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Biomedical subjects

B Russell

Publications and source records attributed to B Russell.

At least 19 recordsLinked to original sources

Pilot treatment program for shoplifting in eating disorders.

OBJECTIVE: There are no established treatment programs for shoplifting in eating disorder patients. Our objective was to observe the effect of an established behavioural treatment program in a series of eating disorder patients. METHODS: Patients with eating disorders who shoplift voluntarily took part in an 8-week behavioral treatment program at the Elizabeth Fry Society of Greater Vancouver, British Columbia. They completed assessments at the first session, last session, and at 1 and 6 months post intervention. RESULTS: Six patients enrolled in the study and three patients completed the treatment program. Only one patient reported a decrease in shoplifting frequency. All subjects reported an increase in self-esteem and ability to control shoplifting impulses. DISCUSSION: Our findings suggest that behavioral therapy may be effective in treating shoplifting in eating disorders, but that longer sessions and follow-up may be necessary to show benefit. A randomized control trial with longer-term follow-up is needed to determine whether there is a benefit.

Adult↗

Sonographic diagnosis of Fallopian tube carcinoma.

Primary Fallopian tube carcinoma (FTC) is one of the rarest gynecological malignancies, accounting for 0.18% to 1.6% of all malignant neoplasms of the female reproductive tract. Preoperative diagnosis of FTC has been previously reported; however, most patients with FTC undergo laparotomy with a presumed diagnosis of ovarian carcinoma. The final diagnosis of FTC is usually established at the time of surgery or on pathological examination. To our knowledge, this is the first report in the English scientific literature in which the preoperative diagnosis of FTC was established by the presence of an adnexal mass with an incomplete septation on transvaginal sonography.

Adenocarcinoma↗

The use of contact lenses to treat visually symptomatic congenital nystagmus.

It has been suggested that contact lens wear improves the visual function of patients with visual loss from congenital nystagmus. In this study, four patients with congenital nystagmus had two evaluations separated by at least one week (one with spectacles, one with contact lenses) including visual acuity, contrast sensitivity, oscillopsia scale, quality of life questionnaire (NEI VFQ-25), and eye movement recording with an infrared tracking system. All patients subjectively preferred contact lenses to spectacles. Their contrast sensitivity and VFQ-25 scores were improved with contact lenses compared with spectacles alone. Several parameters of nystagmus showed no change in two patients, worsening in one patient and improvement in one patient. This suggests that much of the clinical improvement observed in our patients may result from a better optical correction of their refractive error with contact lenses than with spectacles, rather than from a true damping effect of the nystagmus by contact lenses.

Adolescent↗

Calcium not strain regulates localization of alpha-myosin heavy chain mRNA in oriented cardiac myocytes.

Our aim was to test a hypothesis that localization of the alpha-myosin heavy chain (alpha-MyHC) mRNA in oriented neonatal rat cardiomyocytes is regulated either by calcium, or by mechanical strain, or by both. Myocytes, grown on collagen aligned on stretchable silicone membranes, were elongated and had an increased length to width ratio (L/W) compared with randomly oriented myocytes grown on conventional substrata. Oriented cells were stretched by 10% in the longitudinal direction, in the transverse direction or passively unloaded for 6 h. As expected, shape changes followed these mechanical deformations. In situ hybridization was used to determine the localization of alpha-MyHC mRNA by quantitative analysis of optical density under various mechanical perturbations in myocytes that were either spontaneously beating or treated with verapamil (10 mM) to block influx of calcium. Unstretched, longitudinally stretched, and cells stretched transversely all had mRNA dispersed to their extremities. Verapamil treatment resulted in a perinuclear pattern of mRNA under all three mechanical perturbations. Additionally, mRNA distribution was examined in myocytes that were passively unloaded in the presence and absence of verapamil. Unloading myocytes with intact calcium cycling does not result in a perinuclear accumulation of mRNA. These data suggest that calcium is essential for alpha-MyHC mRNA distribution throughout the cell whereas stretch and alignment affect myocyte shape but have little effect on mRNA localization.

Animals↗

Bioterroism.

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Bioterrorism↗

Fabrication of microtextured membranes for cardiac myocyte attachment and orientation.

To understand the role of tissue adaptation to altered physiological states, a more physiologically and dimensionally relevant in vitro model of cardiac myocyte organization has been developed. A microtextured polymeric membrane with micron range dimensions promotes myocyte adhesion through substrate/cell interlocking and, thus, provides a more suitable stretchable matrix for studying overlying cell populations. These microtextured membranes are created using photolithography and microfabrication techniques. Biologically, mechanically, and optically compatible interfaces with specified microarchitecture and surface chemistry have been designed, microfabricated, and characterized for this purpose. Cardiac myocytes plated on these membranes display greater attachment and cell height compared to conventional culture substrates. Advantages of the microtextured membranes include the high degree of reproducibility and the ability to create features on the micron and submicron size scale. Because of the flexibility of substrate material and the ease of creating micron size structures, this technique can be applied to many other physiological and biological systems.

Animals↗

Ultrastructure of detrusor and urethral smooth muscle in women with urinary incontinence.

OBJECTIVE: We performed a quantitative study to determine whether mixed urinary incontinence was associated with any ultrastructural changes in detrusor and urethral smooth muscle. STUDY DESIGN: Detrusor and urethral smooth muscle biopsy specimens were obtained at the time of laparotomy from 5 women aged 35 to 65 years with mixed urinary incontinence and from a control group of 5 continent women. Smooth muscle morphologic characteristics were assessed from a systematic random sample of electron micrographs. A further 16 urethral biopsy specimens were similarly analyzed to confirm the findings of the initial study. RESULTS: The electron-dense portion of the sarcolemma was smaller in urethral biopsy specimens taken from patients with intrinsic sphincter deficiency than in those from control subjects (chi(2)((1)) = 4.9; P =.027). No other morphologic characteristics were unique to patients with incontinence. CONCLUSIONS: Our study suggests that focal adhesion architecture is decreased in urethral smooth muscle of patients with intrinsic sphincter deficiency.

Adult↗

Translation is regulated via the 3' untranslated region of alpha-myosin heavy chain mRNA by calcium but not by its localization.

Posttranscriptional regulation plays an important role in alpha-myosin heavy chain (alpha-MyHC) protein synthesis in cardiac muscle cells. In the present study, we test the effects of calcium and mRNA mislocalization on alpha-MyHC translation in order to determine the mechanism(s) contributing to translational block via the 3' untranslated region (3'UTR). Neonatal rat cardiac myocytes were treated for 6 h with L-isoproterenol (10 microM) to enhance beating, with 10 microM verapamil to block beating and mislocalize mRNA, or with 3 microM colchicine to enhance beating but mislocalize mRNA by depolymerization of the microtubules. In order to determine whether translation is regulated by the 3'UTR, either a control (SV40 3'UTR) or the experimental (alpha-MyHC 3'UTR) was placed after a luciferase reporter gene and transfected into the myocytes. The amount of luciferase protein only decreased significantly in verapamil arrested cells transfected with the alpha-MyHC 3'UTR construct (P < 0.01). To control for the possibility that pharmacological treatments might affect transcription or message stability, we analyzed neomycin and luciferase mRNA levels transcribed from the same transfected plasmid. No significant changes were found with an RNase protection assay. These results suggest that calcium but not mRNA localization regulates protein synthesis and further, this is mediated by the 3' untranslated region of alpha-MyHC.

3' Untranslated Regions↗

Tenotomy decreases reporter protein synthesis via the 3'-untranslated region of the beta-myosin heavy chain mRNA.

We tested the hypothesis that the beta-myosin heavy chain (beta-MHC) 3'-untranslated region (UTR) mediates decreased protein expression after tenotomy of the rat soleus. We also tested the hypothesis that decreased protein expression is the result of RNA-protein interactions within the 3'-UTR. beta-MHC was chosen for study because of its critical role in the function of postural muscles such as soleus. Adult rat soleus muscles were directly injected with luciferase (LUC) reporter constructs containing either the beta-MHC or SV40 3'-UTR. After 48 h of tenotomy, there was no significant effect on LUC expression in the SV40 3'-UTR group. In the beta-MHC 3'-UTR group, LUC expression was 37.3 +/- 4% (n = 5, P = 0.03) of that in sham controls. Gel mobility shift assays showed that a protein factor specifically interacts with the beta-MHC 3'-UTR and that tenotomy significantly increases the level of this interaction (25 +/- 7%, n = 5, P = 0.02). Thus the beta-MHC 3'-UTR is directly involved in decreased protein expression that is probably due to increased RNA-protein binding within the UTR.

3' Untranslated Regions↗

Form follows function: how muscle shape is regulated by work.

What determines the shape, size, and force output of cardiac and skeletal muscle? Chicago architect Louis Sullivan (1856-1924), father of the skyscraper, observed that "form follows function." This is as true for the structural elements of a striated muscle cell as it is for the architectural features of a building. Function is a critical evolutionary determinant, not form. To survive, the animal has evolved muscles with the capacity for dynamic responses to altered functional demand. For example, work against an increased load leads to increased mass and cross-sectional area (hypertrophy), which is directly proportional to an increased potential for force production. Thus a cell has the capacity to alter its shape as well as its volume in response to a need for altered force production. Muscle function relies primarily on an organized assembly of contractile and other sarcomeric proteins. From analysis of homogenized cells and molecular and biochemical assays, we have learned about transcription, translation, and posttranslational processes that underlie protein synthesis but still have done little in addressing the important questions of shape or regional cell growth. Skeletal muscles only grow in length as the bones grow; therefore, most studies of adult hypertrophy really only involve increased cross-sectional area. The heart chamber, however, can extend in both longitudinal and transverse directions, and cardiac cells can grow in length and width. We know little about the regulation of these directional processes that appear as a cell gets larger with hypertrophy or smaller with atrophy. This review gives a brief overview of the regulation of cell shape and the composition and aggregation of contractile proteins into filaments, the sarcomere, and myofibrils. We examine how mechanical activity regulates the turnover and exchange of contraction proteins. Finally, we suggest what kinds of experiments are needed to answer these fundamental questions about the regulation of muscle cell shape.

Adult↗

Expression of insulin growth factor-1 splice variants and structural genes in rabbit skeletal muscle induced by stretch and stimulation.

1. Skeletal muscle is a major source of circulating insulin growth factor-1 (IGF-1), particularly during exercise. It expresses two main isoforms. One of the muscle IGF-1 isoforms (muscle L.IGF-1) is similar to the main liver IGF-1 and presumably has an endocrine action. The other muscle isoform as a result of alternative splicing has a different 3' exon sequence and is apparently designed for an autocrine/paracrine action (mechano-growth factor, MGF). Using RNase protection assays with a probe that distinguishes these differently spliced forms of IGF-1, their expression and also the expression of two structural genes was measured in rabbit extensor digitorum longus muscles subjected to different mechanical signals. 2. Within 4 days, stretch using plaster cast immobilization with the limb in the plantar flexed position resulted in marked upregulation of both forms of IGF-1 mRNA. Electrical stimulation at 10 Hz combined with stretch (overload) resulted in an even greater increase of both types of IGF-1 transcript, whereas electrical stimulation alone, i.e. without stretch, resulted in no significant increase over muscle from sham-operated controls. Previously, it was shown that stretch combined with electrical stimulation of the dorsiflexor muscles in the adult rabbit results in a marked increase in muscle mass involving increases in both length and girth, within a few days. The expression of both systemic and autocrine IGF-1 growth factors provides a link between the mechanical signal and the marked increase in the structural gene expression involved in tissue remodelling and repair. 3. The expression of the beta actin gene was seen to be markedly upregulated in the stretched and stretched/stimulated muscles. It was concluded that the increased expression of this cytoskeletal protein gene is an indication that the production of IGF-1 may initially be a response to local damage. 4. Switches in muscle fibre phenotype were studied using a specific gene probe for the 2X myosin heavy chain gene. Type 2X expression was found to decrease markedly with stimulation alone and when electrical stimulation was combined with stretch. Unlike the induction of IGF-1 and beta actin, the decreased expression of the 2X myosin mRNA was less marked in the 'stretch only' muscles. This indicates that the interconversion of fibre type 2X to 2A may in some situations be commensurate with, but not under the control of IGF-1.

Actins↗

Histologic analysis of needle biopsy of urethral sphincter from women with normal and stress incontinence with comparison of electromyographic findings.

OBJECTIVE: Our goal was to compare urethral sphincter biopsy and needle electromyography between women who had genuine stress incontinence and those who did not. STUDY DESIGN: Seventeen continent women and 10 women with stress incontinence had urethral sphincter needle electromyography and urethral biopsy specimens blindly processed for light and electron microscopy. RESULTS: The continent group had greater skeletal muscle content and percentage in each muscle fascicle and each urethral sphincter. The group with genuine stress incontinence had higher connective tissue content. All urethral skeletal muscle was type 1. The smooth muscle was "multiunit" type and was morphologically indistinguishable between the 2 groups. On electromyography, patients with genuine stress incontinence had significantly more fibrillation potentials, fewer motor unit action potentials, a higher percentage of polyphasia, and less maximum voluntary electrical activity than control subjects. CONCLUSIONS: Women with stress incontinence differ from continent women in skeletal muscle volume, amount of fibrosis, and electromyographic parameters; these differences support a neurogenic contribution to genuine stress incontinence. Urethral sphincter has only type 1 skeletal muscle and "multiunit" type smooth muscle.

Adult↗

Mechanical activity in heart regulates translation of alpha-myosin heavy chain mRNA but not its localization.

Mechanical inactivity depresses protein expression in cardiac muscle tissue and results in atrophy. We explore the mechanical transduction mechanism in spontaneously beating neonatal rat cardiomyocytes expressing the alpha-myosin heavy chain (alpha-MyHC) isoform by interfering with cross-bridge function [2,3-butanedione monoxime (BDM), 7.5 mM] without affecting cell calcium. The polysome content and alpha-MyHC mRNA levels in fractions from a sucrose gradient were analyzed. BDM treatment blocked translation at initiation (162 +/- 12% in the nonpolysomal RNA fraction and 43 +/- 6% in the polysomal fraction, relative to control as 100%; P < 0.05). There was an increase in alpha-MyHC mRNA from the nonpolysomal fraction (120.5 +/- 7.7%; P < 0.05 compared with control) with no significant change in the heavy polysomes. In situ hybridization of alpha-MyHC mRNA was used to estimate message abundance as a function of the distance from the nucleus. The mRNA was dispersed through the cytoplasm in spontaneously beating cells as well as in BDM-treated cells (no significant difference). We conclude that direct inhibition of contractile machinery, but not calcium, regulates initiation of alpha-MyHC mRNA translation. However, calcium, not pure mechanical signals, appears to be important for message localization.

Animals↗

Simultaneous occurrence of two supernumerary autosomal ring chromosomes r(1) and r(16) in twins.

Ring chromosomes are estimated to occur in 3/10000 newborns and the simultaneous occurrence of two autosomal rings must be a very rare event. Recently, the characterisation of these markers using fluorescence in situ hybridisation (FISH) has greatly enhanced cytogenetic-phenotypic correlations in patients with these marker chromosomes. This kind of analysis enabled us to clarify a unique karyotype containing a r(1) and a r(16) in identical twins born after a 26 week gestation with minimal somatic abnormalities. The origin of the rings was identified using a satellite and whole chromosome painting probes. FISH analysis showed the same abnormal female karyotype in both twins, 48,XX,+r(1)(p13q21),+r(16)(p11q11).ish r(1) (D1Z5+,wcpl+), r(16)(D16Z2+,wcp16+) in about two thirds of the cells. Each also had minor clones with a normal female karyotype or with one or the other supernumerary ring. Half of the r(1) contained CBG band negative material and the r(16) appeared to be totally CBG band positive. These twins represent the second report of the simultaneous occurrence of multiple autosomal rings. Their description may help to delineate a new chromosome disorder and shows the usefulness of FISH analysis.

Chromosomes, Human, Pair 1↗

Microtubules are needed for dispersal of alpha-myosin heavy chain mRNA in rat neonatal cardiac myocytes.

In some cell types, microtubules are used for transport of mRNA through the cytoplasm to the translation site. The number of microtubules increases during growth of cardiac myocytes, suggesting a functional role exists. Here, we test the need for microtubules to transport alpha-myosin heavy chain (alpha-MyHC) mRNA through the cytoplasm of neonatal cardiac myocytes. The alpha-MyHC mRNA concentration was assessed by non-radioactive in situ hybridization. The relative mRNA distributions were expressed as slopes (m=OD/micrometer), since optical density declined linearly from the nucleus to the cell periphery. Spontaneously-contracting myocytes displayed a gradual decrease in alpha-MyHC mRNA away from the nucleus (m=-1.27+/-0.12 OD/micrometer). To test whether microtubules were necessary for alpha-MyHC mRNA dispersal, contraction was first arrested with the Ca2+-channel blocker verapamil (10 micrometer) for 18 h, which aggregated the mRNA perinuclearly. Contractile activity was then resumed by washing out verapamil and using isoproterenol (10 micrometer) in the presence or absence of a microtubule depolymerizing drug, colchicine (3 micrometer). Within 6 h, the alpha-MyHC mRNA distribution in myocytes with microtubules returned to normal values (m=-1.11+/-0.14 OD/micrometer), while cells lacking microtubules maintained a perinuclear mRNA distribution (m-1.50+/-0.16 OD/micrometer; P<0.05 from control). Despite this perinuclear pattern of mRNA distribution, the myocytes still produced new myofibrils. These data indicate that microtubules are necessary for dispersal of alpha-MyHC mRNA outward from the nucleus. Furthermore, myofibrillogenesis may occur independently of mRNA localization and microtubule organization.

Animals↗

Pudendal denervation affects the structure and function of the striated, urethral sphincter in female rats.

Our aim was to examine the effects of denervation on urethral anatomy and urine voiding pattern. Rats usually void at one end of their cage, which gives a behavioral index of continence. The voiding preference for denervated rats was decreased to 88.8 + 4.7%, n = 32, P < 0.001, compared to improvements with time for unoperated (117 +/- 10%, n = 16) or sham-operated rats (105 +/- 8%, n = 5). The volume of urine or the frequency of voidings between denervated, unoperated or sham-operated rats did not differ significantly. Urethral sections were analyzed immunochemically and quantified morphometrically. Smooth muscle volume remained constant but skeletal muscle volume decreased after denervation, from 43 +/- 2% to 36 +/- 3% (P < 0.05, n = 5). Fiber diameter decreased from 14.3 +/- 1.4 microm to 8.5 +/- 0.7 microm (P < 0.005). We concluded that pudendal nerve transection in female rats causes behavioral alterations in voiding and muscular atrophy of the striated sphincter.

Animals↗