The role of visual feedback of hand position in the control of manual prehension

 Although it is obvious that vision plays a primary role in reaching and grasping objects, the sources of the visual information used in programming and controlling various aspects of these movements is still being investigated. One source of visual information is feedback relating to the characteristics of the reach itself – for example, the speed and trajectory of the moving limb and the change in the posture of the hand and fingers. The present study selectively eliminated this source of visual information by blocking the subject’s view of the reaching limb with an opaque barrier while still enabling subjects to view the goal object. Thus, a direct comparison was made between standard (closed-loop) and object-only (open-loop) visual-feedback conditions in a situation in which the light levels and contrast between an object and its surroundings were equivalent in both viewing conditions. Reach duration was longer with proportionate increases in both the acceleration and deceleration phases when visual feedback of the reaching limb was prevented. Maximum grip aperture and the proportion of movement time at which it occurred were the same in both conditions. Thus, in contrast to previous studies that did not employ constant light levels across closed- and open-loop reaching conditions, a dissociation was found between the spatial and temporal dimensions of grip formation. It appears that the posture of the hand can be programmed without visual feedback of the hand – presumably via a combination of visual information about the goal object and proprioceptive feedback (and/or efference copy). Nevertheless, maximum grip aperture (like the kinematic markers examined in the transport component) was also delayed when visual feedback of the reaching limb was selectively prevented. In other words, the relative timing of kinematic events was essentially unchanged, reflecting perhaps a tight coupling between the transport and grip components. Received: 3 July 1998 / Accepted: 18 November 1998     

Attenuation of intracavitary applicators in 192Ir-HDR brachytherapy

Unlike the penetrating monoenergetic 662 keV gamma rays emitted by 137Cs LDR sources, the spectrum of 192Ir used in HDR brachytherapy contains low-energy components. Since these are selectively absorbed by the high-atomic number materials of which intracavitary applicators are made, the traditional neglect of applicator attenuation can lead to appreciable dose errors. We investigated the attenuation effects of a uterine applicator, and of a set of commonly used vaginal cylinders. The uterine applicator consists of a stainless steel source guide tube with a wall thickness of 0.5 mm and a density of 8.02 g/cm3, whereas the vaginal cylinders consist of the same stainless steel tube plus concentric polysulfone cylinders with a radius of 1 or 2 cm and a density of 1.40 g/cm3. Monte Carlo simulations were performed to compute dose distributions for a bare 192Ir-HDR source, and for the same source located within the applicators. Relative measurements of applicator attenuation using ion-chambers (0.125 cm3) confirmed the Monte Carlo results within 0.5%. We found that the neglect of the applicator attenuation overestimates the dose along the transverse plane by up to 3.5%. At oblique angles, the longer photon path within applicators worsens the error. We defined attenuation-corrected radial dose and anisotropy functions, and applied them to a treatment having multiple dwell positions inside a vaginal cylinder.     

Magnitude of the inflammatory response to cardiopulmonary bypass and its relation to adverse clinical outcomes

INTRODUCTION: Cardiopulmonary bypass (CPB) induces an inflammatory response believed to contribute to postoperative morbidity. We hypothesized that the magnitude of the inflammatory response following CPB would be associated with adverse clinical outcomes. METHODS: Twenty-nine patients had plasma TNF, IL-6, IL-8, elastase, histamine, complement C5a, and complement C3a measured by ELISA before, during, and after cardiac operations employing CPB. Inflammatory mediator levels were analyzed with respect to outcomes. RESULTS: Mediator levels peaked at 4 h post-CPB and either returned to baseline or substantially decreased by 24 h. Patients with peak mediator levels above the median for the group as a whole were classified as 'hyper-responders'; those with levels below the median were classified as 'normal responders'. While IL-8, C3a, and IL-6 levels were independently associated with adverse outcomes, TNF, histamine, and C5a levels were not. Elastase levels trended towards adverse outcomes. IL-8 'hyper-responders' experienced significantly greater postoperative weight gain and had higher IL-8 levels at 24 h (p<0.05), with trends towards renal impairment and protracted supplemental oxygen requirements. C3a 'hyper-responders' strongly trended towards increased bleeding, delayed extubation, greater postoperative weight gain, and decreased levels of independent functioning at discharge (p < or = 0.10). IL-6 'hyper-responders' experienced significantly more postoperative bleeding, delayed extubation, and higher IL-6 levels at 24 h compared to 'normal responders' (p < 0.05). They strongly trended towards greater postoperative weight gain and decreased levels of independent functioning at discharge (p < or = 0.10). CONCLUSIONS: Patients who have an exaggerated inflammatory response to CPB tend to bleed more, require more respiratory support, demonstrate greater capillary leak via weight gain, and display a decline in independent functioning relative to normal responders. Thus, it appears that the magnitude of the inflammatory response to CPB adversely influences clinical outcomes.     

Drosophila dSAP18 is a nuclear protein that associates with chromosomes and the nuclear matrix, and interacts with pinin, a protein factor involved in RNA splicing

SAP18 is a highly conserved protein that was proposed to be involved in multiple cellular processes from autophagy to gene regulation and mRNA processing. In this paper we show that, in Drosophila, dSAP18 is a predominantly nuclear protein that associates to both chromosomes and the nuclear matrix. dSAP18 becomes nuclear early during development, at the onset of cellularization, and remains so all through embryo development. dSAP18 is also nuclear in salivary glands, ovaries and cultured S2 cells. Here we also show that dSAP18 forms a complex with the Drosophila homolog of pinin (dPnn), a protein factor involved in mRNA splicing. dSAP18-dPnn interaction was confirmed in vivo, through co-immunoprecipitation experiments, as well as in vitro, through GST pull-down assays. These results are discussed in the context of the possible functions played by SAP18.     

Platelets and anticoagulant capacity in patients with inflammatory bowel disease

Patients with inflammatory bowel disease (IBD) are susceptible to thromboembolic complications. Several mechanisms can be responsible, including abnormal regulation of coagulation activity, disturbances of fibrinolysis, inflammatory reactions and thrombocytosis. The aim of this study was to assess hemostatic alterations in these parameters during exacerbation of disease. We studied disease activity in 99 IBD patients receiving anti-inflammatory therapy, in relation to: procoagulant markers, i.e. prothrombin fragment F1 + 2 (F1 + 2), D-dimer and platelet count, anticoagulant markers, i.e. protein C, protein S and antithrombin, and a mediator of inflammation (IL-6). Coagulation activity and platelet count were increased during active disease in IBD patients compared with those in a state of remission. The IL-6 concentrations were positively correlated with disease activity and thrombocytosis in patients with ulcerative colitis, but no association with the anticoagulant capacity could be demonstrated except for a decrease in protein C during high disease activity.     

Smoking Cessation in the Chicago Coronary Prevention Evaluation Program

Quit-rates for cigarette smokers in a lifestyle intervention program aimed at reducing coronary risk were 24 percent for all participants and 34 percent for non-dropouts. Recidivism remained very low during participation in the program. Half of the smokers who quit did so after being in the program more than two years. These data suggest that while engaging in an effort to make other changes in lifestyle, many smokers can be helped to quit. Sustained antismoking efforts in the clinical practice of medicine can be expected to share these same positive aspects. While mass public health programs to eliminate smoking and prevent young people from taking up the habit are being developed, health practitioners can make a significant contribution by including vigorous efforts at smoking cessation as part of routine practice.     

Activation of immunological memory cells in vitro

Peritoneal cell populations from NMRI mice injected three times intraperitoneally with sheep red blood cells do not contain a significant number of plaque-forming cells to sheep red blood cells. However, plaque-forming cells do arise in such populations 3–5 days after transfer into tissue culture. The in vitro activation of these cells into antibody-producing cells occurs without further exposure to the antigen. The culture system contained, in addition to the peritoneal cells, irradiated spleen cells from non-immunized animals which were shown not to respond when cultured alone. The peritoneal cells as well as non-producing spleen cells could be activated in vitro at varying times after the last stimulation of the donor animal up to a period of several weeks. These observations suggest that there is a compartment of resting memory cells whose activation is not dependent on the addition of antigen.     

fMRI activation in the human frontal eye field is correlated with saccadic reaction time

Variation in response latency to identical sensory stimuli has been attributed to variation in neural activity mediating preparatory set. Here we report evidence for a relationship between saccadic reaction time (SRT) and set-related brain activity measured with event-related functional magnetic resonance imaging. We measured hemodynamic activation time-courses during a preparatory "gap" period, during which no visual stimulus was present and no saccades were made. The subjects merely anticipated appearance of the target. Saccade direction and latency were recorded during scanning, and trials were sorted according to SRT. Both the frontal (FEF) and supplementary eye fields showed pre-target preparatory activity, but only in the FEF was this activity correlated with SRT. Activation in the intraparietal sulcus did not show any preparatory activity. These data provide evidence that the human FEF plays a central role in saccade initiation; pre-target activity in this region predicts both the type of eye movement (whether the subject will look toward or away from the target) and when a future saccade will occur.     

Transforming growth factor-beta facilitates breast carcinoma metastasis by promoting tumor cell survival

We have shown recently that the hyaluronan receptor, CD44, and matrix metalloproteinase 9 (MMP-9) form a complex on the surface of TA/St mouse mammary carcinoma cells that activates latent transforming growth factor-beta (TGF-β) and is required for tumor invasion. Disruption of the CD44/MMP-9 complex by expression of soluble CD44 results in the loss of tumor invasiveness and abrogates tumor cell survival in host lung parenchyma following intravenous injection into syngeneic mice. To explore the molecular nature of the survival signals derived from the CD44/MMP-9 complex during the development of tumor metastasis, we investigated the possibility that activation of latent TGF-β by the CD44/MMP-9 complex is responsible for tumor cell survival in host lung parenchyma. TA3 cells overexpressing dominant negative soluble CD44 (TA3sCD44), which compromises native CD44 function and the ability of TA3 cells to develop metastases, were transfected with constitutively active or latent TGF-β2 and tested for their ability to form tumors in syngeneic mice. Our results demonstrate that expression of the constitutively active, but not the latent, form of TGF-β2 rescues TA3sCD44 cells from apoptosis during lung colonization. These observations provide evidence that activation of latent TGF-β constitutes an event downstream of CD44-dependent signals that is required for tumor cell survival and metastatic colony formation. The functional axis composed of CD44, MMP-9 and TGF-β may therefore play an important role in the metastatic proclivity of selected tumor types. Abbreviations: ECM – extracellular matrix; HA – hyaluronan; HSPG – heparan sulfate proteoglycan; MMP – matrix metalloproteinase; TGF-β– transforming growth factor β This revised version was published online in July 2006 with corrections to the Cover Date.