Amplitude spectrum EEG signal evidence for the dissociation of motor and perceptual spatial working memory in the human brain

This study investigated the question whether spatial working memory related to movement plans (motor working memory) and spatial working memory related to spatial attention and perceptual processes (perceptual spatial working memory) share the same neurophysiological substrate or there is evidence for separate motor and perceptual working memory streams of processing. Towards this aim, ten healthy human subjects performed delayed responses to visual targets presented at different spatial locations. Two tasks were attained, one in which the spatial location of the target was the goal for a pointing movement and one in which the spatial location of the target was used for a perceptual (yes or no) change detection. Each task involved two conditions: a memory condition in which the target remained visible only for the first 250 ms of the delay period and a delay condition in which the target location remained visible throughout the delay period. The amplitude spectrum analysis of the EEG revealed that the alpha (8–12 Hz) band signal was smaller, while the beta (13–30 Hz) and gamma (30–45 Hz) band signals were larger in the memory compared to the non-memory condition. The alpha band signal difference was confined to the frontal midline area; the beta band signal difference extended over the right hemisphere and midline central area, and the gamma band signal difference was confined to the right occipitoparietal area. Importantly, both in beta and gamma bands, we observed a significant increase in the movement-related compared to the perceptual-related memory-specific amplitude spectrum signal in the central midline area. This result provides clear evidence for the dissociation of motor and perceptual spatial working memory.     

Moment arms of the knee extensor mechanism in children and adults

In the present study we investigated whether there are differences in the patellar tendon moment arm (PTMA)-knee angle relationship between pre-pubertal children and adults, and whether the PTMA length scales to relevant anthropometric measurements in the two groups. Anthropometric characteristics and the PTMA length-joint angle relationships were determined in 20 adults and 20 pre-pubertal children of both genders. The anthropometric characteristics measured were height, body mass, knee circumference, medio-lateral knee breadth, anterior-posterior knee depth, leg length, femur length and tibia length. The PTMA was quantified from magnetic resonance images using the geometric centre of the femoral condyle method, at every 5° between 55° and 90° of knee flexion (0° is full extension). Adults had a significantly greater PTMA length at all joint angles (4.2 ± 0.4 vs. 3.6 ± 0.3 cm at 90°; P  < 0.01), with the PTMA length decreasing from knee extension to knee flexion similarly in both adults and children. There were no significant and strong correlations between the PTMA and anthropometric measures in adults for any joint angle. In contrast, the PTMA correlated and scaled with anthropometric characteristics for the children ( P  < 0.05, r  = 0.49–0.9) at all joint angles. The PTMA length in children was most accurately predicted at 85° of flexion from the equation PTMA = –0.25 + 0.083·tibia length + 0.02·leg length ( R ² = 0.83). These findings indicate that the knee extensor mechanism in pre-pubertal children should not be considered to be a 'scaled-down' version of that in adults.     

Differential assessment of angiogenic activity and of vascular survival ability (VSA) in breast cancer

Recent reports provide evidence that some growth factors behave as inhibitors of the apoptosis of the endothelial cells, bringing forward the concept of vascular survival as a post-angiogenesis process. At least two different vasculature development processes occur within a tumor: the angiogenic (formation of new vessels) and the vascular survival pathway, which is devoted to the preservation of the newly-formed vessels in layers that lose contact with the adjacent normal tissue. We developed a method to assess these processes in tissue samples. We noted that differences among tumors may exist not only in the tumor angiogenic activity (TAA) but also in the vascular survival ability (VSA). One third of the highly angiogenic breast cancer cases examined had a poor ability to maintain high vessel density in inner tumor areas. Both parameters are independently related to prognosis, while VSA was directly related to tumor dimensions and node involvement. Patients with high TAA and VSA had a particularly poor prognosis. It is suggested that although cancer angiogenic activity is important for the local invasion and dissemination into vessels and lymphatics, the VSA may be important for the effective formation of viable tumor foci in lymph nodes or distant organs. Recognition and quantification of the vascular survival ability in human tumors may significantly improve the prognostic value of the assessment of tumor vasculature, and may help to stratify patients for clinical trials with novel anti-angiogenic or angiotoxic drugs. Elucidation of the pathways may provide additional targets for antiangiogenic therapy. This revised version was published online in July 2006 with corrections to the Cover Date.     

On a relaxation-labelling algorithm for quantitative assessment of tumour vasculature in tissue section images

Although tumour vasculature constitutes a biological factor playing a crucial role in the radiation response of tumours, the current procedures of assessment are semiquantitative, typically employing visual examination of stained histological material. Such techniques are also time consuming, and inefficient of extracting essential information on the vascular network. Image analysis has yet to contribute significantly in this direction, and most studies to date focus on blood vessel segmentation through empirical, user-selected thresholds. The present paper proposes an alternative segmentation approach, based on a probabilistic relaxation algorithm, applied in microscopic images of stained tissues. After image partitioning various information is obtained, such as vascular domains and geometrical characteristics of vessels.     

Reconstruction of the anterior cruciate ligament with a patella-tendon-bone graft may lead to a permanent loss of bone mineral content due to decreased patellar tendon stiffness

Immobilisation induces bone loss. Evidence from studies in animals and healthy humans that were immobilised for a limited time indicates that, in general, bone mass may be restored even in adults. Following conservative management of partial tears of the anterior cruciate ligament (ACL), bone loss is often negligible (2-3%). After surgical reconstruction, however, there is greater bone loss (15-20%), with little or no recovery. Bones adapt to the stresses they experience. Also, the largest forces in the musculoskeletal system arise from muscle pull. Tendons transmit these forces. Many surgical techniques for ACL reconstruction use autologous tendon grafts. We hypothesise that tissue harvesting causes weakening of the formerly intact tendon, which, in turn, leads to reduced muscle pull and subsequent bone loss in those parts of the bone that are loaded by the tendon. If our hypothesis holds true, it may change patients' and surgeons' choice of management. Clinical follow-up should assess the functional result with greater scrutiny, possibly including the assessment of bone mineral content. This may be particularly important since there is accumulating evidence that a decrease in bone mineral density (BMD) preceedes, and hence may be a cause of, osteoarthritis.     

Broad and unexpected phenotypic expression in Greek children with steroid-resistant nephrotic syndrome due to mutations in the Wilms’ tumor 1 (<Emphasis Type="Italic">WT1</Emphasis>) gene

Mutations in the Wilms’ tumor suppressor gene 1 (WT1), most commonly within exons 8 or 9 or intron 9, are found in cases with the overlapping conditions of Denys–Drash and Frasier syndromes, as well as in patients with steroid-resistant nephrotic syndrome (SRNS). This study investigated the presence of WT1 gene mutations in cases with childhood SRNS, along with an evaluation of their clinical outcome. Twenty-seven Greek children with sporadic (19 cases) and familial (8 cases) SRNS were tested. Four phenotypically female patients with sporadic SRNS were found to carry de novo WT1 mutations, including two cases with p.R394W, and one case each with p.R366H, or n.1228+5G>A. Karyotype analysis found 46XX in three cases, but 46XY in one. No phenotype–genotype correlations were apparent in the WT1 gene positive cases since their clinical presentation varied broadly. Interestingly, one patient with a pathological WT1 nucleotide variation responded fully to combined therapy with cyclosporine A and corticosteroids. This study further illustrates that investigation of WT1 gene mutations is clinically useful to support definitive diagnosis in children presenting with SRNS in order to direct the most appropriate clinical management.     

Human tendon behaviour and adaptation, in vivo

Tendon properties contribute to the complex interaction of the central nervous system, muscle-tendon unit and bony structures to produce joint movement. Until recently limited information on human tendon behaviour in vivo was available; however, novel methodological advancements have enabled new insights to be gained in this area. The present review summarizes the progress made with respect to human tendon and aponeurosis function in vivo, and how tendons adapt to ageing, loading and unloading conditions. During low tensile loading or with passive lengthening not only the muscle is elongated, but also the tendon undergoes significant length changes, which may have implications for reflex responses. During active loading, the length change of the tendon far exceeds that of the aponeurosis, indicating that the aponeurosis may more effectively transfer force onto the tendon, which lengthens and stores elastic energy subsequently released during unloading, in a spring-like manner. In fact, data recently obtained in vivo confirm that, during walking, the human Achilles tendon provides elastic strain energy that can decrease the energy cost of locomotion. Also, new experimental evidence shows that, contrary to earlier beliefs, the metabolic activity in human tendon is remarkably high and this affords the tendon the ability to adapt to changing demands. With ageing and disuse there is a reduction in tendon stiffness, which can be mitigated with resistance exercises. Such adaptations seem advantageous for maintaining movement rapidity, reducing tendon stress and risk of injury, and possibly, for enabling muscles to operate closer to the optimum region of the length-tension relationship.     

Circulating leptin and ghrelin are differentially influenced by estrogen/progestin therapy and raloxifene

BACKGROUND: Leptin and ghrelin are increasingly being recognized as cardiotropic hormones, promoting or inhibiting the atherosclerotic process, respectively. Apoptosis may be one pathway through which the actions of these hormones are mediated. Sex hormones are reported to influence the secretion and action of ghrelin and leptin. OBJECTIVE: To evaluate (1) the association of circulating ghrelin and leptin with selected markers of receptor-mediated apoptosis and (2) the effect of estrogen monotherapy, low dose estrogen-progestin therapy, tibolone and raloxifene on serum ghrelin and leptin in healthy postmenopausal women. METHODS: Eighty eight postmenopausal women aged 44-62 years were randomly allocated to daily (1) conjugated equine estrogens 0.625 mg (CEE), (2) 17beta-estradiol 1mg plus norethisterone acetate 0.5 mg (E(2)/NETA), (3) tibolone 2.5mg, (4) raloxifene HCl 60 mg or (5) no treatment. Serum markers of apoptosis sFas, Fas-ligand (Fas-L) and caspase-1 were measured at baseline. Serum leptin and ghrelin were measured at baseline and at 3 months. RESULTS: Body Mass Index (BMI) and estradiol levels correlated positively, while FSH correlated negatively with serum leptin (BMI: r=0.646, p=0.005, estradiol: r=0.432, p=0.001, FSH: r=-0.401, p=0.002). Insulin levels associated positively with circulating leptin (r=0.394, p=0.011) and negatively with circulating ghrelin (r=-0.401, p=0.009). Serum leptin decreased significantly in E2/NETA group (baseline: 2.882+/-0.76 ng/ml, 3 months: 2.687+/-0.66 ng/ml, p=0.043), while it increased significantly in the raloxifene group (baseline: 2.671+/-0.54 ng/ml, 3 months: 2.839+/-0.47 ng/ml). Ghrelin levels decreased significantly only in the raloxifene group (baseline: 1634+/-592 pg/ml, 3 months: 1408+/-534 pg/ml). CONCLUSION: Apoptosis may be a pathway through which leptin exerts a pro-atherogenic effect. Low dose HT may act cardioprotectively by decreasing leptin levels in healthy recently menopaused women.     

In vivo specific tension of the human quadriceps femoris muscle

It is not known to what extent the inter-individual variation in human muscle strength is explicable by differences in specific tension. To investigate this, a comprehensive approach was used to determine in vivo specific tension of the quadriceps femoris (QF) muscle (Method 1). Since this is a protracted technique, a simpler procedure was also developed to accurately estimate QF specific tension (Method 2). Method 1 comprised calculating patellar tendon force (F _t) in 27 young, untrained males, by correcting maximum voluntary contraction (MVC) for antagonist co-activation, voluntary activation and moment arm length. For each component muscle, the physiological cross-sectional area (PCSA) was calculated as volume divided by fascicle length during MVC. Dividing F _t by the sum of the four PCSAs (each multiplied by the cosine of its pennation angle during MVC) provided QF specific tension. Method 2 was a simplification of Method 1, where QF specific tension was estimated from a single anatomical CSA and vastus lateralis muscle geometry. Using Method 1, the variability in MVC (18%) and specific tension (16%) was similar. Specific tension from Method 1 (30 ± 5 N cm⁻²) was similar to and correlated with that of Method 2 (29 ± 5 N cm⁻²; R ² = 0.67; P < 0.05). In conclusion, most of the inter-individual variability in MVC torque remains largely unexplained. Furthermore, a simple method of estimating QF specific tension provided similar values to the comprehensive approach, thereby enabling accurate estimations of QF specific tension where time and resources are limited.