Search

The ventricles of small mammals express mostly α-myosin heavy chain (α-MHC), a fast isoform, whereas the ventricles of large mammals, including humans, express ∼10% α-MHC on a predominately β-MHC (slow isoform) background. In failing human ventricles, the amount of α-MHC is dramatically reduced, leading to the hypothesis that even small amounts of α-MHC on a predominately β-MHC background confer significantly higher rates of force development in healthy ventricles. To test this hypothesis, it is necessary to determine the fundamental rate constants of cross-bridge attachment (fapp) and detachment (gapp) for myosins composed of 100% α-MHC or β-MHC, which can then be used to calculate twitch time courses for muscles expressing variable ratios of MHC isoforms. In the present study, rat skinned trabeculae expressing either 100% α-MHC or 100% α-MHC were used to measure ATPase activity, isometric force, and the rate constant of force redevelopment (ktr) in solutions of varying Ca2+ concentrations. The rate of ATP utilization was -2.5-fold higher in preparations expressing 100% α-MHC compared with those expressing only β-MHC, whereas ktr was 2-fold faster in the α-MHC myocardium. From these variables, we calculated fapp to be approximately threefold higher for α-MHC than β-MHC and gapp to be twofold higher in α-MHC. Mathematical modeling of isometric twitches predicted that small increases in α-MHC significantly increased the rate of force development. These results suggest that low-level expression of α-MHC has significant effects on contraction kinetics. [ABSTRACT FROM AUTHOR]

The participation of nonmuscie myosin in force maintenance is controversial. Furthermore, its regulation is difficult to examine in a cellular context, as the light chains of smooth muscle and nonmuscie myosin comigrate under native and denaturing electrophoresis techniques. Therefore, the regulatory light chains of smooth muscle myosin (SM-RLC) and nonmuscie myosin (NM-RLC) were purified, and these proteins were resolved by iso-electric focusing. Using this method, intact mouse aortic smooth muscle homogenates demonstrated four distinct RLC isoelectric variants. These spots were identified as phosphorylated NM-RLC (most acidic), nonphosphorylated NM-RLC, phosphorylated SM-RLC, and nonphosphorylated SM-RLC (most basic). During smooth muscle activation, NM-RLC phosphorylation increased. During depolarization, the increase in NM-RLC phosphorylation was unaffected by inhibition of either Rho kinase or PKC. However, inhibition of Rho kinase blocked the angiotensin Il-induced increase in NM-RLC phosphorylation. Additionally, force for angiotensin II stimulation of aortic smooth muscle from heterozygous nonmuscie myosin JIB knockout mice was significantly less than that of wild-type littermates, suggesting that, in smooth muscle, activation of nonmuscle myosin is important for force maintenance. The data also demonstrate that, in smooth muscle, the activation of nonmuscle myosin is regulated by Ca2+-calmodulin-activated myosin light chain kinase during depolarization and a Rho kinase-dependent pathway during agonist stimulation. [ABSTRACT FROM AUTHOR]

Abstract: A novel, highly stereoselective method for O-glycosylation of glycals and glycosylbromides is developed using orthoformates as acceptors in the presence of InCl3 to afford the corresponding O-glycopyranosides in 66–94% yield. Both perbenzyl and peracetyl glycals afford the corresponding 2,3-unsaturated-O-glycosides with high α-selectivity. Stoichiometric amounts of orthoformates are sufficient to bring about this transformation instead of large excesses of alcohols. [Copyright &y& Elsevier]

Abstract Purpose  Oral pH triggered drug delivery systems, for targeting to the lower gastrointestinal tract, show erratic behaviour in vivo. This study aimed to establish correlations between in situ gastrointestinal pH, transit time or feed status and the disintegration of pH-responsive dosage forms designed to dissolve above pH 7. Methods  Tablets (radiolabelled with Technetium 99m) coated with Eudragit S were administered to eight healthy subjects in a three-way crossover study after an overnight fast. Food was administered either 30 min after (pre-feed) or 4 h after (fasted) tablet ingestion. Concurrently, a Bravo® pH monitoring capsule (radiolabelled with Indium 111) was administered in a “freefall manner”. In a third arm of the study tablets were given immediately after breakfast (fed). Transit was followed by gamma scintigraphy. Results  Gastrointestinal pH showed variability between and within individuals but no differences were seen between pre-feed and fasted states. Three tablets failed to disintegrate in pre-feed and fed regimens and one in the fasted state; this has been tentatively linked to ileocaecal pH and ileoceacal junction residence time. Conclusions   In vivo performance of “pH-responsive” dosage forms is complex and influenced by a multitude of factors other than just in situ pH. [ABSTRACT FROM AUTHOR]

Summary: Skeletal muscle atrophy occurs as a side effect of treatment with synthetic glucocorticoids such as dexamethasone (DEX) and is a hallmark of cachectic syndromes associated with increased cortisol levels. The E3 ubiquitin ligase MuRF1 (muscle RING finger protein 1) is transcriptionally upregulated by DEX treatment. Differentiated myotubes treated with DEX undergo depletion of myosin heavy chain protein (MYH), which physically associates with MuRF1. This loss of MYH can be blocked by inhibition of MuRF1 expression. When wild-type and MuRF1 −/− mice are treated with DEX, the MuRF1 −/− animals exhibit a relative sparing of MYH. In vitro, MuRF1 is shown to function as an E3 ubiquitin ligase for MYH. These data identify the mechanism by which MYH is depleted under atrophy conditions and demonstrate that inhibition of a single E3 ligase, MuRF1, is sufficient to maintain this important sarcomeric protein. [Copyright &y& Elsevier]

Presents information on the reactions of Indium (II) iodine with various substituted o-quinones solution by successive one-element transfer reactions to give (SQInl2 products. Outline of experimental section; Information on results; Discussions on findings.

Evaluates on improved tumour localization using indium-111 labelled antibodies. Administration of In-anti-CEA with 11 patients; Nuclear medicine techniques; Radiolabelling of antibody.

Objective: To compare indium In 111 altumomab pentetate–labeled antimyosin scintigraphy with magnetic resonance imaging (MRI) in the diagnosis and follow-up of patients with myositis. Design and Methods: Sixteen patients with polymyositis and 1 patient with dermatomyositis, all verified with biopsy samples, were examined during diagnostic evaluation with antimyosin antibody scintigraphy and low-field MRI of the thighs and calves using T[sub 1]- and T[sub 2]-weighted sequences. Both examinations were repeated 6 to 22 months after therapeutic intervention with anti-inflammatory drugs. The performance of the 2 methods for the assessment of the severity of muscle inflammation was evaluated using comparison with clinical examination and the serum creatine kinase level. Results: At diagnosis all patients had increased uptake of antimyosin antibody in the thighs and/or calves. In T[sub 2]-weighted MRI images, increased signal intensity changes reflecting intramuscular edema and inflammation were seen in all patients in at least 1 muscle group in the thighs or calves. After anti-inflammatory drug therapy, the mean uptake of antibody and the mean signal intensity changes in T[sub 2]-weighted MRI had decreased. However, in T[sub 1]-weighted MRI the signal intensity changes reflecting intramuscular fatty degeneration were more pronounced in the follow-up study. The level of serum creatine kinase had decreased markedly by the second examination except in 1 patient who also had more accumulation of antibody in the calves after than before treatment. The clinical condition improved in 8 patients and remained unchanged in 9 patients. Conclusions: Antimyosin scintigraphy and T[sub 2]-weighted MRI are feasible tools for the detection and follow-up of lesions in patients with myositis. Scintigraphy findings correlate with serum creatine kinase activity and seem to reflect disease activity better than T[sub 2]-weighted MRI changes, whereas secondary degenerative intra... [ABSTRACT FROM AUTHOR]

Nucleation and growth of (In,Ga)As–GaAs(100) islands with low In content by molecular-beam epitaxy is investigated by scanning tunneling microscopy. The islands tend to nucleate at upper convex edges of surface steps due to elastic strain relaxation. They are elongated along [01-1] with a flat top (100) facet. The growth of the islands, mainly through uphill transport of the (In,Ga)As material, is characterized by shrinking of the top (100) facet but the ratio of island elongation keeps constant. [ABSTRACT FROM AUTHOR]