bluuebunny/crossref_metadata_2025 huggingface dataset:
MUSCLE-INDUCED PATELLOFEMORAL JOINT LOADING RAPIDLY AFFECTS CARTILAGE mRNA LEVELS IN A SITE SPECIFIC MANNER
Authors: Clark Andrea L. , Mills Linda , Hart David A , Herzog Walter
Published: April 2004

Mechanical loading of articular cartilage affects the synthesis and degradation of matrix macromolecules. Much of the work in this area has involved mechanical loading of articular cartilage explants or cells in vitro and assessing biological responses at the mRNA and protein levels. In this study, we developed a new experimental technique to load an intact patellofemoral joint in vivo using muscle stimulation. The articular cartilages were cyclically loaded for one hour in a repeatable and measurable manner. Cartilage was harvested from central and peripheral regions of the femoral groove and patella, either immediately after loading or after a three hour recovery period. Total RNA was isolated from the articular cartilage and biological responses were assessed on the mRNA level using the reverse transcriptase-polymerase chain reaction. Articular cartilage from intact patellofemoral joints demonstrated heterogeneity at the mRNA level for six of the genes assessed independent of the loading protocol. Cyclical loading of cartilage in its native environment led to alterations in mRNA levels for a subset of molecules when assessed immediately after the loading period. However, the increases in TIMP-1 and decreases in bFGF mRNA levels were transient; being present immediately after load application but not after a three hour recovery period.
POSTERIOR ENDOSCOPIC DISCECTOMY USING ENDOSCOPIC LUMBAR DISCECTOMY SYSTEM (ELDS)
Authors: Hiraizumi Yutaka
Published: April 2004

Characteristics of endoscopic lumbar discectomy system (ELDS) developed in Japan were introduced, and the first 50 cases were clinically evaluated. Patients included: 4 cases of double disc herniationat two levels; 1 cranially and 3 caudally migrated discs; 3 spinal canal stenosis; 1 synovial cyst; and 3 persistent ring apophysis. In 4 central disc herniation cases, 1 case was approached bilaterally and other 3 cases unilaterally. Using a step-dilator system, targeting inter-laminar space was exposed and a tubular retractor either of 16 or 18 mm diameter was inserted through the paravertebral muscle. A 30° endoscope of 3 mm diameter was installed to a tubular retractor. Partial laminectomy and resection of ligamentum flavum were performed using microsurgical instruments, followed by medial retraction of the symptomatic nerve root and incision of the herniated disc. Average surgery time was 119 minutes and estimated blood loss was 49.1 gm. Patients left their bed at 1.9 days post-operative and average hospital-stay was 11.5 days. Recovery ratio of the Japanese Orthopedic Association (JOA) score was 80.7%. Average visual analog pain scale at the first day post-operative was 2.9 cm and CRP at the 7th day was 0.4 mg/dl. Adjacent two-level discectomy was possible with one midline skin incision. Coexistence of severe lumbar spinal canal stenosis was most technically demanding pathology. ELDS provided brightened and magnified surgery field. This can be an effective assistant for minimally invasive lumbar disc surgery.
ASSESSING SUSTAINABILITY OF COMMUNITY-BASED WATER UTILITY PROJECTS IN CENTRAL TANZANIA WITH THE HELP OF CANONICAL CORRELATION ANALYSIS
Authors: KALIBA ALOYCE R. M. , NORMAN DAVID W.
Published: April 2004

Improved access to clean water is important in improving health, relieving drudgery for women, and in designing and implementing effective poverty alleviation strategies. However, few empirical studies have had the objective of establishing the link between community participation and management, and sustainability of community based water utility projects. In addition, there is no consensus on the analytical techniques to use for sustainability assessment. This paper uses data collected from community water utility projects in two regions in Central Tanzania to demonstrate the use of canonical correlation analysis in sustainability assessment. The advantage of canonical correlation analysis is that the results are invariant with respect to the basis in which the variables are transformed. In addition, the analytical technique leads itself to identifying what management issues need to be addressed at the project level, to improve both community participation and management, and hence sustainability of such types of projects.
THE CONSIDERATION OF IMPACTS UPON THE AQUATIC ENVIRONMENT IN ENVIRONMENTAL IMPACT STATEMENTS IN ENGLAND AND WALES
Authors: BADR EL-SAYED A. , CASHMORE MATTHEW , COBB DICK
Published: April 2004

Considerable research has been undertaken on the quality of Environmental Impact Statements as an indicator, albeit superficial, of the effectiveness of Environmental Impact Assessment (EIA) practices. Yet there remains a paucity of empirical data on practices at the more detailed level (e.g., for the consideration of certain environmental components and stages of the EIA process), despite the importance of such analyses for the development of grounded measures for enhancing effectiveness. This study contributes to the development of a detailed empirical understanding of EIA practices by examining analyses of impacts upon the aquatic environment (Water Impact Assessment (WIA)) for a sample of 50 development proposals in England and Wales. The research results indicate that WIA practices have improved over time, but a significant proportion of assessments remain unsatisfactory, and the quality of core elements of WIA (e.g., the consideration of alternatives and impact prediction) is particularly problematic. It is suggested that changes made to the EU EIA legislation have not significantly affected WIA practices in England and Wales. However, practices are not as problematic as research indicates is the case for ecological, socio-economic and cumulative impact assessments. Further strengthening the legislative provisions for EIA would partially address a number of specific problems (e.g., inadequate scoping and provision for monitoring). Nevertheless, a comprehensive and concerted strategy for enhancing effectiveness will be required if WIA is fulfil its potential for contributing to the management maxim of sustainable development.
A REVIEW OF FINNISH SOCIAL AND HEALTH IMPACT ASSESSMENTS
Authors: KAUPPINEN TAPANI , NELIMARKKA KIRSI
Published: April 2004

This article examines the ways in which Human Impact Assessment has been integrated into plans and programmes in Finland. The EIA Act requires that the impacts on humans should also be taken into account in assessment. The programmes reviewed have been selected from various sectors, including traffic, energy, forestry and land use. Some common features, strengths and development needs were revealed in the impact assessments. On the basis of this material, at least three procedural challenges to strategic impact assessment can be identified: the differentiation between impacts caused by the programme and other societal changes; the sufficient assessment of undesirable impacts; and the definition of concepts used in the programmes.
DECENTRALISATION OF ENVIRONMENTAL MANAGEMENT IN MALAWI: LESSONS FROM DONOR-SUPPORTED PROJECTS
Authors: MKANDAWIRE MARTIN , YASSIN BEN
Published: April 2004

Malawi entered a formalisation of a decentralised administration structure through the enactment of the Local Government Act of 1998. The environmental implications and obligations are stated in the Environmental Management Act 1996, which also mandates the Environmental Affairs Department as the co-ordinator for environmental management. Both acts devolve environmental management responsibilities to the District Assemblies. Donors (i.e., UNDP and DANIDA) sponsored and facilitated environmental management decentralisation through projects that strengthened legal and institutional framework, and built capacity. A few of lessons have been learnt from the process, and some are outlined in this paper e.g. the need for capacity building, harmonisation of the major statutes, and institutions where to anchor the mainstreamed decentralised environmental management functions. Other lessons include lack of delineation between devolution and deconcentration leading to local participation apathy, different policies among donor agencies resulted in implementation difficulties, and uncertainty in continuity of the initiative e.g. closure of DANIDA activities resulted in almost halt to the decentralisation of environmental management.
ECOEFFICIENCY MEASUREMENT USING DATA ENVELOPMENT ANALYSIS: RESEARCH AND PRACTITIONER ISSUES
Authors: SARKIS JOSEPH , TALLURI SRINIVAS
Published: April 2004

Ecoefficiency is critical for organisations that seek to be both environmentally conscious and profitable. Ecoefficiency has implications for a "win-win" situation to arise. Studying and managing organisations from this perspective requires an evaluation of ecoefficiency. To aid researchers and managers develop measures for ecoefficiency we review the use of data envelopment analysis (DEA) for this purpose. DEA theory and application has increased greatly. Its use as a tool for environmental performance evaluation has been limited. In this paper we provide a number of DEA models and some extensions and how they can be utilised from both the practitioner and researcher perspective. An illustrative example from published data helps to gain insight into the various models, their capabilities and limitations.
Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR
Authors: Sakamoto Kei , Göransson Olga , Hardie D. Grahame , Alessi Dario R.
Published: April 2004

Activation of AMP-activated protein kinase (AMPK) by exercise and metformin is beneficial for the treatment of type 2 diabetes. We recently found that, in cultured cells, the LKB1 tumor suppressor protein kinase activates AMPK in response to the metformin analog phenformin and the AMP mimetic drug 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR). We have also reported that LKB1 activates 11 other AMPK-related kinases. The activity of LKB1 or the AMPK-related kinases has not previously been studied in a tissue with physiological relevance to diabetes. In this study, we have investigated whether contraction, phenformin, and AICAR influence LKB1 and AMPK-related kinase activity in rat skeletal muscle. Contraction in situ, induced via sciatic nerve stimulation, significantly increased AMPKα2 activity and phosphorylation in multiple muscle fiber types without affecting LKB1 activity. Treatment of isolated skeletal muscle with phenformin or AICAR stimulated the phosphorylation and activation of AMPKα1 and AMPKα2 without altering LKB1 activity. Contraction, phenformin, or AICAR did not significantly increase activities or expression of the AMPK-related kinases QSK, QIK, MARK2/3, and MARK4 in skeletal muscle. The results of this study suggest that muscle contraction, phenformin, or AICAR activates AMPK by a mechanism that does not involve direct activation of LKB1. They also suggest that the effects of excercise, phenformin, and AICAR on metabolic processes in muscle may be mediated through activation of AMPK rather than activation of LKB1 or the AMPK-related kinases.
TNF-α-mediated lysosomal permeabilization is FAN and caspase 8/Bid dependent
Authors: Werneburg Nate , Guicciardi M. Eugenia , Yin Xiao-Ming , Gores Gregory J.
Published: April 2004

TNF-α cytotoxic signaling involves lysosomal permeabilization with release of the lysosomal protease cathepsin B (ctsb) into the cytosol. However, the mechanisms mediating lysosomal breakdown remain unclear. Because caspase-8 and factor associated with neutral sphingomyelinase activation (FAN) have been implicated as proximal mediators of TNF-α-associated apoptosis, their role in lysosomal permeabilization was examined. Cellular distribution of ctsb-green fluorescent protein (ctsb-GFP) in a rat hepatoma cell line was imaged by confocal microscopy. ctsb-GFP fluorescence was punctate under basal conditions but became diffuse after treatment with TNF-α/actinomycin D. This cellular redistribution of ctsb-GFP was blocked by transfection with a vector expressing a dominant-negative Fas-associated protein with death domain (ΔFADD), cytokine response modifier A, or a pharmacological caspase-8 inhibitor, IETD-fmk. Consistent with the concept that caspase 8-mediated apoptosis is also Bid-dependent in hepatocytes, ctsb-GFP release from lysosomes was reduced in hepatocytes from Bid −/− mice. Interestingly, transfection with a vector expressing a dominant-negative FAN (ΔFAN) also blocked ctsb-GFP release and caspase-8 activation. Paradigms that inhibited ctsb-GFP release from lysosomes also reduced apoptosis as assessed by morphology and biochemical criteria. In conclusion, these studies suggest FAN is upstream of caspase-8/Bid in a signaling cascade culminating in lysosomal permeabilization.
Folic acid-mediated inhibition of serum-induced activation of EGFR promoter in colon cancer cells
Authors: Nagothu Kiran K. , Rishi Arun K. , Jaszewski Richard , Kucuk Omer , Majumdar Adhip P. N.
Published: April 2004

Although accumulating evidence suggests a chemopreventive role for folic acid (FA) in colorectal carcinogenesis, the underlying mechanisms are largely unknown. Previously, we reported that supplemental FA inhibits the expression and activation of epidermal growth factor receptor (EGFR) in colon cancer cell lines. To determine the mechanism(s) by which FA affects EGFR function, we have examined whether and to what extent supplemental FA or its metabolites 5-methyltetrahydrofolate (MTF), dihydrofolate (DF), and tetrahydrofolate (TF) will modulate basal and serum-induced activation of the EGFR promoter in the HCT-116 colon cancer cell line. HCT-116 cells were preincubated with or without (control) FA or one of its metabolites (10 μg/ml) for 48 h, transfected with the EGFR promoter luciferase reporter construct, and incubated for 48 h with FA, DF, TF, or 5-MTF in the absence or presence of 10% FBS. Supplemental FA as well as its metabolites markedly inhibited EGFR promoter activity and its methylation status. Exposure of the cells to 10% FBS caused a marked stimulation of EGFR promoter activity and its expression, both of which were greatly abrogated by supplemental FA and 5-MTF. In contrast, serum-induced activation of c- fos promoter activity was unaffected by 5-MTF. The 5-MTF-induced inhibition of serum-mediated stimulation of EGFR promoter activity and EGFR expression was reversed when methylation was inhibited by 5-aza-2′-deoxycytidine. Our data suggest that FA and its metabolite 5-MTF inhibit EGFR promoter activity in colon cancer cells by enhancing methylation. This could partly be responsible for FA-mediated inhibition of growth-related processes in colorectal neoplasia.
Dorsomedial hypothalamic sites where disinhibition evokes tachycardia correlate with location of raphe-projecting neurons
Authors: Samuels B. C. , Zaretsky D. V. , DiMicco J. A.
Published: April 2004

Disinhibition of neurons in the region of the dorsomedial hypothalamus (DMH) elicits sympathetically mediated tachycardia in rats through activation of the brain stem raphe pallidus (RP), and this same mechanism appears to be largely responsible for the increases in heart rate (HR) seen in air jet stress in this species. Neurons projecting to the RP from the DMH are said to be concentrated in a specific subregion, the dorsal hypothalamic area (DA). Here, we examined the hypothesis that the location of RP-projecting neurons in the DA correspond to the sites at which microinjection of bicuculline methiodide (BMI) evokes the greatest increases in HR. To determine the distribution of RP-projecting neurons in the DA, cholera toxin B was injected in the RP in four rats. A consistent pattern of retrograde labeling was seen in every rat. In the hypothalamus, RP-projecting neurons were most heavily concentrated midway between the mammillothalamic tract and the dorsal tip of the third ventricle dorsal to the dorsomedial hypothalamic nucleus ∼3.30 mm caudal to bregma. In a second series of experiments, the HR response to microinjections of BMI (2 pmol/5 nl; n = 76) was mapped at sites in the DA and surrounding areas in 22 urethane-anesthetized rats. All injection sites were located from 2.56 to 4.16 mm posterior to bregma, and the microinjections that evoked the largest increase in HR (i.e., >100 beats/min in some instances) were located in a region where RP-projecting neurons were most densely concentrated. Thus RP-projecting neurons in the DA may mediate DMH-induced tachycardia and thus play a role in stress-induced cardiac stimulation.
Expression, localization, and regulation of urea transporter B in rat urothelia
Authors: Spector David A. , Yang Qing , Liu Jie , Wade James B.
Published: April 2004

Although mammalian urothelia are generally considered impermeable to urinary constituents, in vivo studies in several species suggest urothelial transport of water, urea, and solutes under certain conditions. This study investigates the expression, localization, and regulation of urea transporter-B (UT-B) in rat renal pelvis, ureter, and bladder tissues. Immunoblots of homogenates of tissues identified characteristic ∼40- to 55- and ∼32-kDa bands in the ureter, bladder, and renal inner medulla, but not renal cortex. UT-B was localized by immunocytochemistry and was strongly expressed in all cell membranes (and to a limited extent in intracellular vesicles in the cytoplasm) of epithelial cells lining the rat bladder, ureter, and renal pelvis lumens except the apical membrane of the umbrella cells. It was also present in single-layer papillary surface epithelial cells. There was no difference in immunoblot expression of UT-B in the bladder or ureteral homogenates between groups of rats fed high- or low-protein or high- or low-sodium diets. Water restriction resulted in an increase in UT-B expression in ureters (49%, P = 0.001) but not in bladders (14%, P = not significant). The functional role of UT-B in the genitourinary tract epithelia is unknown. UT-B may participate in the regulation of epithelial cell volume and osmolality, in the dissipation of urea gradients, and in possible net urea transport across uroepithelia.
Sprint training improves contractility in postinfarction rat myocytes: role of Na+/Ca2+ exchange
Authors: Song Jianliang , Zhang Xue-Qian , Wang JuFang , Carl Lois L. , Ahlers Belinda A. , Rothblum Lawrence I. , Cheung Joseph Y.
Published: April 2004

Previous studies in adult myocytes isolated from rat hearts 3–9 wk after myocardial infarction (MI) demonstrated abnormal contractility and decreased Na+/Ca2+ exchanger (NCX1) activity. In addition, a program of high-intensity sprint training (HIST) instituted shortly after MI restored both contractility and NCX1 activity toward normal. The present study examined the hypotheses that reduced NCX1 activity caused abnormal contractility in myocytes isolated from sedentary (Sed) rat hearts 9–11 wk after coronary artery ligation and that HIST ameliorated contractile dysfunction in post-MI myocytes by increasing NCX1 activity. The approach was to upregulate NCX1 in MI-sedentary (MISed) myocytes and downregulate NCX1 in MI-exercised (MIHIST) myocytes by adenovirus-mediated gene transfer. Overexpression of NCX1 in MISed myocytes did not affect sarco(endo)plasmic reticulum Ca2+-ATPase and calsequestrin levels but rescued contractile abnormalities observed in MISed myocytes. That is, at 5 mM extracellular Ca2+ concentration, the subnormal contraction amplitude in MISed myocytes (compared with Sham myocytes) was increased toward normal by NCX1 overexpression, whereas at 0.6 mM extracellular Ca2+ concentration the supernormal contraction amplitude in MISed myocytes was lowered. Conversely, NCX1 downregulation by antisense in MIHIST myocytes abolished the beneficial effects of HIST on contraction amplitudes in MI myocytes. We suggest that decreased NCX1 activity may play an important role in contractile abnormalities in post-MI myocytes and that HIST ameliorated contractile dysfunction in post-MI myocytes partly by enhancing NCX1 activity.
Carbon dioxide added late in inspiration reduces ventilation-perfusion heterogeneity without causing respiratory acidosis
Authors: Brogan Thomas V. , Robertson H. Thomas , Lamm Wayne J. E. , Souders Jennifer E. , Swenson Erik R.
Published: April 2004

We have shown previously that inspired CO2 (3-5%) improves ventilation-perfusion (V̇a/Q̇) matching but with the consequence of mild arterial hypercapnia and respiratory acidosis. We hypothesized that adding CO2 only late in inspiration to limit its effects to the conducting airways would enhance V̇a/Q̇ matching and improve oxygenation without arterial hypercapnia. CO2 was added in the latter half of inspiration in a volume aimed to reach a concentration of 5% in the conducting airways throughout the respiratory cycle. Ten mixed-breed dogs were anesthetized and, in a randomized order, ventilated with room air, 5% CO2 throughout inspiration, and CO2 added only to the latter half of inspiration. The multiple inert-gas elimination technique was used to assess V̇a/Q̇ heterogeneity. Late-inspired CO2 produced only very small changes in arterial pH (7.38 vs. 7.40) and arterial CO2 (40.6 vs. 39.4 Torr). Compared with baseline, late-inspired CO2 significantly improved arterial oxygenation (97.5 vs. 94.2 Torr), decreased the alveolar-arterial Po2 difference (10.4 vs. 15.7 Torr) and decreased the multiple inert-gas elimination technique-derived arterial-alveolar inert gas area difference, a global measurement of V̇a/Q̇ heterogeneity (0.36 vs. 0.22). These changes were equal to those with 5% CO2 throughout inspiration (arterial Po2, 102.5 Torr; alveolar-arterial Po2 difference, 10.1 Torr; and arterial-alveolar inert gas area difference, 0.21). In conclusion, we have established that the majority of the improvement in gas exchange efficiency with inspired CO2 can be achieved by limiting its application to the conducting airways and does not require systemic acidosis.
Suppressing lipolysis increases interleukin-6 at rest and during prolonged moderate-intensity exercise in humans
Authors: Holmes Anna G. , Watt Matthew J. , Febbraio Mark A.
Published: April 2004

IL-6 induces lipolysis when administered to humans. Consequently, it has been hypothesized that IL-6 is released from skeletal muscle during exercise to act in a “hormonelike” manner and increase lipolysis from adipose tissue to supply the muscle with substrate. In the present study, we hypothesized that suppressing lipolysis, and subsequent free fatty acid (FFA) availability, would result in a compensatory elevation in IL-6 at rest and during exercise. First, we had five healthy men ingest nicotinic acid (NA) at 30-min intervals for 120 min at rest [10 mg/kg body mass (initial dose), 5 mg/kg body mass (subsequent doses)]. Plasma was collected and analyzed for FFA and IL-6. After 120 min, plasma FFA concentration was attenuated (0 min: 0.26 ± 0.05 mmol/l; 120 min: 0.09 ± 0.02 mmol/l; P < 0.01), whereas plasma IL-6 was concomitantly increased approximately eightfold (0 min: 0.75 ± 0.18 pg/ml; 120 min: 6.05 ± 0.89 pg/ml; P < 0.001). To assess the effect of lipolytic suppression on the exercise-induced IL-6 response, seven active, but not specifically trained, men performed two experimental exercise trials with (NA) or without [control (Con)] NA ingestion 60 min before (10 mg/kg body mass) and throughout (5 mg/kg body mass every 30 min) exercise. Blood samples were obtained before ingestion, 60 min after ingestion, and throughout 180 min of cycling exercise at 62 ± 5% of maximal oxygen consumption. IL-6 gene expression, in muscle and adipose tissue sampled at 0, 90, and 180 min, was determined by using semiquantitative real-time PCR. IL-6 mRNA increased in Con (rest vs. 180 min; P < 0.01) ∼13-fold in muscle and ∼42-fold in fat with exercise. NA increased (rest vs. 180 min; P < 0.01) IL-6 mRNA 34-fold in muscle, but the treatment effect was not statistically significant (Con vs. NA, P = 0.1), and 235-fold in fat (Con vs. NA, P < 0.01). Consistent with the study at rest, NA completely suppressed plasma FFA (180 min: Con, 1.42 ± 0.07 mmol/l; NA, 0.10 ± 0.01 mmol/l; P < 0.001) and increased plasma IL-6 (180 min: Con, 9.81 ± 0.98 pg/ml; NA, 19.23 ± 2.50 pg/ml; P < 0.05) during exercise. In conclusion, these data demonstrate that circulating IL-6 is markedly elevated at rest and during prolonged moderate-intensity exercise when lipolysis is suppressed.
Role of sensory input from the lungs in control of muscle sympathetic nerve activity during and after apnea in humans
Authors: Khayat Rami N. , Przybylowski Tadeusz , Meyer Keith C. , Skatrud James B. , Morgan Barbara J.
Published: April 2004

We reasoned that, if the lung inflation reflex contributes importantly to apnea-induced sympathetic activation, such activation would be attenuated in bilateral lung transplant recipients (LTX). We measured muscle sympathetic nerve activity (MSNA; intraneural electrodes), heart rate, mean arterial pressure, tidal volume, end-tidal Pco2, and arterial oxygen saturation in seven LTX and seven healthy control subjects (Con) before, during, and after 20-s end-expiratory breath holds. Our evidence for denervation in LTX was 1) greatly attenuated respiratory sinus arrhythmia and 2) absence of cough reflex below the level of the carina. During apnea, the temporal pattern and the peak increase in MSNA were virtually identical in LTX and Con (347 ± 99 and 359 ± 46% of baseline, respectively; P > 0.05). In contrast, the amount of MSNA present in the first 5 s after resumption of breathing was greater in LTX vs. Con (101 ± 4 vs. 38 ± 7% of baseline, respectively; P < 0.05). There were no between-group differences in apnea-induced hypoxemia or hypercapnia, hemodynamic, or ventilatory responses. Thus cessation of the rhythmic sympathoinhibitory feedback that normally accompanies eupneic breathing does not contribute importantly to sympathetic excitation during apnea. In contrast, vagal afferent input elicited by hyperventilation-induced lung stretch plays an important role in the profound, rapid sympathetic inhibition that occurs after resumption of breathing after apnea.
Ozone exposure decreases the effect of a deep inhalation on forced expiratory flow in normal subjects
Authors: Kjærgaard S. K. , Pedersen O. F. , Miller M. R. , Rasmussen T. R. , Hansen J. C. , Mølhave L.
Published: April 2004

Sixteen healthy nonsmoking subjects (7 women), 21-49 yr old, were exposed in a climate chamber to either clean air or 300 parts/billion ozone on 4 days for 5 h each day. Before each exposure, the subjects had been pretreated with either oxidants (fish oil) or antioxidants (multivitamins). The study design was double-blind crossover with randomized allocation to the exposure regime. Full and partial flow-volume curves were recorded in the morning and before and during a histamine provocation at the end of the day. Nasal cavity volume and inflammatory markers in nasal lavage fluid were also measured. Compared with air, ozone exposure decreased peak expiratory flow, forced expiratory volume in 1 s, and forced vital capacity (FVC), with no significant effect from the pretreatment regimens. Ozone decreased the ratio of maximal to partial flow at 40% FVC by 0.08 ± 0.03 (mean ± SE, analysis of variance: P = 0.018) and at 30% FVC by 0.10 ± 0.05 ( P = 0.070). Ozone exposure did not significantly increase bronchial responsiveness, but, after treatment with fish oil, partial flows decreased more than after vitamins during the histamine test, without changing the maximal-to-partial flow ratio. The decreased effect of a deep inhalation after ozone exposure can be explained by changes in airway hysteresis relative to parenchymal hysteresis, due either to ozone-induced airway inflammation or to less deep inspiration after ozone, not significantly influenced by multivitamins or fish oil.
Hemodynamic response and oxygen transport in pigs resuscitated with maleimide-polyethylene glycol-modified hemoglobin (MP4)
Authors: Drobin Dan , Kjellstrom B. Thomas , Malm Elisabeth , Malavalli Ashok , Lohman Jeff , Vandegriff Kim D. , Young Mark A. , Winslow Robert M.
Published: April 2004

Cell-free Hb increases systemic and pulmonary pressure and resistance and reduces cardiac output and heart rate in animals and humans, effects that have limited their clinical development as “blood substitutes.” The primary aim of this study was to evaluate the hemodynamic response to infusion of several formulations of a new polyethylene glycol (PEG)-modified human Hb [maleimide PEG Hb (MalPEGHb)] in swine, an animal known to be sensitive to Hb-induced vasoconstriction. Anesthetized animals underwent controlled hemorrhage (50% of blood volume), followed by resuscitation (70% of shed volume) with 10% pentastarch (PS), 4% MalPEG-Hb in lactated Ringer (MP4), 4% MalPEG-Hb in pentastarch (HS4), 2% MalPEG-Hb in pentastarch (HS2), or 4% stroma-free Hb in lactated Ringer solution (SFH). Compared with baseline, restoration of blood volume after resuscitation was similar and not significantly different for the PS (103%), HS2 (99%), HS4 (106%), and MP4 (87%) animals but significantly less for the SFH animals (66%) ( P < 0.05). All solutions that contained MalPEG-Hb restored mean arterial and pulmonary pressure and cardiac output. Systemic vascular resistance was unchanged, and pulmonary arterial pressure and resistance were increased slightly. Both systemic and pulmonary vascular resistance increased significantly in animals that received SFH, despite less adequate blood volume restoration. Oxygen consumption was maintained in all animals that received MalPEG-Hb, but not PS. Base excess improved only with MalPEG-Hb and PS, but not SFH. Red blood cell O2extraction was significantly increased in animals that received Hb, regardless of formulation. These data demonstrate resuscitation with MalPEG-human Hb without increasing systemic vascular resistance and support our previous observations in animals suggesting that the efficacy of low concentrations of PEG-Hb in the plasma results from reduced vasoconstriction.
Contralateral effects of unilateral resistance training: a meta-analysis
Authors: Munn J. , Herbert R. D. , Gandevia S. C.
Published: April 2004

It is often claimed that strength training of one limb increases the strength of the contralateral limb, but this has not been demonstrated consistently, particularly in well-controlled studies. The aim was to quantitatively combine the results of other studies on the effects of unilateral training on contralateral strength in humans to provide an answer to this physiological question. We analyzed all randomized controlled studies of voluntary unilateral resistance training that used training intensities of at least 50% of maximal voluntary strength for a minimum of 2 wk. Studies were identified by computerized and hand searches of the literature. Data on changes in strength of contralateral and control limbs were extracted and statistically pooled in a meta-analysis. This approach allows conclusions to be based on a statistically meaningful sample size, which might be difficult to achieve in other ways. Seventeen studies met the inclusion criteria, and 13 provided enough data for statistical pooling. The contralateral effects of strength training reported in individual studies varied from -2.7 to 21.6% of initial strength. The pooled estimate of the effect of unilateral resistance training on the maximal voluntary strength of the contralateral limb was 7.8% (95% confidence interval: 4.1-11.6%). This was 35.1% (95% confidence interval: 20.9-49.3%) of the effect on the trained limb. Pooling of all available data shows that unilateral strength training produces modest increases in contralateral strength.
Comparison of two plethysmography systems in assessment of forearm blood flow
Authors: Leslie Stephen J. , Attinà Teresa , Hultsch Ellen , Bolscher Luc , Grossman Matthias , Denvir Martin A. , Webb David J.
Published: April 2004

Venous occlusion plethysmography is widely used to assess forearm blood flow (FBF). We compared the established Hokanson system (HEC4) with a newly developed Filtrass 2001 system (F2001). The HEC4 uses mercury-in-Silastic strain gauges, whereas F2001 detects volume changes with a nonmercury linear displacement device. The aim of this study was to evaluate the new F2001 against the HEC4 in terms of repeatability and systematic bias. Ten subjects were studied on 4 separate days in random order using either the HEC4 on both arms, the F2001 on both arms, the HEC4 on the right arm with the F2001 on the left, or the F2001 on the right arm and the HEC4 on the left. Stroop's colored word conflict test and postocclusive hyperemia were used to increase FBF, and lower body negative pressure was used to lower FBF. Stroop's colored word conflict test and lower body negative pressure increased (24.6 ± 1.5%, n = 240, P < 0.0001) and decreased (18.7 ± 0.8%, n = 240, P < 0.0001) FBF, respectively. Postocclusive hyperemia after occlusion times of 5, 8, and 13 min substantially increased FBF by 390 ± 86, 756 ± 217, and 851 ± 132%, respectively. Repeatability was not different between the devices (0.10 ± 2.37 vs. -0.47 ± 1.92 l/min, n = 125, P > 0.05), and there was no systematic bias. The F2001 is a newly developed plethysmography system that does not utilize mercury and is suitable for assessing changes of FBF in physiological studies.
Influence of expiratory loading and hyperinflation on cardiac output during exercise
Authors: Stark-Leyva Kristy N. , Beck Ken C. , Johnson Bruce D.
Published: April 2004

Patients with obstructive lung disease are exposed to expiratory loads (ELs) and dynamic hyperinflation as a consequence of expiratory flow limitation. To understand how these alterations in lung mechanics might affect cardiac function, we examined the influence of a 10-cmH2O EL, alone and in combination with voluntary hyperinflation (ELH), on pulmonary pressures [esophageal (Pes) and gastric (Pg)] and cardiac output (CO) in seven healthy subjects. CO was determined by using an acetylene method at rest and at 40 and 70% of peak work. At rest and during exercise, EL resulted in an increase in Pes and Pg (7-18 cmH2O; P < 0.05) and a decrease in CO (from 5.3 ± 1.8 to 4.5 ± 1.4, 12.2 ± 2.2 to 11.2 ± 2.2, and 16.3 ± 3.3 to 15.2 ± 3.2 l/min for rest, 40% peak work, and 70% peak work, respectively; P < 0.05), which remained depressed after an additional 2 min of EL. With ELH, CO increased at rest and both exercise loads (relative to EL only) but remained below control values. The changes in CO were due to a reduction in stroke volume with a tendency for stroke volume to fall further with prolonged EL. There was a negative correlation between CO and the increase in expiratory Pes and Pg with EL ( R = -0.58 and -0.60; P < 0.01), whereas the rise in CO with subsequent hyperinflation was related to a more negative Pes ( R = 0.72; P < 0.01). In conclusion, EL leads to a reduction in CO, which appears to be primarily related to increases in expiratory abdominal and intrathoracic pressure, whereas ELH resulted in an improved CO, suggesting that lung inflation has little impact on cardiac function.
Reproducibility and responsiveness of a noninvasive EMG technique of the respiratory muscles in COPD patients and in healthy subjects
Authors: Duiverman Marieke L. , van Eykern Leo A. , Vennik Peter W. , Koëter Gerard H. , Maarsingh Eric J. W. , Wijkstra Peter J.
Published: April 2004

In the present study, we assessed the reproducibility and responsiveness of transcutaneous electromyography (EMG) of the respiratory muscles in patients with chronic obstructive pulmonary disease (COPD) and healthy subjects during breathing against an inspiratory load. In seven healthy subjects and seven COPD patients, EMG signals of the frontal and dorsal diaphragm, intercostal muscles, abdominal muscles, and scalene muscles were derived on 2 different days, both during breathing at rest and during breathing through an inspiratory threshold device of 7, 14, and 21 cmH2O. For analysis, we used the logarithm of the ratio of the inspiratory activity during the subsequent loads and the activity at baseline [log EMG activity ratio (EMGAR)]. Reproducibility of the EMG was assessed by comparing the log EMGAR values measured at test days 1 and 2 in both groups. Responsiveness (sensitivity to change) of the EMG was assessed by comparing the log EMGAR values of the COPD patients to those of the healthy subjects at each load. During days 1 and 2, log EMGAR values of the diaphragm and the intercostal muscles correlated significantly. For the scalene muscles, significant correlations were found for the COPD patients. Although inspiratory muscle activity increased significantly during the subsequent loads in all participants, the COPD patients displayed a significantly greater increase in intercostal and left scalene muscle activity compared with the healthy subjects. In conclusion, the present study showed that the EMG technique is a reproducible and sensitive technique to assess breathing patterns in COPD patients and healthy subjects.
Locomotor activity in spinal cord-injured persons
Authors: Dietz V. , Harkema Susan J.
Published: April 2004

After a spinal cord injury (SCI) of the cat or rat, neuronal centers below the level of lesion exhibit plasticity that can be exploited by specific training paradigms. In individuals with complete or incomplete SCI, human spinal locomotor centers can be activated and modulated by locomotor training (facilitating stepping movements of the legs using body weight support on a treadmill to provide appropriate sensory cues). Individuals with incomplete SCI benefit from locomotor training such that they improve their ability to walk over ground. Load- or hip joint-related afferent input seems to be of crucial importance for both the generation of a locomotor pattern and the effectiveness of the training. However, it may be a critical combination of afferent signals that is needed to generate a locomotor pattern after severe SCI. Mobility of individuals after a SCI can be improved by taking advantage of the plasticity of the central nervous system and can be maintained with persistent locomotor activity. In the future, if regeneration approaches can successfully be applied in human SCI, even individuals with complete SCI may recover walking ability with locomotor training.
Mast cells and reactive oxygen species in citric acid-induced airway constriction
Authors: Wu Li-Ling , Lu Fung-Jou , Lai Yih-Loong
Published: April 2004

The noncholinergic airway constriction is mediated by tachykinins, mainly neurokinin A and substance P, and this bronchoconstriction is usually enhanced during inflammatory episodes. We demonstrated previously that reactive oxygen species play an important role in capsaicin-, hyperventilation-, and citric acid (CA) inhalation-induced noncholinergic airway constriction. For understanding cellular involvement, we further investigated the relationship between mast cells, bradykinin (BK), reactive oxygen species, and noncholinergic airway constriction. Sixty-five guinea pigs were divided into seven groups: saline control; CA; BK + CA; cromolyn sodium (CS) + CA; BK + CS + CA; compound 48/80 + CA; and compound 48/80 + BK + CA. CS was used to stabilize mast cells, whereas a secretagogue, compound 48/80, was for the depletion of mast cells. Each animal was anesthetized, cannulated, paralyzed, and ventilated artificially. In control animals, CA aerosol inhalation caused decreases in dynamic compliance and forced expiratory parameters, indicating CA-induced noncholinergic airway constriction. Either CS or compound 48/80 significantly attenuated the CA-induced airway constriction. Also, we detected a significant increase in lucigenin-initiated chemiluminescence counts of the bronchoalveolar lavage sample in the BK + CA group. Furthermore, CA exposure caused an increase in bronchoalveolar lavage substance P level. Either CS or compound 48/80 prevented the above CA-induced increases in chemiluminescence and substance P. These results suggest that mast cells play an important role in CA aerosol inhalation-induced airway constriction via perhaps releasing constricting factors.
Distribution dynamics of perfluorocarbon delivery to the lungs: an intact rabbit model
Authors: Bull J. L. , Tredici S. , Komori E. , Brant D. O. , Grotberg J. B. , Hirschl R. B.
Published: April 2004

Motivated by the goal of understanding how to most homogeneously fill the lungs with perfluorocarbon for liquid ventilation, we investigate the transport of liquid instilled into the lungs using an intact rabbit model. Perfluorocarbon is instilled into the trachea of the ventilated animal. Radiographic images of the perfluorocarbon distribution are obtained at a rate of 30 frames/s during the filling process. Image analysis is used to quantify the liquid distribution (center of mass, spatial standard deviation, skewness, kurtosis, and indicators of homogeneity) as time progresses. We compare the distribution dynamics in supine animals to those in upright animals for three constant infusion rates of perfluorocarbon: 15, 40, and 60 ml/min. It is found that formation of liquid plugs in large airways, which is affected by posture and infusion rate, can result in a more homogeneous liquid distribution than gravity drainage alone. The supine posture resulted in more homogeneous filling of the lungs than did upright posture, in which the lungs tend to fill in the inferior regions first. Faster instillation of perfluorocarbon results in liquid plugs forming in large airways and, consequently, more uniform distribution of perfluorocarbon than slower instillation rates in the upright animals.
Enhanced arteriolar α-adrenergic constriction impairs dilator responses and skeletal muscle perfusion in obese Zucker rats
Authors: Frisbee Jefferson C.
Published: April 2004

The present study tested the hypothesis that enhanced vascular α-adrenergic constriction in obese Zucker rats (OZR) impairs arteriolar dilation and perfusion of skeletal muscle at rest and with increased metabolic demand. In lean Zucker rats (LZR) and OZR, isolated gracilis arterioles were viewed via television microscopy, and the contralateral cremaster muscle or gastrocnemius muscle was prepared for study in situ. Gracilis and cremasteric arterioles were challenged with dilator stimuli under control conditions and after blockade of α-adrenoreceptors with prazosin, phentolamine, or yohimbine. Gastrocnemius muscles performed isometric twitch contractions of increasing frequency, and perfusion was continuously monitored. In OZR, dilator responses of arterioles to hypoxia (gracilis), wall shear rate (cremaster), acetylcholine, and iloprost (both) were impaired vs. LZR. Treatment with prazosin and phentolamine (and in cremasteric arterioles only, yohimbine) improved arteriolar reactivity to these stimuli in OZR, although responses remained impaired vs. LZR. Gastrocnemius muscle blood flow was reduced at rest in OZR; this was corrected with intravenous infusion of phentolamine or prazosin. At all contraction frequencies, blood flow was reduced in OZR vs. LZR; this was improved by infusion of phentolamine or prazosin at low-moderate metabolic demand only (1 and 3 Hz). At 5 Hz, adrenoreceptor blockade did not alter blood flow in OZR from levels in untreated rats. These results suggest that enhanced α-adrenergic constriction of arterioles of OZR contributes to impaired dilator responses and reduced muscle blood flow at rest and with mild-moderate (although not with large) elevations in metabolic demand.
Inactivation of human muscle Na+-K+-ATPase in vitro during prolonged exercise is increased with hypoxia
Authors: Sandiford S. D. , Green H. J. , Duhamel T. A. , Perco J. G. , Schertzer J. D. , Ouyang J.
Published: April 2004

This study investigated the effects of prolonged exercise performed in normoxia (N) and hypoxia (H) on neuromuscular fatigue, membrane excitability, and Na+-K+-ATPase activity in working muscle. Ten untrained volunteers [peak oxygen consumption (VV̇o2 peak) = 42.1 ± 2.8 (SE) ml·kg-1·min-1] performed 90 min of cycling during N (inspired oxygen fraction = 0.21) and during H (inspired oxygen fraction = 0.14) at ∼50% of normoxic VV̇o2 peak. During N, 3- O-methylfluorescein phosphatase activity (nmol·mg protein-1·h-1) in vastus lateralis, used as a measure of Na+-K+-ATPase activity, decreased ( P < 0.05) by 21% at 30 min of exercise compared with rest (101 ± 53 vs. 79.6 ± 4.3) with no further reductions observed at 90 min (72.8 ± 8.0). During H, similar reductions ( P < 0.05) were observed during the first 30 min (90.8 ± 5.3 vs. 79.0 ± 6.3) followed by further reductions ( P < 0.05) at 90 min (50.5 ± 3.9). Exercise in N resulted in reductions ( P < 0.05) in both quadriceps maximal voluntary contractile force (MVC; 633 ± 50 vs. 477 ± 67 N) and force at low frequencies of stimulation, namely 10 Hz (142 ± 16 vs. 86.7 ± 10 N) and 20 Hz (283 ± 32 vs. 236 ± 31 N). No changes were observed in the amplitude, duration, and area of the muscle compound action potential (M wave). Exercise in H was without additional effect in altering MVC, low-frequency force, and M-wave properties. It is concluded that, although exercise in H resulted in a greater inactivation of Na+-K+-ATPase activity compared with N, neuromuscular fatigue and membrane excitability are not differentially altered.
National Heart, Lung, and Blood Institute Clinical Proteomics Working Group Report
Authors: Granger Christopher B. , Van Eyk Jennifer E. , Mockrin Stephen C. , Anderson N. Leigh
Published: April 2004

The National Heart, Lung, and Blood Institute (NHLBI) Clinical Proteomics Working Group was charged with identifying opportunities and challenges in clinical proteomics and using these as a basis for recommendations aimed at directly improving patient care. The group included representatives of clinical and translational research, proteomic technologies, laboratory medicine, bioinformatics, and 2 of the NHLBI Proteomics Centers, which form part of a program focused on innovative technology development. This report represents the results from a one-and-a-half-day meeting on May 8 and 9, 2003. For the purposes of this report, clinical proteomics is defined as the systematic, comprehensive, large-scale identification of protein patterns (“fingerprints”) of disease and the application of this knowledge to improve patient care and public health through better assessment of disease susceptibility, prevention of disease, selection of therapy for the individual, and monitoring of treatment response.
Complete remission of alopecia universalis after allogeneic hematopoietic stem cell transplantation
Authors: Seifert Bettina , Passweg Jakob R. , Heim Dominik , Rovó Alicia , Meyer-Monard Sandrine , Buechner Stanislaus , Tichelli Andre , Gratwohl Alois
Published: April 2004

This case report is on a 40-year-old male patient with chronic myeloid leukemia (CML) receiving an allogeneic hematopoietic stem cell transplantation (HSCT) in first chronic phase from an HLA-identical sibling brother. He suffered from alopecia universalis occurring 11 years previously. The alopecia involved all body hair, including eyebrows and eyelashes. Between day 40 and day 55 after transplantation, hair started to grow on the chin, eyelashes, and on the top of his head. Immunosuppression was stopped at 6 months because of cytogenetic relapse and incomplete donor chimerism with some renewed hair loss. He returned to full donor chimerism with mild chronic graft-versus-host disease and continued hair growth. With 2 years of follow-up he has remained in continuous remission. Chimerism analyses of hair follicles did not show any donor alleles. Alopecia universalis is probably a chronic autoimmune disorder, curable with replacement of the immune system with an allogeneic HSCT. (Blood. 2005;105:426-427)