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Muscle regeneration depends on muscle stem cell (MuSC) activity. Myogenic regulatory factors, including myoblast determination protein 1 (MyoD), regulate the fate transition of MuSCs. However, the direct target of MYOD in the process is not completely clear. Using previously established MyoD knock-in (MyoD-KI) mice, we revealed that MyoD targets dual-specificity phosphatase (Dusp) 13 and Dusp27. In Dusp13:Dusp27double knock-out mice, the ability for muscle regeneration after injury was reduced. Moreover, single-cell RNA sequencing of MyoD-high expressing MuSCs from MyoD-KI mice revealed that Dusp13and Dusp27are expressed only in specific populations within MyoD-high MuSCs, which also express Myogenin. Overexpressing Dusp13in MuSCs causes premature muscle differentiation. Thus, we propose a model where DUSP13 and DUSP27 contribute to the fate transition of MuSCs from proliferation to differentiation during myogenesis.Graphical Abstract

Myofibers are broadly characterized as fatigue-resistant slow-twitch (type I) fibers and rapidly fatiguing fast-twitch (type IIa/IIx/IIb) fibers. However, the molecular regulation of myofiber type is not entirely understood; particularly, information on regulators of fast-twitch muscle is scarce. Here, we demonstrate that the large Maf transcription factor family dictates fast type IIb myofiber specification in mice. Remarkably, the ablation of three large Mafs leads to the drastic loss of type IIb myofibers, resulting in enhanced endurance capacity and the reduction of muscle force. Conversely, the overexpression of each large Maf in the type I soleus muscle induces type IIb myofibers. Mechanistically, a large Maf directly binds to the Maf recognition element on the promoter of myosin heavy chain 4,which encodes the type IIb myosin heavy chain, driving its expression. This work identifies the large Maf transcription factor family as a major regulator for fast type IIb muscle determination.

The absolute configuration of strongylophorine-26 (1) was determined to be 4S, 5R, 8R, 9S, 10S, 13S, 14Sby single-crystal X-ray diffraction analysis of the derivative 7prepared from the co-occurring metabolite strongylophorine-8 (4) and chemical interconversion to the bislactone 8. Synthetic analogues ()- and (−)-3have been prepared in order to explore the structure−activity relationship for the anti-invasion pharmacophore of stronglylophorine-26. These studies revealed the unanticipated importance of the A ring lactone moiety for the anti-invasion activity of 1.

Laboratory cultures of an undescribed streptomycete obtained from the surface of a British Columbia lichen produce uncialamycin (1), a new enediyne antibiotic. The structure of uncialamycin (1) has been elucidated by analysis of spectroscopic data. Uncialamycin (1) exhibits potent in vitro antibacterial activity against Gram-positive and Gram-negative human pathogens, including Burkholderia cepacia, a major cause of morbidity and mortality in patients with cystic fibrosis.

Biodiesel was prepared in various supercritical alcohol treatments with methanol, ethanol, 1-propanol, 1-butanol, or 1-octanol to study transesterification of rapeseed oil and alkyl esterification of fatty acid at temperatures of 300 and 350°C. The results showed that in transes terification, the reactivity was greatly correlated to the alcohol: the longer the alkyl chain of alcohol, the longer the reaction treatment. In alkyl esterification of fatty acids, the conversion did not depend on the alcohol type because they had a similar reactivity. Therefore, the selection of alcohol in biodiesel production should be based on consideration of its performance of properties and economics.

Although glucocorticoids (GCs) are physiologically essentialfor bone metabolism, it is generally accepted that high dosesof GCs cause bone loss through a combination of decreased boneformation and increased bone resorption. However, the actionof GCs on mature osteoclasts remains contradictory. In thisstudy, we have examined the effect of GCs on osteoclasticbone-resorbing activity and osteoclast apoptosis, by using twodifferent cell types, rabbit unfractionated bone cells andhighly enriched mature osteoclasts (>95% of purity).Dexamethasone (Dex, 10-10–10-7M) inhibited resorption pit formation on a dentine slice by the unfractionated bone cells in a dose- and time-dependent manner.However, Dex had no effect on the bone-resorbing activity of the isolated mature osteoclasts. When the isolated osteoclastswere co-cultured with rabbit osteoblastic cells, the osteoclastic bone resorption decreased in response to Dex,dependent on the number of osteoblastic cells. Like the effecton the bone resorption, Dex induced osteoclast apoptosis in cultures of the unfractionated bone cells, whereas it did not promote the apoptosis of the isolated osteoclasts. An inhibitorof caspases, Z-Asp-CH2-DCB attenuated both the inhibitory effecton osteoclastic bone resorption and the stimulatory effect onthe osteoclast apoptosis. In addition, the osteoblastic cellswere required for the osteoclast apoptosis induced by Dex. These findings indicate that the main target cells of GCs arenon-osteoclastic cells such as osteoblasts and that GCsindirectly inhibit bone resorption by inducing apoptosis ofthe mature osteoclasts through the action of non-osteoclasticcells. This study expands our knowledge about the multifunctional roles of GCs in bone metabolism.

Expression of mRNA protein tyrosine phosphatases (PTPs) was surveyed in an esophageal cancer cell line by RT-PCR using degenerate primers. The mRNAs for eight kinds of PTPs were expressed in the cell line. We examined mRNA expression of these PTPs in 12 cases of esophageal cancer by Northern analysis. Significant signals were obtained for three kinds of PTPs, PTP1B, PTPH1, and PTPD1. The magnitude of expression of each PTP was measured as the ratio of the signal intensity of each PTP to that of a control gene (NADPH), and the ratio was then compared to normal mucosa around the cancer lesion. Among the three kinds of PTPs, the expression of PTP1B mRNA was significantly depressed in cancer lesions compared with that in the surrounding normal mucosa. In contrast, the expression of PTPH1 mRNA was significantly increased in cancer lesions compared with that in normal mucosa. PTPD1 did not show any significant trend in comparisons of cancer and surrounding normal mucosa. The results suggest that PTP1B and PTPH1 are engaged in opposing signaling pathways, the tumor-suppressive and tumor-promoting pathways, respectively, in esophageal carcinogenesis.

We immunohistologically investigated 76 cases of primary colorectal cancer and 13 cases of adenoma to clarify the relationship of MHC class 11 expression with the grade of differentiation, the density of tumor-infiltrating lymphocytes, and the incidence of metastasis to lymph nodes.

Substance P receptor (SPR), which plays a key role in pain transmission, is known to undergo rapid agonist-dependent desensitization and internalization. The present study shows that human SPR undergoes agonist-dependent phosphorylation in intact cells. Immunoprecipitation of SPR from 32Pi-labeled Chinese hamster ovary cells stably expressing human SPR (CHO-hSPR) indicates that substance P (SP) causes a rapid (T1/2 < 1 min), dose-dependent (EC50 = 2 nM), and pronounced (5-fold over basal) phosphorylation of SPR. Because SPR in CHO-hSPR couples to Galphaq, Galphas, and Galphao (), we examined the involvement of various second messenger-activated protein kinases in SPR phosphorylation. Although increases in intracellular cyclic AMP or treatment with the calcium ionophore A23187 do not cause SPR phosphorylation, treatment with the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA) causes a 2.5-fold increase in SPR phosphorylation with a T1/2 of <1 min. However, PKC inhibitor GF109203X has no effect on SP-dependent SPR phosphorylation. Furthermore, although SP treatment phosphorylates SPR on both serine and threonine residues equally, PMA treatment phosphorylates the receptor predominantly on serine residues. Two-dimensional phosphopeptide mapping data indicate that SP-dependent and PMA-dependent phosphorylations of SPR have some unique differences. Taken together, these data suggest that although activation of PKC by PMA can lead to SPR phosphorylation, PKC does not mediate SP-dependent phosphorylation of SPR. In conclusion, the present study represents the first demonstration and characterization of agonist-dependent and PMA-mediated phosphorylation of SPR in intact cells.

The substance P receptor (SPR) is a G protein-coupled receptor (GPCR) that plays a key role in pain regulation. The SPR desensitizes in the continued presence of agonist, presumably via mechanisms that implicate G protein-coupled receptor kinases (GRKs) and beta-arrestins. The temporal relationship of these proposed biochemical events has never been established for any GPCR other than rhodopsin beyond the resolution provided by biochemical assays. We investigate the real-time activation and desensitization of the human SPR in live HEK293 cells using green fluorescent protein conjugates of protein kinase C, GRK2, and beta-arrestin 2. The translocation of protein kinase C betaII-green fluorescent protein to and from the plasma membrane in response to substance P indicates that the human SPR becomes activated within seconds of agonist exposure, and the response desensitizes within 30 s. This desensitization process coincides with a redistribution of GRK2 from the cytosol to the plasma membrane, followed by a robust redistribution of beta-arrestin 2 and a profound change in cell morphology that occurs after 1 min of SPR stimulation. These data establish a role for GRKs and beta-arrestins in homologous desensitization of the SPR and provide the first visual and temporal resolution of the sequence of events underlying homologous desensitization of a GPCR in living cells.

Koshikamide A1, a new cytotoxic linear peptide, was isolated from a marine sponge, Theonellasp. Its structure was elucidated by spectroscopic and chemical methods.

The substance P receptor (SPR) is a G protein-coupled receptor (GPCR) that plays a key role in pain regulation. The SPR desensitizes in the continued presence of agonist, presumably via mechanisms that implicate G protein-coupled receptor kinases (GRKs) and β-arrestins. The temporal relationship of these proposed biochemical events has never been established for any GPCR other than rhodopsin beyond the resolution provided by biochemical assays. We investigate the real-time activation and desensitization of the human SPR in live HEK293 cells using green fluorescent protein conjugates of protein kinase C, GRK2, and β-arrestin 2. The translocation of protein kinase C βII-green fluorescent protein to and from the plasma membrane in response to substance P indicates that the human SPR becomes activated within seconds of agonist exposure, and the response desensitizes within 30 s. This desensitization process coincides with a redistribution of GRK2 from the cytosol to the plasma membrane, followed by a robust redistribution of β-arrestin 2 and a profound change in cell morphology that occurs after 1 min of SPR stimulation. These data establish a role for GRKs and β-arrestins in homologous desensitization of the SPR and provide the first visual and temporal resolution of the sequence of events underlying homologous desensitization of a GPCR in living cells.

Common chickweed (Stellaria mediaVill.) is one of the major weeds in upland and orchard in Japan and has been known to be a species poorly controlled by diphenyl ether herbicides. Laboratory experiments were conducted to determine the physiological basis of the plant's tolerance to the diphenyl ether herbicide oxyfluorfen (2-chloro-4-trifluoromethylphenyl 3-ethoxy-4-nitrophenyl ether). Uptake, translocation, and metabolism of the herbicide, sensitivity of the action site, porphyrin accumulation, and tolerance to singlet oxygen in common chickweed were compared with slender amaranth (Amaranthus viridis) and large crabgrass (Digitaria adscendens), oxyfluorfen-sensitive species. Common chickweed showed a little visible herbicide injury to 10 μM of sprayed oxyfluorfen, while the herbicide significantly reduced the fresh weight of large crabgrass and slender amaranth at 1 μM. Uptake of 14C following [14C]oxyfluorfen application to the adaxial surface of the second leaf for 2 h was similar for common chickweed and large crabgrass, although the initial rate was greater in large crabgrass. No translocation of the herbicide out of the treated leaf was observed in either species. The major part of absorbed 14C was identified as unmetabolized oxyfluorfen in common chickweed and large crabgrass 24 h after application. The herbicide caused protoporphyrin IX accumulation in slender amaranth and large crabgrass. In contrast, no accumulation of the photosensitizing tetrapyrrole was observed in common chickweed. When excised leaf disks of slender amaranth and large crabgrass were treated with the herbicide, the porphyrin accumulation occurred faster than in intact plants. However, no accumulation was detected in leaf disks of common chickweed. Furthermore, vacuum infiltration of oxyfluorfen solution into the leaf disks of common chickweed did not promote the porphyrin accumulation. Protoporphyrinogen oxidase, the target enzyme of the herbicide, in common chickweed was inhibited by oxyfluorfen in vitro. The plant was also more tolerant to the singlet oxygen generating agent, rose bengal, than the susceptible species. However, tolerance of common chickweed to oxyfluorfen is considered to be due mainly to the mechanism which prevents protoporphyrin IX accumulation.

Changes in coordinated eye and hand movements with aging were studied in normal young and elderly subjects. Electrooculograms, flexor and extensor electromyograms, and potentials representing hand movements were recorded and used to evaluate the performance in aiming tasks. The parameters that reflect motor functions did not change significantly with aging in both eye and hand movements. However, elderly subjects commonly showed increases in reaction times of the initial (open-loop) movements in both eye and hand movements. Interestingly, the time increments were almost equivalent in these two functionally distinct motor systems. The durations of error-correcting (closed-loop) movements also increased significantly with aging in both motor systems. These increases suggest that the aging effects are the manifestation of impairment in the sensory process.

1. Discharges of Purkinje cells (P cells) and mossy fibres were recorded from the cerebellar flocculus of monkeys trained to fixate a stationary visual target. The units were tested with a sinusoidally moving random dot pattern (background) which was projected on an entire screen or on part of it. The receptive field organization of the units was tested by changing the area of stimulus presentation on the screen and by changing the direction of visual fixation. 2. When stimulated with sinusoidal movements of the background in the horizontal plane, ninety‐two of 684 Purkinje cells (13.5%) responded to the retinal‐slip velocity. Seventy‐eight of the ninety‐two visually responsive Purkinje cells (84.8%) also showed cyclic modulations in activity during horizontal smooth‐pursuit eye movements (these were so‐called horizontal gaze‐velocity Purkinje cells). 3. In response to the sinusoidal retinal‐slip velocity, the visual Purkinje cells showed six types of discharge patterns. Type 1 Purkinje cells (28/92 or 30.4%) were directionally selective: they showed a peak activity during background movement in one direction and a trough in the other. Both peaks and troughs were related to stimulus velocities. Their receptive fields were relatively large (greater than 45 deg) and included the fovea. 4. Type 2 (8/92 or 8.7%) and type 3 (5/92 or 5.4%) Purkinje cells showed sinusoidal responses similar to those of type 1 Purkinje cells, but the visual inputs were primarily excitatory in type 2 Purkinje cells and inhibitory in type 3 Purkinje cells. Only the peaks in type 2 and troughs in type 3 were related to stimulus velocities. 5. Type 4 (4/92 or 4.3%) and type 5 (11/92 or 12.0%) Purkinje cells showed responses to stimulus movements in both directions (bidirectional). When the moving background was projected with 10 deg of fixation, type 4 Purkinje cells were excited bidirectionally in relation to retinal‐slip velocities. When the periphery of either hemiretina was stimulated, type 5 Purkinje cells were inhibited and the trough activity was stimulus‐velocity dependent. Receptive fields were found in the ipsilateral hemiretinae in seven type 5 Purkinje cells and in the contralateral hemiretinae in the remaining four type 5 Purkinje cells. 6. Type 6 (36/92 or 39.1% Purkinje cells received an excitatory input from the central retina and an inhibitory input from the periphery. The peripheral receptive fields were either in the ipsilateral (69.4%) or contralateral (30.6%) hemiretinae of both eyes.(ABSTRACT TRUNCATED AT 400 WORDS)

Abstract: Osteolysis associated with artificial joint arthroplasty seems to be the result of particles of wear debris (from ultra-high molecular weight polyethylene (UHMWPE), polymethylmethacrylate (PMMA), and metals), causing a macrophage response, Silicon particles, as residual contaminants embedded in the surface of both textured metal implants and polyethylene sockets, may be a factor in osteolysis. We present the case of a 57-year-old woman who had massive and aggressive osteolysis. The osteolytic lesion was isolated in the greater trochanter region 5 years after she had had primary cementless total hip arthroplasty (Cobalt-chromium alloy). There were no signs of mechanical loosening, but she experienced moderate pain. Under a polarized microscope and scanning electron micrography, a biopsied specimen from the osteolytic lesion revealed conglomerates of UHMWPE particles of various sizes between proliferated synovium-like cells. Quantative energy-dispersive X-ray analysis focused on the conglomerates of UHMPWE particles demonstrated a marked presence of silicon. Although the definitive causative factor for a the osteolysis was regarded as a foreign-body reaction induced by UHMWPE particles, the presence of silicon was interesting in terms of the pathogenesis of osteolysis associated with artificial joint surgery.

A computed tomographic method for analyzing the shrinkage of the basis pedunculi (BP) due to the secondary degeneration of the descending fibers was applied in correlation to the site of cerebral lesions in 89 chronic hemiplegic patients. Cerebral lesions in the anterior coronar radiata or the anterior limb of the capsula interna caused shrinkage of the medial BP. Lesions in the central corona radiata or the genu and posterior limb of the capsula interna caused shrinkage of the central BP, while lesions of the posterior corona radiata or the posterior limb of the capsula interna caused shrinkage of the lateral BP. These results suggested that CT images are able to reveal the principle sites of atrophy of the descending fiber tracts in chronic hemiplegia.

The intraperitoneal injection of glycogen in the mouse resulted, shortly thereafter, in the accumulation of 14–23 million neutrophils in the peritoneal cavity and a four-fold increase in the numbers of circulating neutrophils. Preceding the influx of leukocytes, the exudation of plasma proteins and the chemotactic activity for mouse neutrophil in vitro increased in the peritoneal fluid. Among various protease inhibitors examined, chymostatin alone suppressed the plasma protein exudation. Indomethacin and dexamethasone reduced the accumulation of white cells and protein exudation. These nonsteroidal and steroidal antiinflammatory drugs were equally effective whether given simultaneously with or 60 min before glycogen or whether administered intraperitoneally or orally. Colchicine showed a suppressive effect on the leukocyte accumulation but enhanced the protein exudation.

The activity of phospholipase inhibitory protein, lipomodulin, partially purified from rabbit neutrophils, was markedly decreased after treatment with sera from patients with rheumatic diseases such as systemic lupus erythematosus, rheumatoid arthritis, and dermatomyositis. The decrease of the protein's inhibitory activity on phospholipase A2 paralleled the amount of [35S]methionine-labeled lipomodulin precipitated by the sera. Absorption of patients' sera with anti-human IgM (mu chain) or protein A-agarose, but not with anti-human IgG (gamma chain), decreased their ability to decrease the activity of lipomodulin on phospholipase A2 or to precipitate the radioactive lipomodulin. The IgM fraction of patients' sera could precipitate [35S]methionine-labeled lipomodulin (40,000 daltons) which comigrated with highly purified lipomodulin on gel electrophoresis with sodium dodecyl sulfate. All of these observations suggest that the sera of many patients with rheumatic diseases contain autoantibody against lipomodulin. A monoclonal antibody against lipomodulin was also obtained. Stimulating human fibroblasts with bradykinin in the presence of monoclonal antilipomodulin antibody markedly enhanced arachidonic acid release due to the activation of phospholipase(s) in the intact cells, and this stimulatory effect was blocked by adding purified lipomodulin. These findings suggest that lipomodulin regulates the activity of phospholipase(s) on the cell surface and that autoantibodies against lipomodulin may play a role in certain symptoms of rheumatic diseases, especially by the formation of prostaglandins and other metabolites of arachidonic acid.

1. Discharges of Purkinje cells and mossy fibres were recorded from the flocculus of monkeys trained to fixate a small visual target and to track the target when it moved slowly.

Osteolysis associated with artificial joint arthroplasty seems to be the result of particles of wear debris (from ultra-high molecular weight polyethylene (UHMWPE), polymethylmethacrylate (PMMA), and metals), causing a macrophage response. Silicon particles, as residual contaminants embedded in the surface of both textured metal implants and polyethylene sockets, may be a factor in osteolysis. We present the case of a 57-year-old woman who had massive and aggressive osteolysis. The osteolytic lesion was isolated in the greater trochanter region 5 years after she had had primary cementless total hip arthroplasty (Cobalt-chromium alloy). There were no signs of mechanical loosening, but she experienced moderate pain. Under a polarized microscope and scanning electron micrography, a biopsied specimen from the osteolytic lesion revealed conglomerates of UHMWPE particles of various sizes between proliferated synovium-like cells. Quantitative energy-dispersive X-ray analysis focused on the conglomerates of UHMWPE particles demonstrated a marked presence of silicon. Although the definitive causative factor for a 1he osteolysis was regarded as a foreign-body reaction induced by UHMWPE particles, the presence of silicon was interesting in terms of the pathogenesis of osteolysis associated with artificial joint surgery.

Strongylophorine-26 (1), a new meroditerpenoid that shows activity in an anti-invasion assay, has been isolated from the marine sponge Petrosia (Strongylophora) corticata collected in Papua New Guinea. The structure of 1 was elucidated by analysis of spectroscopic data.

Optical absorption efficiency of graphene integrated onto a silicon photonic platform was characterized at around 1.55-μm optical telecommunications wavelength. Micro-Raman spectroscopy performed after the completion of all fabrication processes confirmed that transferred chemical-vapor-deposited graphene is a single layer (${>}90$% coverage) without any significant damage. Absorption efficiencies of the single-layer graphene (SLG) on a silicon wire waveguide, obtained by measuring different lengths (cutback method) of the SLG from 2.5 to 200 μm, were 0.09 and 0.05 dB/μm for TE- and TM-polarized light. The unusual relationship in the polarization dependency can be explained by strong surface-plasmon-porlariton support in the TM mode.

Optical absorption efficiency of graphene integrated onto a silicon photonic platform was characterized at around 1.55-um optical telecommunications wavelength. Micro-Raman spectroscopy performed after the completion of all fabrication processes confirmed that transferred chemical-vapor-deposited graphene is a single layer (>90% coverage) without any significant damage. Absorption efficiencies of the single-layer graphene (SLG) on a silicon wire waveguide, obtained by measuring different lengths (cutback method) of the SLG from 2.5 to 200 um, were 0.09 and 0.05 dB/um for TE- and TM-polarized light. The unusual relationship in the polarization dependency can be explained by strong surface-plasmon-porlariton support in the TM mode.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Changes in coordinated eye and hand movements associated with the progress of bradykinesia were studied in 31 parkinsonian patients and 8 age-matched healthy subjects. Among the parameters expressing the changes in motor behaviour, the interval between the onset of eye and hand movements was most sensitive. This parameter reflected the difference in the progress of the symptom in the two motor systems. An increase in the reaction time of the hand response appeared in patients of grade II bradykinesia; this was observed for eye movements only in patients with grade III (severe) bradykinesia. While the changes in ocular reaction time remained within the physiological range, a lengthening of the reaction time, a reduction in peak velocity, a decrease in the open-loop gain, a prolongation of movement duration, and a slow build-up in EMG activity, appeared from an early stage in hand movement. These signs of motor disturbance may appear eventually in every motor system at an advanced stage, but their development is not synchronous in different motor systems. An analysis of the responses recorded simultaneously from the two motor systems examined made it possible to evaluate the changes in the sensorimotor processes with different grades of bradykinesia A comparison between reaction times for eye and hand movements may be useful for assessing the degree of bradykinesia in parkinsonian patients.

The severity of the disorder of voluntary movement in 89 chronic hemiparetic patients was correlated with the degenerative reduction of descending fibres evaluated by the magnitude of the shrinkage of the cerebral peduncles (CP) in computed tomographic (CT) images. The severity of hemiplegic posture and motor disturbance in the proximal and distal muscles was related to the total amount of residual descending fibres in the CP. In all patients whose CPs were less than 60% of the normal size, recovery from disturbance in reaching and grasping movements and impairment of relative independent finger movements was incomplete. Recovery of these movements occurred when more than 60% of the CP was spared and the degree of recovery from motor weakness was positively correlated with the quantity of intact fibres spared (residual CP ratio). The ability to perform fine and discrete movements with the fingers, known to be an essential function of the pyramidal system, was consistently impaired in patients with severe shrinkage involving the medial division of the CP. There was no particular correlation between the CP shrinkage and neurological signs such as spasticity, hyperreflexia, and pathological reflexes.

Fundamental differences in bradykinesia in parkinsonian patients and nonparkinsonian elderly subjects were analysed. Our method was an aiming task in which the coordination of eye and hand movements was measured when the subject attempted to catch up with a visual target. The coordinated eye and hand movements started towards the target almost simultaneously in the normal subjects when the target was in the periphery of the visual area. The initial abnormality in parkinsonian patients was an isolated delay of coordinated hand movement. In the typical bradykinetic patients, the hand movement did not start while the target was still in the peripheral visual area but only when the image of the target was near or on the fovea. The aiming tasks were then performed step by step following visual confirmation. Thus patients with typical bradykinesia showed a failure of ballistic hand movement preprogrammed to the visual target in the peripheral visual area, and the strategy of coordination was changed. In contrast, the disturbance of the ballistic hand movement in the nonparkinsonian elderly subjects had no consistent strategy for coordination of the visually guided eye and hand movements.