Ligament tension affects nuclear shape in situ: an in vitro study

This study was carried out to test the hypothesis that a relationship exists between ligament tension and ligament cell geometry. Rabbit knee joints were positioned at 70 degrees of joint flexion and the medial collateral ligament (MCL) was mechanically isolated and the femur-MCL-tibia complex was stretched or compressed by displacing the crosshead of a materials testing machine: -2.0 mm (relative compression), 0.0 mm (a reproducible no-load starting point), +/-0.7 mm or + 1.4 mm (relative tension). Each MCL complex was then fixed immediately in 10% neutral buffered formalin. Contralateral knees were dissected similarly with MCLs exposed and fixed in situ at 70 degrees of flexion. Subsequent to histological processing, measurements were made of the profiles of fibrocyte nuclei (since previous work has shown that nuclear shape closely approximates fibrocyte shape) that were located in the central portion of each MCL midsubstance using a video-based computerized morphometry system. Results showed that the dimensions of nuclei in the midsubstance of experimental MCLs were significantly longer and thinner at crosshead displacements that corresponded to increased ligament tension. At +1.4 mm of displacement fibrocyte nuclei were approximately 4 microm longer and 1 microm thinner than those fixed at 0.0 mm, an observation supported by a statistically significant increase in the mean maximum-to-minimum-diameter ratio and a significant decrease in mean cell roundness. These results strongly suggest that mechanical load can directly affect ligament fibrocyte geometry in situ. If a similar phenomenon also occurs in vivo, the metabolism of ligament fibrocytes may be influenced considerably by their loading history.     

Th2-type granuloma development in acute murine schistosomiasis is only partly dependent on CD4+ T cells as the source of IL-4

Schistosome granulomas produce IL-4, important for Th2 granuloma expression. We defined the origins of IL-4 within these granulomas and the role of IL-4-producing CD4(+) T cells in Th2 granuloma development. Dispersed granuloma cells spontaneously produced IL-4 independently of T cells, whereas IL-5 production was T cell dependent. Granuloma IL-4 mRNA localized to the non-T cells and IL-5 to T cells. Granuloma CD4(+) T and NK cells, but not B cells produced IL-4 and IL-5 in vitro. B cell-/- mice generated Th2 granulomas that produced IL-4 and IL-5 normally. Granuloma eosinophils expressed no IL-4 or IL-5 mRNA. Granulomas in WWv mast cell-deficient mice lacked mast cells. The dispersed granuloma cells from WWv mice released IL-4 only after T cell stimulation, suggesting that mast cells influenced the constitutive component of IL-4 production. Rag-1 animals (T/B/NK T cell deficient) given schistosomiasis after reconstitution with splenocytes from naive mice produced Th2 granulomas. Mice reconstituted to create selective CD4(+) T cell IL-4 knockout animals developed eosinophilic granulomas that made IL-4. Thus, granulomas contain several cell types that produce IL-4. Mast cells are not needed to form Th2 granulomas, but influence IL-4 release. Th2 granuloma development in schistosomiasis is only partly dependent on IL-4-producing CD4(+) T cells.     

Myoelectric and Force Feedback in the Facilitation of Isometric Strength Training: A Controlled Comparison

Three groups of 10 normal subjects were trained with 13 maximal isometric contractions on each of 8 days. During 8 of the 13 trials, subject groups received either myoelectric feedback (MFB), or force feedback (FFB), or no feedback. Over the 8 training days all groups increased EMG activity, but no significant group differences in rate of acquisition were obtained. All groups made gains in force over the 8 days. Force feedback produced better acquisition than either MFB or control conditions. However, both MFB and FFB produced comparable and significant differences between feedback and no-feedback trials within a session, highlighting the importance of control group designs in the assessment of biofeedback effects. Dissociation between surface EMG and force was shown not only in the training effects, but also in the difference between feedback and no-feedback performance within a session. An analysis of covariance revealed that during feedback trials MFB produced some EMG facilitation which could not be attributed to increased force production. This effect may have been due to selective reinforcement by MFB of co-contraction in the extraneous musculature, or of changes in motor unit firing patterns. These phenomena may also account for the relative failure of MFB to facilitate force acquisition. A one-month follow-up showed significant retention following similar losses of force in all groups.     

Update of the UMD-FBN1 mutation database and creation of an FBN1 polymorphism database

Fibrillin is the major component of extracellular microfibrils. Mutations in the fibrillin gene on chromosome 15 (FBN1) were first described in the heritable connective disorder, Marfan syndrome (MFS). FBN1 has also been shown to harbor mutations related to a spectrum of conditions phenotypically related to MFS, called "type-1 fibrillinopathies." In 1995, in an effort to standardize the information regarding these mutations and to facilitate their mutational analysis and identification of structure/function and phenotype/genotype relationships, we created a human FBN1 mutation database, UMD-FBN1. This database gives access to a software package that provides specific routines and optimized multicriteria research and sorting tools. For each mutation, information is provided at the gene, protein, and clinical levels. This tool is now a worldwide reference and is frequently used by teams working in the field; more than 220,000 interrogations have been made to it since January 1998. The database has recently been modified to follow the guidelines on mutation databases of the HUGO Mutation Database Initiative (MDI) and the Human Genome Variation Society (HGVS), including their approved mutation nomenclature. The current update shows 559 entries, of which 421 are novel. UMD-FBN1 is accessible at www.umd.be/. We have also recently developed a FBN1 polymorphism database in order to facilitate diagnostics.     

Maximum voluntary weight-bearing by the affected and unaffected legs in standing following stroke

OBJECTIVE: To compare stroke patients to control subjects for ability to transfer body weight onto the affected and unaffected leg in standing; to investigate intra-session reliability. DESIGN: Comparative clinical study conducted within a single session. BACKGROUND: There is a paucity of quantitative data about maximum voluntary weight-bearing in patients during rehabilitation following stroke. METHODS: A Kistler force platform was used to quantify maximum amount of body weight transferred to a single limb in the lateral and forward directions during weight-shifting. Twelve control subjects matched by gender and age (median 64 years) were compared to 12 inpatient stroke patients after a median of 37 days post-onset. RESULTS: The median score for control subjects was approximately 95% of body weight to each leg in both directions. In contrast, stroke patients transferred less body weight (P<0.01) to the affected leg (65.5% lateral; 54.9% forward) and also to the unaffected leg (85.0% lateral; 80.1% forward). For the stroke patients, transfer of body weight was more challenging in the forward direction than the lateral direction on the affected leg (P<0.05). Relative to individual differences in the stroke group, error due to the repeated measurement process was low. CONCLUSION: The testing procedure was found to discriminate between stroke patients and control patients and had high retest reliability within a single session.     

Can simultaneous bilateral movement involve the undamaged hemisphere in reconstruction of neural networks damaged by stroke?

Normalization of upper limb movement remains a difficult problem for a significant subpopulation of hemiplegic stroke patients. Clinical observations prompted investigation of a novel approach using simultaneous identical bilateral movements performed independently. We briefly report 12 controlled single-case experiments using multiple-baseline designs across three separate grasp/reach activities. Unilateral performance tests with the hemiplegic arm using the bilaterally trained actions demonstrated clinically and statistically significant improvements in movement patterns. These improvements were specific to the trained movement and well maintained. Using recent literature we develop a theoretical model proposing that bilateral simultaneous movement promotes interhemispheric disinhibition likely to allow reorganization by sharing of normal movement commands from the undamaged hemisphere. Disinhibition may also encourage recruitment of undamaged neurones to construct new task-relevant neural networks. The potential contribution of spared ipsilateral pathways in the damaged hemisphere, indirect corticospinal pathways and ipsilateral pathways from the undamaged hemisphere is discussed.     

Facilitation of the maximum voluntary contraction in hemiplegia by concomitant cutaneous stimulation

The effects of rapid brushing on the maximum voluntary contraction (MVC) and tonic vibratory reflex (TVR) of various muscles requiring facilitation (quadriceps, biceps femoris and tibialis anterior) were studied in two samples of hemiplegics. Brushing was studied under experimental and placebo conditions. In the first experiment, brushing produced significant facilitation of MVC and TVR in the quadriceps, replicating the findings of Spicer and Matyas (1980) and Matyas and Spicer (1980). However, the effect of the TVR failed to predict the gain in MVC that resulted from brushing. In the second sample of hemiplegics, brushing produced significant facilitation of the MVC and TVR in the biceps femoris but not in the tibialis anterior. The results for biceps femoris confirmed the results obtained with quadriceps. The failure to replicate this effect with tibialis anterior may have resulted from problems with the application of the stimulus to the relevant dermatome. Further exploration of the effect of cutaneous stimulation relating to this muscle is required to resolve this issue. The results of this experiment, with its replication of the facilitatory effect of brushing on TVR and MVC in two muscle groups, suggest that investigations of the effect of cutaneous stimulation on the acquisition and retention of voluntary movement should now take place.     

In situ processing and distribution of intracerebrally injected OVA in the CNS

Drainage and retention of brain-derived antigens are important factors in initiating and regulating immune responses in the central nervous system (CNS). We investigated distribution, immunological processing and retention of intracerebrally infused protein antigen, ovalbumin (OVA), and the subsequent recruitment of CD8(+) T cells into the CNS. We found that protein antigens infused into the CNS can drain rapidly into the cervical lymph node and initiate antigen-specific immune response in the periphery. A portion of the antigens are also retained by CD11b/MAC-1(+) cells in the brain parenchyma where they are recognized by antigen-specific CD8(+) T cells.     

P2 purinoceptors account for the non-nitrergic NANC relaxation in the rat ileum

The transmitters involved in the non-nitrergic component of the non-adrenergic, non-cholinergic (NANC) inhibitory response of the rat small intestinal longitudinal muscle to electrical field stimulation of its nerves is a matter of controversy. The present study is the first one to utilise a combination of a nitric oxide synthase inhibitor and a P₂ purinoceptor antagonist for studying this response. We found that the P₂ purinoceptor antagonist pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS; 5×10⁻⁵ M) abolished the non-nitrergic NANC relaxation to electrical field stimulation (10 Hz). PPADS alone provided a significant, moderate inhibitory action. PPADS specifically inhibited relaxations due to exogenous adenosine 5′-triphosphate (ATP) or α,β-methylene ATP. The guanylate cyclase blocker 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 10⁻⁶ M) did not add to the inhibitory action of N^G-nitro-L-arginine on field stimulation-induced relaxation. ODQ abolished the relaxant effect of the nitric oxide donors nitroglycerin or sodium nitroprusside. These data indicate that: (1) nitric oxide and ATP fully account for the field stimulation-induced relaxation in the rat ileal strip under the experimental conditions of this study, and (2) no ODQ-sensitive guanylate cyclase-mediated mechanism is involved in the non-nitrergic component of the NANC relaxation.