Repair of extensive ionizing-radiation DNA damage at 95 degrees C in the hyperthermophilic archaeon Pyrococcus furiosus

We investigated the capacity of the hyperthermophile Pyrococcus furiosus for DNA repair by measuring survival at high levels of 60Co gamma-irradiation. The P. furiosus 2-Mb chromosome was fragmented into pieces ranging from 500 kb to shorter than 30 kb at a dose of 2,500 Gy and was fully restored upon incubation at 95 degrees C. We suggest that recombination repair could be an extremely active repair mechanism in P. furiosus and that it might be an important determinant of survival of hyperthermophiles at high temperatures.     

Magnetic resonance of the encephalon in 17 patients with ocular Beh?et''s disease

OBJECTIVE: To evaluate the relationships between patient and physician pretreatment expectations of pain relief and subsequent pain relief reported by chronic pain patients immediately after treatment. DESIGN: Prospective study of consecutive patients undergoing a procedure in a pain clinic for treatment of chronic pain. Patients rated their current pain level and their expectation of pain relief immediately prior to undergoing a procedure (e.g., intravenous drug infusion, nerve block) for the treatment of chronic pain. Simultaneously and independently, the treating physician completed a similar questionnaire. At completion of the procedure, patients rated their current pain level and degree of pain relief. SETTING: University of Washington Multidisciplinary Pain Center procedure suite. PATIENTS: Forty-six consecutive chronic pain patients. INTERVENTION: Intravenous drug infusions and nerve blocks. OUTCOME MEASURES: Current pain and pain relief ratings. RESULTS: Patients' pain relief expectation ratings were not correlated significantly with their postprocedure pain relief ratings or pre-post procedure changes in pain ratings. However, a statistically significant correlation was found between physician expectations of pain relief and patient pain relief ratings and patient pre-post procedure changes in pain. CONCLUSIONS: The results of this study suggest that physicians are better predictors than are patients of patients responses to these procedures and/or that physicians may somehow subtly communicate their expectations to patients during the procedure, and these expectations then influence patient response. Patient pretreatment expectations may not always play a significant role in nonspecific treatment effects.     

Ventricular arrhythmias in myocardial hypertrophy of various origins

BACKGROUND: Elevated serum sialic acids are associated with increased cardiovascular mortality, but sialic acid levels have not been studied in cardiac tissue. METHODS: Myocardial samples were obtained at the time of transplantation from 23 patients (age 54 +/- 12 years) with heart failure secondary to ischemic heart disease and 16 patients (age 51 +/- 7 years) with idiopathic dilated cardiomyopathy (DCM). A control group comprised postmortem samples obtained from 14 patients (age 70 +/- 5 years) who died of non-cardiovascular causes. Ventricular sialylation was quantitated using the sialic acid-specific lectins Maackia amurensis agglutinin (MAA) and Sambucus nigra agglutinin (SNA) using a chemiluminescence assay. Results are expressed as the percentage (+/-standard error of the mean) of the binding of lectin to a standardized control sample of human myocardium. RESULTS: Ventricular sialylation recognized by MAA was 55 +/- 7% in patients with heart failure secondary to ischemic heart disease compared with 26 +/- 7% for DCM (p = 0.006) and 32 +/- 8% for controls (p = 0.04), and that recognized by SNA was 69 +/- 7% in patients with heart failure secondary to ischemic heart disease compared with 42 +/- 6% for DCM (p = 0.006) and 38 +/- 7% for controls (p = 0.006). No significant difference in ventricular sialylation was observed between patients with DCM and controls. CONCLUSION: Myocardial levels of sialic acids are significantly increased in patients with heart failure secondary to ischemic heart disease compared with patients with idiopathic dilated cardiomyopathy and controls. Our findings are important in view of recent reports of an association between serum sialic acid concentration and cardiovascular mortality and require further investigation.     

An EIA method on single donor solubilized HLA antigens for the identification of anti-HLA antibodies

Primary biliary cirrhosis (PBC) is an immunologically mediated disease in which activated T lymphocytes attack and destroy epithelial cells in the small intralobular bile ducts of genetically susceptible patients. This article reviews the results of treatment of PBC with immunomodulatory agents. Results with drugs such as glucocorticoids, azathioprine, and chlorambucil have been disappointing because of either limited efficacy (azathioprine), toxicity (chlorambucil), or both (glucocorticoids). Colchicine improved tests of liver function in three prospective studies and was associated with improved survival for up to 4 years. However, survival benefits were lost at 8 years. Colchicine appears to slow the rate of progression of PBC but not to stop it. Preliminary results suggest that colchicine may have synergistic effects if used together with ursodeoxycholic acid, particularly in patients who are only partially responsive to ursodeoxycholic acid. Results with cyclosporine have been disappointing because of limited efficacy and predictable toxicity. The modest improvement in tests of liver function and survival are counterbalanced by the development of hypertension in some and worsening renal function in most. There is little beneficial effect on symptoms or histology. Results with methotrexate are promising. There are improvements in symptoms and tests of liver function that are equal to those seen with ursodeoxycholic acid and significant improvement in liver histology. Some patients, particularly those with striking inflammation and granulomas in portal triads, appear to have achieved sustained remission while on methotrexate. The effects of methotrexate are additive to those of ursodeoxycholic acid in patients whose blood tests have responded only partially to ursodeoxycholic acid. The most effective treatment of PBC will most likely use a combination of drugs such as ursodeoxycholic acid, colchicine, and methotrexate.     

Certain nonlinear partially observable stochastic optimal controlproblems with explicit control laws equivalent to LEQG/LQG problems

This paper is concerned with partially observed stochastic optimal control problems when nonlinearities enter the dynamics of the unobservable state and the observations as gradients of potential functions. Explicit representations for the information state are derived in terms of a finite number of sufficient statistics. Consequently, the partially observed problem is recast as one of complete information with a new state generated by a modified version of the Kalman filter. When the terminal cost is quadratic in the unobservable state and includes the integral of the nonlinearities, the optimal control laws are explicitly computed, similar to linear-exponential-quadratic-Gaussian (LEQG) and linear-quadratic-Gaussian (LQG) tracking problems. The results are applicable to filtering and control of Hamiltonian systems     

Estimating the viewing parameters of random, noisy projections ofasymmetric objects for tomographic reconstruction

The ability to determine the viewing parameters of objects from their projections has enabled well established tomographic techniques to be employed in the 3D reconstruction of objects from images obtained via modalities where the orientation of the objects cannot be controlled. A method is described for the determination of the viewing parameters of randomly acquired projections of asymmetric objects. It extends upon the common lines algorithm by determining the relative orientation of projections from the location of lines of intersection among the Fourier transforms of the projections in 3D Fourier space. A new technique for finding the lines of intersection in the presence of translational displacement, and for subsequently finding the translational displacement, is presented. The complete algorithm is described and its efficacy is demonstrated using real data. A new technique for dealing with noise is also discussed     

Effect of preoperative supplementation with alpha-tocopherol and ascorbic acid on myocardial injury in patients undergoing cardiac operations

Augmentation of antioxidant defenses may help protect tissues against ischemia-reperfusion injury associated with operations involving cardiopulmonary bypass. In this study we examined the effect of pretreating patients with alpha-tocopherol (vitamin E) and ascorbic acid (vitamin C) or placebo on injury to the myocardium. Seventy-six subjects undergoing elective coronary artery bypass grafting participated in a prospective, double-blind, placebo-controlled randomized trial, receiving either placebo or both 750 IU dl-alpha-tocopherol per day for 7 to 10 days and 1 gm ascorbic acid 12 hours before the operation. Plasma alpha-tocopherol concentrations, raised fourfold by supplementation, fell by 70% after the operation in the supplemented group and to negligible levels in the placebo group. There were no significant differences between the groups with respect to release of creatine kinase MB isoenzyme over 72 hours, nor in the reduction of the myocardial perfusion defect determined by thallium 201 uptake. Electrocardiography provided no evidence of a benefit from antioxidant supplementation. Thus the supplementation regimen prevented the depletion of the primary lipid soluble antioxidant in plasma, but provided no measurable reduction in myocardial injury after the operation.     

Voluntary head stabilization in space during oscillatory trunk movements in the frontal plane performed in weightlessness

The ability voluntarily to stabilize the head in space during lateral rhythmic oscillations (0.59+/-0.09 Hz) of the trunk has been investigated during microgravity (microG) and normal gravity (nG) conditions (parabolic flights). Five healthy young subjects, who gave informed consent, were examined. The movements were performed with eyes open or eyes closed, during phases of either microG or nG. The main result was that head orientation with respect to vertical may be stabilized about the roll axis under microG with, as well as without vision, despite the reduction in vestibular afferent and muscle proprioceptive inputs. Moreover, the absence of head stabilization about the yaw axis confirms that the degrees of freedom of the neck can be independently controlled, as was previously reported. These results seem to indicate that voluntary head stabilization does not depend crucially upon static vestibular afferents. Head stabilization in space may in fact be organized on the basis of either dynamic vestibular afferents or a short-term memorized postural body schema.     

Imprudent linking weaves a tangled Web

Hypertext linking is often embraced uncritically by Web authors eager to explore the power of hypertext without first considering its effects on their readers' comprehension. Hypertext linking is not a substitute for thought-we think with ideas, not with dissociated snippets of raw information. Even the most germane bits of information cannot become ideas, regardless of how cleverly they are stacked, listed or linked. Ideas define relevance, provide context and establish patterns. With patterns, most concepts become intelligible, and we need continuity and stability of theme and context to recognize patterns. So, like most powerful technologies, hypertext links are a mixed blessing. Used improperly, they can be detrimental to Web sites. “Loose links” can drive away an audience, dilute the site's message, confuse the reader with irrelevant digressions and become a continuing maintenance headache for site authors and Webmasters