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Biomedical subjects

J Fukushima

Publications and source records attributed to J Fukushima.

At least 19 recordsLinked to original sources

Unusual imaging appearances of pancreatic serous cystadenoma: correlation with surgery and pathologic analysis.

BACKGROUND: We describe imaging and pathologic features of serous cystadenoma of the pancreas on multislice helical computed tomography CT (MS-CT) and surgical resection. METHODS: Radiologic and pathologic features were analyzed in five patients. All patients underwent MS-CT and digital subtraction angiography (DSA), and four patients underwent magnetic resonance (MR) imaging. Preoperatively, three cases showed radiologic evidence of mainly solid appearance on MS-CT, and the suspected diagnoses were solid pancreatic tumors (patients 1-3). The other two cases showed radiologic evidence of macrocystic tumor of the pancreas, and the suspected diagnoses were mucinous cystic tumors (cases 4 and 5). All patients underwent surgery, and the diagnosis of serous cystadenoma was confirmed on pathologic examination. RESULTS: In three cases that showed a solid appearance on MS-CT, a microcystic appearance was identified on microscopic examination, and the tumors were found to be hypervascular lesions on multiphasic contrast-enhanced CT and DSA. In cases 1 and 2, the lesions showed high intensity with internal septation on T2-weighted MR images. In two cases, the tumors were classified as a macrocystic variant of serous cystadenoma, and no mural nodules, papillary projections, or calcifications were seen in the tumors. CONCLUSION: Imaging appearance of serous cystadenoma on MS-CT is various and sometimes indistinguishable from that of solid tumor or mucinous cystic tumors of the pancreas. Imaging findings of hypervascularity and a well-marginated high-intensity lesion with internal septation on T2-weighted MR imaging may be crucial to identify serous cystadenoma that contains no visible cystic compartments on MS-CT.

Adult↗

Prevalence of CD99 protein expression in pancreatic endocrine tumours (PETs).

AIMS: To determine the prevalence of CD99 expression in pancreatic endocrine tumours (PETs). We evaluated CD99 expression and analysed Ki67 labelling by immunohistochemistry in PETs. METHODS AND RESULTS: Thirty-eight PETs from 33 patients were analysed. CD99 immunoreactivity was consistently observed in normal islets of the pancreas, regardless of the cell type. Tumours comprising more than 30% CD99+ cells were defined as positively immunoreactive for CD99. CD99 expression was observed in 20 of the 38 PETs examined, but not in any of the pancreatic tumours of other histological subtypes (10 ductal adenocarcinomas, five intraductal papillary-mucinous tumours, and two acinar cell tumours). Loss of CD99 expression was related to markers of worse prognosis for PET, including gross local invasion, metastasis to the lymph nodes or other organs, lymphatic or blood vessel invasion, and neuroendocrine carcinoma (NEC). Thus, CD99 expression may have an efficiency comparable to that of high Ki67 labelling index (5% or more) for prognostication. CONCLUSIONS: CD99 expression was observed frequently and exclusively in PETs, and loss of CD99 expression in PETs was found to be associated with ominous prognostic indicators.

12E7 Antigen↗

Directional asymmetry in smooth ocular tracking in the presence of visual background in young and adult primates.

The smooth pursuit system moves the eyes in space accurately while compensating for visual inputs from the moving background and/or vestibular inputs during head movements. To understand the mechanisms underlying such interactions, we examined the influence of a stationary textured visual background on smooth pursuit tracking and compared the results in young and adult humans and monkeys. Six humans (three children, three adults) and six macaque monkeys (five young, one adult) were used. Human eye movements were recorded using infrared oculography and evoked by a sinusoidally moving target presented on a computer monitor. Scleral search coils were used for monkeys while they tracked a target presented on a tangent screen. The target moved in a sinusoidal or trapezoidal fashion with or without whole body rotation in the same plane. Two kinds of backgrounds, homogeneous and stationary textured, were used. Eye velocity gains (eye velocity/target velocity) were calculated in each condition to compare the influence of the textured background. Children showed asymmetric eye movements during vertical pursuit across the textured (but not the homogeneous) background; upward pursuit was severely impaired, and consisted mostly of catch-up saccades. In contrast, adults showed no asymmetry during pursuit across the different backgrounds. Monkeys behaved similarly; only slight effects were observed with the textured background in a mature monkey, whereas upward pursuit was severely impaired in young monkeys. In addition, VOR cancellation was severely impaired during upward eye and head movements, resulting in residual downward VOR in young monkeys. From these results, we conclude that the directional asymmetry observed in young primates may reflect a different neural organization of the vertical, particularly upward, pursuit system in the face of conflicting visual and vestibular inputs that can be associated with pursuit eye movements. Apparently, proper compensation matures later.

Adult↗

EBAG9/RCAS1 expression in hepatocellular carcinoma: correlation with tumour dedifferentiation and proliferation.

The oestrogen-responsive gene, EBAG9, whose product is identical to the cancer cell surface antigen RCAS1, is reported to be associated with tumour progression and invasiveness in various carcinomas. In this study, we examined the expression of EBAG9/RCAS1 in hepatocellular carcinoma (HCC), with special reference to its relationship with the stepwise evolution of HCC. Expression was examined by immunohistochemistry and western blotting analysis in 143 HCCs, as well as in non-cancerous liver tissues. After which, the association between enhanced EBAG9/RCAS1 expression and various clinicopathological parameters including Ki-67 labelling index (LI), a marker of proliferative activity, was evaluated. There was a constant low level of EBAG9/RCAS1 expression in non-cancerous liver tissues, with a regular cytoplasmic distribution. Positive immunoreactivity for EBAG9/RCAS1 was detected on the surface and in the cytoplasm of 84 HCC tumours, with an irregular staining pattern. Enhanced EBAG9/RCAS1 expression was correlated with a lower degree of differentiation and Ki-67 LI. Interestingly, expression was enhanced specifically in the less differentiated lesions within 'nodule-in-nodule' tumours. In conclusion, EBAG9/RCAS1 was associated with HCC tumour dedifferentiation and increased proliferative activity. Its exact functional role remains to be established.

Adolescent↗

Human L-type amino acid transporter 1 (LAT1): characterization of function and expression in tumor cell lines.

System L is a major nutrient transport system responsible for the transport of large neutral amino acids including several essential amino acids. We previously identified a transporter (L-type amino acid transporter 1: LAT1) subserving system L in C6 rat glioma cells and demonstrated that LAT1 requires 4F2 heavy chain (4F2hc) for its functional expression. Since its oncofetal expression was suggested in the rat liver, it has been proposed that LAT1 plays a critical role in cell growth and proliferation. In the present study, we have examined the function of human LAT1 (hLAT1) and its expression in human tissues and tumor cell lines. When expressed in Xenopus oocytes with human 4F2hc (h4F2hc), hLAT1 transports large neutral amino acids with high affinity (K(m)= approximately 15- approximately 50 microM) and L-glutamine and L-asparagine with low affinity (K(m)= approximately 1.5- approximately 2 mM). hLAT1 also transports D-amino acids such as D-leucine and D-phenylalanine. In addition, we show that hLAT1 accepts an amino acid-related anti-cancer agent melphalan. When loaded intracellularly, L-leucine and L-glutamine but not L-alanine are effluxed by extracellular substrates, confirming that hLAT1 mediates an amino acid exchange. hLAT1 mRNA is highly expressed in the human fetal liver, bone marrow, placenta, testis and brain. We have found that, while all the tumor cell lines examined express hLAT1 messages, the expression of h4F2hc is varied particularly in leukemia cell lines. In Western blot analysis, hLAT1 and h4F2hc have been confirmed to be linked to each other via a disulfide bond in T24 human bladder carcinoma cells. Finally, in in vitro translation, we show that hLAT1 is not a glycosylated protein even though an N-glycosylation site has been predicted in its extracellular loop, consistent with the property of the classical 4F2 light chain. The properties of the hLAT1/h4F2hc complex would support the roles of this transporter in providing cells with essential amino acids for cell growth and cellular responses, and in distributing amino acid-related compounds.

Amino Acid Transport Systems↗

Adaptive changes in smooth pursuit eye movements induced by cross-axis pursuit-vestibular interaction training in monkeys.

The smooth pursuit system interacts with the vestibular system to maintain the accuracy of eye movements in space. To understand neural mechanisms of short-term modifications of the vestibulo-ocular reflex (VOR) induced by pursuit-vestibular interactions, we used a cross-axis procedure in trained monkeys. We showed earlier that pursuit training in the plane orthogonal to the rotation plane induces adaptive cross-axis VOR in complete darkness. To further study the properties of adaptive responses, we examined here the initial eye movements during tracking of a target while being rotated with a trapezoidal waveform (peak velocity 30 or 40 degrees/s). Subjects were head-stabilized Japanese monkeys that were rewarded for accurate pursuit. Whole body rotation was applied either in the yaw or pitch plane while presenting a target moving in-phase with the chair with the same trajectory but in the orthogonal plane. Eye movements induced by equivalent chair rotation with or without the target were examined before and after training. Before training, chair rotation alone resulted only in the collinear VOR, and smooth eye movement-tracking of orthogonal target motion during rotation had a normal smooth pursuit latency (ca 100 ms). With training, the latency of orthogonal smooth tracking eye movements shortened, and the mean latency after 1 h of training was 42 ms with a mean gain, at 100 ms after stimulus onset, of 0.4. The cross-axis VOR induced by chair rotation in complete darkness had identical latencies with the orthogonal smooth tracking eye movements, but its gains were <0.2. After cross-axis pursuit training, target movement alone without chair rotation induced smooth pursuit eye movements with latencies ca 100 ms. Pursuit training alone for 1 h using the same trajectory but without chair rotation did not result in any clear change in pursuit latency (ca 100 ms) or initial eye velocity. When a new target velocity was presented during identical chair rotation after training, eye velocity was correspondingly modulated by just 80 ms after rotation onset, which was shorter than the expected latency of pursuit (ca 100 ms). These results indicate that adaptive changes were induced in the smooth pursuit system by pursuit-vestibular interaction training. We suggest that this training facilitates the response of pursuit-related neurons in the cortical smooth pursuit pathways to vestibular inputs in the orthogonal plane, thus enabling smooth eye movements to be executed with shorter latencies and larger eye velocities than in normal smooth pursuit driven only by visual feedback.

Adaptation, Physiological↗

Activation of HIV-1-specific immune responses to an HIV-1 vaccine constructed from a replication-defective adenovirus vector using various combinations of immunization protocols.

We constructed a recombinant replication defective adenovirus vector containing the env gene (Ad-Bal) derived from macrophage-trophic HIV-1 (HIV-1 Bal). We then immunized mice with this vector using several administration routes and protocols, and examined the immune response. When the Ad-Bal viral vector (over 1 x 10(7) pfu) was injected subcutaneously, both humoral and cell-mediated immunities were induced. However, immune response induced by the Ad-Bal vector alone was weaker than that induced by the recombinant vaccinia viral vector. We then employed the following three immunization protocols: (l) DNA vaccination followed by immunization with the Ad-Bal; (2) vaccination using the Ad-Bal vector followed by DNA vaccination; and (3) DNA vaccination followed by Ad-Bal infection and passive transfer of dendritic cells (DCs) infected with the Ad-Bal. Among the three protocols, the last gave the strongest humoral and cell-mediated immunity. These results suggest that the combination of DNA vaccination, Ad-Bal vector infection and passive transfer of Ad-Bal-infected DCs can induce strong immunity against HIV-1 Bal.

AIDS Vaccines↗

Human cystinuria-related transporter: localization and functional characterization.

BACKGROUND: Cystinuria has been proposed to be an inherited defect of apical membrane transport systems for cystine and basic amino acids in renal proximal tubules. Although the mutations of the recently identified transporter BAT1/b(0,+)AT have been related to nontype I cystinuria, the function and localization of human BAT1 (hBAT1)/b(0,+)AT have not been well characterized. METHODS: The cDNA encoding hBAT1 was isolated from human kidney. Fluorescence in situ hybridization was performed to map the hBAT1 gene on human chromosomes. Tissue distribution and localization of expression were examined by Northern blot and immunohistochemical analyses. hBAT1 cDNA was transfected to COS-7 cells with rBAT cDNA, and the uptake and efflux of 14C-labeled amino acids were measured to determine the functional properties. The roles of protein kinase-dependent phosphorylation were investigated using inhibitors or activators of protein kinases. RESULTS: The hBAT1 gene was mapped to 19q12-13.1 on the human chromosome, which is the locus of nontype I cystinuria. hBAT1 message was expressed predominantly in kidney. hBAT1 protein was localized in the apical membrane of proximal tubules in human kidney. When expressed in COS-7 cells with a type II membrane glycoprotein rBAT (related to b(0,+)-amino acid transporter), hBAT1 exhibited the transport activity with the properties of amino acid transport system b(0,+), which transported cystine as well as basic and neutral amino acids presumably via a substrate exchange mechanism. BAT1-mediated transport was reduced by the protein kinase A activator and enhanced by the tyrosine kinase inhibitor. CONCLUSIONS: hBAT1 exhibited the properties expected for a transporter subserving the high-affinity cystine transport system in renal proximal tubules. The hBAT1 gene was mapped to the locus of nontype I cystinuria, confirming the involvement of hBAT1 in cystinuria.

ATP-Binding Cassette Transporters↗

Activation of alveolar macrophages in acid-injured lung in rats: different effects of pentoxifylline on tumor necrosis factor-alpha and nitric oxide production.

OBJECTIVE: To determine whether acid instillation augments tumor necrosis factor-alpha and nitric oxide production by alveolar macrophages in rats, and to study the effects of treatment with pentoxifylline before acid instillation on the production of these inflammatory mediators. DESIGN: Controlled laboratory investigation on tumor necrosis factor-alpha and nitric oxide production by alveolar macrophages of rats that had acid-induced lung injury. SETTING: University research laboratory. SUBJECT: Alveolar macrophages of rats. INTERVENTIONS: Alveolar macrophages were recovered by bronchoalveolar lavage at 4, 10, 16, 24, and 72 hrs after unilateral hydrochloric acid (pH, 1.0; volume, 0.1 mL) instillation into the lungs of rats. Alveolar macrophages then were cultured with or without lipopolysaccharide. One group of rats was pretreated with pentoxifylline before acid instillation. MEASUREMENTS AND MAIN RESULTS: Alveolar macrophages from both acid-instilled and contralateral lungs, which had recovered 24 hrs after acid instillation, produced significantly greater tumor necrosis factor-alpha and nitric oxide. Subsequent exposure to lipopolysaccharide, as a surrogate for bacterial infection, further promoted tumor necrosis factor-alpha and nitric oxide release. Alveolar macrophages from rats pretreated with pentoxifylline before acid instillation produced significantly less tumor necrosis factor-alpha and did not overproduce tumor necrosis factor-alpha when exposed to lipopolysaccharide. In contrast, pretreatment with pentoxifylline had no effect on nitric oxide production by alveolar macrophages. CONCLUSIONS: Acid instillation stimulates alveolar macrophages to produce tumor necrosis factor-alpha and nitric oxide. Pentoxifylline preserved innate production of tumor necrosis factor-alpha to lipopolysaccharide and did not inhibit the production of bactericidal nitric oxide. This may partly explain why pentoxifylline reduces acid aspiration-induced lung injury while maintaining the host's ability to combat bacterial infection after acid aspiration.

Animals↗

Iron-Mediated regulation of alkaline proteinase production in Pseudomonas aeruginosa.

We analyzed the regulation by iron of alkaline proteinase (AP) production in Pseudomonas aeruginosa. Extracellular AP production was detected from the mid-logarithmic to the stationary phase by an antibody-based assay system, and was strongly repressed by iron in the medium. This repression was shown by Northern hybridization and primer extension to occur at the level of transcription. The primer extension analysis revealed that the start point of transcription of AP gene was the nucleotide position -84 from the start point of translation. Furthermore, we investigated whether this transcriptional repression involved PvdS protein. Using the mutant strain of pvdS, the alternative sigma factor gene revealed that the PvdS protein is required for the full expression of AP, and a previous study showed that expression of pvdS is also repressed by iron. Therefore, we thought that one mechanism of repression of AP production operated through reduction of the PvdS protein level. Purified AP decomposed the transferrin, and released iron from it. Purified AP added to the medium containing transferrin as the only iron source enhanced the growth of P. aeruginosa. Moreover, mutation in the AP gene decreased the growth rate in the medium containing the transferrin as the only iron source. These results clearly indicated that AP expression should occur in a free-iron-deficient environment and emphasized the importance of AP to iron acquisition in the infection site.

Apoproteins↗

Adaptive eye movements induced by cross-axis pursuit--vestibular interactions in trained monkeys.

We showed previously that smooth pursuit training combined with whole-body rotation in the orthogonal plane induces adaptive cross-axis vestibulo-ocular reflex (VOR). To gain an insight into the possible pathways and the nature of error signals for cross-axis VOR adaptation, we examined further properties of adaptive responses. In the first series, we trained monkeys for vertical pursuit during sinusoidal yaw rotation at 0.5 Hz (+/- 10 degrees) by presenting a target spot either in phase with, or with phase shifts (lead or lag) of 90 degrees to, the chair for 1 h. After training, sinusoidal or trapezoidal yaw rotation was tested in complete darkness without a target. Different training conditions resulted in different amounts of phase shift in cross-axis VOR. Trapezoidal yaw rotation (peak acceleration approximately 780 degrees/s2) revealed further differences in the direction, latency and time course of the adaptive responses depending on the conditions of the pursuit task. At least two (fast and slow) components with different latencies were induced in the cross-axis VOR by trapezoidal rotation after in-phase and phase-shift training. Adaptive responses were accurately simulated by the weighted sum of these two components. In the second series, we examined the effects of sequentially flashed (10 microseconds) targets in the horizontal plane during pitch rotation. The monkeys learned to track such targets by smooth pursuit, and cross-axis VOR was also induced after such apparent motion stimuli without retinal slip of the target image. These results indicate the importance of eye velocity for cross-axis VOR and suggest that this adaptation occurs most probably in the smooth pursuit pathways.

Adaptation, Physiological↗

Rapidly progressive aphasia and motor neuron disease: a clinical, radiological, and pathological study of an autopsy case with circumscribed lobar atrophy.

This report concerns an autopsy case of rapidly progressive aphasia and motor neuron disease. The patient was a Japanese woman who was 75 years old at the time of death. The family history did not reveal hereditary burden. She developed language disturbances and difficulty in swallowing at age 74. Neurological examination 1 month after the disease onset revealed motor aphasia without dementia and bulbar sign, followed by muscle weakness of the four extremities. Neuroradiological examination revealed progressive atrophy of the anterior part of the left temporal lobe. She died of respiratory difficulty 10 months after the disease onset. Macroscopically, neuropathological examination showed circumscribed atrophy of the left perisylvian region and, histologically, neuronal loss in the cerebral cortex, including the primary motor area, substantia nigra, brain stem motor nuclei, and anterior horns of the spinal cord, in addition to obvious degeneration of the pyramidal tracts and presence of Bunina bodies. Ubiquitin-immunoreactive neuronal inclusions were present in the hippocampal dentate granular cells and frontotemporal cortical layer II neurons. Based on these clinicopathological findings and a review of the literature, we concluded that our case is the first reported case of amyotrophic lateral sclerosis with dementia that clinically showed rapidly progressive aphasia.

Aged↗

Development of voluntary control of saccadic eye movements. I. Age-related changes in normal children.

To investigate the development of the voluntary control of saccadic eye movement, we examined eye movements in 99 normal children (4-13 years of age). Subjects were asked to fixate a central light for 3-5 s. A target was then presented, either to its right or left. In visually guided saccades, the mean latencies of the child group were longer than those of the adults, and decreased with age until the age of 12 where they reached adult levels. On the other hand, their peak saccadic velocities were not different from those of the adults. In the antisaccade task, they showed a higher rate of directional errors, indicating an inability to suppress reflexive saccades to the target. Mean latencies of correct antisaccades were significantly longer in the children than in the adults. Error rates and antisaccadic latency tended to decrease with age. We also examined the effects of an auditory warning signal during the fixation period and compared the results with those without. The warning stimulus was less effective in children than in adults in both tasks. Similar peak saccadic velocities between children and adults suggest the earlier development of the saccadic burst generator in the brainstem. In contrast, the delayed development of latency of saccades and antisaccades and the error rates of antisaccades suggest delayed maturation of the cerebral cortex, particularly the frontal association areas that are involved in both eye movement control and attentional processes.

Acoustic Stimulation↗

Th1-biased immune responses induced by DNA-based immunizations are mediated via action on professional antigen-presenting cells to up-regulate IL-12 production.

The efficacy of DNA-based immunization in conferring protective immunity against certain microbial pathogens including human immunodeficiency virus type 1 (HIV-1) has been described. The potential advantage of DNA-based immunization over the traditional vaccines largely results from its capacity to efficiently induce Th1-biased immune responses against an encoded antigen. We describe how Th1-biased immune responses are induced by DNA-based immunization, using a DNA vaccine construct encoding HIV-1 gp160 cDNA and an eukaryotic expression plasmid carrying murine IFN-gamma cDNA. Transfection of an eukaryotic expression plasmid carrying immunostimulatory sequences (ISS) as well as a gene of interest (DNA vaccine) into professional antigen presenting cells (APC) induced transactivation of IL-12 mRNA, which resulted in antigen-specific Th1-biased immune responses against the encoded antigen. Th1-biased immune responses induced by DNA-based immunization were substantially upregulated by a codelivery of an ectopic IFN-gamma expression system, and this augmentation was mediated via action on professional antigen presenting cells to upregulate IL-12 production. Taken together, it appears likely that Th1-biased immune responses induced by DNA-based immunization are mediated via action on professional antigen-presenting cells to produce IL-12. Interestingly, the model provided strikingly resembles that previously described in infection with Listeria monocytogenes, an intracellular Gram-positive bacterium that induces strong Th1-biased immune responses. The result suggests that DNA-based immunization mimics certain aspects of natural infection with microbial organisms like attenuated vaccines, which in turn provides a rationale to the question of why DNA-based immunization so efficiently induces protective immunity against these microbial pathogens.

AIDS Vaccines↗

Activity of smooth pursuit-related neurons in the monkey periarcuate cortex during pursuit and passive whole-body rotation.

Smooth pursuit and vestibularly induced eye movements interact to maintain the accuracy of eye movements in space (i.e., gaze). To understand the role played by the frontal eye fields in pursuit-vestibular interactions, we examined activity of 110 neurons in the periarcuate areas of head-stabilized Japanese monkeys during pursuit eye movements and passive whole-body rotation. The majority (92%) responded with the peak of their modulation near peak stimulus velocity during suppression of the vestibuloocular reflex (VOR) when the monkeys tracked a target that moved with the same amplitude and phase and in the same plane as the chair. We classified pursuit-related neurons (n = 100) as gaze- velocity if their peak modulation occurred for eye (pursuit) and head (VOR suppression) movements in the same direction; the amplitude of modulation during one less than twice that of the other; and modulation was lower during target-stationary-in-space condition (VOR x1) than during VOR suppression. In addition, we examined responses during VOR enhancement (x2) in which the target moved with equal amplitude as, but opposite direction to, the chair. Gaze-velocity neurons responded maximally for opposite directions during VOR x2 and suppression. Based on these criteria, the majority of pursuit-related neurons (66%) were classified as gaze-velocity with preferred directions uniformly distributed. Because the majority of the remaining cells (32/34) also responded during VOR suppression, they were classified as eye/head-velocity neurons. Thirteen preferred pursuit and VOR suppression in the same direction; 13 in the opposite direction, and 6 showed biphasic modulation during VOR suppression. Eye- and gaze-velocity sensitivity of the two groups of cells were similar; mean (+/- SD) was 0.53 +/- 0.30 and 0.50 +/- 0.44 spikes/s per degrees /s, respectively. Gaze-velocity (but not eye/head-velocity) neurons showed significant correlation between eye- and gaze-velocity sensitivity, and both groups maintained their responses when the tracking target was extinguished briefly. The majority of pursuit-related neurons (28/43 = about 65%) responded to chair rotation in complete darkness. When the monkeys fixated a stationary target, more than half of cells tested (21/40) discharged in proportion to the velocity of retinal motion of a second laser spot (mean velocity sensitivity = 0.20 +/- 0.16 spikes/s per degrees /s). Preferred directions of individual cells to the second spot were similar to those during pursuit. Visual responses to the second spot movement were maintained even when it was extinguished briefly. These results indicate that both retinal image- and gaze-velocity signals are carried by single periarcuate pursuit-related neurons, suggesting that these signals can provide target-velocity-in-space and gaze-velocity commands during pursuit-vestibular interactions.

Animals↗

Cross axis VOR induced by pursuit training in monkeys: further properties of adaptive responses.

We have shown recently in alert monkeys that repeated interaction between the pursuit and vestibular systems in the orthogonal plane induces adaptive changes in the VOR. To examine further properties of adaptive cross axis VOR induced by pursuit training, sinusoidal whole body rotation was applied either in the pitch or yaw plane while presenting a target spot that moved orthogonally to the rotation plane with either 90 degrees phase-lead or 90 degrees phase-lag to the chair signal. After one hour of training at 0.5 Hz (+/- 10 degrees), considerable phase-shift was observed in orthogonal eye movement responses consistent with the training paradigms by identical chair rotation in complete darkness, with further lead at lower frequencies and lag at higher frequencies. However, gains (eye/chair) induced by phase- shift pursuit training was different during pitch and yaw rotation. Although frequency tuning was maintained during pitch in the phase-shift paradigms, it was not maintained during yaw, resulting in higher gains at lower stimulus frequencies compared to the gains during yaw. This difference may reflect otolith contribution during pitch rotation. To understand further the nature of signals that induce adaptive cross axis VOR, we examined interaction of pursuit, whole field-visual pattern and vestibular stimuli. Magnitudes of the cross axis VOR with a spot alone on one hand and with a spot and pattern moving together in the same plane on the other during chair rotation were similar, and when one of the two visual stimuli was stationary during chair rotation, our well trained monkeys did not induce the cross axis VOR. These results suggest that the cross axis VOR induced by pursuit training shares common mechanisms with the cross axis VOR induced by whole field-slip stimuli and that if conflicting information is given between the two visual stimuli, adaptive changes are inhibited. Horizontal GVPs were recorded in the cerebellar floccular lobe during pitch rotation coupled with horizontal pursuit stimuli. These GVPs did not respond to pitch in the dark before training, but responded after 60 min of pursuit training with eye velocity sensitivities similar to those before training. Adaptive change in the VOR was specific to smooth eye movements but not to saccades in our paradigms.

Adaptation, Physiological↗