Bimanual co-ordination in Huntington's disease

The ability of Huntington's disease patients to co-ordinate their two hands with and without external cueing was investigated. Twelve Huntington's disease patients and sex- and age-matched controls performed a bimanual cranking task at two speeds (0.5 Hz, 1.5 Hz) and phase relationships (in-phase, anti-phase), with and without an external metronome cue. Data were sampled at 200 Hz, and raw displacement data for each hand, mean and standard deviation measures of the relative positions of the two hands and their velocities were then calculated. All participants could perform the in-phase movement, at both speeds; however, the Huntington's disease patients were more variable and less accurate than the control participants, particularly at the fast speed. While controls could perform the anti-phase movement, in which rotation of the cranks differed by 180 degrees at both speeds, Huntington's disease patients were unable to do so at either speed, reverting to the in-phase movement at the slow speed. An external metronome cue did not improve the performance of the Huntington's disease patients, which differentiated this group from patients suffering from Parkinson's disease. The Huntington's disease patients' inability to perform the anti-phase movement may be due to damage to the basal ganglia and its output regions.

Reply to comments on "Oxidation mechanism of Si3N4-bonded SiC ceramics by CO, CO2 and steam," by Balat et al.

First of all, we would like to clarify that the passive to active transition was determined not by using Solgasmix [1], but by combining thermodynamic equilibrium and mass balance for the oxidation of SiC under pure CO2 and pure CO. The model used in our paper [2]was an extension ofWagner’s model [3], in a similar way as Balat et al. [4] did for the oxidation of SiC in oxygen.

Heterogeneous distribution of isoactins in cultured vascular smooth muscle cells does not reflect segregation of contractile and cytoskeletal domains

We have previously demonstrated that or-smooth muscle (alpha -SM) actin is predominantly distributed in the central region and beta -non-muscle (beta -NM) actin in the periphery of cultured rabbit aortic smooth muscle cells (SMCs). To determine whether this reflects a special form of segregation of contractile and cytoskeletal components in SMCs, this study systematically investigated the distribution relationship of structural proteins using high-resolution confocal laser scanning fluorescent microscopy. Not only isoactins but also smooth muscle myosin heavy chain, alpha -actinin, vinculin, and vimentin were heterogeneously distributed in the cultured SMCs. The predominant distribution of beta -NM actin in the cell periphery was associated with densely distributed vinculin plaques and disrupted or striated myosin and ol-actinin aggregates, which may reflect a process of stress fiber assembly during cell spreading and focal adhesion formation. The high-level labeling of alpha -SM actin in the central portion of stress fibers was related to continuous myosin and punctate alpha -actinin distribution, which may represent the maturation of the fibrillar structures. The findings also suggest that the stress fibers, in which actin and myosin filaments organize into sar-comere-like units with alpha -actinin-rich dense bodies analogous to Z-lines, are the contractile vimentin structures of cultured SMCs that link to the network of vimentin-containing intermediate alpha -actinin filaments through the dense bodies and dense plaques.

Perturbed upper limb movements cause short-latency postural responses in trunk muscles

Addition of a load to a moving upper limb produces a perturbation of the trunk due to transmission of mechanical forces. This experiment investigated the postural response of the trunk muscles in relation to unexpected limb loading. Subjects performed rapid, bilateral shoulder flexion in response to a stimulus. In one third of trials, an unexpected load was added bilaterally to the upper limbs in the first third of the movement. Trunk muscle electromyography, intra-abdominal pressure and upper limb and trunk motion were measured. A short-latency response of the erector spinae and transversus abdominis muscles occurred similar to 50 ms after the onset of the limb perturbation that resulted from addition of the load early in the movement and was coincident with the onset of the observed perturbation at the trunk. The results provide evidence of initiation of a complex postural response of the trunk muscles that is consistent with mediation by afferent input from a site distant to the lumbar spine, which may include afferents of the upper limb.

Race and sex effects on the association between muscle strength, soft tissue, and bone mineral density in healthy elders: The Health, Aging, and Body Composition Study

Two factors generally reported to influence bone density are body composition and muscle strength. However, it is unclear if these relationships are consistent across race and sex, especially in older persons. If differences do exist by race and/or sex, then strategies to maintain bone mass or minimize bone loss in older adults may need to be modified accordingly. Therefore, we examined the independent effects of bone mineral-free lean mass (LM), fat mass (FM), and muscle strength on regional and whole body bone mineral density (BMD) in a cohort of 2619 well-functioning older adults participating in the Health, Aging, and Body Composition (Health ABC) Study with complete measures. Participants included 738 white women, 599 black women, 827 white men, and 455 black men aged 70-79 years. BMD (g/cm(2)) of the femoral neck, whole body, upper and lower limb, and whole body and upper limb bone mineral-free LM and FM was assessed by dual-energy X-ray absorptiometry (DXA). Handgrip strength and knee extensor torque were determined by dynamometry. In analyses stratified by race and sex and adjusted for a number of confounders, LM was a significant (p < 0.001) determinant of BMD, except in white women for the lower limb and whole body. In women, FM also was an independent contributor to BMD at the femoral neck, and both PM and muscle strength contributed to limb BMD. The following were the respective Beta-weights (regression coefficients for standardized data, Std beta) and percent difference in BMD per unit (7.5 kg) LM: femoral neck, 0.202-0.386 and 4.7-6.9 %; lower limb,.0.209-0.357 and 2.9-3.5%; whole body, 0.239-0.484 and 3.0-4.7 %; and upper limb (unit = 0.5 kg), 0.231-0.407 and 3.1-3.4%. Adjusting for bone size (bone mineral apparent density [BMAD]) or body size BMD/height) diminished the importance of LM, and the contributory effect of FM became more pronounced. These results indicate that LM and FM were associated with bone mineral depending on the bone site and bone index used. Where differences did occur, they were primarily by sex not race. To preserve BMD, maintaining or increasing LM in the elderly would appear to be an appropriate strategy, regardless of race or sex.

Co-morbidity between alcohol, tobacco and cannabis use: reply to David Fergusson

No abstract

Postural activity of the diaphragm is reduced in humans when respiratory demand increases

1. Respiratory activity of the diaphragm and other respiratory muscles is normally co-ordinated with their other functions, such as for postural control of the trunk when the limbs move. The integration may occur by summation of two inputs at the respiratory motoneurons. The present study investigated whether postural activity of the diaphragm changed when respiratory drive increased with hypercapnoea. 2. Electromyographic (EMG) recordings of the diaphragm and other trunk muscles were made with intramuscular electrodes in 13 healthy volunteers. Under control conditions and while breathing through increased dead-space,subjects made rapid repetitive arm movements to disturb the stability of the spine for four periods each lasting 10 s, separated by 50 s. 3. End-tidal CO2, and ventilation increased for the first 60-120 s of the trial then reached a plateau. During rapid arm movement at the start of dead-space breathing, diaphragm EMG became tonic with superimposed modulation at the frequencies of respiration and arm movement. However, when the arm was moved after 60 s of hypercapnoea, the tonic diaphragm EMG during expiration and the phasic activity with arm movement were reduced or absent. Similar changes occurred for the expiratory muscle transversus abdominis, but not for the erector spinae. The mean amplitude of intra-abdominal pressure and the phasic changes with arm movement were reduced after 60 s of hypercapnoea. 4. The present data suggest that increased central respiratory drive may attenuate the postural commands reaching motoneurons. This attenuation can affect the key inspiratory and expiratory muscles and is likely to be co-ordinated at a pre-motoneuronal site.

The co-segregation of psychosis and selected physical disorders within families of patients with psychosis versus well controls

While it has been reported that individuals with psychosis are at increased or decreased risk of various physical disorders such as cancer and rheumatoid arthritis, there has been less research on the co-segregation of physical disorders within the first-degree relatives of those with psychosis compared to relatives of well controls. The aim of this study was to examine these issues in an epidemiologically informed catchment-area based case-control study. Patients with psychosis were drawn from a prevalence study undertaken as part of the Australian National Mental Health Survey. In addition, we recruited well controls who resided in the same catchment area. For each subject, we drew pedigrees and used a structured checklist to assess the presence of selected psychiatric disorders, and selected disorders such as multiple sclerosis, epilepsy, spina bifida, thyroid disorders, diabetes, asthma and eczema. Data based on pedigrees from 293 individuals with psychosis and 292 well controls was available. As expected, the odds of havingschizophrenia and affective disorders were significantly increased in the families of cases versus controls. The odds of havingeczema were significantly reduced in the relatives of those with psychosis. All other disorders occurred with equal frequency in cases versus control pedigrees. Current theories of eczema suggest that an absence of early life exposure to antigens and infectious agents may fail to prime the na¨ıve immune system, and leave the person at increased risk of eczema. The results of this study suggest that genetic andror environmental factors that facilitate psychosis may protect against eczema. The Stanley Foundation supported this project.

Tubular system volume changes in twitch fibres from toad and rat skeletal muscle assessed by confocal microscopy

The volume of the extracellular compartment (tubular system) within intact muscle fibres from cane toad and rat was measured under various conditions using confocal microscopy. Under physiological conditions at rest, the fractional volume of the tubular system (t-sys(Vol)) was 1.38 +/- 0.09% (n = 17),1.41 +/- 0.09% (n = 12) and 0.83 +/- 0.07% (n = 12) of the total fibre volume in the twitch fibres from toad iliofibularis muscle, rat extensor digitorum longus muscle and rat soleus muscle, respectively. In toad muscle fibres, the t-sys(Vol) decreased by 30% when the tubular system was fully depolarized and decreased by 15% when membrane cholesterol was depleted from the tubular system with methyl-beta-cyclodextrin but did not change as the sarcomere length was changed from 1.93 to 3.30 mum. There was also an increase by 30% and a decrease by 25% in t-sys(Vol) when toad fibres were equilibrated in solutions that were 2.5-fold hypertonic and 50% hypotonic, respectively. When the changes in total fibre volume were taken into consideration, the t-sys(Vol) expressed as a percentage of the isotonic fibre volume did actually decrease as tonicity increased, revealing that the tubular system in intact fibres cannot be compressed below 0.9% of the isotonic fibre volume. The results can be explained in terms of forces acting at the level of the tubular wall. These observations have important physiological implications showing that the tubular system is a dynamic membrane structure capable of changing its volume in response to the membrane potential, cholesterol depletion and osmotic stress but not when the sarcomere length is changed in resting muscle.

Relationship of interleukin-6 and tumor necrosis factor-alpha with muscle mass and muscle strength in elderly men and women: The health ABC study

Background. A decline in muscle mass and muscle strength characterizes normal aging. As clinical and animal studies show it relationship between higher cytokine levels and low muscle mass, the aim of this study was to investigate whether markers, of inflammation are associated with muscle mass and strength in well-functioning elderly persons. Methods. We Used baseline data (1997-1998) of the Health, Aging, and Body Composition (Health ABC) Study on 3075 black and white men and women aged 70-79 years. Midthigh muscle cross-sectional area (computed tomography), appendicular muscle mass (dual-energy x-ray ab absorptiometry). isokinetic knee extensor strength (KinCom). and isometric inip strength were measured. plasma levels of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were assessed by enzyme-linked immunosorbent assay (ELISA). Results. Higher cytokine levels were generally associated with lower muscle mass and lower muscle strength. The most consistent relationship across the gender and race groups was observed for IL-6 and grip strength: per SD increase in IL-6, grip strength was 1.1 to 2.4 kg lower (p < .05) after adjustment for age, clinic Site. health status, medications, physical activity. smoking. height. and body fat. Ail overall measure of elevated cytokine level was created by combining the levels of IL-6 and TNF-alpha. With the exception of white men, elderly persons having high levels of IL-6 (> 1.80 pg/ml) as well as high levels of TNF-alpha (> 3.20 pg/ml) had a smaller muscle area, less appendicular mass. a lower knee extensor strength. and a lower grip strength compared to those with low levels of both cytokines. Conclusions. Higher plasma concentrations of IL-6 and TNF-alpha are associated with lower muscle mass and lower muscle strength in well-functioning older men and women. Higher cytokine levels. as often observed in healthy older persons. may contribute to the loss Of muscle mass and strength that accompanies aging.

Properties of the vertebrate skeletal muscle tubular system as a sealed compartment

Confocal imaging of impermeant fluorescent dyes trapped in the tubular (t-) system of skeletal muscle fibres of rat and cane toad was used to examine changes in the morphology of the t-system upon mechanical skinning, the time course of dye loss from the sealed t-systern in mechanically skinned fibres and the influence of rapid application and removal of glycerol on the morphology of the sealed t-system. In contrast to intact fibres, which have a t-systern open to the outside, the sealed t-systern of toad mechanically skinned fibres consistently displayed local swellings (vesicles). The occurrence of vesicles in the sealed t-system of rat-skinned fibres was infrequent. Application and removal of 200-400 mM glycerol to the sealed t-system did not produce any obvious changes in its morphology. The dyes fluo-3, fura-2 and Oregon green 488 were lost from the sealed t-system of toad fibres at different rates suggesting that the mechanism of organic anion transport across the tubular wall was not by indiscriminate bulk transport. The rate of fluo-3 and fura-2 loss from the sealed t-system of rat fibres was greater in rat than in toad fibres and could be explained by differences in surface area: volume ratio of the t-system in the two fibre types. Based on the results presented here and on other results from this laboratory, an explanation is given for the formation of numerous vesicles in toad-skinned fibres and lack of vesicle formation in rat-skinned fibres. This explanation can also help with better understanding the mechanism responsible for vacuole formation in intact fibres. (C) 2002 Elsevier Science Ltd. All rights reserved.

Identification of the coupling between skeletal muscle store-operated Ca2+ entry and the inositol trisphosphate receptor

Examination of store-operated Ca2+ entry (SOC) in single, mechanically skinned skeletal muscle cells by confocal microscopy shows that the inositol 1,4,5-trisphosphate (IP3) receptor acts as a sarcoplasmic reticulum [Ca2+] sensor and mediates SOC by physical coupling without playing a key role in Ca2+ release from internal stores, as is the case with various cell types in which SOC was investigated previously. The results have broad implications for understanding the mechanism of SOC that is essential for cell function in general and muscle function in particular. Moreover, the study ascribes an important role to the IN receptors in skeletal muscle, the role of which with respect to Ca2+ homeostasis was ill defined until now.

Patterns of co-morbidity between alcohol use and other substance use in the Australian population

The present study describes patterns of co-morbidity between alcohol use and other substance use problems in the Australian population using data from the 1997 National Survey of Mental Health and Well-Being. Multiple regression analyses examined whether the observed associations between alcohol and other drug use disorders were explained by other variables, including demographic characteristics and neuroticism. We also assessed whether the presence of co-morbid substance use disorders affected treatment seeking for a mental health problem. Alcohol use was related strongly to the use of other substances. Those who did not report alcohol use within the past 12 months were less likely to report using tobacco, cannabis, sedatives, stimulants or opiates. Higher rates again were observed among those with alcohol use disorders: half (51%) of those who were alcohol-dependent were regular tobacco smokers, one-third had used cannabis (32%); 15% reported other drug use; 15% met criteria for a cannabis use disorder and 7% met criteria for another drug use disorder. These associations were not accounted for by the demographic and other variables considered here. Co-morbid substance use disorders (sedatives, stimulants or opioids) predicted a high likelihood of seeking treatment for a mental health problem among alcohol-dependent people.

Blockade of vascular smooth muscle cell proliferation and intimal thickening after balloon injury by the sulfated oligosaccharide PI-88: Phosphomannopentaose sulfate directly binds FGF-2, blocks cellular signaling, and inhibits proliferation

Percutaneous transluminal coronary angioplasty is a frequently used interventional technique to reopen arteries that have narrowed because of atherosclerosis. Restenosis, or renarrowing of the artery shortly after angioplasty, is a major limitation to the success of the procedure and is due mainly to smooth muscle cell accumulation in the artery wall at the site of balloon injury. In the present study, we demonstrate that the antiangiogenic sulfated oligosaccharide, PI-88, inhibits primary vascular smooth muscle cell proliferation and reduces intimal thickening 14 days after balloon angioplasty of rat and rabbit arteries. PI-88 reduced heparan sulfate content in the injured artery wall and prevented change in smooth muscle phenotype. However, the mechanism of PI-88 inhibition was not merely confined to the antiheparanase activity of this compound. PI-88 blocked extracellular signal-regulated kinase-1/2 (ERK1/2) activity within minutes of smooth muscle cell injury. It facilitated FGF-2 release from uninjured smooth muscle cells in vitro, and super-released FGF-2 after injury while inhibiting ERK1/2 activation. PI-88 inhibited the decrease in levels of FGF-2 protein in the rat artery wall within 8 minutes of injury. PI-88 also blocked injury-inducible ERK phosphorylation, without altering the clotting time in these animals. Optical biosensor studies revealed that PI-88 potently inhibited (K-i 10.3 nmol/L) the interaction of FGF-2 with heparan sulfate. These findings show for the first time the capacity of this sulfated oligosaccharide to directly bind FGF-2, block cellular signaling and proliferation in vitro, and inhibit injury-induced smooth muscle cell hyperplasia in two animal models. As such, this study demonstrates a new role for PI-88 as an inhibitor of intimal thickening after balloon angioplasty. The full text of this article is available online at http://www.circresaha.org.