bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebellar Contribution to Saccades and Gaze Holding
Authors: GLASAUER STEFAN 
Published: January 2004

AbstractThe possible role of the cerebellum for the control of saccades and gaze holding is reconsidered using a computational modeling approach. As suggested by previous research, control of gaze holding is assumed to be enhanced by the floccular lobe, whereas control of the saccadic pulse is governed by the oculomotor vermis and fastigial nucleus. In the present work, a negative feedback loop via the paramedian tract neurons and the floccular lobe that contains a forward model of the oculomotor plant is supposed to enhance the time constant of the brainstem integrator. Control of saccadic amplitude is hypothesized to be achieved by a more complex network: feedforward projections from the superior colliculus via the nucleus reticularis tegmenti pontis to the oculomotor vermis and fastigial nucleus cooperate with feedback connections from excitatory burst neurons to overcome the sluggishness of the assumed local feedback loop formed via the superior colliculus and to implement inverse dynamics of downstream neural and motor processing.
Saccade Dysmetria during Functional Perturbation of the Caudal Fastigial Nucleus in the Monkey
Authors: GOFFART LAURENT , CHEN LONGTANG L. , SPARKS DAVID L. 
Published: January 2004

AbstractThe caudal fastigial nucleus (cFN) is the output nucleus by which the medioposterior cerebellum influences the brainstem saccade generator. In the monkey, inactivation of one cFN by local injection of muscimol impairs all saccades: ipsiversive saccades become hypermetric, contraversive saccades become hypometric, and saccades aimed at a target located in the upper or lower visual fields are biased horizontally toward the injected side. The pharmacological action of muscimol does not allow deficits that are presaccadic to be distinguished from those occurring during saccade execution. To determine the interval during which altered cFN activity affects saccade accuracy, we applied low‐frequency electrical microstimulation (100 Hz for 100‐300 ms) to the cFN of three monkeys while they were making saccades toward a flashed target. Similar to the effect of muscimol injection in cFN, low‐frequency microstimulation biased all saccades toward the ipsilateral side. When the microstimulation was applied after target flash and before saccade onset, the ipsilateral bias was absent. However, when the stimulation was applied during the ongoing movement, the saccade trajectory was biased toward the stimulated side. The muscimol‐like effect of the microstimulation suggests that the stimulation inhibits cFN activity, possibly by recruiting the inhibitory afferents from the cerebellar vermis (axons of Purkinje cells). Low‐frequency microstimulation had to be applied during the saccade to bias its trajectory. These data suggest that the ipsilateral horizontal bias observed during muscimol inactivation results from an imbalance in the intrasaccadic activity between the two caudal fastigial nuclei.
Multimodal Signal Integration in Vestibular Neurons of the Primate Fastigial Nucleus
Authors: BÜTTNER U. , GLASAUER S. , GLONTI L. , GUAN Y. , KIPIANI E. , KLEINE J. , SIEBOLD C. , TCHELIDZE T. , WILDEN A. 
Published: January 2004

AbstractThe rostral fastigial nucleus contains vestibular neurons, which presumably are involved in spinal mechanisms (neck, gait, posture) and which are not modulated with individual eye movements. Single‐unit recordings in the alert behaving monkey during natural stimulus conditions reveal that virtually all neurons demonstrate integration of several sensory inputs. This applies not only for canal‐canal and canal‐otolith interaction, but also for otolith‐otolith interaction. There is also some evidence that most neurons receive not only an utriculus but also a sacculus input. Furthermore, most neurons also respond to large‐field optokinetic stimulation, reflecting visual‐vestibular interaction. Neurons are also affected by the head on trunk position, which would allow these neurons to operate in a body‐centered rather than a head‐centered reference frame. These complex, multisensory features could permit fastigial nucleus neurons to rather specifically affect spinal motor functions.
Discharge Properties of Saccade‐Related Neurons in the Primate Fastigial Oculomotor Region
Authors: KLEINE J. F. , GUAN Y. , BÜTTNER U. 
Published: January 2004

AbstractTo clarify the mechanisms by which the cerebellar fastigial oculomotor region (FOR) contributes to the control of saccadic eye movements, we recorded saccade‐related FOR units in alert monkeys that made horizontal saccades between neighboring points of a three‐by‐three grid of target positions (16° amplitude). As in previous studies, FOR units exhibited saccade‐related bursts that occurred earlier for contralateral than for ipsilateral saccades. In addition, many FOR units reflected variations in the kinematic profiles of the saccades by exhibiting bursts with earlier onset and shorter peak latencies and higher peak discharge rates for fast as compared with slow saccades of the same amplitude. Moreover, reflecting systematic differences in saccade velocity rather than an influence of eye position itself, FOR bursts showed subtle but recurrent and, at the population level, statistically significant differences between centripetal and centrifugal saccades that closely paralleled the eye position dependency of saccadic dysmetria seen after FOR lesions. We conclude that the FOR output signal is not, as previously proposed, specifically related to the temporal properties of the saccade, but also contains information about saccade velocity. Moreover, the FOR output signal appears to change systematically depending on the actual kinematic properties of the saccade, in a way that would help to maintain saccadic accuracy.
Neurons in the Caudal Frontal Eye Fields of Monkeys Signal Three‐Dimensional Tracking
Authors: KURKIN SERGEI , TAKEICHI NORIHITO , AKAO TEPPEI , SATO FUMIE , FUKUSHIMA JUNKO , KANEKO CHRIS R.S. , FUKUSHIMA KIKURO 
Published: January 2004

AbstractTo maintain optimal clarity of objects moving in three dimensions, precise coordination of binocular eye movements is required in frontal‐eyed primates. Caudal parts of the frontal eye fields (FEFs) contain smooth pursuit neurons and the discharge of the majority of them is related to vergence eye movements as well. However, whether or not those pursuit neurons carry true binocular signals has not been tested critically. Using dichoptic stimuli that dissociate horizontal movements of the left and right eyes, we found that all pursuit‐related, FEF neurons tested carried binocular signals.
Prolonged Optokinetic Stimulation Generates Podokinetic after Rotation
Authors: GORDON CARLOS R. , TAL DROR , GADOTH NATAN , SHUPAK AVI 
Published: January 2004

AbstractPrevious studies showed that after prolonged stepping in place on the center of a rotating platform blindfolded subjects could no longer step in place on a firm floor. Instead, they invariably rotated themselves relative to space without perceiving their rotation, a phenomenon termed podokinetic after‐rotation (PKAR). We speculated that prolonged optokinetic stimulation (OK) alone may generate similar PKAR. The purpose of this study was to evaluate the effects of prolonged OK on podokinetic (PK) responses. Ten healthy subjects participated in the study. After a control stepping test, they were seated in a circular closed cage and randomly (right or left) exposed to an OK (45°/s) covering the whole visual field for 30 min. After this procedure, blindfolded subjects attempted to step in place on the stationary floor for 30 min. When trying to do so, all subjects turned relative to space without any perception of rotation. The direction of this optokinetically after‐rotation (oPKAR) was opposite of that of the direction of OK. Mean peak velocity of oPKAR was 7.8 ± 4.1°/s, and it was reached after approximately 6 min of stepping. After that, there was a progressive velocity decay, which exhibited a discharging time constant on the order of 42 min toward a final positive asymptote of 3.1°/s. We conclude that OK alone causes oPKAR. Long‐term OK probably charges a storage element for podomotor activity with a relatively prolonged time constant. This novel form of neural interaction and adaptive plasticity may have significant implications for the treatment of vestibular and parietal lobe disorders.
A Modeling Approach to the Human Spatial Orientation System
Authors: MERGNER T. , BECKER W. 
Published: January 2004

AbstractThe human spatial orientation system is highly complex and nonlinear. It is difficult, therefore, to arrive at an unequivocal model of the underlying processing by merely combining the known elementary mechanisms (“bottom‐up” approach); additional “top‐down” concepts are required to narrow the choice between several formally equivalent solutions. We here suggest a concept in which sensorimotor control is based on a meta‐level that provides an internal representation of the physical stimuli acting upon a subject (e.g., tilt of the support surface), whereas the classic reflex concept essentially proceeds from a direct coupling between physiological stimuli, sensors and actuators. At the hypothesized meta‐level, the axial body segments are represented as a stack of superimposed platforms with the lowermost platform (generally the feet) riding on a support surface that acts as the buttress for the subject's active movements. From the sensory point of view, this stack constitutes a system of nested references. This concept explains data from various experiments dealing with self‐ and object motion perception and body stabilization in a more exhaustive way than does the classic concept. In our view, it provides a robust, flexible, and modular framework for perception and action in space.
Evaluating Small Eye Movements in Patients with Saccadic Palsies
Authors: GARBUTT SIOBHAN , HARWOOD MARK R. , KUMAR ARUN N. , HAN YANNING H. , LEIGH R. JOHN 
Published: January 2004

AbstractSlow saccades are an important diagnostic feature of a range of degenerative, metabolic, and genetic diseases of the nervous system. Many affected patients have difficulty initiating saccades, and the movements themselves may be small, making it difficult to make comparisons with control subjects. A large‐field optokinetic stimulus may elicit quick phases of nystagmus in patients who cannot initiate voluntary saccades, but these movements may also be small. We show that it is still possible to compare amplitude‐duration and amplitude‐peak velocity relations with controls if data are fit with a power function (rather than an exponential equation). When analyzed this way, the dynamic properties of small saccades and quick phases from patients with progressive supranuclear palsy (PSP) could be differentiated from fast movements made by patients with idiopathic Parkinson's disease or controls. Normal saccades show a fairly constant ratio: peak velocity/mean velocity (Q ∼1.6 for vertical saccades). This ratio was abnormally high (Q >3) for some larger saccades made by patients with PSP, suggesting that either these movements were not entirely saccadic or that they were composed of a series of small saccades.
Adaptations and Deficits in the Vestibulo‐Ocular Reflex after Peripheral Ocular Motor Palsies
Authors: SHARPE JAMES A. , TWEED DOUGLAS , WONG AGNES M.F. 
Published: January 2004

AbstractPalsy of a nerve might be expected to lower vestibulo‐ocular reflex (VOR) responses in its fields of motion, but effects of peripheral neuromuscular disease were unknown. We recorded the VOR during sinusoidal head rotations in yaw, pitch, and roll at 0.5‐2 Hz and static torsional gain in 43 patients with unilateral nerve palsies. Sixth nerve palsy (n= 21) reduced both abduction and adduction VOR gains in darkness. In light, horizontal visually enhanced VOR (VVOR) gains were normal in moderate and mild palsy. In severe palsy, horizontal VVOR gains remained low in the paretic eye when it was fixating, whereas gains in the nonparetic eye became higher than normal. Third nerve palsy (n= 10) decreased VOR and VVOR gains during abduction, adduction, elevation, depression, extorsion, and intorsion. Fourth nerve palsy (n= 13) reduced VOR gains of the paretic eye during intorsion, extorsion, elevation, depression, abduction, and adduction, but in light vertical and horizontal VVOR gains were normal. In the nonparetic eye, all gains were normal. Reduced VOR gains in the direction of paretic muscles and also in the direction of their antagonists, together with normal gains in the nonparetic eye, indicate a selective adjustment to the antagonists of paretic muscles. Increase of VVOR gains to normal in the paretic eye, when used for fixation, without conjugate increase in gains in the occluded nonparetic eye, provides further evidence of selective adaptation for the paretic eye. Motions of the eyes after nerve palsies indicate monocular VOR adaptation in three dimensions.
Mortality After Cure of Testicular Seminoma
Authors: Zagars Gunar K. , Ballo Matthew T. , Lee Andrew K. , Strom Sara S. 
Published: January 2004

Purpose To determine the incidence of potentially treatment-related mortality in long-term survivors of testicular seminoma treated by orchiectomy and radiation therapy (XRT). Patients and Methods From all 477 men with stage I or II testicular seminoma treated at The University of Texas M.D. Anderson Cancer Center (Houston, TX) with postorchiectomy megavoltage XRT between 1951 and 1999, 453 never sustained relapse of their disease. Long-term survival for these 453 men was evaluated with the person-years method to determine the standardized mortality ratio (SMR). SMRs were calculated for all causes of death, cardiac deaths, and cancer deaths using standard US data for males. Results After a median follow-up of 13.3 years, the 10-, 20-, 30-, and 40-year actuarial survival rates were 93%, 79%, 59%, and 26%, respectively. The all-cause SMR over the entire observation interval was 1.59 (99% CI, 1.21 to 2.04). The SMR was not excessive for the first 15 years of follow-up: SMR, 1.30 (95% CI, 0.93 to 1.77); but beyond 15 years the SMR was 1.85 (99% CI, 1.30 to 2.55). The overall cardiac-specific SMR was 1.61 (95% CI, 1.21 to 2.24). The cardiac SMR was significantly elevated only beyond 15 years (P < .01). The overall cancer-specific SMR was 1.91 (99% CI, 1.14 to 2.98). The cancer SMR was also significant only after 15 years of follow-up (P < .01). An increased mortality was evident in patients treated with and without mediastinal XRT. Conclusion Long-term survivors of seminoma treated with postorchiectomy XRT are at significant excess risk of death as a result of cardiac disease or second cancer. Management strategies that minimize these risks but maintain the excellent hitherto observed cure rates need to be actively pursued.
CEBPA Mutations in Younger Adults With Acute Myeloid Leukemia and Normal Cytogenetics: Prognostic Relevance and Analysis of Cooperating Mutations
Authors: Fröhling Stefan , Schlenk Richard F. , Stolze Ina , Bihlmayr Jörg , Benner Axel , Kreitmeier Sylvia , Tobis Karen , Döhner Hartmut , Döhner Konstanze 
Published: January 2004

Purpose To assess the prognostic relevance of mutations in the CEBPA gene encoding CCAAT/enhancer binding protein alpha (C/EBPα) in a large prospective series of younger adults with acute myeloid leukemia (AML) and normal cytogenetics. Patients and Methods The entire CEBPA coding region was sequenced in diagnostic samples from 236 AML patients 16 to 60 years of age with normal cytogenetics who were uniformly treated on two consecutive protocols of the AML Study Group Ulm, and CEBPA mutation status was correlated with clinical outcome. Results CEBPA mutations were detected in 36 (15%) of 236 patients. Twenty-one (9%) of 236 patients had mutations predicted to result in loss of C/EBPα function. Remission duration and overall survival (OS) were significantly longer for the 36 patients with CEBPA mutations (P = .01 and P = .05, respectively). On multivariate analysis, wild-type CEBPA was an independent prognostic marker affecting remission duration (hazard ratio, 2.85; P = .01) and OS (hazard ratio, 1.87; P = .04). Analysis of cooperating mutations (both types of activating FLT3 mutations and MLL partial tandem duplications) showed that FLT3 mutations had no significant prognostic influence in patients with CEBPA mutations. Furthermore, there was no significant overlap between the subgroup of patients with CEBPA mutation with predicted loss of C/EBPα function and patients with FLT3 or MLL mutations, suggesting that CEBPA loss-of-function mutations define a distinct biologic subclass of AML with normal cytogenetics. Conclusion Mutant CEBPA predicts favorable prognosis and may improve risk stratification in AML patients with normal cytogenetics.
Trans-Activation of Mutant Follicle-Stimulating Hormone Receptors Selectively Generates Only One of Two Hormone Signals
Authors: Ji Inhae , Lee ChangWoo , Jeoung MyoungKun , Koo YongBum , Sievert Gail A. , Ji Tae H. 
Published: January 2004

AbstractPreviously, we reported that a liganded LH receptor (LHR) is capable of activating itself (cis-activation) and other nonliganded LHRs to induce cAMP (trans-activation). Trans-activation of the LHR raises two crucial questions. Is trans-activation unique to LHR or common to other G protein-coupled receptors? Does trans-activation stimulate phospholipase Cβ as it does adenylyl cyclase? To address these questions, two types of novel FSH receptors (FSHRs) were constructed, one defective in hormone binding and the other defective in signal generation. The FSHR, a G protein-coupled receptor, comprises two major domains, the N-terminal extracellular exodomain that binds the hormone and the membrane-associated endodomain that generates the hormone signals. For signal defective receptors, the exodomain was attached to glycosyl phosphatidylinositol (ExoGPI) or the transmembrane domain of CD8 immune receptor (ExoCD). ExoGPI and ExoCD can trans-activate another nonliganded FSH. Surprisingly, the trans-activation generates a signal to activate either adenylyl cyclase or phospholipase Cβ, but not both. These results indicate that trans-activation in these mutant receptors is selective and limited in signal generation, thus providing new approaches to investigating the generation of different hormone signals and a novel means to selectively generate a particular hormone signal. Our data also suggest that the FSHR’s exodomain could not trans-activate LHR.
Original Paper: Assays for thyroid-stimulating hormone using dried blood spotted filter paper specimens to screen for hypothyroidism in older children and adults
Authors: Hofman L F , Foley T P , Henry J J , Naylor E W 
Published: January 2004

Objective: Symptoms of hypothyroidism in adults can be mistaken for medical and psychiatric diseases, as well as for general signs of ageing such as weakness, lethargy and fatigue. The incidence of hypothyroidism is many-fold higher in adults than in newborn children. The latter have been routinely screened for the condition using filter paper dried blood spots (DBS) for nearly three decades but this cost-effective screening technique has only recently been applied to adults. This study was undertaken to show that DBS testing in adults and older children is an accurate way to screen for hypothyroidism. Methods: Serum and DBS specimens were collected from adults and children. Assays were run on both specimens and the results correlated. In addition 972 specimens were collected from adults at community centres and nursing homes. Follow-up studies were performed on patients with positive results. Results: The correlation coefficient for 118 matched serum and DBS specimens was 0.99. Thyroid-stimulating hormone (TSH) values were elevated in 50 of the 972 adults from nursing homes and community centres. Thirteen of these individuals were on thyroid medication and 28 had either high serum TSH or high thyroglobulin (TgAb) or thyroid peroxidase (TPOAb) antibody levels. Conclusions: Individuals can be screened for hypothyroidism by collecting finger stick DBS specimens at community centres, nursing homes and other locations which can be mailed by regular postal service to a central laboratory for accurate and inexpensive testing.
Original Paper: Hereditary haemochromatosis and hepatocellular carcinoma in males: a strategy for estimating the potential for primary prevention
Authors: Haddow J E , Palomaki G E , McClain M , Craig W 
Published: January 2004

Objectives: Homozygosity for the C282Y mutation of the HFE gene is the main cause of iron overload in hereditary haemochromatosis. This study calculated the number of hepatocellular carcinoma cases among a cohort of white males that could be attributed to C282Y homozygosity. A better understanding of the extent of potentially preventable mortality arising from this cancer might help with decision making about the feasibility of population screening. Methods: We combined information from published life tables, age-specific cancer rates and DNA studies of archived liver biopsy specimens to calculate the number of cases of hepatocellular carcinoma that might occur during the lifetime of a cohort of 1,000,000 men, including a subgroup of 5000 C282Y homozygotes. Results: Hepatocellular carcinoma was estimated to occur in 2673 men in the cohort (1:374); 267 of these cases were in the subgroup of 5000 C282Y homozygotes (1:17). If these 267 cases were prevented, the remaining lifetime risk among all males would be 1:416. The relative risk for this cancer in C282Y homozygotes is 23. Conclusions: There continues to be uncertainty about the efficacy of screening for haemochromatosis. Hepatocellular carcinoma is the most readily quantifiable serious health problem attributable to this source. Further confirmatory DNA (C282Y) studies would be helpful in larger, unbiased sets of archived biopsy specimens, as a way to confirm the present estimate. Any strategy designed to prevent attributable liver cancer is likely to prevent other serious problems from haemochromatosis as well.
Original Paper: Contribution of clinical breast examination to mammography screening in the early detection of breast cancer
Authors: Bancej C , Decker K , Chiarelli A , Harrison M , Turner D , Brisson J 
Published: January 2004

Objectives: As the benefit of clinical breast examination (CBE) over that of screening mammography alone in reducing breast cancer mortality is uncertain, it is informative to monitor its contribution to interim measures of effectiveness of a screening programme. Here, the contribution of CBE to screening mammography in the early detection of breast cancer was evaluated. Setting: Four Canadian organised breast cancer screening programmes. Methods: Women aged 50-69 receiving dual screening (CBE and mammography) (n=300,303) between 1996 and 1998 were followed up between screen and diagnosis. Outcomes assessed by mode of detection (CBE alone, mammography alone, or both CBE and mammography) included referral rate, positive predictive value, pathological features of tumours (size, nodal status, morphology), and cancer detection rates overall and for small cancers (≤10 mm or node-negative). Heterogeneity in findings across programmes was also assessed. Results: On first versus subsequent screen, CBE alone resulted in 28.5-36.7% of referrals, and 4.6-5.9% of cancers compared with 52.6-60.1% of referrals and 60.0-64.3% of cancers for mammography alone. Among cancers detected by CBE, 83.6-88.6% were also detected by mammography, whereas for mammographically detected cancers only 31.7-37.2% were also detected by CBE. On average, CBE increased the rate of detection of small invasive cancers by 2-6% over rates if mammography was the sole detection method. Without CBE, programmes would be missing three cancers for every 10,000 screens and 3-10 small invasive cancers in every 100,000 screens. Conclusions: Inclusion of CBE in an organised programme contributes minimally to early detection.