Biomedical subjects

J S Frank

Publications and source records attributed to J S Frank.

At least 19 recordsLinked to original sources

PubMed2005

An evaluation of sensorimotor integration during locomotion toward a target in Parkinson's disease.

Recent research suggests that basal ganglia dysfunction may result in problems integrating concurrent vision and proprioception during movement. We evaluated dopaminergic system involvement in this sensorimotor process during locomotion within a large sample of Parkinson's disease (PD) patients while "On" and "Off" their dopaminergic medications (n=25), in conditions that selectively manipulated the availability of proprioception, vision or both. The present experiment focused on two main objectives: i) to examine the relative influence of visual and proprioceptive inputs on locomotion and target accuracy in patients with PD; and ii) to examine the influence of dopamine replacement therapy on sensorimotor integration while moving toward the target. All participants walked at a self-selected pace on a GAITRite carpet in two baseline conditions (light and dark), as well as four experimental darkness conditions: a) to a remembered target (i.e. proprioception only), b) to a remembered target with light on chest for body position awareness (proprioception plus), c) with vision of a lit target, also with light on chest (vision and proprioception), d) pushed in wheelchair to remembered target (no proprioception or vision). Final position was measured by 2-D radial error, and revealed a group by condition interaction, suggesting that PD patients "Off" their medications move to targets with less accuracy, but approach the accuracy of healthy participants when in the "On" state. Both PD and healthy improved their accuracy with availability of concurrent vision and proprioception (condition c). Interestingly, our results demonstrate that PD "Off" performed the task with greater difficulty than when "On" medication, but only when proprioception was the sole source of feedback. Since PD, whether medicated or unmedicated were even more affected when proprioception was removed (wheelchair), a memory-related explanation can be ruled out. Our results suggest that the basal ganglia are not specifically involved in visuoproprioceptive integration; however, assimilation of proprioceptive feedback to guide an ongoing movement may be a critical function of the basal ganglia.

Adult↗

PubMed2004

Control of dynamic stability during gait termination on a slippery surface.

There are three common ways by which to successfully terminate gait: decreased acceleration of whole-body center of mass (COM) through a flexor synergy in the trail leg, increased deceleration of whole-body COM through an extensor synergy in the front limb, and an energy/momentum transfer to dissipate any remaining momentum if the first two strategies are unsuccessful. Healthy individuals were asked to stop on a slippery surface while we examined their unexpected response to the slippery surface. Kinetic data from the forceplates revealed lower braking forces in the slip trials compared with normal gait-termination trials. Subjects were unable to control their center of pressure (COP) to manipulate the COM as revealed by increased deviations and maximum absolute ranges of COP movement. Subject COM deviated farther in both horizontal planes and lowered further during the slip compared with normal gait-termination trials. Arm movements were effective in dissipating forward COM movement. In addition, there likely was a transfer of forward to lateral momentum to stop forward progression. All recorded muscle activity in the lower limbs and back increased during the slip to provide support to the lower limbs and correct upright balance. The trailing limb shortened its final step to provide support to the lowering COM. The balance-correction response seen here resembles previous reactions to perturbations during locomotion suggesting there is a generalized strategy employed by the nervous system to correct for disturbances and maintain balance.

Adult↗

PubMed2004

Influence of postural anxiety on postural reactions to multi-directional surface rotations.

Previous studies have shown significant effects of increased postural anxiety in healthy young individuals when standing quietly or performing voluntary postural tasks. However, little is known about the influence of anxiety on reactive postural control. The present study examined how increased postural anxiety influenced postural reactions to unexpected surface rotations in multiple directions. Ten healthy young adults (mean age: 25.5 yr, range: 22-27 yr) were required to recover from unexpected rotations of the support surface (7.5 degrees amplitude, 50 degrees/s velocity) delivered in six different directions while standing in a low postural threat (surface height: 60 cm above ground) or high postural threat (surface height: 160 cm above ground) condition. Electromyographic data from 12 different postural leg, hip, and trunk muscles was collected simultaneously. Full body kinematic data were also used to determine total body center of mass (COM) and segment displacements. Four distinct changes were observed with increased postural anxiety: increased amplitude in balance-correcting responses (120-220 ms) in all leg, trunk, and arm muscles; decreased onset latency of deltoid responses; reduced magnitude of COM displacement; and reduced angular displacement of leg, pelvis, and trunk. These observations suggest that changes in dynamic postural responses with increased anxiety are mediated by alterations in neuro-muscular control mechanisms and thus may contribute significantly to the pathophysiology of balance deficits associated with aging or neurological disease.

Adult↗

PubMed2004

Improved measurement of the K+-->pi+nunu; branching ratio.

An additional event near the upper kinematic limit for K+-->pi(+)nunu; has been observed by experiment E949 at Brookhaven National Laboratory. Combining previously reported and new data, the branching ratio is B(K+-->pi(+)nunu;)=(1.47(+1.30)(-0.89))x10(-10) based on three events observed in the pion momentum region 211<P<229 MeV/c. At the measured central value of the branching ratio, the additional event had a signal-to-background ratio of 0.9.

Journal Article↗

PubMed2002

Further evidence for the decay K+ -->pi+nu(nu).

Additional evidence for the rare kaon decay K+-->pi+nu(nu) has been found in a new data set with comparable sensitivity to the previously reported result. One new event was observed in the pion momentum region examined, 211 pi+nu(nu)) = 1.57(+1.75)(-0.82)x10(-10).

Journal Article↗

PubMed2001

The influence of postural threat on the control of upright stance.

In order to utilize static posturography as a tool with which to diagnose pathological balance disorders, it is necessary to understand the contribution of psychological factors such as fear of falling. In this study we examined kinetic and kinematic parameters during quiet stance of eight young healthy adults standing under three conditions which posed increasing levels of postural threat. Participants were required to stand quietly, both with and without visual information and with normal or reduced vestibular information for 2-min periods at each of three surface conditions: ground level (low threat), 81 cm above the ground completely surrounded by a support surface (medium threat) and 81 cm above ground at the edge of the surface (high threat). In addition to calculating displacement and frequency measures for movements of centre of pressure (COP) and centre of mass (COM), a measure of stiffness was derived from the difference between COP-COM signal. Mean EMG activity was recorded bilaterally from anterior and posterior muscles of the lower and upper leg. A stiffening strategy was adopted when individuals stood under high threat conditions involving significant changes in kinematic, kinetic and EMG variables. The A-P stiffness constant increased significantly (27.5%) for the high threat compared to low threat condition, independent of vision or vestibular information. Changes in stiffness were accompanied by: (1) backward shift of the mean A-P position of COP and COM, (2) increased mean power frequency and decreased amplitude displacement of the COP and (3) decreased amplitude displacements of the COM. Of the significant changes observed in mean EMG activity with increased postural threat, only tibialis anterior was significantly correlated with increased stiffness, while activity in soleus, medial gastrocnemius and rectus femoris was highly correlated with mean position of COP.

Accidental Falls↗

PubMed2001

Sampling duration effects on centre of pressure summary measures.

The purpose of the present study was to examine the effect of sample duration on the magnitude and reliability of centre of pressure (COP) summary measures commonly used to characterize the control of upright stance. COP was recorded from 49 participants who stood quietly during three consecutive 120 s trials. Each record was subdivided into 15, 30, 60 and 120 s samples and root mean square (RMS), mean power frequency (MPF) and mean position of COP were calculated for each sample. RMS significantly increased and MPF values significantly decreased as sample duration increased. Substantial increases in the reliability of both RMS and MPF were observed with increased sample duration.

Adult↗

PubMed2001

Influence of a visuo-spatial, verbal and central executive working memory task on postural control.

In this study, participants were required to perform different working memory (WM) tasks (a verbal task, a visuo-spatial task with two levels of difficulty and a central executive task) under different challenges to postural control (sitting, shoulder width stance and tandem stance). When a WM task was added, changes in postural sway were characterized by an increase in frequency and decrease in amplitude of sway indicating a tighter control. We found no changes in postural control between the different types of WM tasks, which might support a general capacity limitation hypothesis. However, no changes were found in performance of the WM when postural stance was modified and no changes were found in postural sway, when the difficulty level of the visuo-spatial task was modified. Consequently, the results seem to indicate that the addition of a WM task, regardless of task type or task difficulty, forces the central nervous system to choose a tighter control strategy.

Adult↗

PubMed2001

Sequestration of aggregated LDL by macrophages studied with freeze-etch electron microscopy.

The detailed morphology of macrophages involved in the uptake and intracellular processing of low density lipoprotein (LDL) and, ultimately, formation of macrophage-derived foam cells of atherosclerotic lesions has long fascinated investigators. This study examined localization of LDL in subcellular compartments of macrophage-derived intimal foam cells in cardiac valves isolated from rabbits by diet-induced hypercholesterolemia and, as an in vitro model of formation of foam cells, in cultured human monocyte-macrophages incubated for 2;-120 h with aggregated LDL produced by vortexing or phospholipase C lipolysis. The quasi-three-dimensional morphology of macrophages involved in endocytosis was preserved by ultrarapid freezing and freeze-etch microscopy in conjunction with thin-section electron microscopy. This approach produced unique images of subcellular compartments in human monocyte-macrophages involved in the uptake and processing of aggregated LDL with a clarity not previously reported. Three-dimensional ultrastructural analyses revealed a complex network of coated and uncoated vesicles, surface-connected saclike compartments, and endosomal/lysosomal compartments including the labyrinth of vesicular/tubular lysosomes all enmeshed in the microtubular, microfilament cytoskeletal network. These dynamic views of subcellular structures at the high resolution of the electron microscope provide an additional framework to better understand how lipoprotein particles are transported into, and processed within, macrophages during foam cell formation in atherogenesis.

Animals↗

PubMed2000

Postural control is scaled to level of postural threat.

This study investigated control of posture when standing at different surface heights above ground level. Alterations in surface height were used to modify threat to postural control. Sixty-two healthy adults (mean+/-S.D.=20.3+/-1.3 years) stood quietly on a force plate 40 cm (LOW threat), 100 cm (MEDIUM threat) or 160 cm (HIGH threat) above ground level. Each standing trial was performed with eyes open for 120 s. Postural threat was presented in ascending (n=31) or descending (n=31) order with the first threat condition in each series (LOW threat for ascending group, HIGH threat for descending group) repeated. This manipulation allowed for an examination of set effects (i.e. prior experience of postural threat) on postural control. The results demonstrated scaling of postural control variables to level of postural threat. Amplitude of centre of pressure (COP) displacement decreased and frequency of COP displacement increased linearly as postural threat increased from LOW to HIGH. The central nervous system progressively tightened control of posture as postural threat increased. Initial exposure to the HIGH or LOW threat condition influenced postural control differently. The group who received the HIGH threat condition first (descending) demonstrated increased amplitude of COP displacement in the anterior-posterior direction compared with the group who received the LOW threat condition first (ascending). A 'first trial' effect was observed when standing for two consecutive trials but only at the LOW threat condition. Decreased amplitude and increased frequency of COP displacement were observed on the first trial compared to the second trial. The results of this study demonstrated that control of posture is influenced not only by the threat to posture but also by the order in which the threat to posture is experienced.

Accidental Falls↗

PubMed2000

Centrally initiated postural adjustments in parkinsonian patients on and off levodopa.

This study investigates the effects of parkinsonism and dopamine replacement therapy (levodopa) on centrally initiated postural activity preceding rising onto the toes. The electromyographic (EMG) and force magnitude, scaling, sequencing, and postural stabilization were compared when rising-to-toes under two conditions, slow/low versus fast/high, for parkinsonian patients and elderly control subjects. Parkinsonian subjects were tested after withholding their levodopa medication for 12-16 h and again 1 h after taking their medication when parkinsonian signs were diminished. Parkinsonian subjects showed reduced magnitudes and delayed timing of the postural and voluntary components of the rise-to-toes task, as if they had difficulty turning off the postural, tibialis anterior (TIB) component and initiating the voluntary, gastrocnemius (GAS) component. Dopamine improved the relative timing, as well as the magnitude of both postural and voluntary components of rise-to-toes. Although the magnitude of dorsiflexion torque was smaller for parkinsonian subjects ON and OFF than for healthy elderly controls, the parkinsonian subjects showed intact scaling of the magnitude of postural activity. Parkinsonian subjects do not perform the rise-to-toes task like normal subjects who are instructed to rise slowly; the relative timing of TIB and GAS activation was different even at comparable speeds of performance. Parkinsonian subjects, both ON and OFF, exhibited greater risk of falling than elderly control subjects when rising to toes. This increased risk of falling was reflected in a smaller safety margin between the peak center of mass (CoM) and peak center of pressure (CoP) during the task. The magnitude of mean postural dorsiflexion torque in the rise-to-toes task was highly correlated with a clinical rating scale of gait and balance, suggesting that force control is a critical factor influencing postural control in patients with Parkinson's disease.

Accidental Falls↗

PubMed2000

Genetic control of HDL levels and composition in an interspecific mouse cross (CAST/Ei x C57BL/6J).

Strain CAST/Ei (CAST) mice exhibit unusually low levels of high density lipoproteins (HDL) as compared with most other strains of mice, including C57BL/6J (B6). This appears to be due in part to a functional deficiency of lecithin:cholesterol acyltransferase (LCAT). LCAT mRNA expression in CAST mice is normal, but the mice exhibit several characteristics consistent with functional deficiency. First, the activity and mass of LCAT in plasma and in HDL of CAST mice were reduced significantly. Second, the HDL of CAST mice were relatively poor in phospholipids and cholesteryl esters, but rich in free cholesterol and apolipoprotein A-I (apoA-I). Third, the adrenals of CAST mice were depleted of cholesteryl esters, a phenotype similar to that observed in LCAT- and acyl-CoA:cholesterol acyltransferase-deficient mice. Fourth, in common with LCAT-deficient mice, CAST mice contained triglyceride-rich lipoproteins with "panhandle"-like protrusions. To examine the genetic bases of these differences, we studied HDL lipid levels in an intercross between strain CAST and the common laboratory strain B6 on a low fat, chow diet as well as a high fat, atherogenic diet. HDL levels exhibited complex inheritance, as 12 quantitative trait loci with significant or suggestive likelihood of observed data scores were identified. Several of the loci occurred over plausible candidate genes and these were investigated. The results indicate that the functional LCAT deficiency is unlikely to be due to variations of the LCAT gene. Our results suggest that novel genes are likely to be important in the control of HDL metabolism, and they provide evidence of genetic factors influencing the interaction of LCAT with HDL.

Adrenal Glands↗

PubMed1999

Balance in chronic low back pain patients compared to healthy people under various conditions in upright standing.

OBJECTIVE: To determine whether balance responses of chronic low back pain patients differed from healthy controls under various upright standing conditions which challenged the balance system. METHODS: Eight chronic low back pain patients and eight controls performed seven postural tasks which involved manipulation of visual, vestibular, and proprioceptive input as well as body orientation. The unbiased root mean square, the mean power frequency and the mean position of the centre of pressure were calculated from force plate readings. A pain scale and two questionnaires were used to evaluate the severity of disability and the scores were correlated with the force plate measures. The reliability of the force plate measures was determined. RESULTS: A significant increase in the root mean square in the medial-lateral direction for the chronic low back pain patients as a group was found during tasks which involved removal of vision, especially when combined with increased task complexity. The root mean square and mean power frequency in the medial-lateral plane were reliable for the majority of the tasks. CONCLUSION: The root mean square in the medial-lateral direction was reliable and sensitive enough to measure an increase in postural sway of chronic low back pain patients as a group compared to healthy controls when the task involved increased complexity and removal of visual information. RELEVANCE: A reliable measure of whole body performance obtained during simple postural tasks, such as the root mean square in the medial-lateral plane, may be used to distinguish chronic low back pain patients as a group from a healthy population. Further uses may include the development and guidance of chronic low back pain treatment and evaluation of recovery progress.

Adult↗

PubMed1999

Ultrastructure of early lipid accumulation in ApoE-deficient mice.

Apolipoprotein (apo) E-deficient mice develop severe hypercholesterolemia and have lesions that progress from fatty streaks to fibrous plaques distributed in lesion-prone areas throughout the aorta. Lesions develop in apoE-deficient mice on a regular chow diet and will occur faster on a diet higher in cholesterol. Examination of the aortas from these mice on a chow diet by high-resolution, freeze-etch electron microscopy demonstrated lipid retention in the intima by 3 weeks of age. Lipid was retained in the matrix as individual particles between 33 and 48 nm in diameter, aligned along the collagen fibrils and in aggregates consisting of lipid particles with average diameters of 33 and 68 nm. Larger particles seemed to have formed from fusion of smaller particles. Lipid retention was more widespread in 5- and 9-week-old mice. Monocyte attachment to endothelial cells was observed by electron microscopy at 5 weeks of age. The appearance of the intimal lipid was similar to that previously described in rabbit models and suggests that lipid interaction with matrix filaments and subsequent aggregation of lipid particles are critical first steps in the process of foam cell formation.

Aging↗

PubMed1999

Minimally modified low-density lipoprotein induces monocyte adhesion to endothelial connecting segment-1 by activating beta1 integrin.

We have shown previously that treatment of human aortic endothelial cells (HAECs) with minimally modified low-density lipoprotein (MM-LDL) induces monocyte but not neutrophil binding. This monocyte binding was not mediated by endothelial E-selectin, P-selectin, vascular cell adhesion molecule-I, or intercellular adhesion molecule-I, suggesting an alternative monocyte-specific adhesion molecule. We now show that moncytic alpha4beta1 integrins mediate binding to MM-LDL-treated endothelial cells. We present data suggesting that the expression of the connecting segment-1 (CS-1) domain of fibronectin (FN) is induced on the apical surface of HAEC by MM-LDL and is the endothelial alpha4beta1 ligand in MM-LDL-treated cells. Although the levels of CS-1 mRNA and protein were not increased, we show that MM-LDL treatment causes deposition of FN on the apical surface by activation of beta1integrins, particularly those associated with alpha5 integrins. Activation of beta1 by antibody 8A2 also induced CS-1-mediated monocyte binding. Confocal microscopy demonstrated the activated beta1 and CS-1colocalize in concentrated filamentous patches on the apical surface of HAEC. Both anti-CS-1 and an antibody to activated beta1 showed increased staining on the luminal endothelium of human coronary lesions with active monocyte entry. These results suggest the importance of these integrin ligand interactions in human atherosclerosis.

Cell Adhesion↗

PubMed1999

Apo A-I inhibits foam cell formation in Apo E-deficient mice after monocyte adherence to endothelium.

We have previously shown that expression of the human apo A-I transgene on the apo E-deficient background increases HDL cholesterol and greatly diminishes fatty streak lesion formation. To examine the mechanism, prelesional events in atherosclerotic plaque development were examined in 6- to 8-week-old apo E-deficient and apo E-deficient/human apo A-I transgenic mice. A quantitative assessment of subendothelial lipid deposition by freeze-fracture and deep-etch electron microscopy indicated that elevated apo A-I did not affect the distribution or amount of aortic arch subendothelial lipid deposits. Immunohistochemical staining for VCAM-1 demonstrated similar expression on endothelial cells at prelesional aortic branch sites from both apo E-deficient and apo E-deficient/human apo A-I transgenic mice. Transmission electron microscopy revealed monocytes bound to the aortic arch in mice of both genotypes, and immunohistochemical staining demonstrated that the area occupied by bound mononuclear cells was unchanged. Serum paraoxonase and aryl esterase activity did not differ between apo E-deficient and apo E-deficient/human apo A-I transgenic mice. These data suggest that increases in apo A-I and HDL cholesterol inhibit foam cell formation in apo E-deficient/human apo A-I transgenic mice at a stage following lipid deposition, endothelial activation, and monocyte adherence, without increases in HDL-associated paraoxonase.

Animals↗

PubMed1999

Surface height effects on postural control: a hypothesis for a stiffness strategy for stance.

One possible factor influencing the control of upright stance is the perceived threat to one's personal safety, i.e. balance confidence. We explored this factor by examining the control of stationary stance when standing on an elevated platform under various conditions of reduced visual and vestibular inputs. Twenty-eight adults (14 male and 14 female, mean age = 23.5 years) participated in the experiment. Postural control was examined by recording the amplitude variability (RMS) and mean power frequency (MPF) of center of pressure excursions (COP) over a 2-minute interval while participants stood in a normal stance on a low (0.19 m) and a high (0.81 m) platform with toes positioned either at or away from the edge of the platform. Vision was manipulated through eyes open and eyes closed trials. Vestibular input was reduced by tilting the head into extension [1]. Anterior-posterior RMS and MPF of COP were significantly influenced by an interaction between surface height and vision. When vision was available, a significant decrease in RMS was observed during quiet standing on a high surface compared to a low surface independent of step restriction. When vision was available MPF increased when subjects were raised from a low to a high surface. The mean position of the COP was significantly influenced by an interaction between height and step restriction. Differences in RMS and MPF responses to height manipulation were observed between genders in eyes closed conditions. Vestibular input influenced postural control at both low and high levels with significant increases in RMS when vestibular input was reduced. The reciprocal changes observed in RMS and MPF suggest modifications to postural control through changes in ankle stiffness. Vision appears to play a role in increasing ankle stiffness when balance confidence is compromised.

Accidental Falls↗

PubMed1997

Subcellular distribution of ankyrin in developing rabbit heart--relationship to the Na+-Ca2+ exchanger.

Ankyrins are a multigene family of proteins that function as adapters between the cytoskeleton and trans-membrane proteins, such as ion channels. Previous studies have shown the linkage between ankyrin and ionic transport proteins such as Na+-K+ ATPase, voltage-dependent Na+ channels and Ca2+ channels. In the present study, we have investigated the subcellular distribution of ankyrin and its relationship to the Na+-Ca2+ exchange protein in immature and adult rabbit ventricular myocytes. Isolated single cardiomyocytes from neonatal, juvenile and adult rabbit hearts were examined by immunofluorescence labeling techniques, using antibodies against ankyrin and the Na+-Ca2+ exchanger. We found that in neonatal rabbit cardiac myocytes, ankyrin labeling was mainly present at the Z disk, whereas the Na+-Ca2+ exchanger was only present on the peripheral sarcolemma. At 2 weeks of age, ankyrin labeling was still predominantly observed at the level of the Z disks as well as in the partially developed T-tubules. In the adult cells, however, ankyrin and the Na+-Ca2+ exchanger seem to be co-localized within T-tubules and at the costamere region of the peripheral sarcolemma. Immunogold labeling studies at the higher resolution electron microscopic level using cyrosection tissues of rabbit heart at different ages confirm these findings. These results indicate that the distribution pattern of ankyrin and the Na+-Ca2+ exchanger changes with development in rabbit ventricular myocytes.

Age Factors↗