Polarized gamma-ray emission from the crab.

Pulsar systems accelerate particles to immense energies. The detailed functioning of these engines is still poorly understood, but polarization measurements of high-energy radiation may allow us to locate where the particles are accelerated. We have detected polarized gamma rays from the vicinity of the Crab pulsar using data from the spectrometer on the International Gamma-Ray Astrophysics Laboratory satellite. Our results show polarization with an electric vector aligned with the spin axis of the neutron star, demonstrating that a substantial fraction of the high-energy electrons responsible for the polarized photons are produced in a highly ordered structure close to the pulsar.

The multiple immune-evasion genes of murine cytomegalovirus are not redundant: m4 and m152 inhibit antigen presentation in a complementary and cooperative fashion.

Both human cytomegaloviruses (HCMVs) and murine cytomegaloviruses (MCMVs) encode multiple genes that interfere with antigen presentation by major histocompatibility complex (MHC) class I, and thus protect infected targets from lysis by virus-specific cytotoxic T lymphocytes (CTLs). HCMV has been shown to encode four such genes and MCMV to encode two. MCMV m152 blocks the export of class I from a pre-Golgi compartment, and MCMV m6 directs class I to the lysosome for degradation. A third MCMV gene, m4, encodes a glycoprotein which is expressed at the cell surface in association with class I. Here we here show that m4 is a CTL-evasion gene which, unlike previously described immune-evasion genes, inhibited CTLs without blocking class I surface expression. m152 was necessary to block antigen presentation to both K(b)- and D(b)-restricted CTL clones, while m4 was necessary to block presentation only to K(b)-restricted clones. m152 caused complete retention of D(b), but only partial retention of K(b), in a pre-Golgi compartment. Thus, while m152 effectively inhibited D(b)-restricted CTLs, m4 was required to completely inhibit K(b)-restricted CTLs. We propose that cytomegaloviruses encode multiple immune-evasion genes in order to cope with the diversity of class I molecules in outbred host populations.

The murine cytomegalovirus immune evasion protein m4/gp34 forms biochemically distinct complexes with class I MHC at the cell surface and in a pre-Golgi compartment.

We have recently demonstrated that the murine CMV (MCMV) gene m4 is an immune evasion gene that protects MCMV-infected targets from some virus-specific CTL clones. m4 encodes m4/gp34, a 34-kDa glycoprotein that binds to major histocompatibility complex class I in the endoplasmic reticulum and forms a detergent-stable complex that is exported to the surface of the cell. To investigate how m4/gp34 promotes CTL evasion, we analyzed the assembly and export of m4/gp34-K(b) complexes. We found that 50-70% of K(b) exported over the course of MCMV infection was m4/gp34 associated. Because these complexes are present at the cell surface, it is possible that m4 mediates CTL evasion by interfering with contact between class I and receptors on the T cell. In addition, we found that K(b) retained by the MCMV immune evasion gene m152 formed a novel type of complex with Endo H-sensitive m4/gp34; these complexes are distinguished from the exported complexes by being stable in 1% digitonin and unstable in 1% Nonidet P-40. Because this association occurs in a pre-Golgi compartment, m4/gp34 might also interfere with Ag presentation by affecting some aspect of class I assembly, such as peptide loading. Although m4/gp34 requires beta(2)-microglobulin to bind class I, there was no significant binding of m4/gp34 to beta(2)-microglobulin in the absence of class I H chain, demonstrating that m4/gp34 forms Nonidet P-40-stable complexes specifically with folded conformations of class I. We conclude that m4/gp34 promotes immune evasion by a novel mechanism involving altered assembly and/or T cell recognition of class I molecules.

Evasion of cytotoxic T lymphocytes by murine cytomegalovirus.

Murine cytomegalovirus causes lifelong infections with little pathology in normal host animals. Control of viral replication and prevention of pathology depend on both innate and adaptive immune mechanisms, and cytolytic T lymphocytes play a key role in this process. The virus encodes a number of genes which alter the normal assembly of class I major histocompatability complex proteins, and thus interfere with the ability of infected cells to present antigen to CD8(+)T cells. This review will examine what is known about these viral genes, and present some unanswered questions regarding the role of CTL evasion in the viral infectious cycle.

Progressive infection in a subset of HIV-1-positive chimpanzees.

Chimpanzees are susceptible to infection with human immunodeficiency virus (HIV)-1; however, infected animals usually maintain normal numbers of CD4(+) T lymphocytes and do not develop immunodeficiency. We have examined 10 chronically infected HIV-1-positive chimpanzees for evidence of progressive infection. In addition to 1 animal that developed AIDS, 3 chimpanzees exhibit evidence of progressive HIV infection. All progressors have low CD4(+) T cell counts (<200 cells/microL), severe CD4:CD8 inversion, and marked reduction in interleukin-2 receptor expression by CD4(+) T cells. In comparison with HIV-positive nonprogressor chimpanzees, progressors have higher plasma and lymphoid virus loads, greater CD38 expression in CD8(+)/HLA-DR(+) T cells, and greater serum concentrations of soluble tumor necrosis factor type II receptors and beta2-microglobulin, all markers of HIV progression in humans. These observations show that progressive HIV-1 infection can occur in chimpanzees and suggest that the pathogenesis of progressive infection in this species resembles that in humans.

Hemispheric stroke following cardiac surgery: a case-control estimate of the risk resulting from ipsilateral asymptomatic carotid artery stenosis.

A case-control study was undertaken to determine if asymptomatic carotid artery stenosis (ACS) is independently associated with ipsilateral hemispheric stroke following cardiac surgery (CS). All CS patients (3069) who were at two hospitals between 1989 and 1994 were reviewed. Cases (31) selected for this study were those with hemispheric stroke within 30 days following CS. Controls (69) were taken from those without hemispheric stroke. Case-control analysis demonstrated that ACS of 50-90% and of 80-90% increased the risk of ipsilateral stroke 5.2-fold (95% confidence interval [CI] = 1.5-16.3, p = 0.01) and 24.3-fold (CI = 2.6-114.9, p = 0.002), respectively. Other variables with significant odds ratios (OR) were age > or =65 years (OR = 4.0, CI = 1.3-10.5, p = 0.01), peripheral vascular disease (OR = 3.4, CI = 1.3-8.8, p = 0.02), hypertension (OR = 3.0, CI = 1.2-7.0, p = 0.02), and female gender (OR = 3.0, CI = 1.2-7.1, p = 0.04). A second conservative analysis for missing data demonstrated a significant association for ACS of 80-90% alone (OR = 13.1, CI = 1.5-60.9, p = 0.01). This association remained significant after multivariate adjustment with propensity score stratification. ACS (80-90%) appears to be independently associated with ipsilateral hemispheric stroke following CS when evaluated against the present study variables. This finding supports the need for a properly conducted prospective natural history study, including an evaluation of aortic arch atherosclerosis, to determine the clinical relevance of this observation.

Is Canadian cardiac surgeons' management of asymptomatic carotid artery stenosis at coronary artery bypass supported by the literature? A survey and a critical appraisal of the literature.

OBJECTIVE: To document and compare the management of asymptomatic carotid stenosis (ACS) by Canadian cardiac surgeons at coronary artery bypass grafting (CABG) against a critical literature analysis. DESIGN: A multiple choice survey and a structured literature review. DATA SOURCES: Seventy-seven surgeons and 272 publications selected from the English literature between 1980 and 1997. Search terms used were "carotid," "coronary bypass," and "cardiac surgery." STUDY SELECTION: Five natural history studies were identified, and 58 studies were found that had objective documentation of ACS of 50% or more before cardiac surgery, and both operative stroke and mortality data reported for CABG with and without carotid endarterectomy (CEA). DATA EXTRACTION: Natural history and outcome studies were independently rated against published guidelines. Outcome data were independently pooled and compared. Data discrepancy was resolved by consensus. Survey results were tabulated for simple descriptive statistics. DATA SYNTHESIS: No methodologically sound natural history studies were found to document an increased risk of stroke from ACS after CABG. There were no randomized controlled studies to guide treatment recommendations. Pooled data for stroke or death did not support CEA for risk reduction from ACS at CABG (relative risk 0.9, p = 0.5). Ninety-four percent of surgeons believed that the literature is insufficient to support the routine use of CEA to reduce the risk of stroke from ACS after CABG. Despite this, 20% of surgeons advocated CEA for this purpose. CONCLUSION: The management of ACS at CABG by the majority of Canadian cardiac surgeons is consistent with the results of the literature review; however, significant management variation exists.

The predictive value of intraoperative duplex for early vein graft patency in lower extremity revascularization.

This study was undertaken to evaluate the ability of intraoperative duplex scanning during infrainguinal vein bypass to identify technical abnormalities and to determine the relation between intraoperative scan result and early primary graft patency. We retrospectively reviewed of 78 consecutive intraoperative duplex scans for infrainguinal vein bypass that were performed between October 1993 and October 1996 during the course of infrainguinal vein bypass. Duplex scans were classified as normal or abnormal based on B-mode image and/or Doppler velocity spectra. Grafts were grouped according to duplex findings and intraoperative action: group I, normal intraoperative scan; group II, abnormal intraoperative scan, revised; group III, abnormal intraoperative scan, not revised. The relationship of intraoperative duplex scan findings to intraoperative graft revision to 1-month and 6-month primary graft patency by life table was analyzed. The analysis demonstrates that the results of intraoperative duplex scans can be used to identify grafts at low risk for early postoperative graft failure (groups I and II), and those at high risk for early postoperative graft failure (group III).

The utility of selective screening for carotid stenosis in cardiac surgery patients.

PURPOSE: To determine if any of 8 categorical clinical variables can be used to select patients and improve the yield of a screening program for severe carotid stenosis (> or = 80%) in elective cardiac surgery patients. METHODS: A prospective cohort analysis of 200 consecutive patients prior to elective cardiac surgery for the following variables: age, gender, smoking carotid bruit, peripheral vascular disease, hyperlipidaemia, previous neurologic symptoms and diabetes mellitus. All patients were subsequently screened with carotid duplex scanning for the presence of severe carotid stenosis. Positive scans were confirmed by angiography. RESULTS: Sixteen patients (8%) were identified with severe carotid stenosis. Univariate analysis identified three variables that increase risk for carotid stenosis: carotid bruit (relative risk (RR)=16.4, 5.4-57.6 95% confidence interval, p<0.001), neurological history (RR=10.3, 3.9-23.2, p<0.001) and peripheral vascular disease (RR=5.3, 1.9-14.9, p<0.001). Stepwise logistic regression analysis identified previous neurologic history and carotid bruit as independent predictors of stenosis. If screening for carotid stenosis was limited to patients with these two variables, then 37 (18.5% of total) patients would have been screened. Fourteen of these 37 (37.8%) had a severe carotid stenosis. Two patients with stenosis (12.5% of those with carotid stenosis, 1% of total patient population) would not have been screened. CONCLUSIONS: Clinical variables can be used to improve the yield of a preoperative screening program for carotid stenosis.

Fate of the iliac arteries after repair of abdominal aortic aneurysm with an aortobifemoral bypass graft.

The objective of this study is to determine the fate of the iliac arteries after repair of abdominal aortic aneurysm with an aortobifemoral bypass graft. It is a prospective natural history study at a university-affiliated urban teaching hospital. Thirty-two patients with retrograde flow to the iliac circulation after repair of an abdominal aortic aneurysm by aortobifemoral bypass grafting were studied. All patients were followed prospectively with repeat CAT scans, clinical assessment, and selective angiography to determine the fate of the iliac circulation. We were particularly interested in subsequent vessel thrombosis or aneurysmal dilation. Patient survival was analyzed with a Kaplan-Meier life-table and survival curve. Graft patency was analyzed using life-table analysis. Primary outcomes included iliac artery size, graft patency, and patient survival. The iliac arteries remained constant in size or thrombosed in all study patients. Iliac expansion did not occur in any of the study patients. Secondary graft patency was 100%. The cumulative survival rate at 47 months was 0.55 (0.37-0.74, 95% confidence interval). Retrograde perfusion of diseased iliac arteries after aortobifemoral bypass for repair of abdominal aortic aneurysm is safe. Iliac artery atherosclerotic, ectatic or small aneurysmal disease (< or = 3 cm) does not appear to be a contraindication to retrograde iliac artery perfusion.

Bovine herpesvirus-1 infection affects the peptide transport activity in bovine cells.

Infection of cattle with bovine herpesvirus-1 (BHV-1) impairs the cell-mediated immune response (CMI) of the affected host. We investigated the location of interference of BHV-1 with the major histocompatibility complex (MHC) class I antigen presentation pathway by employing an assay that allows assessment of the peptide transport activity of the Transporter associated with Antigen Presentation (TAP) from the cytoplasm into the endoplasmic reticulum (ER). We found a considerable down-regulation of the peptide transport activity in bovine epithelial cells, taking place as early as 2 h after virus infection. This down-regulation was also dose-dependent, and, at high multiplicities of infection (moi), led to an almost complete shutdown of TAP. By inhibiting peptide transport into the ER, the virus impairs loading of MHC class I molecules and their subsequent egress from the ER to the cell surface. This may lead to defective priming of cytotoxic T lymphocytes. Thus, BHV-1 is yet another member of its family Herpesviridae that selectively interferes with the host's antigen presentation machinery to evade the host's immune response in vivo.

Videoendoscopic thoracic aorta-to-femoral artery bypass. A feasibility study in a canine model.

PURPOSE: This study was undertaken to determine whether videoendoscopic thoracic aorta-to-femoral artery bypass is a technically feasible operation. METHODS: An acute canine study involving five mongrel dogs was carried out. After the dogs had been given a general anesthetic, the femoral arteries were exposed in the traditional fashion. On the left side, a retroperitoneal, retrorenal tunnel was extended from the common femoral artery to the diaphragm. Under videoendoscopic control, the tunnel was opened through the posterior thoracic attachments of the diaphragm into the thoracic cavity. A Dacron graft was tunneled from the thoracic cavity on the left to the left groin. The thoracic aorta was controlled with a side-biting clamp, and an endoscopically performed end graft-to-side thoracic aortic anastomosis was created. After completion of the thoracic anastomosis, the left femoral anastomosis was created in a traditional manner. A left-to-right femoral bypass completed the lower extremity vascular procedure. An open thoracotomy was avoided. RESULTS: Videoendoscopic thoracic aorta-to-femoral artery bypass was successfully performed in all five animals. All components of the thoracic procedure, including exposure, dissection, vessel control, cross-clamping, and anastomosis, were performed through the thoracic ports with conventional laparoscopic instruments. Blood loss was minimal. All animals survived the procedure before being killed. CONCLUSION: Videoendoscopic thoracic aorta-to-femoral artery bypass is a technically feasible operation in a canine model. Advantages of this unique approach over the experimental laparoscopic and the traditional transperitoneal open aortofemoral bypass include ease of aortic exposure, ability to control a segment of disease-free aorta, and anastomosis in a disease-free segment of aorta. Potential advantages include decreased perioperative morbidity rates with the videoendoscopic approach. Before there is clinical consideration of this surgical approach, long-term experiments are required to demonstrate the safety of the procedure.

Should patients be screened for asymptomatic carotid artery stenosis?

OBJECTIVE: To evaluate, against published guidelines, the potential role of screening to reduce the risk of stroke and death from asymptomatic carotid artery stenosis (ACAS). DATA SOURCES: Papers selected for review were identified through a GRATEFUL MED literature search, from personal files and from references documented in identified papers. STUDY SELECTION: Population studies concerning disease prevalence, natural history studies related to risk of stroke, randomized controlled trials related to carotid endarterectomy and natural history studies related to the risk of developing ACAS were considered for review. DATA EXTRACTION: An estimate was made of the potential for stroke resulting from ACAS in the general population. This was evaluated against the positive predictive value of duplex scanning, and the number of patients needing to be screened to prevent a stroke was estimated. DATA SYNTHESIS: The prevalence of ACAS in the general population was estimated to range from 2% to 8% for ACAS 50% or greater and to range form 1% to 2% for ACAS 80% or greater. The yearly risk of stroke or death from undetected ACAS was estimated to be 0.16% for ACAS 50% or greater and 0.06% for ACAS 80% or greater. The estimated number of patients needing to be screened to prevent 1 stroke would range from 850 to 1700 (and potentially as high as 8500). CONCLUSIONS: General screening for ACAs to prevent stroke and death cannot be recommended when evaluated against guidelines. The decision to screen individual patients will require judgement, continued evaluation and surveillance of the results of such screening by the treating physician.

Emotional and semantic priming as a measure of information processing in young people with school refusal: a research note.

We investigated semantic and emotional priming of lexical decision-making in 20 school refusers and 20 attenders aged 11-16 years, matched for sex and reading ability. We hypothesised that: semantic and emotional priming would be demonstrable in both samples; and that the school refusers would show emotional priming of school-related words to aversive primes. Both samples showed semantic priming; emotional priming was shown by the attenders and 11 school refusers without a history of depression. School-refusing children did not show emotional priming for school-related words. Nine school-refusing children with either current or past depression showed a general reduction in their priming. These results show that both semantic and emotional priming can be detected in this age-range. They do not support school refusal being typically associated with anxiety about school. The reduction in priming in those with a depressive history is similar to inhibition in information processing in depressed adults. Priming is therefore sensitive to at least some psychiatrically relevant states or traits in this age-range. It is concluded that priming could be a useful measure of information processing in this age-group, and further research is warranted.

Selective processing of shape-related words in women with eating disorders, and those who have recovered.

OBJECTIVES: This study sought to investigate whether women with anorexia or bulimia nervosa and women who had recovered showed cognitive bias towards shape, food and adolescent issues. DESIGN: A five-group analysis of variance design was used, in which the different client groups were the independent variables. The dependent variable was performance on an emotional Stroop task. METHODS: Current anorexia sufferers (N = 31), current bulimia sufferers (N = 24), recovered anorexics (N = 23), recovered bulimics (N = 11) and women who had never suffered from eating disorders (N = 33) were recruited through health-care professionals, support groups and newspapers. Colour-naming times for target and comparison Stroop cards were measured. RESULTS: Women currently suffering from bulimia, and women who had recovered from anorexia, were found to be more distracted by shape concerns than women who had never suffered eating disorders and women who had recovered from bulimia. CONCLUSIONS: The results suggest that there may be an enduring cognitive bias among women who have recovered from anorexia. This is the first study in which impairment on an emotional Stroop task has been found to persist after recovery from a clinical condition.