Disinhibition of return: unnecessary and unlikely

Recently, from data obtained with a temporal order judgment (TOJ) task, Gibson and Egeth (1994) concluded that inhibition of return (IOR; a response time effect that reveals slower responding to targets at previously cued versus uncued locations) reflects impaired perceptual processing. By replotting their data, we demonstrate that the perception of temporal order is influenced only by the facilitatory effect of a cue at short stimulus onset asynchronies (SOAs) and is unaffected by IOR at long SOAs. The target paper proposed that, when extra stimuli are presented at task-relevant locations (i.e., in the TOJ task), IOR is prevented by a hypothetical process that is known as disinhibition of return (DOR). We argue that the assumptions that IOR affects perceptual processing and that DOR exists are unnecessary, as a more parsimonious response-based interpretation of IOR is consistent with their data. Further, we summarize recent results and present new data that demonstrate that DOR is unlikely.     

CD28-independent, TRAF2-dependent costimulation of resting T cells by 4-1BB ligand

4-1BB ligand (4-1BBL) is a member of the tumor necrosis factor (TNF) family expressed on activated antigen-presenting cells. Its receptor, 4-1BB, is a member of the TNF receptor family expressed on activated CD4 and CD8 T cells. We have produced a soluble form of 4-1BBL using the baculovirus expression system. When coimmobilized on plastic with anti-CD3, soluble 4-1BBL induces interleukin (IL)-2 production by resting CD28+ or CD28- T cells, indicating that 4-1BBL can function independently of other cell surface molecules, including CD28, in costimulation of resting T cell activation. At low concentrations of anti-CD3, 4-1BBL is inferior to anti-CD28 in T cell activation. However, when 4-1BB ligand is provided together with strong TCR signals, then 4-1BBL and anti-CD28 are equally potent in stimulation of IL-2 production by resting T cells. We find that TNF receptor-associated factor (TRAF)1 or TRAF2 associate with a glutathione S-transferase-4-1BB cytoplasmic domain fusion protein in vitro. In T cells, we find that association of TRAF1 and TRAF2 with 4-1BB requires 4-1BB cross-linking. In support of a functional role for TRAF2 in 4-1BB signaling, we find that resting T cells isolated from TRAF2-deficient mice or from mice expressing a dominant negative form of TRAF2 fail to augment IL-2 production in response to soluble 4-1BBL. Thus 4-1BB, via the TRAF2 molecule, can provide CD28-independent costimulatory signals to resting T cells.     

Successful delayed thrombolytic therapy in a patient with massive pulmonary embolism

Pica is the persistent, culturally and developmentally inappropriate ingestion of non-nutritive substances (DSM-IV). AB is a 75-year-old lady with a 40-year history of schizophrenia and a 20-year history of pica who, at emergency laparotomy, had 175.32 Pounds of loose change in her stomach. Although pica has been reported to coexist with schizophrenia, she had had no positive symptoms of schizophrenia for at least 20 years. She has CT evidence of fronto-tempotal atrophy most marked on the left in the temporal lobe and on the right in the frontal lobe. Pica has been found to be related to cognitive deficits and hyperoral behaviour to temporal lesions. Neuropsychological testing reveals deficits closely related to these changes.     

Effect of phenylglyoxal-modified alpha2-antiplasmin on urokinase-induced fibrinolysis

1. In this study the mechanisms of the acute vasodilator action of bacterial lipopolysaccharide (LPS) were investigated in the rat Langendorff perfused heart. 2. Infusion of LPS (5 microg ml(-1)) caused a rapid and sustained fall in coronary perfusion pressure (PP) of 59 +/- 4 mmHg (n = 12) and a biphasic increase in NO levels determined in the coronary effluent by chemiluminescent detection. Both the fall in PP and the increase in NO release were completely abolished (n = 3) by pretreatment of hearts with the NO synthase inhibitor L-NAME (50 microM). 3. LPS-induced vasodilatation was markedly attenuated to 5 +/- 4 mmHg (n 3) by pretreatment of hearts with the B2 kinin receptor antagonist Hoe-140 (100 nM). 4. Vasodilator responses to LPS were also blocked by brief pretreatment with mepacrine (0.5 microM, n = 3) or nordihydroguaiaretic acid (0.1 microM, n = 4) and markedly attenuated by WEB 2086 (3 microM, n = 4). 5. Thirty minutes pretreatment of hearts with dexamethasone (1 nM), but not progesterone (1 microM), significantly modified responses to LPS. The action of dexamethasone was time-dependent, having no effect when applied either simultaneously with or pre-perfused for 5 min before the administration of LPS but inhibiting the response to LPS by 91 +/- 1% (n = 4) when pre-perfused for 15 min. The inhibition caused by dexamethasone was blocked by 15 min pretreatment with the glucocorticoid receptor antagonist RU-486 (100 nM) or by 2 min pre-perfusion of a 1:200 dilution of LCPS1, a selective antilipocortin 1 (LC1) neutralizing antibody. 6. Treatment with the protein synthesis inhibitor, cycloheximide (10 microM, for 15 min) selectively blunted LPS-induced vasodilatation, reducing the latter to 3 +/- 5 mmHg (n = 3), while having no effect on vasodilator responses to either bradykinin or sodium nitroprusside. 7. These results indicate that LPS-induced vasodilatation in the rat heart is dependent on activation of kinin B2 receptors and synthesis of NO. In addition, phospholipase A2 (PLA2) is activated by LPS resulting in the release of platelet-activating factor (PAF) and lipoxygenase but not cyclo-oxygenase products. These effects are dependent on de novo synthesis of an intermediate protein which remains to be identified.     

Uncertainty analysis methods for comparing predictive models and biomarkers: A case study of dietary methyl mercury exposure

Biologically based markers (biomarkers) are currently used to provide information on exposure, health effects, and individual susceptibility to chemical and radiological wastes. However, the development and validation of biomarkers are expensive and time consuming. To determine whether biomarker development and use offer potential improvements to risk models based on predictive relationships or assumed values, we explore the use of uncertainty analysis applied to exposure models for dietary methyl mercury intake. We compare exposure estimates based on self-reported fish intake and measured fish mercury concentrations with biomarker-based exposure estimates (i.e., hair or blood mercury concentrations) using a published data set covering 1 month of exposure. Such a comparison of exposure model predictions allowed estimation of bias and random error associated with each exposure model. From these analyses, both bias and random error were found to be important components of uncertainty regarding biomarker-based exposure estimates, while the diary-based exposure estimate was susceptible to bias. Application of the proposed methods to a simple case study demonstrates their utility in estimating the contribution of population variability and measurement error in specific applications of biomarkers to environmental exposure and risk assessment. Such analyses can guide risk analysts and managers in the appropriate validation, use, and interpretation of exposure biomarker information.     

Dens evaginatus on a wisdom tooth: a diagnostic dilemma. Case report

BACKGROUND: Skin manifestations have been described in 25% of patients with Mycoplasma pneumoniae infection. CASE REPORT: We report a case of Mycoplasma pneumoniae infection in a 29-year-old man who developed a polymorphous erythema-like reaction. Skin manifestations were associated with voluminous lymph node enlargement and high eosinophil levels both in serum and alveolar lavage. Seroconversion against Mycoplasma pneumoniae IgG was documented with ELISA. The clinical course was favorable with erythromycin. DISCUSSION: ELISA IgG seroconversion is sufficient to confirm the diagnosis of Mycoplasma pneumoniae infection as this test has an 80-90% specificity. This case was unusual by its clinical presentation and high eosinophil counts in serum and tissue samples, similar to what is found in drug-induced hypersensitivity.     

Survival of Taenia solium cysticerci in carcasses of pigs kept at 4 C

In the present study, the survival of cysticerci of Taenia solium in carcasses of 1 Small-Ear-Miniature and 2 Landrace Small-Ear-Miniature pigs kept in a refrigerator at 4 C was determined. The viability of the cysticerci was determined by observing evagination and active movement of the scolex under a fluorescent light after digestion in pig bile. Although no viable cysticerci were found after day 30, 58.8% cysticerci survived between day 26 and day 30. Moreover, more than 80% of the cysticerci were viable between day 1 and day 25. These findings indicate that taeniasis solium can be transmitted through eating raw or undercooked pork or viscera of pigs following refrigeration at 4 C for less than 30 days.     

Design and synthesis of a series of potent and orally bioavailable noncovalent thrombin inhibitors that utilize nonbasic groups in the P1 position

As part of an ongoing effort to prepare therapeutically useful orally active thrombin inhibitors, we have synthesized a series of compounds that utilize nonbasic groups in the P1 position. The work is based on our previously reported lead structure, compound 1, which was discovered via a resin-based approach to varying P1. By minimizing the size and lipophilicity of the P3 group and by incorporating hydrogen-bonding groups on the N-terminus or on the 2-position of the P1 aromatic ring, we have prepared a number of derivatives in this series that exhibit subnanomolar enzyme potency combined with good in vivo antithrombotic and bioavailability profiles. The oxyacetic amide compound 14b exhibited the best overall profile of in vitro and in vivo activity, and crystallographic studies indicate a unique mode of binding in the thrombin active site.