Flat affect in schizophrenia does not reflect diminished subjective experience of emotion.

Although accorded historical significance, affective features of schizophrenia have only begun to receive systematic empirical attention. Interestingly, both early psychopathology writers and more recent investigators have reported frequent discrepancies between schizophrenics' feelings and outward expressions of emotion. Using a more comprehensive assessment of emotion, the present study examines the relationship between emotional experience and expression in a sample of medication-free schizophrenics. Compared with their normal counterparts, schizophrenics were indeed much less facially expressive of both positive and negative emotions during emotion-eliciting films, yet they reported experiencing as much positive and negative emotion. Therefore, the blunted affect typical of some schizophrenics misrepresents their underlying emotional experience. Future research into an inhibition hypothesis is recommended. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Strength and will: theoretical and methodological issues from the standpoint of risk in epidemiology and HIV/AIDS prevention

Large granular lymphocytes require adherence to hyphae of Candida albicans to inhibit growth of this fungus. This study was undertaken to identify the lymphocyte surface structures that mediate this adhesion. Monoclonal antibodies specific for epitopes of the alpha subunit (CD11b) and the beta 2 subunit (CD18) of Mac-1 eliminated lymphocyte adhesion to C. albicans hyphae. Significant inhibition of lymphocyte adhesion to C. albicans was also achieved with known protein ligands of Mac-1. These proteins included the extracellular matrix proteins vitronectin, laminin, and fibrinogen as well as two engineered peptides containing RGD (arginine-glycine-aspartic acid) sequences. Carbohydrates including N-acetyl-D-glucosamine which have been demonstrated to inhibit Mac-l-mediated adhesion to whole yeast and yeast zymosan also blocked lymphocyte adhesion to hyphae. These results identify Mac-1 (CD11b/CD18) as the surface structure that mediates lymphocyte adhesion to C. albicans. A model is proposed for lymphocyte Mac-1 activation by microbial ligands.     

Spinal effects of bicuculline: modulation of an allodynia-like state by an A1-receptor agonist, morphine, and an NMDA-receptor antagonist

Single-unit recordings were made in the intact anesthetized rat of the responses of dorsal horn neurons to C-, Adelta-, and Abeta-fiber stimulation. The postdischarge and windup responses of the same cells along with responses to innocuous stimuli, prod and brush, also were measured. The effects of (-)-bicuculline-methobromide (0.5, 5, 50, and 250 microg) were observed on these neuronal responses. The C- and Adelta-fiber-evoked responses were facilitated significantly in a dose-dependent manner. The input was facilitated, but as the final overall response was not increased by the same factor, windup appeared to be reduced. However, postdischarge, resulting from the increase in the excitability produced by windup, tended to be facilitated. After doses of >/=5 microg bicuculline, stimulation at suprathreshold Abeta-fiber-evoked activity caused enhanced firing, mainly at later latencies corresponding to Adelta-fiber-evoked activity in normal animals. Few cells responded consistently to brush and so no significant change was observed. Responses evoked by innocuous pressure (prod) always were observed in cells that concurrently responded to electrical stimulation with a C-fiber response. This tactile response was facilitated significantly by bicuculline. The effects of N6-cyclopentyladenosine (N6-CPA), an adenosine A1-receptor agonist, was observed after pretreatment with 50 microg bicuculline, as were the effects of morphine and 7-chlorokynurenate (7-CK). N6-CPA inhibited prod, C- and Adelta-fiber-evoked responses as well as the initial and overall final response to the train of C-fiber strength stimuli. Inhibitions were reversed with 8(p-sulphophenyl) theophylline. Morphine, the mu-receptor agonist, also inhibited the postbicuculline responses to prod, C-, and Adelta-fiber responses and initial and final responses to a train of stimuli. Inhibitory effects of morphine were reversed partly by naloxone. 7-CK, an antagonist at the glycine site on the N-methyl-D-aspartate-receptor complex, inhibited the responses to C- and Adelta-fiber-evoked activity as well as prod. The postdischarges were inhibited by this drug. Again both the initial and overall responses of the cell were inhibited. To conclude, bicuculline caused an increase in the responses of deep dorsal horn cells to prod, Adelta-fiber-evoked activity, increased C-fiber input onto these cells along with the appearance of responses at latencies normally associated with Adelta fibers, but evoked by suprathreshold Abeta-fiber stimulation. These alterations may be responsible for some aspects of the clinical phenomenon of allodynia and hyperalgesia. These altered and enhanced responses were modulated by the three separate classes of drugs, the order of effectiveness being 7-CK, N6-CPA, and then morphine.     

Improved left ventricular endocardial border delineation and opacification with OPTISON (FS069), a new echocardiographic contrast agent. Results of a phase III Multicenter Trial

We investigated whether changes in iron metabolism and the transferrin receptor (TRF-R) expression were involved in the antileukaemic effects of arabinoside cytosine (ara-C). Treatment with 100 nM ara-C for 48h reduced thymidine uptake and increased the surface expression of the TRF-R on leukaemic blasts derived from 13/16 (81%) patients and on the HL-60 and U-937 cell lines. Whereas intracellular non-haem iron was strongly depleted 24 h after ara-C addition, TRF-R up-regulation and recovery of intracellular non-haem iron concentration occurred together after a longer exposure of the cultured cells to the drug. Since iron is an essential regulator of cell proliferation we have evaluated the effects of the combination between ara-C and the iron chelator desferioxamine (DSF) on the growth of HL-60 and U-937 cells. We found that desferioxamine strongly potentiated the effects of ara-C on leukaemic cell growth inhibition and apoptosis. This is the first report of a positive interaction between ara-C and an iron chelator in terms of antileukaemic effects.     

Melting of a DNA hairpin without hyperchromism

UV absorbance spectroscopy is the most common method for detecting nucleic acid structural transitions and obtaining thermodynamic parameters. UV-detected melting has been used to determine stabilities of nucleic acid hairpins, duplexes, triplexes, and higher order structures and to determine thermodynamic effects of unusual or modified bases and mismatched base-pairs. We report that in some cases UV absorbance spectroscopy is an inadequate analytical technique for these purposes. Some critical transitions are invisible to UV absorbance spectroscopy. For example, the conversion of dodecamer d(CGCAAATTCGCG) from hairpin to random coil is not accompanied by hyperchromism. Circular dichroism (CD) spectroscopy (263 nm) clearly detects two transitions for this dodecamer, each giving a pronounced change in ellipiticity. The concentration dependence of the low-temperature transition and the concentration independence of the high-temperature transition indicate that the predominant state converts from duplex to hairpin to random coil as the temperature increases. These assignments are confirmed by comparison to oligonucleotides of similar sequence that undergo a hairpin to coil transition only. In contrast to CD spectroscopy, UV absorbance spectroscopy shows only a single transition. The transition detected by UV absorbance spectroscopy corresponds to the low-temperature transition detected by CD. UV absorbance spectroscopy does not detect the second transition at any wavelength (from 218 to 310 nm) (by changes) in either absorbance or its derivative with temperature.     

Phase I trial of weekly scheduling and pharmacokinetics of titanocene dichloride in patients with advanced cancer

PURPOSE: To determine the maximum-tolerated dose (MTD) and the dose-limiting toxicities (DLTs) of a weekly schedule of titanocene dichloride (TD) and to define the pharmacokinetics of titanium in plasma and urine. PATIENTS AND METHODS: Twenty patients with a median age of 58 years received 83 courses of TD. TD was given as 1-hour infusion at escalating doses from 70 to 185 mg/m2/wk. Pharmacokinetic analysis was performed in eight patients for total plasma titanium (TPTi) and in three patients for ultrafiltrable titanium (UFTi). RESULTS: At the fifth dose level (185 mg/m2/wk), a variety of DLTs were seen in five patients: fatigue in three, bilirubinemia in one, and hypokalemia in two. A further six patients were treated at 140 mg/m2; only one had dose-limiting creatinine elevation and this dose was therefore defined as the MTD. No myelosuppression or alopecia were observed. One patient with adenocarcinoma of unknown primary had a minor response. Pharmacokinetic analysis showed that TPTi maximum concentration (Cmax) values were linear with dose and elimination of TPTi was triphasic with a long terminal half-life (t1/2; median, 165 hours; range, 89 to 592). Between 7% and 24.3% of the total of administered titanium was eliminated in urine over the first 24 hours. In contrast, UFTi elimination was described by a one-compartment model with a t1/2 of 0.41 hours; peak levels of UFTi were 5.2% +/- 2.5% those of TPTi. CONCLUSION: The MTD of TD given on a weekly schedule is 140 mg/m2, with cumulative, but reversible creatinine and bilirubin elevation being the DLTs.     

gain bounds for systems with sector bounded and slope‐restricted nonlinearities

This paper proposes a new method for calculating a bound on the gain of a system comprising a linear time invariant part and a static nonlinear part, which is odd, bounded, zero at zero and has a restriction on its slope. The nonlinear part is also assumed to be sector bounded, with the sector bound being (possibly) different from that implied by the slope restriction. The computation of the gain bound is found by solving a set of linear matrix inequalities, which arise from an integral quadratic constraint formulation of a multiplier problem involving both Zames‐Falb and Popov multipliers. Examples illustrate the effectiveness of the results, and comparisons are made against the state‐of‐the‐art. Copyright © 2011 John Wiley & Sons, Ltd.