Cortical activation during fast repetitive finger movements in humans: steady-state movement-related magnetic fields and their cortical generators.

OBJECTIVE: To study the cortical physiology of fast repetitive finger movements. METHODS: We recorded steady-state movement-related magnetic fields (ssMRMFs) associated with self-paced, repetitive, 2-Hz finger movements in a 122-channel whole-head magnetometer. The ssMRMF generators were determined by equivalent current dipole (ECD) modeling and co-registered with anatomical magnetic resonance images (MRIs). RESULTS: Two major ssMRMF components occurred in proximity to EMG onset: a motor field (MF) peaking at 37+/-11 ms after EMG onset, and a postmovement field (post-MF), with inverse polarity, peaking at 102+/-13 ms after EMG onset. The ECD for the MF was located in the primary motor cortex (M1), and the ECD for the post-MF in the primary somatosensory cortex (S1). The MF was probably closely related to the generation of corticospinal volleys, whereas the post-MF most likely represented reafferent feedback processing. CONCLUSIONS: The present data offer further evidence that the main phasic changes of cortical activity occur in direct proximity to repetitive EMG bursts in the contralateral M1 and S1. They complement previous electroencephalography (EEG) findings on steady-state movement-related cortical potentials (ssMRCPs) by providing more precise anatomical information, and thereby enhance the potential value of ssMRCPs and ssMRMFs for studying human sensorimotor cortex activation non-invasively and with high temporal resolution.

Cortical activation during fast repetitive finger movements in humans: dipole sources of steady-state movement-related cortical potentials.

Fast repetitive finger movements are associated with characteristic EEG patterns described in humans as steady-state movement-related cortical potentials (ssMRCPs). The objective of the present study was to determine the electrical generators of ssMRCPs (movement rate, 2 Hz) by dipole modelling. The generators for the initial ssMRCP phase (peak approximately 60 msec before EMG onset) were located in the central region bilaterally, with largely radial orientation, consistent with activation of the crown of the precentral gyrus. The generator of the next phase (peak approximately 10 msec after EMG onset) was located in the contralateral central region with tangential posterior orientation, consistent with activation of the anterior wall of the central sulcus. The postmovement phase (peak approximately 95 msec after EMG onset) was explained by another source in the contralateral central region with tangential anterior orientation, consistent with activation of the posterior wall of the central sulcus. This pattern probably corresponds to a sequence of activation of the bilateral dorsal premotor cortex, contralateral primary motor, and primary somatosensory cortex that takes place within approximately 200 msec around EMG onset. Steady-state movement-related cortical potentials in combination with dipole modelling provide a novel, noninvasive approach to assessing changes of human cortical premotor, motor, and somatosensory activation in the millisecond range.

Steady-state movement-related cortical potentials: a new approach to assessing cortical activity associated with fast repetitive finger movements.

Traditionally, studies of movement-related cortical potentials have focused on the preparation of single self-paced movements performed slowly. We studied MRCPs elicited by metronome-paced, fast repetitive finger movements (2/s) with 28-channel (10 normal subjects) and 122-channel (two subjects) EEG. EMG-locked averaging of 500 ms time windows (300 ms before to 200 ms after each EMG onset) produced a distinct pattern of phasic MRCPs (steady-state MRCPs). The main components were a pre-movement peak (pre-MP), 57 ms before EMG onset, and a post-movement peak (post-MP), 93 ms after EMG onset. From timing information and topographic mapping results, we propose that the pre-MP is largely generated by a tangential source in the anterior bank of the central sulcus and reflects precentral motor processing, whereas the post-MP is generated in the posterior bank of the central sulcus and represents post-central feedback processing. Steady-state MRCPs require actual recording times of less than 10 min, and show excellent inter-session reproducibility. These characteristics may make them convenient for studying sensorimotor cortex activity experimentally and clinically.

The production of a new water-soluble polysaccharide by Acetobacter xylinum NCI 1005 and its structural analysis by NMR spectroscopy.

A new water-soluble polysaccharide (WSP) was isolated from a culture of Acetobacter xylinum NCI 1005 grown on sucrose. The structure of the WSP was analysed by nuclear magnetic resonance spectroscopy and determined to be a beta-(2-->6)-linked polyfructan, which is structurally different from the polymer synthesized from glucose instead of sucrose by the same strain. The discovery of this new polysaccharide has revealed that the bacterium is able to synthesize two different kinds of water-soluble polysaccharides.

Hippocampal responses to corticosterone and stress, one of which is the 35,000 M(r) protein, glycerol phosphate dehydrogenase.

Previously, the synthesis of a hippocampal 35,000 M(r) protein increased in response to glucocorticoid treatment and a variety of stressors. We now show by immunoprecipitation that this cytosolic protein is glycerol 3-phosphate dehydrogenase (E.C.1.1.1.8; GPDH). In addition, four polypeptides encoded by glucocorticoid-induced mRNAs co-migrated with hippocampal protein synthetic products on two-dimensional polyacrylamide gels, including 35,000 M(r) protein of approximately pl 6.3, that had previously been identified as GPDH by hybrid-selection with a GPDH cDNA clone. The 35,000 M(r) in vitro translation product was also immunoprecipitated with the GPDH antibody. Using radiolabeled hippocampal slices and two-dimensional gel analysis, a 35,000 M(r) polypeptide of approximately pl 6.4 increased five-fold after 30 min of intermittent tail-shock. This protein was found predominantly in the 20,000 x g pellet and did not immunoprecipitate with the GPDH antibody. However, a 35,000 M(r) polypeptide was also found in the cytosol as a minor component after stress, which did immunoprecipitate with the GPDH antibody. Therefore, there are at least two shock-induced 35,000 M(r) proteins, one of which is GPDH. These results establish that increases in GPDH mRNA prevalence and protein synthesis occur in response to both glucocorticoids and stress in the adult rat hippocampus. Based on the increased enzyme activity seen in the nervous system in response to glucocorticoids, dietary restriction, and nerve injury, the induction of GPDH may have functional consequences in cellular adaptation to stress.

Frequency doubling of a Nd:YAG laser using a crystal-cored fiber of an organic 4-(N,N-dimethylamino)-3-acetamidonitrobenzene.

Optical second-harmonic generation from a glass-clad fiber with an organic core crystal of 4-(N,Ndimethylamino)-3-acetamidonitrobenzene (DAN) is demonstrated. Phase matching was due to cerenkov radiation. Linear and nonlinear optical properties of DAN, a fabrication technique of a crystal-cored fiber, and a focusing method of the generated second-harmonic wave are studied.

Increased synthesis of two polypeptides in area CA1 of the hippocampus in response to repetitive electrical stimulation.

Changes in the pattern of newly synthesized polypeptides were investigated in the in vitro hippocampal slice following exposure to repetitive stimulation with and without the induction of long-term potentiation. Using [35S]methionine labeling of polypeptides and two-dimensional gel electrophoresis, we detected an increase in the rate of synthesis of two polypeptides (48 kDa and 89 kDa) in CA1 in response to repetitive stimulation of the Schaffer collaterals. The synthesis of the 48 kDa polypeptide (pI approximately 6.6) increased 240% in response to high-frequency stimulation (100 Hz) relative to the same protein from unstimulated slices (n = 14), and increased 220% in response to low-frequency stimulation (1 Hz) (n = 5). Blockade of the N-methyl-D-aspartate (NMDA) receptor induced the protein 180%, with no further increase following tetanic stimulation. An 89 kDa doublet (pI approximately 6.8) increased 150% following high-frequency and 140% following low-frequency stimulation. Blockade of the NMDA receptor increased this protein as well (180% of the unstimulated control) and no further increase was observed following high-frequency stimulation. Based on physicochemical and electrophysiological properties, these proteins are not identifiable as any of those previously associated with long-term potentiation or repetitive electrical stimulation.

Effects of recombinant murine interferon-gamma on pregnant mice and their fetuses.

Recombinant murine interferon-gamma (Rec-MuIFN-gamma) was administered intramuscularly to C3H/HeNCrj mice on Days 6-15 of gestation at dosage levels of 8 X 10(5), 4 X 10(6), and 2 X 10(7) u/kg/day. Dams were killed for examination of fetuses on Day 18 of gestation. Pregnant females that received 2 X 10(7) u/kg/day of Rec-MuIFN-gamma showed uterine bleeding on Days 10-15 of gestation and could not maintain their pregnancy. These dams died on Days 13-17 or were killed in extremis on Days 10-15 for examination, and therefore no fetal data were available for this group. In the 2 X 10(7) u/kg/day group, the mean absolute weights of the lung and spleen increased and the mean absolute weight of the liver, red blood cells (RBC), hematocrit, and hemoglobin decreased significantly. Surviving dams in the 8 X 10(5) and 4 X 10(6) u/kg/day groups showed significant increases in the mean absolute weights of the lung, liver, kidneys, and spleen and a decrease in platelet count. Significant increases in the weights of the heart and ovaries and decreases in RBC, hematocrit, and hemoglobin were observed in the 4 X 10(6) u/kg/day group. Histopathological examination revealed increased extramedullary hematopoiesis in the spleen of the 4 X 10(6) and 2 X 10(7) u/kg/day groups. Fetuses showed no external, visceral, or skeletal malformations and variations caused by the administration of Rec-MuIFN-gamma in any of the treated groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of beraprost sodium (TRK-100) on acetic acid-induced skin ulcer.

Effect of beraprost sodium (TRK-100), a stable PGI2 analog, on experimentally induced skin ulcer was studied in rats. An experimental skin ulcer was developed by intradermal injection of acetic acid. Injection of glacial acetic acid to the skin in the left hind leg instep of rats resulted in the necrosis of the skin, and a skin ulcer developed in 3 days. The ulcer area reached its peak on the 5th day, and recovered to its control level within 4 weeks. The effects of TRK-100 and indomethacin on the ulcer were tested. TRK-100 showed suppressive effects on the development of the ulcer. A dose of 30 micrograms/kg (p.o.) accelerated healing of the ulcer when scored macroscopically on the 9th or 15th day. At a dose of 100 micrograms/kg (p.o.), it reduced the development of the ulcer and accelerated healing with statistical significance from the 5th day and thereafter. Indomethacin also reduced the development of the ulcer and accelerated healing with statistical significance from the 7th day and thereafter. These results suggest TRK-100 may be effective on the inhibition of the development and accelerated the healing of the skin ulcer formed in various pathological states.

Host-mediated antitumor effect of interferon in nude mice transplanted with human tumor.

Mouse interferon (MuIFN) strongly suppressed the growth of human nasopharynx carcinoma (KB) transplanted into nude mice when given by subcutaneous injection around the tumor, though KB cells were insensitive not only to the antiproliferative activity of MuIFN, but also to natural killer (NK) activity in vitro. Moreover, the antitumor effect of MuIFN was not influenced by treatment with anti-asialo GM1, which eliminates NK activity in vivo. These results indicate that NK activity is not essential to the antitumor effect of IFN mediated by the host. Subcutaneous injection of MuIFN was more efficacious than intraperitoneal injection, suggesting the existence of regional tumor resistance of the host induced by IFN. The sera of mice treated with MuIFN showed no inhibitory activity on the growth of KB cells in vitro, indicating that no antiproliferative agent secondarily induced by IFN treatment is present in the serum. There was no difference between control and MuIFN-treated group in terms of the histology of tumor tissues in nude mice. An undefined host-dependent antitumor mechanism distinct from the proposed immune modulatory effect of IFN might be present.

Effects of human fibroblast interferon on human tumors transplanted into nude mice: sensitivity of human tumors to interferon.

The antitumor effect of human fibroblast interferon (HuIFN-beta) was examined using a nude mouse-human tumor xenograft group. Eight subcutaneously transplanted tumors--one line each of ovarian carcinoma, laryngeal carcinoma, carcinoma of the nasopharynx and hepatoma, and two lines each of lung carcinoma and melanoma--were used. HuIFN-beta at 1 X 10(5) IU/mouse was injected subcutaneously around the tumor or into the tumor itself. In the former case, statistically significant growth-suppressive effects were observed in one lung carcinoma (PC-12) and both melanomas (AM-1 and SK-14), but no effect was seen on the other five tumors. Further studies were made to ascertain the effects of intratumoral injections. Increased growth inhibition was observed in both melanomas (AM-1 and SK-14), but not in lung cancer (PC-12). Complete regression was seen in 3 of 8 mice carrying SK-14. The sensitivity of tumors to HuIFN-beta was correlated to the inhibitory effect of HuIFN-beta on cell division detected by histological observation.

Antitumor effect of human fibroblast interferon on the growth of human melanoma cells implanted in nude mice.

The antitumor effect of human fibroblast interferon (HuIFN-beta) on the growth of human melanoma cells (HMV-1) in vitro and in vivo was examined. In in vitro experiments, HMV-1 cells were highly sensitive to HuIFN-beta compared to other human cells. The cell growth in nude mice was also suppressed by daily administration of HuIFN-beta, depending on the dosage and administration route. The most prominent effect was obtained by intratumoral injection and a lesser therapeutic effect was achieved by subcutaneous injection around the inoculated tumor. Intraperitoneal injection of HuIFN-beta was unsuccessful. Pharmacokinetic studies of HuIFN-beta in nude mouse indicated that the three administration routes gave similar blood plasma levels and decline curves, suggesting that there is no correlation between the plasma HuIFN-beta level and the therapeutic efficacy. However, a relatively high interferon titer was detected for a long time after intratumoral injection of HuIFN-beta. Because of the species specificity of interferon and the use of the nude mouse system lacking T-cell function, the antitumor effect observed in the present study might reflect an anticellular activity of HuIFN-beta retained in the tumor region.