Detrended fluctuation analysis detects altered coordination of running gait in athletes following a heavy period of training

Objectives

To investigate whether functional overreaching affects locomotor system behaviour when running at fixed relative intensities and if any effects were associated with changes in running performance.

Effect of arachidonic acid metabolites on bone resorption by isolated rat osteoclasts

Arachidonic acid metabolites (eicosanoids) have major effects on bone but their role is unclear. Many are known to stimulate bone resorption in organ culture, but paradoxically, previous work has suggested that at least some of them act as direct inhibitors of osteoclastic function. In an attempt to clarify the role of eicosanoids in bone physiology, we have defined the duration of action and relative potencies of prostaglandin (PG) E1 and E2 and have extended the range of eicosanoids tested on isolated osteoclasts. We have found that PGE1 and PGE2 inhibited bone resorption by isolated osteoclasts for at least 6 h. Inhibition was followed by recovery to control, not supranormal levels. Bone resorption was inhibited in the range 10(-5)-10(-9) M for PGE1 and PGE2, and the rank order as resorption inhibitors was PGE1 greater than 6-keto PGE1 greater than PGE2 greater than PGA2 greater than PGB2. None of the products of lipoxygenase metabolism showed a significant direct effect. The effects of PGE1 and PGE2 were not antagonistic. Prostaglandin production does not seem to be implicated as a second messenger for the action of calcitonin. Although inhibition of osteoclasts by PGs was less prolonged than that observed in the presence of calcitonin, the sensitivity of osteoclasts to inhibition by PGs, and the duration of the effect without subsequent direct stimulation, suggests that inhibition of osteoclastic resorption is a major physiological role of PG production in bone.     

PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells

PADGEM protein (PADGEM), also known as GMP140, is a platelet alpha- granule membrane protein that is translocated to the external membrane after platelet activation. Although the biosynthesis of this protein was originally thought to be confined to megakaryocytes, the synthesis of PADGEM in endothelial cells was recently demonstrated (McEver et al: Blood 70:1974a, 1987). We now describe the subcellular localization of this protein in endothelial cells. Immunofluorescence staining of permeabilized human umbilical vein endothelial cells with KC4, a well characterized monoclonal antibody to PADGEM, showed positively stained elongated structures similar in distribution and shape to Weibel-Palade bodies. Their identity as Weibel-Palade bodies was confirmed by double label immunofluorescence using KC4 and a polyclonal antiserum to von Willebrand factor (vWf), a protein known to be specifically stored in these organelles. All Weibel-Palade bodies were found to contain PADGEM. In contrast to strong perinuclear staining produced with anti- vWf antibodies, no significant perinuclear staining was obtained with KC4, indicating that relatively little PADGEM is present in the endoplasmic reticulum and in the Golgi apparatus. In endothelial cells treated with secretagogues that stimulate vWf release the elongated structures positive for PADGEM disappeared, further identifying these structures as Weibel-Palade bodies. This observation extends the parallels between Weibel-Palade bodies and alpha-granules and suggests a possible functional association between vWf and PADGEM.     

Adjustment issues related to bilateral prophylactic mastectomy in women at elevated risk of developing breast cancer.

Breast cancer is the most common cancer diagnosis for North American and Western European women. Increased knowledge in availability of genetic testing has helped to identify those women at high risk of eventually developing breast cancer. This has resulted in more women considering bilateral prophylactic mastectomy as a viable preventative option. Although the efficacy of the procedure has been established, much less is known about the psychological impact of undergoing this procedure. In order to assess these factors, we reviewed what is currently known about the psychological impact of undergoing bilateral prophylactic mastectomy. Searches were conducted and inclusion criteria revealed articles that focused on the psychological components involved with undergoing a bilateral prophylactic mastectomy. The findings are summarized and fell broadly into one or more of the following three areas: (1) satisfaction or regret following the surgery, (2) psychosocial functioning after the surgery, and (3) predictors of quality of life. Plastic surgery nurses have a unique opportunity to impact important psychological considerations, such as expectations of the early postoperative period, body image concerns, and psychological distress.     

Occurrence of the t(2;5)(p23;q35) in non-Hodgkin's lymphoma

Primary CD30(Ki-1)-positive anaplastic large-cell lymphoma (ALCL) is considered by some to be a distinct clinicopathologic entity associated with the t(2;5) (p23;q35). However, the specificity of t(2;5) for ALCL has not been carefully studied. Therefore, we performed a detailed analysis of all cases of ALCL with abnormal cytogenetics results in the Nebraska Lymphoma Study Group registry, as well as all other cases of non-Hodgkin's lymphoma with t(2;5) in the registry. We found the t(2;5) in only five of 10 cases of ALCL, four of whom were young patients. However, we also found the t(2;5) in 11 other cases of nonanaplastic lymphoma, including eight children with typical peripheral T-cell lymphomas of various types. The t(2;5) was also found in three older adults with B-cell lymphomas of various types. Thus, the t(2;5) was not specific for CD30+ ALCL. However, t(2;5) may define a clinicopathologic entity in children and young adults characterized by variable morphologies with a T-cell or indeterminate phenotype, CD30-positivity, nodal disease with frequent extranodal involvement, advanced stage, and an excellent response to therapy, including bone marrow transplantation for relapsed disease. The clinical relevance of the t(2;5) in older patients requires further study.     

Response of joint capsule neurons to axial stress and strain during dynamic loading in cat

1. Experiments were conducted to test the hypothesis that the responses of joint capsule mechanoreceptors better encode tissue stress or tissue strain. The experimental model was a small ligament from the cat knee capsule, which was stretched uniaxially in vitro. Experiments were done with either force or displacement as the controlled variable, and with steps, sinusoids, or pseudorandom Gaussian noise (PGN) as the input function. 2. The strength of coupling between neural discharge and both strain and stress was quantified during step experiments using linear correlation coefficients. The correlation between the frequency of neural discharge and stress was 0.93 +/- 0.09 (SD). The correlation between frequency of neural discharge and strain was -0.91 +/- 0.06. The magnitudes of these correlation coefficients were not significantly different. 3. The strength of coupling between neural discharge and both strain and stress during sinusoidal and PGN experiments was quantified by the use of an information theoretic statistic, transinformation. Out of 282 sinusoidal runs, transinformation between neural discharge and stress was significantly greater than transinformation between strain and neural discharge 241 times. Transinformation between strain and neural discharge was significantly greater 15 times. 4. During PGN experiments, transinformation between stress and neural discharge was greater than transinformation between strain and neural discharge in all 19 experimental runs. 5. Conditional transinformation between strain and neural discharge, given stress, was calculated for all sinusoidal and pseudorandom experiments. This statistic was greater than zero in 268 out of 289 experimental runs, indicating that a component of strain independent of stress is being signaled in the neural discharge.     

Effectiveness of electroconvulsive therapy in community settings.

BACKGROUND: Clinical trials indicate that electroconvulsive therapy (ECT) is the most effective treatment for major depression, but its effectiveness in community settings has not been examined. METHODS: In a prospective, naturalistic study involving 347 patients at seven hospitals, clinical outcomes immediately after ECT and over a 24-week follow-up period were examined in relation to patient characteristics and treatment variables. RESULTS: The sites differed markedly in patient features and ECT administration but did not differ in clinical outcomes. In contrast to the 70%-90% remission rates expected with ECT, remission rates, depending on criteria, were 30.3%-46.7%. Longer episode duration, comorbid personality disorder, and schizoaffective disorder were associated with poorer outcome. Among remitters, the relapse rate during follow-up was 64.3%. Relapse was more frequent in patients with psychotic depression or comorbid Axis I or Axis II disorders. Only 23.4% of ECT nonremitters had sustained remission during follow-up. CONCLUSIONS: The remission rate with ECT in community settings is substantially less than that in clinical trials. Providers frequently end the ECT course with the view that patients have benefited fully, yet formal assessment shows significant residual symptoms. Patients who do not remit with ECT have a poor prognosis; this underscores the need to achieve maximal improvement with this modality.     

p70 lupus autoantigen binds the enhancer of the T-cell receptor beta-chain gene.

The p70 (Ku) autoantigen has been described as a nonhistone nuclear protein recognized by antibodies from lupus patients. In our studies on the regulation of T-cell receptor (TCR) beta-chain gene expression we have identified the p70 lupus autoantigen as a DNA-binding protein that binds the enhancer of the TCR beta-chain gene. This enhancer is essential for expression of the TCR beta gene. The core TCR beta enhancer contains the E3 motif, which we show here is essential for enhancer activity. The protection of the E3 motif in T cells and the marked reduction in enhancer activity when the E3 motif is mutated underline its physiological importance in regulating beta enhancer activity. The p70 lupus autoantigen gene was identified by screening T-cell lambda gt11 libraries with an E3 probe. The gene encodes a protein which binds the E3 motif in a sequence-specific manner. The identification of a 70-kDa protein as a major E3-binding protein by UV crosslinking is consistent with the conclusion that the p70 lupus autoantigen binds the beta enhancer. Finally, we have shown that T-cell nuclear proteins which bind the E3 motif bear p70 (Ku) lupus autoantigenic determinants. Together these data suggest that the p70 autoantigen binds a critical motif in the beta enhancer and probably regulates TCR beta gene expression.     

Treatment of Vancomycin-Resistant Enterococci,with a Focus on Quinupristin-Dalfopristin

Enterococci are the second most common cause of hospital-acquired infections, and drug resistance among these organisms is a growing problem. Vancomycin-resistant enterococci (VRE) now account for 7.9% of the nosocomial enterococcal infections. There is no standard therapy for VRE. Although some agents have shown in vitro activity alone or in combination, including ciprofloxacin, doxycycline, novobiocin, teicoplanin, chloramphenicol, and rifampin, treatment options are limited to combinations of drugs with marginal efficacy against the pathogens. Quinupristin-dalfopristin is a new investigational agent with activity against gram-positive cocci, including VRE.