Studies on metabolism and disposition of sizofiran (SPG), an anti-tumor polysaccharide. III. Degradation and excretion of SPG in rats

Degradation and excretion of Sizofiran (SPG), an anti-tumor polysaccharide, were studied in rats after a single or multiple administration. After a single intravenous injection of [14C]SPG (3 mg/kg), SPG distributed in the liver was degraded at very slow rate to SPG-like substances (SPGLS) having lower molecular weight than that of SPG, while SPG in the spleen and mesenteric lymph node was metabolized at much slower rate than that in the liver. In the experiment with multiple subcutaneous administration, SPG was also found to be present mainly as SPGLS in the liver, but almost as an unchanged SPG in the spleen. SPG was excreted in the urine mainly as metabolites with a molecular weight of less than 10000. These results indicate that degradation of SPG to lower molecular weight-SPGLS is a prerequisite for efficient urinary excretion and the degradation occurs mainly in the liver.     

An oculomotor representation area within the ventral premotor cortex

We explored the ventral part of the premotor cortex (PMV) with intracortical microstimulation (ICMS) while monkeys performed a visual fixation task, to see whether the PMV is involved in oculomotor control. ICMS evoked saccades from a small-restricted region in the PMV, without evoking movements in the limbs, neck, or body. We found the saccade-evoking site in the PMV in a total of three hemispheres in two monkeys. Quantitative analysis of the effects of eye position on saccades evoked by microstimulation of the PMV characterized the evoked saccades as goal directed. The nature of the saccades evoked in the PMV contrasted with the fixed vector nature of saccades evoked by ICMS of the frontal eye field. We also found that neurons in this restricted area of the PMV were active while the animals were performing a saccade task that required them to make saccades toward targets without arm movements. These data provide evidence for the presence of an oculomotor-specific subregion within the PMV. This subregion and the surrounding skeletomotor-representing regions of the PMV seem to coordinate oculomotor and skeletomotor control in performing goal-directed motor tasks.     

Contrasting neuronal activity in supplementary and precentral motor cortex of monkeys. I. Responses to instructions determining motor responses to forthcoming signals of different modalities

The present report contrasts neuronal activity in two motor cortical fields after instructions that determine which of two sensory signals will trigger a movement and which will not. The goal of the study was to determine possible differential roles of the two cortical fields in the process of preparing to move in response to one external cue and to ignore another. Single-cell recordings were made from the supplementary motor area (SMA) and the precentral motor area (PCM) of monkeys trained to perform key-press movements in two different modes. In the auditory mode, an instruction signal warned the animal to prepare to start the movement promptly in response to a forthcoming 1,000-Hz tone burst (trigger signal), but to remain motionless if the signal was vibrotactile (nontrigger signal). In the tactile mode, the trigger and nontrigger signals were reversed: a different instruction signal warned the animal to prepare to perform the key-press movement in response to the vibrotactile cue, but to withhold it in response to the 1,000-Hz tone. The instruction signals were auditory tones of 300 Hz for the auditory mode and 100 Hz for the tactile mode. Out of 259 task-related SMA neurons, 128 (49%) responded to instructions. Three types of instruction responses were observed: 1) 95 neurons showed continuous instruction-induced activity changes lasting until the occurrence of the movement-triggering signal, regardless of whether an intervening nontrigger signal occurred. 2) 24 neurons showed increased activity until the occurrence of the nontriggering signal, after which the activity subsided. When there was no nontrigger signal, the activity increased during a period when the nontrigger signal might have been given. 3) Nine neurons responded with a transient, short-latency discharge after the instruction. The responses of SMA neurons to two instructions were often different. Forty-four SMA neurons exhibited a selective response to only one of the two instructions. In 43 neurons the response was differential, with the magnitude of activity increase or decrease being at least three times greater after one instruction than the other. In the remaining 41 neurons the response was nondifferential. Out of 112 task-related PCM neurons, 25 (22%) responded to the instructions. In the majority of them (21 neurons), the instruction response was nondifferential.(ABSTRACT TRUNCATED AT 400 WORDS)     

Influence of adjuvant anastrozole on bone mineral density in Japanese postmenopausal breast cancer patients: is there a racial difference?

Recently, the Arimidex, Tamoxifen, Alone or in Combination (ATAC)trial has clearly shown that anastrozole is better than tamoxifenin terms of improving disease-free survival, with fewer adverseeffects such as thrombophlebitis, pulmonary embolism, strokeand endometrial cancer [1]. Thus, anastrozole is now widelyaccepted as a treatment of choice     

Responses of pyramidal tract neurons in the postcentral cortex to tactile inputs

Pyramidal tract neurons were recorded from postcentral cortex of awake monkeys and their responses to step indentation and vibratory stimulus were studied. The majority of them exhibited slowly adapting response to the indentation stimulus but failed to show phase-locked response to 50-200 Hz vibrations. The response properties appeared to be in contrast to those of non-pyramidal tract neurons whose responses were largely quickly adapting.     

Ubiquitin-related proteins in neuronal and glial intranuclear inclusions in intranuclear inclusion body disease

Recent studies have shown that eosinophilic intranuclear inclusions (INI) in the brain of patients with intranuclear inclusion body disease (INIBD) are immunopositive for ubiquitin and ubiquitin-related proteins (URP). However, the extent and frequency of URP-immunoreactive inclusions in INIBD are uncertain. We immunohistochemically examined the brain, spinal cord and dorsal root ganglia from five patients with INIBD, using a virtual slide system with sequential staining of the same sections with hematoxylin and eosin and by immunolabeling with antibodies against ubiquitin and URP (NEDD8, NUB1, SUMO-1 and SUMO-2). Intranuclear inclusions were widely distributed in neurons and glial cells in all the cases. Sequential staining revealed that 100% of INI in neurons and glial cells were positive for ubiquitin. Moreover, the majority or a significant proportion of INI were positive for NEDD8, NUB1, SUMO-1 and SUMO-2. However, the proportions of NEDD8-, NUB1- and SUMO-1-positive inclusions were significantly higher in neurons than in glial cells (P < 0.05). These findings suggest that proteins related to ubiquitination and proteasomal degradation are involved in the formation of INI in INIBD.