Motor unit properties from three synergistic muscles during ramp isometric elbow extensions

Many tasks require synergistic activation of muscles that possess different architectural, mechanical, and neural control properties. However, investigations of the motor unit (MU) mechanisms which modulate force are mostly restricted to individual muscles and low forces. To explore the pattern of MU recruitment and discharge behavior among three elbow extensors (lateral and long heads of the triceps brachii, and anconeus) during ramp isometric contractions, recruitment thresholds of 77 MUs in five young men were determined and corresponding MU discharge rates were tracked in 1-s epochs over forces ranging from 0 to 75 % of maximal voluntary isometric force (MVC). Across all forces, MUs in the lateral head discharged at higher rates than those in the anconeus (p < 0.001, Δ = 0.23). When all MUs were considered, recruitment thresholds in the long head of the triceps brachii were higher than the lateral head (p < 0.05, Δ = 0.70) with a trend (p = 0.08, Δ = 0.48) for higher recruitment thresholds in the long head compared with the anconeus. Together, these data indicate a potential mechanical disadvantage of the long head of the triceps brachii at 0° shoulder flexion. However, among low-threshold MUs (<10 % MVC), recruitment thresholds were lower in the anconeus than in both heads of the triceps brachii consistent with the expected twitch contractile and fiber type differences among these muscles. These findings illustrate the importance of considering synergistic relations among muscles used for a coordinated task, and the sensitivity of synergies to muscle architectural, mechanical, and possibly specific synaptic input factors.     

Identification of viral genomic elements responsible for rabies virus neuroinvasiveness

Attenuated tissue culture-adapted and natural street rabies virus (RV) strains differ greatly in their neuroinvasiveness. To identify the elements responsible for the ability of an RV to enter the CNS from a peripheral site and to cause lethal neurological disease, we constructed a full-length cDNA clone of silver-haired bat-associated RV (SHBRV) strain 18 and exchanged the genes encoding RV proteins and genomic sequences of this highly neuroinvasive RV strain with those of a highly attenuated nonneuroinvasive RV vaccine strain (SN0). Analysis of the recombinant RV (SB0), which was recovered from SHBRV-18 cDNA, indicated that this RV is phenotypically indistinguishable from WT SHBRV-18. Characterization of the chimeric viruses revealed that in addition to the RV glycoprotein, which plays a predominant role in the ability of an RV to invade the CNS from a peripheral site, viral elements such as the trailer sequence, the RV polymerase, and the pseudogene contribute to RV neuroinvasiveness. Analyses also revealed that neuroinvasiveness of an RV correlates inversely with the time necessary for internalization of RV virions and with the capacity of the virus to grow in neuroblastoma cells.     

Evaluation of erythropoiesis in long-term hamster bone marrow suspension cultures: absence of a requirement for adherent monolayer cells

In long-term hamster bone marrow cultures, proliferation and differentiation of hemopoietic stem cells occurs for several months without need for hydrocortisone or adherent stromal elements, which are requirements for bone marrow growth in all other species studied. Only the most primitive erythroid progenitors (BFU-E) are produced in the cultures. Following treatment of the cells with erythropoietin, these progenitor cells undergo differentiation into mature hemoglobinized red blood cells. Concomitant addition of erythropoietin (Epo) and prostaglandin-E1 (PGE1) results in the production of large numbers of maturing red blood cells. In cultures stimulated with Epo and PGE1, as many as 70% of the cells are benzidine-positive, while Epo alone stimulated as many as 45% of the cells to become erythroid. Epo and PGE1 do not have any apparent deleterious effect on the continuous hemopoiesis occurring in these cultures. Under identical conditions, syngeneic adherent cell cultures do not produce any erythroid elements. The development of mature red blood cells from primitive erythroid precursors occurs in the presence of Epo alone and without any apparent need for adherent stromal elements. These cultures provide a useful in vitro model for dissecting the positive and negative signals that regulate erythropoiesis.     

Alcoholism susceptibility loci: confirmation studies in a replicate sample and further mapping

BACKGROUND: There is substantial evidence for a significant genetic component to the risk for alcoholism. A previous study reported linkage to chromosomes 1, 2, and 7 in a large data set that consisted of 105 families, each with at least three alcoholic members. METHODS: Additional genotyping in the 105 families has been completed in the chromosomal regions identified in the initial analyses, and a replication sample of 157 alcoholic families ascertained under identical criteria has been genotyped. Two hierarchical definitions of alcoholism were employed in the linkage analyses: (1) Individuals who met both Feighner and DSM-III-R criteria for alcohol dependence represented a broad definition of disease; and (2) individuals who met ICD-10 criteria for alcoholism were considered affected under a more severe definition of disease. RESULTS: Genetic analyses of affected sibling pairs supported linkage to chromosome 1 (LOD = 1.6) in the replication data set as well as in a combined analysis of the two samples (LOD = 2.6). Evidence of linkage to chromosome 7 increased in the combined data (LOD = 2.9). The LOD score on chromosome 2 in the initial data set increased after genotyping of additional markers; however, combined analyses of the two data sets resulted in overall lower LOD scores (LOD = 1.8) on chromosome 2. A new finding of linkage to chromosome 3 was identified in the replication data set (LOD = 3.4). CONCLUSIONS: Analyses of a second large sample of alcoholic families provided further evidence of genetic susceptibility loci on chromosomes 1 and 7. Genetic analyses also have identified susceptibility loci on chromosomes 2 and 3 that may act only in one of the two data sets.     

Fc gamma receptor II (CD32) on malignant B cells influences modulation induced by anti-CD19 monoclonal antibody

Antigenic modulation is one of many factors determining the effectiveness of monoclonal antibody (MoAb)-mediated therapy. To select the isotype of a CD19 MoAb most suitable for radioimmunotherapy of patients with B-cell malignancies, we studied the influence of MoAb isotype on modulation, after binding of the MoAb to different cell-line cells. The CD19-IgG1 MoAb was found to induce modulation of CD19 antigens on Daudi cell line cells more rapidly than did its IgG2a switch variant. We provide evidence that this difference in modulation rate is caused by the expression of Fc gamma receptor II (Fc gamma RII) on these cells. Experiments aimed at elucidating the mechanism of Fc gamma RII involvement in modulation induction by CD19-IgG1 showed that Fc gamma RII did not comodulate with CD19 MoAbs. However, cocrosslinking of CD19 and Fc gamma RII with CD19-IgG1 MoAb resulted in enhanced calcium mobilization in Daudi cells. This increased signal induction accompanies the enhanced capping and subsequent modulation of CD19 antigens. Because Fc gamma RII is expressed in varying densities on malignant B cells in all differentiation stages, our results have implications for the MoAb isotype most suitable for use in MoAb-based therapy of patients with B-cell malignancies.     

Restraint stress and ethanol consumption in two mouse strains

Background: This study examined the interaction between restraint stress and ethanol drinking in mice that consume low and high amounts of ethanol. Methods: Two strains of mice (129SVEV and C57BL/6J) underwent 1 hour of restraint stress twice per day for 4 days in the presence of a CRF‐1 receptor antagonist, a glucocorticoid receptor antagonist or vehicle. Ethanol preference and consumption were assessed using a two bottle choice design. In another study, mice were implanted with pellets containing corticosterone; ethanol preference and consumption were assessed using a two bottle choice design. Results: Restraint stress significantly increased ethanol preference and consumption in 129SVEV mice but not in C57BL/6J mice. Then 129SVEV mice underwent the identical stress procedure; however, mice received either the CRF‐1 receptor antagonist, R121919 (15 or 20 mg/kg, ip) or vehicle 30 minutes prior to stress. R121919 did not block the stress‐induced change in ethanol preference despite causing a significant blunting in the HPA axis. Negative results were also obtained using the CRF‐1 receptor antagonist, Antalarmin (20 mg/kg, ip). In another study, 129SVEV mice were administered either the glucocorticoid receptor antagonist Mifepristone (25, 50 or 100 μg/kg, ip) or vehicle under the same procedure. Mifepristone did not alter ethanol preference. Moreover, the three receptor antagonist did not alter nonstress ethanol consumption either. In the last study, both mouse strains underwent active or sham adrenalectomy, then pellets containing corticosterone or placebo were implanted and preference for ethanol versus water was tested. Corticosterone administration decreased ethanol consumption in a strain‐dependent manner. Conclusion: These data show the restraint model for stress can modestly increase ethanol consumption in 129SVEV mice but not in C57BL/6J mice. Pharmacologic manipulation of CRF and corticosterone did not blunt baseline or stress‐induced change in ethanol preference nor did administration of corticosterone mimic the effects of restraint stress on ethanol consumption. These findings suggest the mechanism responsible for increasing ethanol consumption in this model is independent of the HPA axis and extra‐hypothalamic CRF.     

Differences in participation based on self-esteem in power and manual wheelchair users on a university campus: a pilot study

Objectives: To examine the relationship of self-esteem and wheelchair type with participation of young adult manual and power wheelchair users with diverse physical disabilities. Design: Cross-sectional survey study. Setting: Large University Campus. Participants: A convenience sample of college students (N?=?39) with self-reported physical disabilities who are full time wheelchair users (>40 per week) and are two or more years post illness or injury. Interventions: Not applicable. Main outcome measures: The Rosenberg Self-Esteem Scale was used to measure self-esteem, and the Craig Handicap Assessment and Reporting Technique was used to measure participation. Results: Self-esteem correlated highly with cognitive independence (CI) (r?=?0.58), mobility (r?=?0.67) and social integration (SI) (r?=?0.52). Use of manual wheelchair was significantly related to higher levels of CI and mobility while longer use of any wheelchair (power or manual) was significantly associated with higher levels of mobility and SI. In addition higher self-esteem independently predicted a significant proportion of the variance in CI, mobility and SI, while type of wheelchair predicted a significant proportion of the variance in CI (p?Conclusions: High self-esteem was found to be the strongest predictor of participation in a population of young adults with mobility limitations. Better understanding of the factors influencing participation may help to facilitate new interventions to minimize the disparities between persons with disabilities and their able bodied peers.

• Implication for Rehabilitation

• A total of 46.8% of wheelchair users report the desire for increased community participant but face significant barriers.

• The type of wheelchair has been identified as having a large impact on participation.

• This study found self-esteem to be the strongest predictor of participation, which is notable because self-esteem is a characteristic that is potentially modifiable with treatment.

     

Screening for colorectal cancer in a high-risk population. Results of a mathematical model

A mathematical model was used to estimate the cost-effectiveness of colorectal cancer screening strategies for people who are at high risk because of a first-degree relative with colorectal cancer. The model uses indirect evidence about such factors as cancer incidence, sensitivity and specificity of different tests, and treatment effectiveness. The analysis indicates that for screening people over 40 yr old an annual fecal occult blood test may reduce colorectal cancer mortality by about one-third, either colonoscopy or barium enema may reduce mortality by approximately 85%, a 3-5-yr frequency for endoscopies or barium enemas preserves 70%-90% of the effectiveness of an annual frequency, and beginning screening at age 50 reduces effectiveness by 5%-10%. Although both barium enemas and colonoscopies appear to be effective in reducing mortality, the lower cost of the barium enema makes it a more cost-effective strategy. All of these estimates depend on the baseline estimates of each of the factors incorporated in the model; the conclusions are most sensitive to assumptions about the natural history of adenomatous polyps, the bleeding of adenomas and presymptomatic cancers, and the sensitivity of the fecal occult blood test. Recommendations about colorectal cancer screening must also consider factors such as discomfort, inconvenience, and the availability of various technologies.