Control strategies in directing the hand to moving targets

Summary We have evaluated the use of visual information about the movement of a target in two tasks tracking and interceptions — involving multi-joint reaching movements with the arm. Target velocity was either varied in a pseudorandom order (random condition) or was kept constant (predictable condition) across trials. Response latency decreased as target velocity increased in each condition. A simple model that assumes that latency is the sum of two components — the time taken for target motion to be detected, and a fixed processing time — provides a good fit to the data. Results from a step-ramp experiment, in which the target stepped a small distance immediately preceding the onset of the ramp motion, were consistent with this model. The characteristics of the first 100 ms of the response depended on the amount of information about target motion available to the subject. In the tracking task with randomly varied target velocities, the initial changes in hand velocity were largely independent of target velocity. In contrast, when the velocity was predictable the initial hand velocity depended on target velocity. Analogously, the initial changes in the direction of hand motion in the interception task were independent of target velocity in the random condition, but depended on target velocity in the predictable condition. The time course for development of response dependence was estimated by controlling the amount of visual information about target velocity available to the subject before the onset of limb movement. The results suggest that when target velocity was random, hand movement started before visual motion processing was complete. The response was subsequently adjusted after target velocity was computed. Subjects displayed idiosyncratic strategies during the catch-up phase in the tracking task. The peak hand velocity depended on target velocity and was similar for all subjects. The time at which the peak occurred, in contrast, varied substantially among subjects. In the interception task the hand paths were straighter in the predictable than in the random condition. This appeared to be the result of making adjustments in movement direction in the former condition to correct for initially inappropriate responses.     

Primitive neuroectodermal tumors of the central nervous system. Patterns of expression of neuroendocrine markers, and all classes of intermediate filament proteins

Snap-frozen samples from 22 primitive neuroectodermal tumors (PNETs) primary in the central nervous system were studied with antibodies to synaptophysin, bombesin, somatostatin, substance P, vasoactive intestinal polypeptide, all classes of intermediate filaments, and desmoplakins I and II. Frozen sections were immunostained by the avidin-biotin peroxidase complex and indirect immunofluorescence microscopy methods. Selected cases were also studied by double and triple label immunofluorescence microscopy, and by two-dimensional gel electrophoresis and immunoblot analysis. We found that all 22 PNETs expressed synaptophysin extensively. Focal expression of 2 or more neuropeptides was noted in 10 samples studied. All PNETs expressed vimentin, 21 of 22 expressed glial filament protein (GFP), 16 of 22 expressed neurofilament proteins (NFP), 4 of 22 expressed desmin, and 3 of 22 expressed cytokeratins. In only one case were focal and questionable reactions with desmoplakin antibodies seen. Immunoblots confirmed the presence of desmin. Double and triple immunofluorescence revealed a number of antigenic coexpressions in individual cells including: synaptophysin with vimentin, GFP, NFP and desmin, vimentin-GFP, vimentin-NFP, vimentin-cytokeratin, vimentin-desmin and desmin-NFP; similarly, combinations of vimentin-GFP-NFP, vimentin-GFP-desmin, and vimentin-GFP-cytokeratin were found. The consistent expression of synaptophysin and 2 or more neuropeptides indicates that central nervous system PNETs have significant phenotypic features in common with neuroendocrine tumors. Their complex and variable intermediate filament complement patterns combined with their consistent expression of specific neuroendocrine differentiation markers, suggest that central nervous system PNETs comprise a distinct, albeit heterogeneous group of neoplasms.     

MR demonstration of cryptic vascular malformation producing a palatal myoclonus--a case report

A 47-year-old man had suffered oscillopsia associated with palatal myoclonus for 10 years. High-field magnetic resonance imaging (MRI) revealed a cryptic vascular malformation within the "Guillain-Mollaret triangle" which was thought to be the responsible lesion.     

A pilot study of bortezomib in Korean patients with relapsed or refractory myeloma

Recent clinical trials showed that bortezomib, a novel proteasome inhibitor, had therapeutic activity in multiple myeloma. However, there was no data about the feasibility of bortezomib in Korean patients. We performed a pilot study of bortezomib in patients with relapsed or refractory myeloma (1.3 mg/m2 twice weekly for 2 week in a 3-week cycle). Seven patients were enrolled. The median age of patients was 59 yr. All patients previously received VAD (vincristine, doxorubicin and dexamethasone) and thalidomide chemotherapy. Three patients previously received alkylator-containing chemotherapy and 4 patients, autologous stem cell transplantation. Bortezomib monotherapy resulted in 3 partial remissions (43%), 3 no changes (43%) and 1 progressive disease (14%). One patient who had no response to bortezomib monotherapy experienced partial remission after addition of dexamethasone to bortezomib. The most common serious toxicity was thrombocytopenia (grade 3/4, 10 of 20 cycles (50%)) and grade 3 peripheral neuropathy was developed in 2 of 20 cycles (10%). Drug-related adverse event led to discontinuation of bortezomib in 1 patient. There was no treatment related mortality. Overall, bortezomib seems to be effective and feasible. Conduction of larger clinical studies on Korean patients is necessary to characterize clinical efficacy and safety of bortezomib more precisely.     

Serratia marcescens bacteremia at a medical center in southern Taiwan: high prevalence of cefotaxime resistance.

Antimicrobial resistance of isolates and risk factors for mortality were retrospectively investigated in 71 adult patients with Serratia marcescens bacteremia. During the 4-year study period, 78 clinically significant episodes of S. marcescens bacteremia occurred in 71 patients. The mean age of the patients was 65 years (range, 25-86 years) with a male predominance (45 patients, 63%). Most of the bacteremic episodes were nosocomial (78%), and 34% were polymicrobial. The overall mortality rate within 2 weeks after the onset of bacteremia was 41%. The presence of malignancy and critical illness at initial presentation were independent risk factors for mortality. By disk susceptibility test, 72 isolates were resistant to cefotaxime (92%) but susceptible to ceftazidime (99%). All isolates were susceptible to meropenem. Among the 47 patients with monomicrobial S. marcescens bacteremia, the mortality rate within 5 days of onset in patients receiving appropriate empirical antimicrobial therapy was lower than that in patients receiving inappropriate therapy although this difference was not significant (14% vs 28%, p = 0.27). Among the patients with cefotaxime-resistant but ceftazidime-susceptible S. marcescens bacteremia treated with ceftazidime, 6 of 7 patients (86%) survived for more than 2 weeks, suggesting the potential effectiveness of ceftazidime in the treatment of cefotaxime-resistant Serratia infections. Further clinical studies are required to delineate the clinical role of ceftazidime therapy for infections caused by S. marcescens with this resistant phenotype.     

Measurement of IgG-blocking antibodies by ELISA using monoclonal antibody and fluorogenic substrate

An enzyme-linked immunosorbent assay (ELISA) using mouse monoclonal antihuman gamma-chain antibody and a fluorogenic substrate has been developed for quantitation of IgG-blocking antibodies in human serum. Generation of fluorescent product was linear with time to 60 min. Using optimal conditions the ELISA was sensitive to less than 1 ng/ml of specific IgG to short ragweed pollen. The assay demonstrated consistently parallel dilution curves with 51 sera (mean interdilutional coefficient of variation = 8.8%). Reproducibility was determined by constructing precision profiles for intra and interassay variation for the entire working range of the assay. Intraassay CVs ranged from a mean of 13% at threshold to less than 5% at higher antibody concentration. Interassay reproducibility similarly ranged from 18 to 10%. In this assay the effect of serum dilution on nonspecific binding was minimal and specific binding of 4-10 ng IgG antibody to the antigen-adsorbed wells was largely complete (75.8 +/- 4.8%) and highly specific (greater than 98%). This application of ELISA for ragweed IgG antibody measurement has performance specifications equal or superior to previously developed radioimmunoassay and ELISA systems.     

Virulence of Staphylococcus aureus mutants altered in type 5 capsule production.

Most clinical isolates of Staphylococcus aureus produce microcapsules (uronic acid-containing extracellular polysaccharides) that are detectable by serologic methods but are not visible by negative staining. Among the 11 reported serotypes, capsule types 5 and 8 comprise approximately 75% of all isolates. Transposon mutagenesis was performed on S. aureus to create mutants altered in capsule expression. Tn918 was introduced into the capsule type 5 strain Reynolds by filter mating, and a capsule-deficient transconjugate, JL236, was isolated. The wild-type strain was transformed with JL236 chromosomal DNA to confirm that transfer of the appropriate-size chromosomal fragment containing Tn918 generated a capsule-deficient transformant. Strain Reynolds was mutagenized with ethyl methanesulfonate to obtain a capsule-negative mutant (strain JL240). Capsular phenotypes were determined by colony immunoblots, antibody adsorption experiments, and transmission electron microscopy. The virulences of the parental and mutant strains in mice were compared. The 50% lethal doses for strains Reynolds, JL236, and JL240 were similar (10(8.59), 10(8.98), and 10(8.93) CFU, respectively). Animals injected intraperitoneally with either wild-type or mutant strains had comparable levels of bacteremia at 3 and 24 h after challenge. Quantitative cultures of blood and kidneys from animals challenged intravenously with sublethal doses of the S. aureus strains also showed no differences in bacterial clearance or renal abscess formation. These studies indicate that the type 5 S. aureus microcapsule does not promote bacterial virulence in the animal models tested.     

Changes in the level of acetylcholinesterase of Nematospiroides dubius and Trichostrongylus colubriformis following paralysis by levamisole in vivo

Acetylcholinesterase (acetylcholine acetylhydrolase; EC 3.1.1.7) levels of Nematospiroides dubius from laboratory mice and Trichostrongylus colubriformis from lambs have been measured. The anthelmintic levamisole (leavo isomer of 2,3,5,6-tetrahydro-6-phenylimidazo-(2,1b)-thiazole (Tetramizole)) did not affect the level of acetylcholinesterase in N. dubius in vivo but caused a reduction in the level of the enzyme in T. colubriformis following paralysis in vivo. The effect of levamisole on acetylcholinesterase in the nematodes is explained in terms of the differing roles of the enzyme in these two species.     

Evolutionary variants of simian virus 40: cloned substituted variants containing multiple initiation sites for DNA replication.

Two cloned evolutionary variants of simian virus 40 (SV40) containing substitutions of cellular DNA have been characterized by restriction endonuclease analysis, electron microscopic heteroduplex mapping, and DNA-DNA hybridization. Each variant genome is made up of a small, tandemly repeated segment of DNA consisting of cellular DNA and that portion of the SV40 genome containing the initiation signal for viral DNA replication. Cellular DNA sequences are different in the two variants, indicating that recombination between cell DNA and SV40-DNA can occur at more than one site. However, one end of the SV40 segment (0.68 SV40 map-units) is the same in each variant. The data suggest that substituted variants arise by integration of SV40-DNA into cellular DNA followed by excision of a small substituted genome which is subsequently amplified to a size compatible with encapsidation; the presence of multiple initiation signals in each molecule results in selective replication.     

High levels of estradiol impair spatial performance in the Morris water maze and increase 'depressive-like' behaviors in the female meadow vole

The present study investigated sex differences and the effect of a high level of estradiol in the female meadow vole on performance in the forced swim test (FST) and the Morris water maze in meadow voles. Female meadow voles were ovariectomized (OVX) and administered either vehicle (sesame oil) or estradiol for 2 days prior to performing the FST. Four days following the FST, all animals were run in the Morris water maze. Results indicated that estradiol-injected female meadow voles showed more 'depressive-like' behaviors in the FST (greater time spent immobile and less time spent swimming) than vehicle-treated female or male meadow voles. In addition, estradiol-treated females had impaired performance (greater latencies and distance swam to reach the hidden platform) than both vehicle-treated female and male meadow voles, consistent with previous data. Despite the fact that estradiol administration increased 'depressive-like' behaviors in the FST and impaired performance in the Morris water maze, there was no correlation between the two behaviors indicating that 'depressive-like' behaviors did not account for the differences seen in spatial performance in the Morris water maze. To our knowledge, this is the first demonstration in rodents indicating that estradiol-mediated changes in behavior in the FST is not indicative of subsequent performance in the Morris water maze.