Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026837 (muscle rigidity)
 1,077 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Striated muscle contracts in the absence of calcium at low concentrations of MgATP ([MgATP]), and this has been termed rigor activation because rigor cross bridges attach and activate adjacent actin sites. This process is well characterized in skeletal muscle but not in cardiac muscle. Rigor cross bridges are also thought to increase calcium binding to troponin C and play a synergistic role in activation. We tested the hypothesis that cross bridge-dependent activation results in an increase in contractile activity at normal and low pH values. Myofibrillar ATPase activity was measured as a function of pCa and [MgATP] at pH 7.0, and the data showed that, at pCa values of >/=5.5, there was a biphasic relationship between activity and [MgATP]. Peak activity occurred at 10-50 microM MgATP, and [MgATP] for peak activity was lower with increased pCa. The ATPase activity of rat cardiac myofibrils as a function of [MgATP] at a pCa of 9.0 was measured at several pH levels (pH 5.4-7.0). The ATPase activity as a function of [MgATP] was biphasic with a maximum at 8-10 microM MgATP. Lower pH did not result in a substantial decrease in myofibrillar ATPase activity even at pH 5.4. The extent of shortening, as measured by Z-line spacing, was greatest at 8 microM MgATP and less at both lower and higher [MgATP], and this response was observed at all pH levels. These studies suggest that the peak ATPase activity associated with low [MgATP] was coupled to sarcomere shortening. These results support the hypothesis that cross bridge-dependent activation of contraction may be responsible for contracture in the ischemic heart.
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PMID:Cross bridge-dependent activation of contraction in cardiac myofibrils at low pH. 1033 Feb 28

Nonadherence to accepted design principles for randomized trials has been a limitation of school-based intervention research. Designed to overcome these limitations, the Hutchinson Smoking Prevention Project (HSPP) is a 15-year randomized trial to determine the extent to which a school-based (grades 3-12) tobacco use prevention intervention can deter youth tobacco use throughout and beyond high school. This paper presents the HSPP experimental design, together with methods for its implementation, and an evaluation of the degree to which HSPP has adhered to principles of randomized trials. Results from the experimental design and its conduct include (1) a recruitment rate of 97.6% (40 of 41 targeted school districts), (2) full and active participation for the trial's duration by 100% of the 40 school districts recruited, (3) implementation by virtually all teachers (99%+), with 86% implementation fidelity, and (4) outcome determination for 94.3% (7910) of 8388 original study participants identified 12 years previously at baseline. The high degree of rigor achieved by the HSPP experimental design ensures confidence in the trial's soon-to-be available intervention effectiveness results. Equally important, for future school-based trials, the HSPP design and its execution have illustrated that school-based research can adhere to the principles of rigorous randomized trials, with high rates of implementation, and very high rates of recruitment, maintenance, and follow-up of study participants, even for studies with decade-long follow-up periods. Rigor in school-based trials can be achieved through a combination of (1) commitment to the principles of randomized trials, (2) attention to the special challenges of trials specific to the school setting, (3) adoption and meticulous execution of proven methods for trial conduct, and (4) establishment at the outset of principles for maintaining positive collaborative relationships with participating school districts for the duration of the trial. These findings are important in light of the great potential for using the nation's schools to access youth for health promotion/risk-factor prevention.
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PMID:Experimental design and methods for school-based randomized trials. Experience from the Hutchinson Smoking Prevention Project (HSPP). 1071 12

Rigor mortis is thought to be related to falling ATP levels in muscles postmortem. We measured rigor mortis as tension determined isometrically in three rat leg muscles in liquid paraffin kept at 37 degrees C or 25 degrees C--two red muscles, red gastrocnemius (RG) and soleus (SO) and one white muscle, white gastrocnemius (WG). Onset, half and full rigor mortis occurred earlier in RG and SO than in WG both at 37 degrees C and at 25 degrees C even though RG and WG were portions of the same muscle. This suggests that rigor mortis directly reflects the postmortem intramuscular ATP level, which decreases more rapidly in red muscle than in white muscle after death. Rigor mortis was more retarded at 25 degrees C than at 37 degrees C in each type of muscle.
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PMID:Onset of rigor mortis is earlier in red muscle than in white muscle. 1092 41

Rigor mortis development in turkey breast muscle and the effect of electrical stunning on this process are not well characterized. Some electrical stunning procedures have been known to inhibit postmortem (PM) biochemical reactions, thereby delaying the onset of rigor mortis in broilers. Therefore, this study was designed to characterize rigor mortis development in stunned and unstunned turkeys. A total of 154 turkey toms in two trials were conventionally processed at 20 to 22 wk of age. Turkeys were either stunned with a pulsed direct current (500 Hz, 50% duty cycle) at 35 mA (40 V) in a saline bath for 12 seconds or left unstunned as controls. At 15 min and 1, 2, 4, 8, 12, and 24 h PM, pectoralis samples were collected to determine pH, R-value, L* value, sarcomere length, and shear value. In Trial 1, the samples obtained for pH, R-value, and sarcomere length were divided into surface and interior samples. There were no significant differences between the surface and interior samples among any parameters measured. Muscle pH significantly decreased over time in stunned and unstunned birds through 2 h PM. The R-values increased to 8 h PM in unstunned birds and 24 h PM in stunned birds. The L* values increased over time, with no significant differences after 1 h PM for the controls and 2 h PM for the stunned birds. Sarcomere length increased through 2 h PM in the controls and 12 h PM in the stunned fillets. Cooked meat shear values decreased through the 1 h PM deboning time in the control fillets and 2 h PM in the stunned fillets. These results suggest that stunning delayed the development of rigor mortis through 2 h PM, but had no significant effect on the measured parameters at later time points, and that deboning turkey breasts at 2 h PM or later will not significantly impair meat tenderness.
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PMID:Rigor mortis development in turkey breast muscle and the effect of electrical stunning. 1109 45

This phase II study determined the efficacy and safety of alemtuzumab, a humanized anti-CD52 monoclonal antibody, delivered subcutaneously as first-line therapy, over a prolonged treatment period of 18 weeks in 41 patients with symptomatic B-cell chronic lymphocytic leukemia (B-CLL). Injections were administered subcutaneously 3 times per week, from week 2 to 3 onward. An overall response rate (OR) of 87% (95% CI, 76%-98%; complete remission [CR], 19%; partial remission [PR], 68%) was achieved in 38 evaluable patients (81% of intent-to-treat population). CLL cells were cleared from blood in 95% patients in a median time of 21 days. CR or nodular PR in the bone marrow was achieved in 66% of the patients and most patients achieved this after 18 weeks of treatment. An 87% OR (29% CR) was achieved in the lymph nodes. The median time to treatment failure has not yet been reached (18+ months; range, 8-44+ months). Transient injection site skin reactions were seen in 90% of patients. Rigor, rash, nausea, dyspnea, and hypotension were rare or absent. Transient grade IV neutropenia developed in 21% of the patients. Infections were rare, but 10% patients developed cytomegalovirus (CMV) reactivation. These patients rapidly responded to intravenous ganciclovir. One patient, allergic to cotrimoxazole prophylaxis, developed Pneumocystis carinii pneumonia. Alemtuzumab is highly effective as first-line treatment in patients with B-CLL. Prolonged treatment is important for maximal bone marrow response. Subcutaneous administration induced very few "first-dose" flulike symptoms and may reduce health care costs in comparison with the intravenous infusions.
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PMID:Phase II trial of subcutaneous anti-CD52 monoclonal antibody alemtuzumab (Campath-1H) as first-line treatment for patients with B-cell chronic lymphocytic leukemia (B-CLL). 1213 Apr 84

Health and spiritual phenomena are viewed differently depending on the cultural perspective. This study describes spirituality as perceived and experienced by older Thai persons. Specific aims were to describe how spirituality helped older Thai persons maintain their health and to describe what they valued most as they aged. A qualitative, descriptive study informed by ethnographic methods was utilized. The sample included 9 older Thai persons from an urban U.S. community. Data were generated using ethnographic interviews and participant observation. Data analysis incorporated coding, categorizing, and theme development. Rigor was guided by Lincoln and Guba. Five major themes emerged from the data: Connecting with spiritual resources provided comfort and peace, finding harmony through a healthy mind and body, living a valuable life, valuing tranquil relationships with family and friends, and experiencing meaning and confidence in death. For these Thai participants, health and spirituality coexisted and were linked to all of life.
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PMID:Spirituality and health in older Thai persons in the United States. 1258 66

As of yet, only a few strategies to prevent myocardial reperfusion injury have been tested clinically. In the first minutes of reperfusion, the myocardium can be damaged by contracture development, causing mechanical stiffness, tissue necrosis, and the "stone heart" phenomenon. Reperfusion-induced contracture can have two different causes, namely, Ca2+overload-induced contracture or rigor-type contracture. Ca2+ contracture results from rapid re-energization of contractile cells with a persistent Ca2+ overload. Strategies to prevent this type of injury are directed at cytosolic Ca2+ control or myofibrillar Ca2+ sensitivity. Rigor-contracture occurs when re-energization proceeds very slowly. It does not depend on Ca2+ overload. It may be prevented by strategies improving early mitochondrial reactivation
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PMID:Cellular mechanisms of ischemia-reperfusion injury. 1260 6

Clenbuterol is a beta2-adrenoceptor agonist primarily used for treating bronchospasm and alleviating the symptoms of chronic obstructive pulmonary disease (COPD) in the horse. In other species (rats, mice, sheep, and cattle), chronic high doses of clenbuterol (typically in the milligram per kilogram body weight range) has been shown to cause a muscle directed protein anabolic response. Clenbuterol can also modify muscle fibre composition and therefore potentially affect muscle function. This has implications for the performance of exercising horses being treated with therapeutic doses of clenbuterol (typically in the microgram per kilogram body weight range) for bronchospasm or COPD. It is not known whether clenbuterol treatment affects muscle fibre function in horses. The purpose of this study was to examine the effects of a therapeutic dose of clenbuterol, with and without exercise, on the contractile activation characteristics of single membrane permeabilized fibres prepared from muscle biopsies. We tested the hypothesis that therapeutic treatment with clenbuterol would not affect muscle fibre function. Unfit Standardbred mares were treated for 8 weeks with; clenbuterol (2.4 microg/kg twice/day, 5 days/week) plus exercise (20 min at 50% VO2(max) 3 d/wk; CLENEX), clenbuterol only (CLEN), or exercise only (EX). Muscle biopsies were taken from the gluteus medius muscle before and after treatment and stored in a glycerol-based solution to prepare permeabilized muscle fibres. The force-pCa relationship for fibres from CLEN horses was steeper (P < 0.05) indicative of greater cooperative interactions within the thin filament, however, fibre sensitivity to Ca2+ was unchanged. In contrast, the steepness of the force-pCa relationship was not changed in fibres from EX and CLENEX horses and Ca2+ sensitivity was also unaffected. Rigor force, activation in the absence of ATP, was not affected by any treatment indicating an approximately equivalent number of participating cross-bridges during activation. The results indicate that a therapeutic dose of clenbuterol to Standardbred horses does not affect the Ca(2+)-activated contractile characteristics of isolated muscle fibres.
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PMID:Therapeutic clenbuterol treatment does not alter Ca2+ sensitivity of permeabilized fast muscle fibres from exercise trained or untrained horses. 1467 50

As a first step toward freeze-trapping and 3-D modeling of the very rapid load-induced structural responses of active myosin heads, we explored the conformational range of longer lasting force-dependent changes in rigor crossbridges of insect flight muscle (IFM). Rigor IFM fibers were slam-frozen after ramp stretch (1000 ms) of 1-2% and freeze-substituted. Tomograms were calculated from tilt series of 30 nm longitudinal sections of Araldite-embedded fibers. Modified procedures of alignment and correspondence analysis grouped self-similar crossbridge forms into 16 class averages with 4.5 nm resolution, revealing actin protomers and myosin S2 segments of some crossbridges for the first time in muscle thin sections. Acto-S1 atomic models manually fitted to crossbridge density required a range of lever arm adjustments to match variably distorted rigor crossbridges. Some lever arms were unchanged compared with low tension rigor, while others were bent and displaced M-ward by up to 4.5 nm. The average displacement was 1.6 +/- 1.0 nm. "Map back" images that replaced each unaveraged 39 nm crossbridge motif by its class average showed an ordered mix of distorted and unaltered crossbridges distributed along the 116 nm repeat that reflects differences in rigor myosin head loading even before stretch.
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PMID:Electron tomography of fast frozen, stretched rigor fibers reveals elastic distortions in the myosin crossbridges. 1545 Feb 96

The role of cardiac myosin binding protein-C (MyBP-C) on myocardial stiffness was examined in skinned papillary muscles of wild-type (WT(+/+)) and homozygous truncated cardiac MyBP-C (MyBP-C(t/t) male mice. No MyBP-C was detected by gel electrophoresis or by Western blots in the MyBP-C(t/t) myocardium. Rigor-bridge dependent myofilament stiffness, i.e., rigor minus relaxed stiffness, in the MyBP-C(t/t) myocardium (281 +/- 44 kN/m2) was 44% that in WT(+/+) (633 +/- 141 kN/m2). The center-to-center spacing between thick filaments as determined by X-ray diffraction in MyBP-C(t/t) (45.0 +/- 1.2 nm) was not significantly different from that in WT(+/+) (43.2 +/- 0.9 nm). The fraction of cross-sectional area comprised of myofibrils, as determined by electron microscopy, was reduced in the MyBP-C(t/t) (39.9%) by 10% compared to WT(+/+) (44.5%). These data suggest that the 56% reduction in rigor-bridge dependent stiffness of the skinned MyBP-C(t/t) myocardium could not be due solely to a 10% reduction in the number of thick filaments per cross-sectional area and must also be due to approximately 50% reduction in the stiffness of the rigor-bridge attached thick filaments lacking MyBP-C.
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PMID:Reduced cross-bridge dependent stiffness of skinned myocardium from mice lacking cardiac myosin binding protein-C. 1552 68


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