit CD8(+) and CD4(+) T-cell responses. We also compared the efficacy between gp100 gene-modified DCs and naked DNA (pCDNA3/gp100)-based vaccines at inducing anti-tumor immunity. DCs were generated from murine bone marrow and transfected in vitro with plasmid DNA containing the gp100 gene. These gp100-modified DCs (DC/gps) were used to stimulate syngeneic naive spleen T cells in vitro or to immunize mice in vivo. Antigen-specific, MHC-restricted CTLs were generated when DC/gps were used to prime T cells both in vitro and in vivo. Thus, these CTLs were cytolytic for gp100-transfected syngeneic (H-2(b)) tumor MCA106 (MCA/gp) and vaccinia-pMel17/gp100-infected syngeneic B16 and MCA106, but not parental tumor MCA106 and B16, or gp100-transfected allogeneic tumor P815 (H-2(d)). Immunization with DC/gp protected mice from subsequent challenge with MCA/gp but not parental MCA106. Antibody-mediated T-cell subset depletion experiments demonstrate that induction of CTLs in vivo is dependent on both CD4(+) and CD8(+) T cells. Furthermore, DC/gp immunization elicits an antigen-specific CD4(+) T-cell response, suggesting that DC/gps present MHC class II epitopes to CD4(+) T cells. In addition, our data show that gene-modified, DC-based vaccines are more effective than the naked DNA-based vaccines at eliciting anti-tumor immunity in both prophylactic and therapeutic models. These results suggest that the use of DCs transfected with plasmid DNA containing a gene for TAA may be superior to peptide-pulsed DCs and naked DNA-based vaccines for immunotherapy and could provide an alternative strategy for tumor vaccine design.

Animals↗
PubMed1999

A novel role for cardiac neural crest in heart development.

Ablation of premigratory cardiac neural crest results in defective development of the cardiac outflow tract. The purpose of the present study was to correlate the earliest functional and morphological changes in heart development after cardiac neural crest ablation. Within 24 hours after neural crest ablation, the external morphology of the hearts showed straight outflow limbs, tighter heart loops, and variable dilations. Incorporation of bromodeoxyuridine in myocytes, an indication of proliferation, was doubled after cardiac neural crest ablation. The myocardial calcium transients, which are a measure of excitation-contraction coupling, were depressed by 50% in both the inflow and outflow portions of the looped heart tube. The myocardial transients could be rescued by replacing the cardiac neural crest. The cardiac jelly produced by the myocardium was distributed in an uneven, rather than uniform, pattern. An extreme variability in external morphology could be attributed to the uneven distribution of cardiac jelly. In the absence of cardiac neural crest, the myocardium was characterized by somewhat disorganized myofibrils that may be a result of abnormally elevated proliferation. In contrast, endocardial development appeared normal, as evidenced by normal expression of fibrillin-2 protein (JB3 antigen) and normal formation of cushion mesenchyme and trabeculae. The signs of abnormal myocardial development coincident with normal endocardium suggest that the presence of cardiac neural crest cells is necessary for normal differentiation and function of the myocardium during early heart development. These results indicate a novel role for neural crest cells in myocardial maturation.

Animals↗
PubMed1999

Damage control surgery.

The triad of hypothermia, acidosis, and coagulopathy during initial operative and resuscitation efforts has been recognized as a significant cause of death in patients with traumatic injuries. A staged surgical approach with a brief initial laparotomy, subsequent intensive care unit resuscitation, and a planned reoperation is an emerging technique used in trauma surgery, with application to a variety of other surgical challenges. Successful damage control therapy requires a coordinated multidisciplinary team effort by a trauma team experienced in the process of damage control operations, intensive care unit priorities, and potential complications of this innovative surgical approach.

Acidosis↗
PubMed1997

Excitation-contraction coupling in the day 15 embryonic chick heart with persistent truncus arteriosus.

Ca2+ transients were examined in embryonic chick hearts with an experimentally induced cardiac neural crest-related outflow tract defect known as persistent truncus arteriosus (PTA). In all of the animal models of neural crest-related heart defects, prenatal mortality is too high to be attributed to structural defects of the heart alone, suggesting that there is altered development of the myocardium. Earlier reports indicating reduced L-type Ca2+ current in hearts with PTA suggest that poor viability may be related to impairment of cardiac excitation-contraction coupling. To test this hypothesis, direct measurements of the systolic Ca2+ transient in fura-2-loaded myocytes from normal hearts and hearts with PTA were carried out. We found that Ca2+ transients were severely depressed in hearts with PTA and difficult to measure above background noise unless signal averaged or treated with isoproterenol (ISO). We confirmed that the reduced Ca2+ transients were due, at least partly, to a reduction in L-type Ca2+ current. In addition we found that although ISO could raise the L-type current in hearts with PTA to the level found in normal hearts in the absence of ISO, it could not fully restore the Ca2+ transient. Furthermore, caffeine-stimulated Ca2+ transients were diminished in size and the time-to-peak and the decaying phase were significantly slowed. Interestingly, these observations were not accompanied by a reduction in the number of Ca2+ release channels. These results indicated an impairment of SR function in addition to the reduction in L-type Ca2+ current. These results strongly support our hypothesis that the poor viability of embryos with PTA is due to impaired cardiac excitation-contraction coupling.

Animals↗
PubMed1994

Myocardial enlargement in defective heart development.

BACKGROUND: The cardiac neural crest (neural crest extending from the mid-otic placode to the caudal region of somite 3) provides ectomesenchymal cells that contribute to aortic arch development and are essential for aortico-pulmonary septation of the outflow tract. Bilateral ablation of the cardiac neural crest in the chick embryo, prior to migration, leads to aortic arch anomalies and failure of septation of the cardiac outflow tract, which produces a severe defect known as persistent truncus arteriosus (PTA). Altered hemodynamics resulting from abnormal aortic arch artery development and PTA and other unknown factors related to the absence of neural crest, are likely to alter the developmental history of the myocardium. METHODS: In this study the wet and dry weights of ventricles and whole embryos, the total number of myocytes per ventricle and the myocyte density (number of myocytes per unit volume of ventricular myocardium) were compared in control (unwindowed eggs), sham-operated and cardiac neural crest ablated chick embryos at day 11 of incubation. RESULTS: We found that the wet and dry weights of ventricles from hearts with PTA were not different from normal hearts in control and sham-operated embryos. However, the embryos with PTA weighed less than embryos with normal hearts. Thus, the ventricle to embryo weight ratios were greater in embryos with PTA compared to control and sham-operated embryos for both wet (14 and 20%, respectively) and dry (30 and 59%) weights. The data further implied that more water was present with respect to body weight in comparison with sham-operated and control embryos which indicated that the embryos with PTA were edematous. The total number of myocytes and the number of myocytes per unit volume were not different when comparing sham-operated with PTA. Further, there was no indication that the myocardium from hearts with PTA was abnormal despite the small size and edema of the embryos. CONCLUSIONS: It appears that hemodynamic stresses, resulting from the structural defects produced by neural crest ablation, are insufficient to increase heart growth, although cardiac function is depressed as evidenced by edema and failure of the embryo to thrive.

Animals↗
PubMed1994

Psychosocial needs of family caregivers of terminally ill patients.

The primary caregivers (mean age = 63 yr.) of 28 terminally ill veterans (mean age = 67 yr.) who were living at home were surveyed for their concrete and psychosocial needs. The caregivers also completed the Beck Depression Inventory, the Life Satisfaction Index, the Provision of Social Relations scale, and the Burden Inventory. The rank order of concrete and psychosocial needs is reported for these caregivers. Increased scores on depression were associated with decreased life satisfaction as was low social support. Not surprisingly, higher numbers of concrete and psychosocial needs were associated with increases in depression.

Adult↗
PubMed1993

Hospital bed usage by people with HIV disease: experience in a provincial setting.

In order to describe hospital bed usage by people with HIV disease in a provincial setting, a retrospective analysis of admissions to hospital wards in Oxford was undertaken for people admitted to hospital with all HIV-related illnesses or complications of HIV-related treatment. A total of 83 people were identified as having been admitted to hospital between January 1986 and the end of August 1990. Average length of hospital stay, the number of admissions per observed person-year and the in-patient days per observed person-year decreased. Of the 2,446 days spent in hospital, 913 were by people with an AIDS diagnosis; 1,533 days were spent by people who did not fulfil the World Health Organisation/Centers for Disease Control (WHO/CDC) classification for AIDS but who were admitted because of their HIV disease. AIDS is an end-point of infection with HIV. Pre-AIDS morbidity, a spectrum of illness of increasing severity from minor illness up to the point of WHO/CDC level AIDS, is a major determinant of hospital care and has previously been underestimated. In order to calculate the best estimates of hospital care needed, HIV disease should be regarded as a single entity and the artificial barrier dividing HIV illnesses from AIDS should be discarded.

Adolescent↗
PubMed1989

Five thousand seven hundred sixty cardiovascular injuries in 4459 patients. Epidemiologic evolution 1958 to 1987.

Large epidemiologic analyses of cardiovascular injuries have been limited to studies of military campaigns compiled from many surgeons working in many hospitals with variable protocols. A detailed civilian vascular trauma registry provides a unique opportunity for an epidemiologic evolutionary profile. During the last 30 years in a single civilian trauma center directed by a consistent evaluation and treatment philosophy, 4459 patients were treated for 5760 cardiovascular injuries. Eighty-six per cent of the patients were male, and the average age was 30.0 years. Penetrating trauma was the etiology in more than 90% (GSW,51.5%; SW,31.1%; SGW,6.8%). All other injuries were iatrogenic or secondary to blunt trauma. Truncal injuries (including the neck) accounted for 66% of all injuries treated, while lower extremity injuries (including the groin) accounted for only 19%. Injuries to the abdominal vasculature accounted for 33.7% of the injuries. One thousand fifty-seven patients had 2 or more concurrent vascular injuries, and 32 patients had 4 or more separate vascular injuries. The 27 patients-per-year average of the early 1960s has risen to a current average of 213 patients per year. Economic and population factors influenced wounding agents and injury patterns during the evaluation period. This extensive civilian series presents epidemiologic profiles that are distinctly different from military reports and serves as a guide for current trauma center and health planners.

Adolescent↗
PubMed1989

Prospective MAST study in 911 patients.

Nine hundred eleven patients with systolic blood pressures less than or equal to 90 mm Hg were randomized to MAST and No-MAST groups, and all taken to a single Level I Trauma Center. Epidemiologic analysis of etiology, age, race, sex, Trauma Scores, and Injury Severity Scores revealed the two groups to be statistically identical. Seven hundred eighty-four patients were analyzed in detail. The principal injury location was thorax in 41%, abdomen in 32%, extremity in 16%, head in 7%, and neck in 4%. In patients with head and extremity wounds, the mortality rate was clearly not a function of MAST use. In the chest, abdomen, and neck, MAST did not improve survival. Although the total prehospital time was 35.8 + 10.4 minutes for MAST patients and 32.5 +/- 10.7 minutes for No-MAST patients, 70% of patients with MAST had prehospital times greater than 30 minutes compared to 55% of the No-MAST patients. When the prehospital time was greater than 30 minutes, 31% of the MAST patients died, compared to 21% of the No-MAST patients. MAST application adversely affected the outcome most significantly for patients with cardiac and thoracic vascular injury. The overall mortality of 31% in the MAST group, compared to 25% in the No-MAST group was statistically significant (p = 0.05).

Adolescent↗
PubMed1988

Morbidity of Hurricane Elena.

On Sept 2, 1985, Hurricane Elena struck the Gulf Coast of Mississippi. We conducted a retrospective review of Emergency Department logs for a one-week period before and a two-week period after the storm to determine what additional support would be needed to manage such a disaster. There was a significant increase in the number of patients treated for psychiatric problems and trauma. These findings are similar to the results obtained in a study at the same hospital after Hurricane Frederic in 1979.

Adolescent↗
PubMed1988

Testing reliability of plaque and gingival indices. Two methods.

This investigation was undertaken to compare two methods of interexaminer and intraexaminer reliability in the evaluation of Plaque and Gingival Indices prior to a study of toothbrushing. Inter-/intraexaminer reliabilities were compared using a projected slide series consisting of 40 slides of clinical examples of gingival inflammation and plaque accumulation. Time between assessments was three weeks. Using the slide technique, intraexaminer reliability was established for: (1) Gingival Indices and (2) Plaque Indices. Interexaminer reliability was also established for Gingival Indices. Interexaminer reliability could not be established for Plaque Indices on the first assessment but was established on the post-assessment. Intraexaminer reliability was also determined through clinical examinations of patients. A third clinician was used to manipulate the tissue while investigators evaluated bleeding on provocation and plaque accumulation. Significant results were established for the Gingival Indices and Plaque Indices. Results of this investigation suggest that significant inter-/intraexaminer reliabilities may be obtained for gingival indices using the slide technique. In addition, the clinic technique appeared useful for assessing interexaminer reliability for Gingival Indices. Plaque Indices using the slide technique required more practice than those using the clinic technique.

Dental Health Surveys↗