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A temporal order judgment task was developed for mice. After training male mice (C57BL6NCrj, n=15) to poke their noses into a hole, two stimuli (brief puffs of air) were delivered to the whiskers with a fixed interval of 750 ms in one of four orders: right (R)-left (L), L-R, L-L, and R-R. The mice were rewarded when they oriented their heads toward the first (n=5) or second (n=10) stimulus after a visual go signal. The mice were trained for up to 50 days. All mice met the criterion for task achievement (daily correct response rate >70% on 3 consecutive days) in response to unilateral stimuli (L-L and R-R), and 9 of the 15 mice met the criterion for task achievement in response to bilateral stimuli (L-R and R-L). The median periods for task achievement were 15 and 34 days for unilateral and bilateral stimuli, respectively. The correct response rate dropped to approximately the chance level after all whiskers had been removed. The nine successful mice were trained further and tested with smaller interstimulus intervals. The probability of right-first judgment plotted against the stimulation interval was fitted with a sigmoid function (r2=0.92) with asymptotes of 0.29 and 0.73 and a temporal resolution of 160 ms. The sigmoid curve was biased horizontally by 133 ms, reflecting the fact that stimuli delivered simultaneously were judged as left-first rather than right-first. The results show that mice can be trained to judge the temporal order of tactile stimuli delivered to whiskers and that such judgment might be lateralized to the right hemisphere.

Tetrathiomolybdate (TM), a drug developed for Wilson's disease, produces an anti-angiogenic and anti-inflammatory effect by reducing systemic copper levels. TM therapy has proved effective in inhibiting the growth of tumors in animal tumor models and in cancer patients. We have hypothesized that TM may be used for the therapy of rheumatoid arthritis and have examined the efficacy of TM on adjuvant-induced arthritis in the rat, which is a model of acute inflammatory arthritis and inflammatory cachexia. TM delayed the onset of and suppressed the severity of clinical arthritis on both paw volume and the arthritis score. Histological examination demonstrated that TM significantly reduces the synovial hyperplasia and inflammatory cell invasion in joint tissues. Interestingly, TM can inhibit the expression of vascular endothelial growth factor in serum synovial tissues, especially in endothelial cells and macrophages. Moreover, the extent of pannus formation, which leads to bone destruction, is correlated with the content of vascular endothelial growth factor in the serum. There was no mortality in TM-treated rat abnormalities. TM also suppressed inflammatory cachexia. We suggest that copper deficiency induced by TM is a potent approach both to inhibit the progression of rheumatoid arthritis with minimal adverse effects and to improve the well-being of rheumatoid arthritis patients.

Despite the growing use of organotellurium compounds in the chemical and biomedical fields, there has been no great concern about their toxicity until now. To test the possibility that diphenyl ditelluride (DPDT) and tellurium chloride (TeCl2), organic and inorganic tellurium compounds, may exert adverse action on mammals, their effects on rat thymocytes were examined under in vitro conditions using a flow cytometer with fluorescent probes. Incubation of thymocytes with DPDT at 300 nM or more for 24 h significantly increased the populations of shrunken cells and of cells with hypodiploidal DNA. Z-VAD-FMK, a paninhibitor of caspases, greatly suppressed the DPDT-induced increase in the hypodiploidal cell population, suggesting the involvement of caspase activation in DPDT toxicity. Hence, it is possible that DPDT would increase the population of thymocytes undergoing apoptosis if the blood concentration in mammals reached at least 300 nM or more. TeCl2 was much less potent than DPDT in increasing the population of hypodiploidal cells., (Copyright 2004 Wiley Periodicals, Inc.)

A new and convenient procedure for synthesis of homoallylic alcohols in generally good to excellent yields has been developed. The bismuth-mediated Barbier-type allylation of aldehydes (aromatic, aliphatic, alicyclic and heterocyclic) with allyl bromide has been carried out smoothly in water in the presence of fluoride ions.

We examined effects of handedness on the judgment of temporal order of successive taps delivered to both hands. When the subjects' arms were uncrossed, the temporal resolution (84% correct responses) of right-handed subjects (52 +/- 4 ms, n = 16) was significantly better than that of left-handed subjects (83 +/- 9 ms, n = 16). When their arms were crossed, both groups tended to invert their judgment to a similar extent at intervals as long as 200-300 ms. In the arms crossed condition, right handed subjects inverted their judgment more often in response to left-hand-first stimuli than to right-hand-first stimuli, whereas left-handed subjects did not show the same asymmetry. We infer that hemispheric lateralization, which is generally stronger in right- than in left-handed subjects, contributes to the relatively better temporal resolution of right-handed subjects in the uncrossed condition, as well as to the asymmetric effect of stimulation order in the crossed condition.

We examined the relationship between MRI lesions and electro-clinical findings with special attention to the localising value of aura sensations and the sides of interictal epileptiform discharges in 327 patients with symptomatic localisation-related epilepsy. As a result, while autonomic as well as psychic auras were correlated with temporal lesions, simple motor seizures were associated with extra-temporal ones. Within the group of patients with temporal lobe epilepsy, autonomic but not psychic auras concurred significantly more often with medial temporal structural lesions. Furthermore, there was a significant difference between concordance rates between sides of MRI lesions and EEG foci as a function of laterality: while the right-sided MRI lesions constantly showed ipsilateral EEG foci, EEG foci concurring with the left-sided MRI lesions proved to be often falsely lateralising. From these results, we assumed that lateral as well as medial temporal involvement is needed in the genesis of the psychic aura in contrast to the autonomic aura, which could be induced without lateral temporal involvement, and lesions in the left hemisphere are more apt to induce secondarily epileptogenic than those in the right hemisphere.

Seven typical cases of dementia with motor neuron disease (D-MND) are reported. Among 1,000 dementia cases, D-MND was more frequent than Pick's disease, Lewy body disease or Creutzfeldt-Jakob disease. D-MND accounted for 30.4% of all forms of frontal lobe dementia (FLD) including FLD and Pick's disease. These data support that this combined syndrome may be more frequent than previously reported. As the subcortical neuropathology of D-MND is identical with MND, D-MND is rather the cortical manifestation of MND than a new disease entity., (Copyright 2003 S. Karger AG, Basel)

To investigate the effects of total knee arthroplasty on joint proprioception, the absolute angular error of the knee in 38 consecutive patients before and after total knee arthroplasty for osteoarthritis and in 23 age-matched control subjects were examined. Varus and valgus laxity of the knee and muscle strengths of the thigh were measured using appropriate instruments. There were no significant differences in absolute angular error before and after total knee arthroplasty, independent of retaining or substituting the posterior cruciate ligament. The absolute angular error of the knee with a normal appearing anterior cruciate ligament was larger than that with a missing anterior cruciate ligament before total knee arthroplasty and decreased significantly after surgery. The absolute angular error correlated with the varus and valgus laxity of the knee, but did not correlate with the strength of thigh muscles after total knee arthroplasty. These results suggest that deficiency of the anterior cruciate ligament may not adversely affect proprioception in severe knee osteoarthritis. In addition, proper ligament balance may partly contribute to better proprioception after total knee arthroplasty.