Motor cortical representation of position and velocity during reaching

This study examines motor cortical representation of hand position and its relationship to the representation of hand velocity during reaching movements. In all, 978 motor cortical neurons were recorded from the proximal arm area of rostral motor cortex. The results demonstrate that position and velocity are simultaneously encoded by single motor cortical neurons in an additive fashion and that the relative weights of the position and velocity signals change dynamically during reaching. The two variables--hand position and hand velocity--are highly correlated in the standard center-out reaching task. A new reaching task (standard reaching) is introduced to minimize these correlations. Likewise, a new decoding method (indirect OLE) was developed to analyze the data by simultaneously decoding both three-dimensional (3D) hand position and 3D hand velocity from correlated neural activity. This method shows that, on average, the reconstructed velocity led the actual hand velocity by 122 ms, whereas the reconstructed position signal led the actual hand position by 81 ms.     

Shared idiotopes among antibodies encoded by heavy-chain variable region (VH) gene members of the J558 VH family as basis for cross-reactive regulation of clones with different antigen specificity.

A wide idiotype cross-reactivity was observed among six groups of monoclonal antibodies specific for arsonate and nitrophenyl haptens, hemagglutinin of PR8 and X31 influenza viruses, dextran, A48-idiotype, and a set of six monoclonal antibodies with unknown antigenic specificity. All of these antibodies are encoded by heavy-chain variable region (VH) genes belonging to the J558 VH family. This idiotypic cross-reactivity was determined by studying the binding of these antibodies to a panel of six monoclonal anti-idiotype antibodies, each one raised against a member of the six groups of monoclonal antibodies. The administration at birth of two such monoclonal anti-idiotype antibodies induced a long-lasting suppression not only of the corresponding idiotype but also of VH-related idiotypes with different antigenic specificities. These results suggest that the idiotypes encoded by VH genes that belong to the same VH gene family are interactive one with another. The possible physiological consequences of this immunochemical cross-reactivity are discussed.     

Reversible oxidant-induced increases in albumin transfer across cultured endothelium: alterations in cell shape and calcium homeostasis

To determine whether reactive oxygen molecules could directly and reversibly increase the transfer of albumin across an endothelial barrier, we measured albumin transfer across monolayers of endothelium cultured on micropore filters before and after exposure to xanthine and xanthine oxidase. Xanthine and xanthine oxidase increased endothelial albumin transfer in a dose-dependent fashion. Parallel phase contrast and fluorescence microscopy demonstrated retraction of adjacent cells from one another and disruption of the actin filaments. The oxidant- induced increases in albumin transfer and changes in cell shape were reversed by removing xanthine oxidase and then incubating the monolayers for 3 1/2 hours in tissue culture media enriched with fetal bovine serum. However, incubation in tissue culture media without serum resulted in progressive injury and cell death. Hence, the brief exposure to oxidants initiated a progressive injury process that was reversed by incubation in serum. Because intracellular and extracellular calcium are important determinants of cell shape, and because some oxidized membrane lipids act as calcium ionophores, we asked whether oxidants altered endothelial calcium homeostasis. Xanthine-xanthine oxidase increased release of 45Ca++ from preloaded cells. The calcium antagonist lanthanum chloride prevented xanthine- xanthine oxidase increases in endothelial albumin transfer and prevented the changes in cell shape; chelation of extracellular calcium inhibited lysis of endothelium by xanthine-xanthine oxidase; and the calcium ionophore A23187 increased endothelial albumin transfer and mimicked the oxidant-induced changes in cell shape. Lanthanum chloride inhibited these effects of A23187. These data suggest that oxygen radicals can reversibly increase endothelial permeability to macromolecules, that this is associated with reversible changes in endothelial cell shape and actin filaments, and that the changes in cell shape are related to oxidant-induced changes in endothelial calcium homeostasis.     

Graded responses of human neutrophils induced by serum-treated zymosan

A modified zymosan preparation was used to probe the interaction of particulate stimuli with human neutrophils (PMNs). After extraction with alkali and detergent, the zymosan particles retained their ability to be opsonized in serum and to stimulate PMNs. Serum-treated zymosan (STZ) induced dose-dependent superoxide (O2-) production and membrane potential depolarization in the range of 1 to 10 mg/mL of STZ. The rate and extent of secretion of lysozyme and beta-glucuronidase were also dose-dependent in the range of 1 to 10 mg/mL of STZ. Cytochemical studies using nitroblue tetrazolium, however, showed that 92% of PMNs were stimulated to produce O2- at 0.1 mg/mL of STZ. The dose response of O2- production induced by STZ is therefore due to increasing O2- production by individual PMNs and not to the stimulation of more PMNs to produce O2-. Evidence for O2- production was found only in the area of PMN-zymosan contact, suggesting a mechanism for the graded responses of PMNs treated with particulate stimuli. In order to determine the nature of the dose dependence of depolarization (a measure of PMN activation), PMNs equilibrated with the fluorescent probe 3,3'- dipentyloxacarbocyanine were analyzed by flow cytometry. The results demonstrate that STZ induces a dose-dependent depolarization of the membrane potential of individual PMNs. These results also demonstrate that increasing concentrations of STZ can induce increasing PMN responses even when all of the PMNs have been activated. These results are consistent with the hypothesis that receptor-mediated particulate stimulation of PMNs is a phenomenon that results in graded PMN responses.     

Watery diarrhea-hypokalemia-achlorhydria syndrome and carcinoma of the esophagus

The watery diarrhea-hypokalemia-achlorhydria syndrome associated with ectopic secretion of vasoactive intestinal peptide has only been conclusively documented with tumors originating in the pancreas or sympathetic chain. We report here the case of a 50-yr-old woman who developed this syndrome 3 wk after an apparently effective course of radiotherapy for an obstructing, mixed-cell carcinoma of the esophagus. High concentrations of vasoactive intestinal peptide were found in plasma (100-200 pmol/L; normal less than 20 pmol/L) and in the metastatic skin nodules (750 pmol/g) that later developed and that contained one of the two cell types from the original tumor. Stool volumes reached a plateau of 15-20 L/day, and potassium requirements were greater than 1000 mmol/day. Symptoms failed to respond to any of the regimens previously described as effective in this syndrome. After 14 wk of massive fecal fluid and electrolyte losses, symptoms resolved dramatically with the first dose of 5-fluorouracil. Plasma vasoactive intestinal peptide concentration returned to normal, where it remained despite subsequent evidence of renewed tumor spread. This case illustrates the unpredictability of the response of this syndrome to medical treatment, and suggests that vasoactive intestinal peptide secretion may occur in a wider range of tumors than has so far been described.     

Endocardial activation mapping and endocardial pace-mapping using a balloon apparatus

The relation between endocardial activation mapping and endocardial pace-mapping was evaluated in 8 dogs while they were on cardiopulmonary bypass. Pacing or recording was accomplished by using a balloon apparatus (with 32 bipolar electrodes) inserted through a left apical ventriculotomy. Ventricular tachycardia (VT) was produced by occlusion followed by reperfusion of the left anterior descending coronary artery. During each VT, activation mapping was performed and early sites determined. Pace-map correlates (sites at which endocardial pacing produced a similar QRS morphology to that of the VT) were also determined. Isochronous maps were constructed for activation mapping and pace-mapping. There was a total of 29 morphologically distinct VTs. Groups were delineated according to correlations between activation mapping and pace-mapping. In 14 episodes of VT (group 1), pace-mapping confirmed the findings of activation mapping with all early sites being pace-map correlates (total number of early sites (tES) = 19; total number of pace-map correlates (tPMC) = 88; tES same as tPMC = 19). In 9 episodes of VT (group 2), there was a partial correlation between pace-mapping and activation mapping, such that pace-mapping when used with activation mapping appeared to further delineate the region of arrhythmogenesis (tES = 31; tPMC = 59; tES same as tPMC = 14). In 6 episodes of VT (group 3), there was no correlation between pace-mapping and activation mapping (tES = 15; tPMC = 0). With the balloon apparatus, endocardial activation mapping can be performed without the need for sustained monomorphic VT, and endocardial pace-maps may be generated easily.(ABSTRACT TRUNCATED AT 250 WORDS)