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Biomedical subjects

B Russell

Publications and source records attributed to B Russell.

At least 37 records · Page 2Linked to original sources
PubMed1997

The effects of aminorex and related compounds on brain monoamines and metabolites in CBA mice.

Acute and long-term neurochemical effects of aminorex, an appetite-suppressing drug related to amphetamine in chemical structure, and stereoisomers of its analogues were examined and compared with those of 3.4-methylenedioxymethylamphetamine (MDMA) and fenfluramine. Aminorex and its analogues, with exception of 4S, 5S-dimethylaminorex, did not cause the long-term neurotransmitter depletion in either the dopaminergic or 5-HT-ergic systems that was observed after MDMA or fenfluramine in CBA mice. These results are discussed in terms of possible structurally related mechanisms of neurotoxicity. The acute neurochemical effects showed that aminorex and analogues all produced increases in 5-hydroxytryptamine (5-HT) levels, unlike fenfluramine and MDMA in the present study or in published data. This suggests that inhibition of 5-HT metabolism, rather than direct 5-HT release, may be involved in their anorectic effect. The parallel study of acute dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC) changes suggest that in CBA mice MDMA may be a better dopamine releaser and this may contribute to its dopaminergic neurotoxicity. However the ability to release dopamine or 5-HT, or both, may be important, but not the only factor involved in causing the long-term neurotoxicity observed with amphetamine derivatives.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1997

Localization of cardiac (alpha)-myosin heavy chain mRNA is regulated by its 3' untranslated region via mechanical activity and translational block.

We have altered the spontaneous contractile activity of neonatal cardiac myocytes in culture to investigate the re-lationship between mechanical forces, myofibril assembly, and the localization and translation of (alpha)-myosin heavy chain mRNA. Immunofluorescence and in situ hybridization techniques revealed that contracting myocytes display well aligned myofibrils and a diffuse distribution of (alpha)-myosin heavy chain mRNA. Inhibition of contractile activity with the calcium channel blocker verapamil (10 microM) resulted in myofibril disassembly and a perinuclear mRNA distribution within six hours. There was a significant decrease (P<0. 05) of mRNA levels, 5 to 15 micron away from the nucleus following 6 hours of verapamil treatment compared with control cells. Inhibition of protein synthesis with cycloheximide (10 microM) also resulted in perinuclear mRNA localization despite having little effect on contractile activity or myofibril assembly. To determine if the 3' untranslated region of (alpha)-myosin heavy chain mRNA was sufficient for localizing the entire message, a chimeric construct composed of beta-galactosidase coding region followed by (alpha)-myosin heavy chain 3' untranslated region sequences was made as a reporter plasmid and transfected into cultured myocytes. A perinuclear accumulation of ss-galactosidase was exhibited in many of the contractile arrested cells (48.3+/-2.4%, n=7). In contrast, significantly fewer (P<0.05) contracting control (29.1+/-3.3%, n=7) and strongly contracting, isoproterenol-treated cells (27.2+/-6.1%, n=3) exhibited a perinuclear localization of protein. The distribution of the reporter protein was not affected by the contractile state in cells transfected with a constitutively translated 3'UTR. We propose that mechanical activity of neonatal cardiac myocytes regulates the intracellular localization of alpha-myosin heavy chain mRNA via the 3' untranslated region mediated by an initial block in translation.

Animals↗
PubMed1997

Characterization of two human flavin-containing monooxygenase (form 3) enzymes expressed in Escherichia coli as maltose binding protein fusions.

To examine the possibility for drug metabolism polymorphism, adult human flavin-containing monooxygenases (form 3) (EC 1.14.13.8) that differ at one amino acid were expressed in Escherichia coli as maltose binding protein fusions. The cDNA that was first reported during the cloning of adult human flavin-containing monooxygenase was designated the wild type lys158 enzyme. A second cDNA has been identified as a common polymorphism in some human populations and was designated the glu158 enzyme. The cDNA that encodes both enzymes was subcloned into a high yield protein fusion expression system, expressed, and the protein was partially purified by affinity chromatography and characterized for enzyme activity with selective functional substrate probes. N- and S-oxygenation activity of both enzymes was determined with 10-(N,N-dimethylaminopentyl)-2-(trifluoromethyl)phenothiazine and methyl p-tolyl sulfide, respectively. It was found that expression of both lys158 and glu158 enzymes of the human flavin-containing monooxygenase form 3 as fusions with the maltose binding protein resulted in an enzyme that was soluble and greatly stabilized and had a reduced requirement for detergent during enzyme purification and during the assay for activity. Expression of the fusion proteins has allowed the preparation of stable and highly active enzyme at greater purity than was readily possible in the past. With the exception of the stability and solubility characteristics, the physical and chemical properties of lys158 and glu158 maltose binding fusion proteins of human flavin-containing monooxygenase form 3 variants resembled that of flavin-containing monooxygenase enzyme activity associated with human liver microsomes and enzyme isolated from a previous Escherichia coli expression system that lacked the protein fusion. Comparison of the catalytic activity of the two fusion proteins showed that while both forms were active, there were differences in their substrate specificities. Expression of the adult human flavin-containing monooxygenase form 3 as a maltose binding protein has allowed considerable advances over the previously reported cDNA-expressed enzyme systems and may provide the basis for examining the role of the flavin-containing monooxygenase in human xenobiotic or drug metabolism.

ATP-Binding Cassette Transporters↗
PubMed1996

Levator ani muscle in women with genitourinary prolapse: indirect assessment by muscle histopathology.

The objective of this study was to assess the state of innervation in levator ani muscle sites using muscle histopathology. Asymptomatic women and patients with genitourinary prolapse were included. Histopathologic analysis allows indirect assessment of a muscle's innervation. Therefore, levator ani muscle was collected in a standardized fashion during abdominal surgery and frozen in the operating room using isopentane slush cooled by liquid nitrogen. Serial sections of levator ani muscle in cross-section were studied with standard histochemical and immunohistochemical techniques. The staining patterns from these histochemical techniques allowed quantitative determination of the ratios of fiber types I, IIA, and IIB and their fiber diameters. Objective assessment of fiber type grouping was performed. The distribution of both fiber type percentage and diameter were non-parametric. Therefore, the Mann-Whitney U-test was used to analyze the data for statistical differences between the means for these variables. There was no statistical difference in levator ani muscle fiber type percentage and diameter in patients with prolapse and/or urinary incontinence when compared to asymptomatic women. Levator ani muscles have a higher proportion of slow fibers (66%) than found in other human female muscle (48%). There was no evidence for denervation/reinnervation in any of the biopsy specimens. In this study, levator ani muscle biopsies from incontinent and/or prolapse patients were neither denervated nor reinnervated.

Adult↗
PubMed1996

Morphometry of the aging female rat urethra.

Muscles in the limbs change with age, but the aging process of urethral muscles is unknown. Therefore, we compared smooth and striated muscle content in the female rat urethra in young (12 month) and old (32 month) animals, using immunochemical techniques. All the striated skeletal fibers at both ages contain slow myosin. Urethral diameter does not change with age (young, 1.44 +/- 0.08 mm; old, 1.46 +/- 0.10 mm, n = 5), nor does the external sphincter width (young, 0.088 +/- 0.016 mm; old, 0.080 +/- 0.017 mm, n = 5). Neither smooth nor skeletal muscle volume in the urethra is changed with age (skeletal: young, 20.72 +/- 2.94%; old, 19.95 +/- 2.35%. Smooth: young, 22.26 +/- 2.98%; old, 26.75 +/- 2.35%, n = 5). The external striated sphincter is separate and distinct from the pubococcygeal region of the levator ani muscle, but is closely apposed to another layer of longitudinally oriented fibers into the vaginal musculature. The morphometric analysis shows no difference in urethral architecture in aging female rats.

Aging↗
PubMed1996

Physiological role of phosphorylation of the cyclic AMP response element binding protein in rat cardiac nuclei.

We determine whether the cyclic AMP signal transduction pathway affects phosphorylation of cyclic AMP response element binding protein and increases muscle gene expression in the heart. Elevation of cyclic AMP results in phosphorylation of the binding protein which is detected using an antibody specific for the phosphorylated, but not the unphosphorylated, form. The protein is present, but not phosphorylated, within the nuclei of myocytes in intact neonatal rat hearts and in high-density cultures. It is not expressed in low-density cultures. Increasing the amount of phosphorylated cyclic AMP with either isoproterenol or forskolin also increases the frequency and force of the beating. The phosphorylated form of the response element binding protein is visible in the nuclei by 10 min and persists for 2 h of drug treatment. A 1.5-fold increase in skeletal alpha-actin and alpha-myosin gene expression is detected after 48 h of isoproterenol treatment. However, blockage of beating with a calcium channel blocker (verapamil) in the presence of cyclic AMP results in a similar increased gene expression. This suggests that muscle gene expression can be regulated directly by the cyclic AMP pathway, probably via phosphorylation of the cyclic AMP response element binding protein but independent of contractile activity.

Actins↗
PubMed1996

Beating affects the posttranscriptional regulation of alpha-myosin mRNA in cardiac cultures.

Contractile arrest of cardiac myocytes results in increased abundance of alpha-myosin heavy chain (MHC) mRNA but decreased alpha-MHC protein content. Our aim is to determine the posttranscriptional mechanisms regulating alpha-MHC mRNA-protein uncoupling in cultured neonatal rat hearts during altered contractile activity. Spontaneously contracting myocytes were arrested by the use of verapamil (10 mumol/l; a Ca(2+)-channel blocker) or by 2,3-butanedione monoxime (5 mmol/l; a cross-bridge inhibitor). Inhibition of transcription with amanitin (0.5 mumol/l) decreased the alpha-MHC mRNA in normally beating myocytes to a minimal baseline. However, the alpha-MHC mRNA did not fall this low in amanitin-treated nonbeating myocytes. Concurrently, the alpha-MHC mRNA shifted toward a heavier polysome complex when beating was blocked. Together, these data suggest that contractile arrest regulates alpha-MHC mRNA abundance posttranscriptionally by stabilizing the message at the elongation phase of translation. These posttranscriptional regulatory steps are dependent on beating itself and are independent of Ca2+ entry.

Animals↗
PubMed1996

Setting a standard for leg ulcer assessment.

District nurses in one division of Highland Communities NHS Trust set a standard for the assessment of leg ulcers and audited their practice against it. The standard was that 'each patient referred with a leg ulcer is assessed by a trained nurse, using the agreed ulcer assessment form and Doppler ultrasound, within two weeks of referral'. This paper describes the audit processes which have led to the development of a multidisciplinary team approach for the management of leg ulcers in the community. It was found that only 30% (n = 7) of the nurses surveyed met with the required standard. The survey will be repeated following the official implementation of the standard.

Community Health Nursing↗
PubMed1995

Perinatal changes in avian muscle: implications from ultrastructure for the development of endothermy.

Endothermic heat production and the capacity to shiver develop soon after hatching in birds, permitting chicks to regulate their body temperature. Physiological studies have not clearly identified the developmental events causing this change in function. Here, we use electron microscopy to examine the development of structures involved in muscle activation, contraction, and metabolism coincident with the development of shivering thermogenesis. A stereological study was used to compare the ultrastructure of chicken iliofibularis before endothermic heat production was present (24 h before hatching) and 120 h later, when the iliofibularis had substantial capacity for shivering. Profound increases were found in the t-tubule system and terminal cisternae, mitochondrial cristae, and lipids. The number of triadic profiles increased 3.8-fold (7.6 +/- 1.31/100 microns 2 to 28.5 +/- 2.90/100 microns 2 fiber area). The surface area of cristae per mitochondrial volume doubled (12.0 +/- 1.50 microns 2/microns 3 to 25.7 +/- 1.84 microns 2/microns 3). Lipid droplets were rare in the iliofibularis of embryos about to hatch, but accounted for 4.4% of the muscle fiber volume in day 4 birds. We suggest that these ultrastructural changes more fully activate the iliofibularis, allow it to produce more heat both from calcium pumping and from contraction, and increase its endurance, thus permitting the muscle to be effective in thermogenesis.

Aging↗
PubMed1995

The Association for Professionals in Infection Control and Epidemiology, Inc.

The Association for Professionals in Infection Control and Epidemiology, Inc. (APIC) is a multidisciplinary voluntary international organization with over 10,000 members. Its purpose is to influence, support, and improve the quality of healthcare through the practice and management of infection control and the application of epidemiology in all health settings. The organization, which is based in Washington, DC, is led by an elected board of members who volunteer their time and expertise.

Epidemiology↗
PubMed1995

MRF4, Myf-5, and myogenin mRNAs in the adaptive responses of mature rat muscle.

We studied the possible role of specific muscle regulatory factors (MRF) in the adaptive response to changes in contractile activity in mature skeletal muscle. The tibialis anterior muscle of anesthetized female rats was subjected to low-frequency stimulation, static stretch, or a combination of both. Message levels of MRF were observed after 2 h of activity, and the subsequent 20-h recovery period by slot blot and in situ hybridizations for MRF4, Myf-5, and myogenin. A combination of stimulation and stretch for 2 h increased MRF4 (11.6 +/- 5.3-fold) and Myf-5 (6.6 +/- 1.4-fold). In situ hybridization showed abundance in some regions of the muscle with positive staining near peripheral nuclei of both large and small fibers. Message levels remained high for 30 min and declined to near control levels by 20 h of recovery. Myogenin mRNA levels were unaffected by any manipulations. Neither stretch alone nor 10 Hz of electrical stimulation alone induced a significant increase in MRF. We conclude that myonuclei, and possibly activated myoblasts, increase expression of Myf-5 and MRF4 after a combination of both stimulation and stretch for 2 h.

Adaptation, Physiological↗
PubMed1994

The cAMP response element binding protein is expressed and phosphorylated in cardiac myocytes.

Cardiac cells grow in response to a number of stimuli that activate intracellular signaling pathways. The cAMP-signaling pathway mediates the activation of gene transcription in other cell types by the cAMP response element binding protein (CREB-P). Our aim was to explore the physiological role of CREB-P in response to elevated cAMP in cardiac cells by determining if phosphorylation of CREB-P (to phosphoCREB-P) rapidly induces transcription in culture. Primary embryonic chick heart cultures were used in which cAMP was raised by forskolin (5 mumol/L) or isoproterenol (10 mumol/L) treatment. Since both these agents have inotropic effects, tension production was controlled with 2,3-butanedione monoxime (BDM). This allowed us to determine whether the cAMP-signaling pathway or the contractile state was regulating phosphorylation and transcription. The responses for time periods up to 2 hours were assayed with antibodies to detect phosphoCREB-P and by quantitative filter hybridization for creb gene expression. The staining intensity of the phosphoprotein increased in myocyte nuclei after 10 minutes and persisted for 1 hour with either forskolin or isoproterenol treatment. An increase in creb mRNA abundance was also detected, with the maximum level of expression being at 1 hour with forskolin treatment. These changes are independent of the contractile state, because BDM itself caused no change. BDM plus forskolin induced the same pattern of creb expression as observed with forskolin alone. Therefore, we conclude that elevation of cAMP leads to phosphorylation of CREB-P and an increase in creb mRNA abundance.

Animals↗
PubMed1993

Role of infection control practitioners in human immunodeficiency virus testing. APIC Bloodborne Pathogens Committee.

BACKGROUND: As a result of the HIV epidemic, the role of the ICP has changed; acute care settings have developed a variety of policies regarding patient and health care worker (HCW) HIV testing and issues related to the HIV-infected HCW. APIC conducted a survey to determine the extent to which ICPs were involved in HCW and patient HIV testing and counseling, the prevalence of routine HIV testing for patients, institutional policies on HIV testing of patients and HCWs, and the management of HIV infected HCWs. METHODS: In 1990, a questionnaire was sent to ICPs in a simple random sample of 1300 acute care hospitals (approximately 20%) in the United States. RESULTS: Response rate was 52.8%. Of the 686 respondents, 54.8% provided counseling to the HCW after an exposure incident. ICPs were involved not only in HIV testing and counseling for patients and HCWs but also in institutional policy development for HIV-related issues. Most facilities (73.8%) obtained written consent for testing from the patient after an employee exposure. When a direct care giver was known to be HIV positive, 61.5% of the respondents evaluated each case individually. CONCLUSIONS: The ICP has a significant role in the development and implementation of institutional policies on HIV testing and counseling and on the management of HIV-infected workers. These findings affirm the need for APIC to provide educational opportunities on the issues related to HIV testing and counseling.

AIDS Serodiagnosis↗
PubMed1993

IIx and slow myosin expression follow mitochondrial increases in transforming muscle fibers.

Metabolic profile and contractile isoform expression commonly define classic fiber types in skeletal muscle. Little is known about how metabolic requirements determine expression of fast IIx and slow myosin isoforms in muscles undergoing fiber type conversion. Tibialis anterior muscles from female New Zealand White rabbits were stimulated continuously at 10 Hz for 4-21 days. Quantitative fiber analysis was made for oxidative potential by histochemistry and for fast IIx and slow myosin mRNA content by in situ hybridization. In control muscle we found 3 +/- 0.27% fibers coexpress both fast IIx and slow myosin mRNA and so were not assignable to a classic fiber type. After stimulation, increase in fiber oxidative potential was detectable by 4 days and preceded IIx mRNA increases on a fiber-by-fiber basis. Slow myosin transcripts were detected by 7 days in fibers with higher oxidative levels. Coexpression of IIx and slow transcripts peaked at 22 +/- 2.5% of fibers by 7 days. IIx then declined, leaving slow myosin expressed in 62 +/- 0.45% of fibers by 3 wk. We conclude that during fiber type transformation individual fibers can transcribe two myosin mRNAs synchronously. Metabolic demand precedes and may be linked to IIx and slow myosin isoform expression.

Animals↗
PubMed1993

A myogenic regulatory gene, qmf1, is expressed by adult myonuclei after injury.

Myogenic regulatory factors (MRFs) induce differentiation in developing muscle. We examined the role of MRFs in the repair of adult muscle using a model of stretch-induced injury in 5-wk-old chickens. The anterior latissimus dorsi muscle was stretched by loading the wing with 10% of body weight, while the contralateral muscle served as a control. At various intervals (0.5-72 h), chickens were killed by CO2 asphyxiation and the muscles were frozen. Slot hybridizations showed that the onset of high qmf1 expression occurred as early as 0.5 h, which was before regenerative processes involving satellite cell proliferation were observed. Maximal qmf1 expression varied among animals from 3 to 16 h and returned to control levels by 72 h. Within a muscle, in situ hybridization showed that maximal qmf1 expression varied spatially with > 60% of the nuclei within active fascicles being positive. We interpret this high percentage to mean that many of the nuclei of preexisting muscle fibers must be expressing qmf1. The expression of the protooncogene c-myc (presumably by proliferating cells such as satellite cells, fibroblasts, and capillary epithelial cells) and the MRF qmf1 (by myoblasts and adult muscle nuclei) are among the early molecular responses of injured muscle. We conclude that myogenic regulatory factors are not permanently repressed after embryonic development and that derepression plays a role in the repair of terminally differentiated myofibers.

Animals↗