Biomedical subjects

Michael J Baker

Publications and source records attributed to Michael J Baker.

6 recordsLinked to original sources

PubMed2005

Early effects of mechanical ventilation on isotonic contractile properties and MAF-box gene expression in the diaphragm.

This study aimed to determine the time-dependent effects of diaphragmatic inactivity on its maximum shortening velocity (V(max)) and the muscle atrophy F-box (MAF-box, atrogin-1) gene expression during controlled mechanical ventilation (CMV). Twenty-four New Zealand White rabbits were grouped into 1 day, 2 days, and 3 days of CMV and controls in equal numbers. The in vitro isotonic contractile properties of the diaphragm were determined. In addition, myosin heavy chain protein and mRNA, myosin light chain, MAF-box mRNA, and volume density of abnormal myofibrils were measured. Tetanic force decreased, and V(max) increased from control of 6.4 to 6.6, 7.7, and 8.1 muscle lengths per second after 1, 2, and 3 days of CMV, respectively (P < 0.02). The increased V(max) compensated for the decreased tetanic force; consequently, compared with the controls, maximum power output was unchanged after 3 days of CMV. V(max) correlated with the volume density of abnormal myofibrils [y = 0.1x + 5.7 (r = 0.87, P < 0.01)]. In the diaphragm, MAF-box was overexpressed (355% of control) after 1 day of CMV, before the evidence of structural myofibril disarray. In conclusion, CMV produced a time-dependent increase in V(max) that was associated with the degree of myofibrillar disarray and independent of changes in myosin isoform expression. Furthermore, CMV produced an increase in MAF-box mRNA levels that may be partially or completely responsible for the degree of myofibrillar disarray resulting from CMV.

Animals↗

PubMed2004

Genistein stimulates electrogenic Cl(-) secretion in mouse jejunum.

We used the short-circuit current (I(sc)) technique to investigate the effects of the isoflavone genistein on the electrogenic Cl(-) secretion of the mouse jejunum. Genistein stimulated a sustained increase in I(sc) that was dose dependent. Bumetanide inhibited 76 +/- 5% of the genistein-stimulated I(sc) consistent with activation of Cl(-) secretion. Genistein failed to stimulate I(sc) following maximal activation of the cAMP pathway by forskolin. In addition, forskolin had a reduced effect on I(sc) of the mouse jejunum in the presence of genistein. Glibenclamide, a blocker of CFTR, eliminated the genistein-stimulated increase of I(sc) and reduced the forskolin-activated I(sc). Clotrimazole, a Ca(2+)-activated K(+) channel blocker, failed to reduce the genistein-stimulated I(sc). Vanadate, a blocker of tyrosine-dependent phosphatases, reduced the genistein-activated I(sc). Tyrphostin A23, a tyrosine kinase inhibitor, reduced basal I(sc), after which genistein failed to stimulate I(sc). These data suggest that genistein activated a sustained Cl(-) secretory response of the mouse jejunum and that the effect of genistein was via a tyrosine-dependent phosphorylation pathway.

Animals↗

PubMed2004

Effects of denervation on cell cycle control in laryngeal muscle.

Denervation of skeletal muscle is thought to lead to an accelerated proliferation of myogenic stem cells known as satellite cells. The transition of these cells from a quiescent to a proliferative state is thought to require satellite cells to enter the cell cycle and replicate. Little is known about the expression of genes associated with cell cycle control, and so the objective of this study was to examine the effects of denervation and reinnervation of the posterior cricoarytenoid (PCA) muscle on key cell cycle genes. Female Sprague-Dawley rats were assigned to control, denervated, or reinnervated groups. Animals were killed at 7, 14, and 30 days after ligation of the recurrent laryngeal nerve. The PCA muscle was then analyzed for changes in the messenger RNA levels of key genes associated with cell cycle control, differentiation, and proliferation. Cyclin D1 is a key gene responsible for initiating progression of the cell cycle from G1 to S phase. Interestingly, neither denervation nor reinnervation affected the expression of this gene. In contrast, we found large increases in key cell cycle inhibitors (p21 and the growth arrest and DNA destruction 45 [GADD45] gene) in both the denervated and reinnervated groups. We interpret the increases in these cell cycle inhibitors to reflect (1) an inhibition of satellite cell proliferation and/or (2) a special form of apoptosis that results in the loss of myonuclei known to occur under atrophic conditions. To our knowledge, this is the first study to examine the effects of denervation on cell cycle regulation.

Analysis of Variance↗

PubMed2004

The plasticity of denervated and reinnervated laryngeal muscle: focus on single-fiber myosin heavy-chain isoform expression.

No studies have examined the effects of denervation on the single-fiber distribution of myosin heavy-chain (MyHC) isoforms in laryngeal muscle. The fast type IIB MyHC isoform represents the largest proportion of the myosin pool in the posterior cricoarytenoid (PCA) and the thyroarytenoid (TA) muscles. However, the fast type IIB MyHC isoform is distributed differently at the single-fiber level. Hence, we hypothesized that denervation would result in markedly different patterns of MyHC isoform expression at the single-fiber level. To test this hypothesis, we assigned animals to the following 3 groups: (1) control group; (2) denervation group; or (3) reinnervation group. Animals were killed 7, 14, 30, 90, and 180 days after denervation or reinnervation. Subsequently, the distribution of MyHC isoforms were electrophoretically determined in approximately 7200 single fibers. There were 4 key findings to emerge from this study: (1) The MyHC isoform profile of the PCA muscle, at both the whole-muscle and single-fiber level, is more malleable than that of the TA muscle. (2) In the PCA and TA muscles, denervation produced some similar changes, resulting in a large increase in the pool of fibers coexpressing fast type IIX and IIB MyHC isoforms. (3) Reinnervation of the TA muscle produced significant alterations in the single-fiber distribution of MyHC isoforms while having little effect on the whole-muscle MyHC isoform composition. (4) Since the transitions in MyHC isoform expression associated with denervation were limited primarily to fast type IIB to fast type IIX, we postulate that only minor reductions in muscle function would result (as defined by maximum shortening velocity and the force-velocity relationship).

Analysis of Variance↗

PubMed2003

Single-fiber myosin heavy chain polymorphism: how many patterns and what proportions?

Previous studies have reported the existence of skeletal muscle fibers that coexpress multiple myosin heavy chain isoforms. These surveys have usually been limited to studying the polymorphic profiles of skeletal muscle fibers from a limited number of muscles (i.e., usually <4). Additionally, few studies have considered the functional implications of polymorphism. Hence, the primary objective of this study was to survey a relatively large number of rat skeletal muscle/muscle regions and muscle fibers (n approximately 5,000) to test the hypothesis that polymorphic fibers represent a larger fraction of the total pool of fibers than do so-called monomorphic fibers, which express only one myosin heavy chain isoform. Additionally, we used Hill's statistical model of the force-velocity relationship to differentiate the functional consequences of single-fiber myosin heavy chain isoform distributions found in these muscles. The results demonstrate that most muscles and regions of rodent skeletal muscles contain large proportions of polymorphic fibers, with the exception of muscles such as the slow soleus muscle and white regions of fast muscles. Several muscles were also found to have polymorphic profiles that are not consistent with the I<-->IIA<-->IIX<-->IIB scheme of muscle plasticity. For instance, it was found that the diaphragm muscle normally contains I/IIX fibers. Functionally, the high degree of polymorphism may 1) represent a strategy for producing a spectrum of contractile properties that far exceeds that simply defined by the presence of four myosin heavy chain isoforms and 2) result in relatively small differences in function as defined by the force-velocity relationship.

Animals↗

PubMed2003

External fixation indications and patient selection.

Since its modest beginnings in the mid-nineteenth century, external fixation has seen great changes in its design and application. Once thought of as chiefly a fracture management tool, this modality has found its way into the arenas of corrective osteotomies, Charcot management, limb lengthening, nonunion treatment, and malalignment correction. As external fixation has evolved, great improvements in associated complications have also occurred. This is attributed to evolving frame design, subsequent increased stability, and advances in pin/wire insertion techniques. Paley and Herzenberg describe three factors to consider when evaluating whether to use external or internal fixation [2]. 1. Risk versus benefit of the method used for that specific indication. 2. Surgeon's experience with the specific method. 3. Ability to treat the potential complications of the surgery. The authors agree with these factors but would also include psychological tolerance, compliance with postoperative self-treatment, and personal hygiene. In this article the indications for external fixation were described in terms of pathology and individual patient factors were discussed for the surgeon's consideration. The surgeon must consider the patient's bone quality, age, cognitive ability, psychological tolerance, and compliance level. With these factors kept in mind and evaluated appropriately, the surgeon should be able to select the patient and indications for which external fixation will yield a superior result.

Europe↗