bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of age on cutaneous vasoconstrictor responses to norepinephrine in humans
Authors: Wilson Thad E. , Monahan Kevin D. , Short Daniel S. , Ray Chester A.
Published: October 2004

To test the hypothesis that cutaneous vasoconstrictor responsiveness to exogenous norepinephrine is reduced in older compared with young subjects, dose-response relations between norepinephrine and skin blood flow were established. Seven doses of norepinephrine (1·10−8 to 10−2 log M) were perfused (2 μl/min) intradermally (4 min/dose) using cutaneous microdialysis (2 probes/subject). To account for possible differences in endogenous norepinephrine between groups, one microdialysis probe was perfused with bretylium tosylate to locally block noradrenergic vesicle release before establishing the norepinephrine dose-response relations. Skin blood flow was indexed via laser-Doppler flowmetry directly over both microdialysis probe sites and is expressed as cutaneous vascular conductance (laser-Doppler flux/mean arterial blood pressure). Local skin temperature was maintained at 34°C at both sites throughout the protocol. Dose-response relation between norepinephrine and cutaneous vascular conductance was similar between control and bretylium-pretreated sites in young subjects (EC50 = −5.18 ± 0.27 and −5.03 ± 0.27 log M, respectively). In contrast, the dose-response relation was significantly shifted to the right (i.e., a higher dose of norepinephrine was needed to produce the same vasoconstrictor response) in the bretylium-pretreated site in older subjects (EC50 = −5.46 ± 0.23 and −4.53 ± 0.23 log M, respectively). Significant increases in EC50 were observed in older compared with young subjects at the bretylium-pretreated but not the control sites. These data indicate that cutaneous vasoconstrictor responsiveness is decreased in older subjects when endogenous release of norepinephrine is antagonized. Furthermore, these findings suggest that differences in presynaptic norepinephrine release between older and younger subjects are profound enough to affect dose-response relations between norepinephrine and cutaneous vascular conductance.
Endothelial nitric oxide synthase-deficient mice exhibit increased susceptibility to endotoxin-induced acute renal failure
Authors: Wang Wei , Mitra Amit , Poole Brian , Falk Sandor , Lucia M. Scott , Tayal Shalini , Schrier Robert
Published: October 2004

Acute renal failure (ARF) in septic patients drastically increases the mortality to 50–80%. Nitric oxide (NO) has been shown to be increased in sepsis. Endothelial nitric oxide synthase (eNOS) is one of the major regulators of arterial blood pressure and regional blood flow; however, its in vivo role in septic ARF is still unclear. We hypothesized that eNOS affords a protective effect against the renal vasoconstriction during endotoxemia. Because there are no specific inhibitors for eNOS, the study was therefore undertaken in eNOS knockout mice. There was no significant difference in baseline glomerular filtration rate (GFR) between the wild-type mice and the eNOS knockout mice (140 ± 10 vs. 157 ± 18 μl/min, n = 9, P = not significant). However, renal blood flow (RBF) was significantly decreased in eNOS knockout mice compared with the wild-type controls (0.62 ± 0.05 ml/min, n = 6 vs. 0.98 ± 0.13 ml/min, n = 8, P < 0.05). Mean arterial pressure (MAP) was significantly higher in eNOS knockout mice than the wild-type controls (109 ± 5 vs. 80 ± 1 mmHg, n = 10, P < 0.01). Thus renal vascular resistance (RVR) was much higher in eNOS knockout mice than in the wild-type mice (176 ± 2, n = 6 vs. 82 ± 1 mmHg·ml−1·min−1, n = 8, P < 0.01). When 1.0 mg/kg LPS was injected, there was no change in MAP in either the wild-type (84 ± 3 mmHg, n = 10) or the eNOS knockout mice (105 ± 5 mmHg, n = 10). Although GFR (154 ± 22 μl/min, n = 8) and RBF (1.19 ± 0.05 ml/min, n = 9) remained unchanged with the 1.0-mg/kg dose of LPS in the wild-type mice, GFR (83 ± 18 vs. 140 ± 10 μl/min, n = 6, P < 0.01) and RBF (0.36 ± 0.04 vs. 0.62 ± 0.05 ml/min, n = 6, P < 0.01) decreased significantly in the eNOS knockout mice. Fractional excretion of sodium increased significantly in eNOS knockout mice during endotoxemia (3.61 ± 0.78, n = 7 vs. 0.95 ± 0.14, n = 6, P < 0.01), whereas it remained unchanged in the wild-type mice (0.59 ± 0.16, n = 9 vs. 0.42 ± 0.05, n = 6, P = not significant). In summary, eNOS knockout mice have increased RVR and are more susceptible to endotoxemic ARF than wild-type mice despite higher MAP.
Ceramide synthase is essential for endonuclease-mediated death of renal tubular epithelial cells induced by hypoxia-reoxygenation
Authors: Basnakian Alexei G. , Ueda Norishi , Hong Xiaoman , Galitovsky Valentin E. , Yin Xiaoyan , Shah Sudhir V.
Published: October 2004

Ceramide is known to play a role in the cell signaling pathway involved in apoptosis. Most studies suggest that enhanced ceramide generation is the result of hydrolysis of sphingomyelin by sphingomyelinases. However, the role of ceramide synthase in enhanced ceramide generation has not been previously examined in hypoxia-reoxygenation injury. In the present study, we demonstrated that 60-min hypoxia of rat renal tubular epithelial NRK-52E cells in a gas chamber with 95% N2-5% CO2with glucose deprivation resulted in a significant increase in ceramide generation. The ceramide level further increased after reoxygenation for 60 min. Exposure of cells to hypoxia-reoxygenation resulted in a significant increase in ceramide synthase activity without any significant change in acid or neutral sphingomyelinase. The hypoxia-reoxygenation of NRK-52E cells was also associated with the release of endonuclease G (EndoG) from mitochondria to cytoplasm measured by Western blot analysis and endonuclease activity assay. It further led to the fragmentation of DNA and cell death. A specific inhibitor of ceramide synthase, fumonisin B1 (50 μM), suppressed hypoxia-reoxygenation-induced ceramide generation and provided protection against hypoxia-reoxygenation-induced EndoG release, DNA fragmentation, and cell death. Taken together, our data suggest that hypoxia-reoxygenation results in an activation of ceramide synthase rather than sphingomyelinase and that ceramide synthase-dependent ceramide generation is a key modulator of EndoG-mediated cytotoxicity in hypoxia-reoxygenation injury to renal tubular epithelial cells.
Acute hypoxia and pulmonary vasoconstriction in humans: uncovering the mechanism of the pressor response
Authors: Fishman Alfred P.
Published: October 2004

This essay looks at the historical significance of an APS classic paper that is freely available online:

Motley HL, Cournand A, Werko L, Himmelstein A, and Dresdale D. The influence of short periods of induced acute anoxia upon pulmonary artery pressures in man. Am J Physiol 150: 315–320, 1947 ( http://ajplegacy.physiology.org/cgi/reprint/150/2/315 ).
Discovery of the luteinizing hormone of the anterior pituitary gland
Authors: Goodman H. Maurice
Published: October 2004

This essay looks at the historical significance of an APS classic paper that is freely available online:

Fevold HL, Hisaw FL, Leonard SL. The gonad stimulating and the luteinizing hormones of the anterior lobe of the hypophesis. Am J Physiol 97: 291—301, 1931 ( http://ajplegacy.physiology.org/cgi/reprint/97/2/291 ).
The pioneering use of systems analysis to study cardiac output regulation
Authors: Hall John E.
Published: October 2004

This essay examines the historical significance of an APS classic paper that is freely available online:

Guyton AC, Lindsey AW, and Kaufmann BN. Effect of mean circulatory filling pressure and other peripheral circulatory factors on cardiac output. Am J Physiol 180: 463-468, 1955 ( http://ajplegacy.physiology.org/cgi/reprint/180/3/463 ).
The development of clearance methods for measurement of glomerular filtration and tubular reabsorption
Authors: Hostetter T. H. , Meyer T. W.
Published: October 2004

This essay looks at the historical significance of four APS classic papers that are freely available online:

Jolliffe N, Shannon JA, and Smith HW. The excretion of urine in the dog. III. The use of non-metabolized sugars in the measurement of the glomerular filtrate. Am J Physiol 100: 301—312, 1932 ( http://ajplegacy.physiology.org/cgi/reprint/100/2/301 ).

Shannon JA. The excretion of inulin by the dog. Am J Physiol 112: 405—413, 1935 ( http://ajplegacy.physiology.org/cgi/reprint/112/3/405 ).

Shannon JA and Fisher S. The renal tubular reabsorption of glucose in the normal dog. Am J Physiol 122: 765—774, 1938 ( http://ajplegacy.physiology.org/cgi/reprint/122/3/765 ).

Shannon JA, Farber S, and Troast L. The measurement of glucose Tm in the normal dog. Am J Physiol 133: 752—761, 1941 ( http://ajplegacy.physiology.org/cgi/reprint/133/3/752 ).
The basis for transport across epithelial cells
Authors: Montrose Marshall H.
Published: October 2004

This essay looks at the historical significance of two APS classic papers that are freely available online:

Ingraham RC and Visscher MB. Further studies on intestinal absorption with the performance of osmotic work. Am J Physiol 121: 771–785, 1938 ( http://ajplegacy.physiology.org/cgi/reprint/121/3/771 ).

Visscher MB, Fetcher ES Jr, Carr CW, Gregor HP, Bushey MS, and Barker DE. Isotopic tracer studies on the movement of water and ions between intestinal lumen and blood. Am J Physiol 142: 550–575, 1944 ( http://ajplegacy.physiology.org/cgi/reprint/142/4/550 ).
The paper that completely altered our thinking about cerebral blood flow measurement
Authors: Traystman Richard J.
Published: October 2004

Kety SS and Schmidt CF. The determination of cerebral blood flow in man by the use of nitrous oxide in low concentrations. Am J Physiol 143: 53—66, 1945 ( http://ajplegacy.physiology.org/cgi/reprint/143/1/53 ).
Understanding pulmonary gas exchange: ventilation-perfusion relationships
Authors: West John B.
Published: October 2004

This essay looks at the historical significance of four APS classic papers that are freely available online:

Fenn WO, Rahn H, and OTIS AB. A theoretical study of the composition of the alveolar air at altitude. Am J Physiol 146: 637-653. 1946 ( http://ajplegacy.physiology.org/cgi/reprint/146/5/637 ).

Rahn H. A concept of mean alveolar air and the ventilation-bloodflow relationships during pulmonary gas exchange. Am J Physiol 158: 21-30, 1949 ( http://ajplegacy.physiology.org/cgi/reprint/158/1/21) ).

Riley RL. And Cournand A. "Ideal" Alveolar air and the analysis of ventilation-perfusion relationships in the lungs. J Appl Physiol 1: 825-847. 1949 ( http://jap.physiology.org/cgi/reprint/1/12/825) .

Riley RL. And Cournand A. Analysis of factors affecting partial pressures of oxygen and carbon dioxide in gas and blood of lungs: theory. J Appl Physiol 4: 77-101. 1951 ( http://jap.physiology.org/cgi/reprint/4/2/77) .
Rapid formation of functional muscle in vitro using fibrin gels
Authors: Huang Yen-Chih , Dennis Robert G. , Larkin Lisa , Baar Keith
Published: October 2004

The transition of a muscle cell from a differentiated myotube into an adult myofiber is largely unstudied. This is primarily due to the difficulty of isolating specific developmental stimuli in vivo and the inability to maintain viable myotubes in culture for sufficient lengths of time. To address these limitations, a novel method for rapidly generating three-dimensional engineered muscles using fibrin gel casting has been developed. Myoblasts were seeded and differentiated on top of a fibrin gel. Cell-mediated contraction of the gel around artificial anchors placed 12 mm apart culminates 10 days after plating in a tubular structure of small myotubes (10-μm diameter) surrounded by a fibrin gel matrix. These tissues can be connected to a force transducer and electrically stimulated between parallel platinum electrodes to monitor physiological function. Three weeks after plating, the three-dimensional engineered muscle generated a maximum twitch force of 329 ± 26.3 μN and a maximal tetanic force of 805.8 ± 55 μN. The engineered muscles demonstrated normal physiological function including length-tension and force-frequency relationships. Treatment with IGF-I resulted in a 50% increase in force production, demonstrating that these muscles responded to hormonal interventions. Although the force production was maximal at 3 wk, constructs can be maintained in culture for up to 6 wk with no intervention. We conclude that fibrin-based gels provide a novel method to engineer three-dimensional functional muscle tissue and that these tissues may be used to model the development of skeletal muscle in vitro.
Impact of changes in inspired oxygen and carbon dioxide on respiratory instability in the lamb
Authors: Wilkinson Malcolm H. , Sia Kah-Ling , Skuza Elizabeth M. , Brodecky Vojta , Berger Philip J.
Published: October 2004

We examined the effect of hypoxia and hypercapnia administered during deliberately induced periodic breathing (PB) in seven lambs following posthyperventilation apnea. Based on our theoretical analysis, the sensitivity or loop gain (LG) of the respiratory control system of the lamb is directly proportional to the difference between alveolar Po2and inspired Po2. This analysis indicates that during PB, when by necessity LG is >1, replacement of the inspired gas with one of reduced Po2lowers LG; if we made inspired Po2approximate alveolar Po2, we predict that LG would be approximately zero and breathing would promptly stabilize. In six lambs, we switched the inspired gas from an inspiratory oxygen fraction of 0.4 to one of 0.12 during an epoch of PB; PB was immediately suppressed, supporting the view that the peripheral chemoreceptors play a pivotal role in the genesis and control of unstable breathing in the lamb. In the six lambs in which we administered hypercapnic gas during PB, breathing instability was also suppressed, but only after a considerable time lag, indicating the CO2effect is likely to have been mediated through the central chemoreceptors. When we simulated both interventions in a published model of the adult respiratory controller, PB was immediately suppressed by CO2inhalation and exacerbated by inhalation of hypoxic gas. These fundamentally different responses in lambs and adult humans demonstrate that PB has differing underlying mechanisms in the two species.
Attenuation of induced bronchoconstriction in healthy subjects: effects of breathing depth
Authors: Salerno Francesco G. , Pellegrino Riccardo , Trocchio Gianluca , Spanevello Antonio , Brusasco Vito , Crimi Emanuele
Published: October 2004

The effects of breathing depth in attenuating induced bronchoconstriction were studied in 12 healthy subjects. On four separate, randomized occasions, the depth of a series of five breaths taken soon (∼1 min) after methacholine (MCh) inhalation was varied from spontaneous tidal volume to lung volumes terminating at ∼80, ∼90, and 100% of total lung capacity (TLC). Partial forced expiratory flow at 40% of control forced vital capacity (V̇part) and residual volume (RV) were measured at control and again at 2, 7, and 11 min after MCh. The decrease in V̇partand the increase in RV were significantly less when the depth of the five-breath series was progressively increased ( P < 0.001), with a linear relationship. The attenuating effects of deep breaths of any amplitude were significantly greater on RV than V̇part( P < 0.01) and lasted as long as 11 min, despite a slight decrease with time when the end-inspiratory lung volume was 100% of TLC. In conclusion, in healthy subjects exposed to MCh, a series of breaths of different depth up to TLC caused a progressive and sustained attenuation of bronchoconstriction. The effects of the depth of the five-breath series were more evident on the RV than on V̇part, likely due to the different mechanisms that regulate airway closure and expiratory flow limitation.
Echocardiographic parameters discriminating myocardial infarction with pulmonary congestion from myocardial infarction without congestion in the mouse
Authors: Finsen Alexandra Vanessa , Christensen Geir , Sjaastad Ivar
Published: October 2004

Our aim was to establish parameters describing systolic and diastolic function in mice after myocardial infarction (MI) that distinguish MI with pulmonary congestion from MI without congestion. Echocardiography, left ventricular (LV) catheterization, and infarct size measurements were performed on days 3, 5, 7, and 14 after ligation of the left coronary artery in C57BL/6 mice. Sham-operated mice were used as controls (Sham). MI mice with lung weight normalized to tibial length >125% of the average in the corresponding Sham group were considered to have pulmonary congestion (MIchf). MI mice with a smaller increase were called MI nonfailing (MInf). An infarct >40% of total LV circumference measured in two-dimensional long axis distinguished MIchf from MInf on both an average and an individual basis. Mean maximum rate of rise of LV pressure, LV fractional shortening, and posterior wall shortening velocity were significantly lower in MIchf compared with Sham at all time points and to MInf at 7 days. The diastolic parameters mitral flow deceleration velocity, LV end-diastolic pressure, and maximum rate of decline in LV pressure (LVdP/d tmin) discriminated the MIchf groups from Sham at all time points. Mitral flow deceleration velocity and LVdP/d tmin separated MIchf from MInf at 7 days. In addition to distinguishing all the groups on an average basis, left atrial diameter distinguished all MIchf animals from Sham and MInf. In conclusion, significantly increased left atrial diameter and infarct size >40% of total LV circumference may serve as major criteria for heart failure with pulmonary congestion after MI in mice.
Ventilatory behavior during sleep among A/J and C57BL/6J mouse strains
Authors: Friedman Lee , Haines Abby , Klann Ken , Gallaugher Laura , Salibra Lawrence , Han Fang , Strohl Kingman P.
Published: October 2004

The pattern of breathing during sleep could be a heritable trait. Our intent was to test this genetic hypothesis in inbred mouse strains known to vary in breathing patterns during wakefulness (Han F, Subramanian S, Dick TE, Dreshaj IA, and Strohl KP. J Appl Physiol 91: 1962–1970, 2001; Han F, Subramanian S, Price ER, Nadeau J, and Strohl KP, J Appl Physiol 92: 1133–1140, 2002) to determine whether such differences persisted into non-rapid eye movement (NREM) and rapid eye movement (REM) sleep. Measures assessed in C57BL/6J (B6; Jackson Laboratory) and two A/J strains (A/J Jackson and A/J Harlan) included ventilatory behavior [respiratory frequency, tidal volume, minute ventilation, mean inspiratory flow, and duty cycle (inspiratory time/total breath time)], and metabolism, as performed by the plethsmography method with animals instrumented to record EEG, electromyogram, and heart rate. In all strains, there were reductions in minute ventilation and CO2 production in NREM compared with wakefulness ( P < 0.001) and a further reduction in REM compared with NREM ( P < 0.001), but no state-by-stain interactions. Frequency showed strain ( P < 0.0001) and state-by-strain interactions ( P < 0.0001). The A/J Jackson did not change frequency in REM vs. NREM [141 ± 15 (SD) vs. 139 ± 14 breaths/min; P = 0.92], whereas, in the A/J Harlan, it was lower in REM vs. NREM (168 ± 14 vs. 179 ± 12 breaths/min; P = 0.0005), and, in the B6, it was higher in REM vs. NREM (209 ± 12 vs. 188 ± 13 breaths/min; P < 0.0001). Heart rate exhibited strain ( P = 0.003), state ( P < 0.0001), and state-by-strain interaction ( P = 0.017) and was lower in NREM sleep in the A/J Harlan ( P = 0.035) and B6 ( P < 0.0001). We conclude that genetic background affects features of breathing during NREM and REM sleep, despite broad changes in state, metabolism, and heart rate.
GABAB Receptor Activation Modulates GABAA Receptor-Mediated Inhibition in Chicken Nucleus Magnocellularis Neurons
Authors: Lu Yong , Burger R. Michael , Rubel Edwin W
Published: October 2004

Neurons of nucleus magnocellularis (NM), a division of avian cochlear nucleus that performs precise temporal encoding, receive glutamatergic excitatory input solely from the eighth nerve and GABAergic inhibitory input primarily from the ipsilateral superior olivary nucleus. GABA activates both ligand-gated Cl− channels [GABAA receptors (GABAARs)] and G protein-coupled receptors (GABAB receptors). The net effect of GABAAR-mediated input to NM is inhibitory, although depolarizing. Several studies have shown that this shunting, inhibitory GABAergic input can evoke action potentials in postsynaptic NM neurons, which could interfere with their temporal encoding. While this GABA-mediated firing is limited by a low-voltage-activated K+ conductance, we have found evidence for a second mechanism. We investigated modulation of GABAAR-mediated responses by GABABRs using whole cell recording techniques. Bath-applied baclofen, a GABABR agonist, produced dose-dependent suppression of evoked inhibitory postsynaptic currents (eIPSCs). This suppression was blocked by CGP52432 , a potent and selective GABABR antagonist. Baclofen reduced the frequency but not the amplitude of miniature IPSCs (mIPSCs) and did not affect postsynaptic currents elicited by puff application of a specific GABAAR agonist muscimol, suggesting a presynaptic mechanism for the GABABR-mediated modulation. Firing of NM neurons by synaptic stimulation of GABAergic inputs to NM was eliminated by baclofen. However, endogenous GABABR activity in the presynaptic inhibitory terminals was not observed. We propose that presynaptic GABABRs function as autoreceptors, regulating synaptic strength of GABAAR-mediated inhibition, and prevent NM neurons from generating firing during activation of the inhibitory inputs.
Transcriptional reprogramming and ultrastructure during atrophy and recovery of mouse soleus muscle
Authors: Däpp Christoph , Schmutz Silvia , Hoppeler Hans , Flück Martin
Published: October 2004

This study investigated the use of the hindlimb suspension (HS) and reloading model of mice for the mapping of ultrastructural and gene expressional alterations underlying load-dependent muscular adaptations. Mice were hindlimb suspended for 7 days or kept as controls ( n = 12). Soleus muscles were harvested after HS (HS7, n = 23) or after resuming ambulatory cage activity (reloading) for either 1 day (R1, n = 13) or 7 days (R7, n = 9). Using electron microscopy, a reduction in mean fiber area (−37%) and in capillary-to-fiber ratio (from 1.83 to 1.42) was found for HS7. Subsequent reloading caused an increase in interstitial cells (+96%) and in total capillary length (+57%), whereas mean fiber area and capillary-to-fiber ratio did not significantly change compared with HS. Total RNA in the soleus muscle was altered with both HS (−63%) and reloading (+108% in R7 compared with control). This is seen as an important adaptive mechanism. Gene expression alterations were assessed by a muscle-specific low-density cDNA microarray. The transcriptional adjustments indicate an early increase of myogenic factors during reloading together with an overshoot of contractile (MyHC I and IIa) and metabolic (glycolytic and oxidative) mRNA amounts and suggest mechano-sensitivity of factors keeping the sarcomeres in register (desmin, titin, integrin-β1). Important differences to published data from former rat studies were found with the mouse HS model for contractile and glycolytic enzyme expression. These species-specific differences need to be considered when transgenic mice are used for the elucidation of monogenetic factors in mechano-dependent muscle plasticity.
The ‘System’ of Automobility
Authors: Urry John
Published: October 2004

This article is concerned with how to conceptualize and theorize the nature of the ‘car system’ that is a particularly key, if surprisingly neglected, element in ‘globalization’. The article deploys the notion of systems as self-reproducing or autopoietic. This notion is used to understand the origins of the 20th-century car system and especially how its awesome pattern of path dependency was established and exerted a particularly powerful and self-expanding pattern of domination across the globe. The article further considers whether and how the 20th-century car system may be transcended. It elaborates a number of small changes that are now occurring in various test sites, factories, ITC sites, cities and societies. The article briefly considers whether these small changes may in their contingent ordering end this current car system. The article assesses whether such a new system could emerge well before the end of this century, whether in other words some small changes now may produce the very large effect of a new post-car system that would have great implications for urban life, for mobility and for limiting projected climate change.
Mobility and Safety
Authors: Beckmann Jörg
Published: October 2004

The article offers an insight into road traffic accidents by unravelling both the internal elements and the social context of the so-called car–driver hybrid. It takes a critical perspective on the art of designing road safety. More importantly, it seeks to contribute to social studies of transport and mobility through development of analytical concepts within the discipline. The points of departure are the inherent ambiguities of mobility. The author suggests that ‘being in traffic’ is always determined by coexisting forms of mobility and immobility. This ambivalent stage is then called motility. The author discusses car-drivers as motile hybrids, as they are mobile and immobile, as well as subjects and objects at the same time. In order to apply these concepts, the question of what happens to hybrids in crashes is addressed, employing Bruno Latour’s concept of ‘immutable mobiles’. The article concludes with a discussion of the social role of road safety experts, arguing that transport safety experts create a specific kind of spatio-temporal order within which the motile hybrid exists. It is the safety professional who decides when to take agency away from the subject and give it to the object, and it s/he who determines where to slow down and where to speed up the car–driver hybrid.
Automotive Emotions
Authors: Sheller Mimi
Published: October 2004

Car cultures have social, material and, above all, affective dimensions that are overlooked in current strategies to influence car-driving decisions. Car consumption is never simply about rational economic choices, but is as much about aesthetic, emotional and sensory responses to driving, as well as patterns of kinship, sociability, habitation and work. Through a close examination of the aesthetic and especially kinaesthetic dimensions of automobility, this article locates car cultures (and their associated feelings) within a broader physical/material relational setting that includes both human bodies and car bodies, and the relations between them and the spaces through which they move (or fail to move). Drawing on both the phenomenology of car use and new approaches in the sociology of emotions, it is argued that everyday car cultures are implicated in a deep context of affective and embodied relations between people, machines and spaces of mobility and dwelling in which emotions and the senses play a key part – the emotional geographies of car use. Feelings for, of and within cars (‘automotive emotions’) come to be socially and culturally generated across three scales involved in the circulations and displacements performed by cars, roads and drivers: embodied sensibilities and kinaesthetic performances; familial and sociable practices of ‘caring’ through car use; and regional and national car cultures that form around particular systems of automobility. By showing how people feel about and in cars, and how the feel of different car cultures generates habitual forms of automobilized life and different dispositions towards driving, it is argued that we will be in a better position to re-evaluate the ethical dimensions of car consumption and the moral economies of car use.
Engaging the public in the regulation of xenotransplantation: would the Canadian model of public consultation be effective in the US?
Authors: Allspaw Kathleen M.
Published: October 2004

The value of engaging the public in science policymaking is becoming increasingly controversial. In the US, however, the regulation of biotechnologies remains in the domain of the scientific elite. By contrast, Canada recently conducted a very public process aimed at including the public in the regulation of xenotransplantation. Members of the US xenotransplantation community were asked to comment on the public consultation process with specific attention given to the Canadian consultation on xenotransplantation. These scientists agreed that gathering public opinion is usually desirable but expressed some serious concerns about the methods used to gather these opinions. They challenged the notion of an informed public as defined by the organizers of the Canadian consultation. Therefore, in order for the Canadian model of public consultation to be well received in the US, there would have to be more stringent adherence to representative sampling and more rigorous public education strategies.
Accounting for explanation in popular science texts—an analysis of popularized accounts of superstring theory
Authors: Turney Jon
Published: October 2004

This paper argues that explanation is central to much science communication and seeks ways of describing explanation through text as it is achieved in popular science writing. It is suggested that a framework elaborated by Ogborn et al. (1996) for analyzing the explanatory performance of science teachers in the classroom may be adapted for analysis of popular texts. The suggestion is elaborated through an extended case study of popular works on superstring theory, notably Brian Greene’s The Elegant Universe (2000). It is concluded that Ogborn’s scheme is useful, but the demands of this theory expose some of the limitations of the framework, and perhaps of textual— that is, non-mathematical—explanation in general.
Risk and the environment reporters: a four-region analysis
Authors: Sachsman David B. , Simon James , Valenti Joann Myer
Published: October 2004

Who are the environment reporters who explain the science of the environment to the general public? Do they consider risk when writing environmental stories? How often do they say they use a risk assessment angle compared to other issues? Are they concerned that they may be exaggerating environmental risks, excessively frightening their readers and viewers?

This study used a census approach to interview 354 environment reporters in four regions of the United States. The majority of environment reporters in all four regions said they used risk angles at least sometimes, many more than might have been true in the past. However, the journalists said they more frequently framed their stories using government, human-interest, business, nature, pollution, politics, science, and health angles, and some reporters, ranging from 28.3 percent in New England to 41.8 percent in the Pacific Northwest, said they rarely or never included risk assessment in their environmental stories. Although most journalists in the four regions did not believe that news reports generally sensationalized environmental risks, some reporters (16.9–25.0 percent) said that environmental journalists generally have overblown environmental risks, unduly alarming the public.
Early Forms of Relatedness in Autism: A Longitudinal Clinical and Quantitative Single-Case Study
Authors: Alvarez Anne , Lee Anthony
Published: October 2004

The aim of this single-case study was to identify early forms of interpersonal relatedness in a child with autism and to examine changes in these forms over a period of 3 years. The child was videotaped in a standard therapeutic setting with a clinician. Observations made by the clinician were accompanied by quantitative data drawn from videotaped recordings. Both sources highlighted an increase in dyadic forms of relating. There was no conclusive evidence for change in the level of triadic relating. The authors discuss the need to distinguish between deviant and delayed functioning and the importance of assessing the exact level of developmental delay in social relatedness. Attention to these areas promises a more precise definition of the social deficit in autism and may serve as a means to investigate its ‘mutability’.
Family Engagement, Consumer Satisfaction and Treatment Outcome in the New Era of Child and Adolescent In-Patient Psychiatric Care
Authors: Brinkmeyer Mary Y. , Eyberg Sheila M. , Nguyen Mathew L. , Adams Robert W.
Published: October 2004

This study examined the association between family engagement and consumer satisfaction for the seriously emotionally disturbed children and adolescents admitted to an in-patient psychiatric unit in a large medical center. Participants were 45 male and female in-patients, aged 7–17, and their parents. At the time their child was discharged, parents completed a demographic questionnaire, the Achenbach Child Behavior Checklist, and the Inpatient Parental Satisfaction Index. At the same time, the child’s psychiatrist completed the Family Engagement Questionnaire. Results indicated that engagement is related to satisfaction, prior in-patient treatment is negatively related to engagement, and satisfaction with prior in-patient services is highly predictive of satisfaction with current services. At 9-month follow-up, 32% of the sample had been re-hospitalized. Rehospitalization was associated with poorer engagement in treatment and lower parent ratings of satisfaction with care. These results suggest the existence of a group of patients who undergo repeat hospitalizations with poor levels of engagement in their care.
Characteristics of the Residents of In-Patient Child and Adolescent Mental Health Services in England and Wales
Authors: O’Herlihy Anne , Worrall Adrian , Lelliott Paul , Jaffa Tony , Mears Alex , Banerjee Sube , Hill Peter
Published: October 2004

This study describes the characteristics of the young people who use the full range of child and adolescent psychiatric in-patient units in England and Wales. Consultant psychiatrists or key workers were asked to complete a structured schedule about every resident on a census day – 19 October 1999. Schedules were returned from 71 of the 80 units in England and Wales, concerning 663 residents. Residents aged 13 or under had a wide range of diagnoses and more were male (58%). In contrast, two-thirds of residents aged 14–18 were categorized into one of three diagnostic groups – eating disorder, schizophrenia, delusional or psychotic disorders or mood disorders – and about two-thirds were female. In-patients had more severe problems than a group of young people using community services, particularly with hallucinations and delusions, emotional and related problems and problems of self-care and independence. The range of disorders treated by these units demonstrates the need for a range of specialist in-patient services to be available to children and adolescents in all regions.
Separation Anxiety Triggered by Atypical Neuroleptic Medication in an Adolescent with Tourette’s Syndrome
Authors: Becker Katja , Holtmann Martin , El-Faddagh Mahha , Schmidt Martin H.
Published: October 2004

This article describes the case of a 13-year-old male Tourette’s syndrome patient who developed separation anxiety disorder during combined treatment with risperidone and tiapride. In the 1980s, neuroleptic separation anxiety syndromes in patients with Tourette’s syndrome were described, and an association between the neuroleptic medication and the induced separation anxiety disorder in our patient seems probable. We conclude that future investigations of atypical anti-psychotics and their possible tendency to elicit separation anxiety are essential. Physicians should pay attention to the occurrence or exacerbation of separation anxiety in patients with Tourette’s syndrome who are receiving either typical or atypical neuroleptics.
De novo generation of CD4 T cells against viruses present in the host during immune reconstitution
Authors: Kalina Tomas , Lu Hailing , Zhao Zhao , Blewett Earl , Dittmer Dirk P. , Randolph-Habecker Julie , Maloney David G. , Andrews Robert G. , Kiem Hans-Peter , Storek Jan
Published: October 2004

T cells recognizing self-peptides are typically deleted in the thymus by negative selection. It is not known whether T cells against persistent viruses (eg, herpesviruses) are generated by the thymus (de novo) after the onset of the infection. Peptides from such viruses might be considered by the thymus as self-peptides, and T cells specific for these peptides might be deleted (negatively selected). Here we demonstrate in baboons infected with baboon cytomegalovirus and baboon lymphocryptovirus (Epstein-Barr virus–like virus) that after autologous transplantation of yellow fluorescent protein (YFP)–marked hematopoietic cells, YFP+ CD4 T cells against these viruses were generated de novo. Thus the thymus generates CD4 T cells against not only pathogens absent from the host but also pathogens present in the host. This finding provides a strong rationale to improve thymopoiesis in recipients of hematopoietic cell transplants and, perhaps, in other persons lacking de novo–generated CD4 T cells, such as AIDS patients and elderly persons.
Monoclonal antibodies that mimic the action of anti-D in the amelioration of murine ITP act by a mechanism distinct from that of IVIg
Authors: Song Seng , Crow Andrew R. , Siragam Vinayakumar , Freedman John , Lazarus Alan H.
Published: October 2004

The mechanism of action of intravenous immunoglobulin (IVIg) and polyclonal anti-D–mediated reversal of immune thrombocytopenia (ITP) is still unclear. However, in a murine model of ITP, the therapeutic effect of IVIg appears to be wholly dependent upon the expression of the inhibitory Fc receptor, FcγRIIB. We previously demonstrated that, similar to anti-D in humans, 2 erythrocyte-reactive monoclonal antibodies (TER119 and M1/69) ameliorated murine ITP and inhibited reticuloendothelial system (RES) function at doses that protected against thrombocytopenia. The current study evaluated the involvement of the inhibitory and activating Fc receptors, FcγRIIB and FcγRIIIA, respectively, in the TER119 and M1/69-mediated inhibition of thrombocytopenia. In contrast to IVIg, in FcγRIIB-deficient mice, both monoclonal antibodies ameliorated ITP and both significantly down-regulated the level of expression of the activating FcγRIIIA in splenic macrophages. These results indicate that anti-erythrocyte antibodies that ameliorate ITP act independently of FcγRIIB expression but are dependent upon the activating FcγRIIIA.
Regional intravascular delivery of AAV-2-F.IX to skeletal muscle achieves long-term correction of hemophilia B in a large animal model
Authors: Arruda Valder R. , Stedman Hansell H. , Nichols Timothy C. , Haskins Mark E. , Nicholson Matthew , Herzog Roland W. , Couto Linda B. , High Katherine A.
Published: October 2004

In earlier work, we showed that adeno-associated virus–mediated delivery of a Factor IX gene to skeletal muscle by direct intramuscular injection resulted in therapeutic levels of circulating Factor IX in mice. However, achievement of target doses in humans proved impractical because of the large number of injections required. We used a novel intravascular delivery technique to achieve successful transduction of extensive areas of skeletal muscle in a large animal with hemophilia. We provide here the first report of long-term (> 3 years, with observation ongoing), robust Factor IX expression (circulating levels of 4%-14%) by muscle-directed gene transfer in a large animal, resulting in essentially complete correction of the bleeding disorder in hemophilic dogs. The results of this translational study establish an experimental basis for clinical studies of this delivery method in humans with hemophilia B. These findings also have immediate relevance for gene transfer in patients with muscular dystrophy.
Underweight is independently associated with mortality in post-operative and non-operative patients admitted to the intensive care unit: a retrospective study
Authors: Finkielman Javier D , Gajic Ognjen , Afessa Bekele
Published: October 2004

Background

Low and high body mass index (BMI) have been recently shown to be associated with increased and decreased mortality after ICU admission, respectively. The objective of this study was to determine the impact of BMI on mortality and length of stay in patients admitted to the intensive care unit (ICU).

Methods

In this retrospective cohort study, the Acute Physiology and Chronic Health Evaluation (APACHE) III database of patients admitted to the ICUs of a tertiary academic medical center, from January 1997 to September 2002, was crossed with a Hospital Rule-based Systems database to obtain the height and weight of the patients on admission to the ICU. The cohort was divided in post-operative and non-operative groups. We created the following five subgroups based on the BMI: <18.5, 18.5 to 24.9, 25 to 29.9, 30.0 to 39.9, ≥ 40.0 Kg/m2. A multiple logistic regression analysis was used to determine the independent impact of BMI on hospital mortality. The ICU length of stay ratio was defined as the ratio of the observed to the predicted LOS. P-value < 0.05 was considered significant. The 95% confidence interval (CI) was calculated for the odds ratio (OR).

Results

BMI was available in 19,669 of the 21,790 patients in the APACHE III database; 11,215 (57%) of the patients were admitted post-operatively. BMI < 18.5 was associated with increased mortality in both post-operative (OR = 2.14, 95% CI, 1.39 to 3.28) and non-operative (OR = 1.51, 95% CI, 1.13 to 2.01) patients. Post-operative patients with a BMI between 30.0 to 39.9 had a lower mortality rate (OR = 0.68, 95% CI, 0.49 to 0.94). Post-operative patients with BMI <18.5 or BMI ≥ 40 had an ICU length of stay ratio significantly higher than patients with BMI between 18.5 to 24.9. The addition of BMI < 18.5 did not improve significantly the accuracy of our prognostic model in predicting hospital mortality.

Conclusions

Low BMI is associated with higher mortality in both post- and non-operative patients admitted to the ICU. LOS is increased in post-operative patients with low and high BMIs.
An unusual case of chronic meningitis
Authors: Boos Christopher , Daneshvar Cyrus , Hinton Anna , Dawes Matthew
Published: October 2004

Background

Chronic meningitis is defined as symptoms and signs of meningeal inflammation and persisting cerebrospinal fluid abnormalities such as elevated protein level and pleocytosis for at least one month.

Case presentation

A 62-year-old woman, of unremarkable past medical history, was admitted to hospital for investigation of a four-week history of vomiting, malaise an associated hyponatraemia. She had a low-grade pyrexia with normal inflammatory markers. A CT brain was unremarkable and a contrast MRI brain revealed sub-acute infarction of the right frontal cortex but with no evidence of meningeal enhancement. Due to increasing confusion and patient clinical deterioration a lumbar puncture was performed at 17 days post admission. This revealed gram-negative coccobacilli in the CSF, which was identified as Neisseria meningitidis group B. The patient made a dramatic recovery with high-dose intravenous ceftriaxone antibiotic therapy for meningococcal meningitis.

Conclusions

1) Chronic bacterial meningitis may present highly atypically, particularly in the older adult. 2) There may be an absent or reduced febrile response, without a rise in inflammatory markers, despite a very unwell patient. 3) Early lumbar puncture is to be encouraged as it is essential to confirm the diagnosis.4) Despite a delayed diagnosis appropriate antibiotic therapy can still lead to a good outcome.
Classification between normal and tumor tissues based on the pair-wise gene expression ratio
Authors: Yap YeeLeng , Zhang XueWu , Ling MT , Wang XiangHong , Wong YC , Danchin Antoine
Published: October 2004

Background

Precise classification of cancer types is critically important for early cancer diagnosis and treatment. Numerous efforts have been made to use gene expression profiles to improve precision of tumor classification. However, reliable cancer-related signals are generally lacking.

Method

Using recent datasets on colon and prostate cancer, a data transformation procedure from single gene expression to pair-wise gene expression ratio is proposed. Making use of the internal consistency of each expression profiling dataset this transformation improves the signal to noise ratio of the dataset and uncovers new relevant cancer-related signals (features). The efficiency in using the transformed dataset to perform normal/tumor classification was investigated using feature partitioning with informative features (gene annotation) as discriminating axes (single gene expression or pair-wise gene expression ratio). Classification results were compared to the original datasets for up to 10-feature model classifiers.

Results

82 and 262 genes that have high correlation to tissue phenotype were selected from the colon and prostate datasets respectively. Remarkably, data transformation of the highly noisy expression data successfully led to lower the coefficient of variation (CV) for the within-class samples as well as improved the correlation with tissue phenotypes. The transformed dataset exhibited lower CV when compared to that of single gene expression. In the colon cancer set, the minimum CV decreased from 45.3% to 16.5%. In prostate cancer, comparable CV was achieved with and without transformation. This improvement in CV, coupled with the improved correlation between the pair-wise gene expression ratio and tissue phenotypes, yielded higher classification efficiency, especially with the colon dataset – from 87.1% to 93.5%. Over 90% of the top ten discriminating axes in both datasets showed significant improvement after data transformation. The high classification efficiency achieved suggested that there exist some cancer-related signals in the form of pair-wise gene expression ratio.

Conclusion

The results from this study indicated that: 1) in the case when the pair-wise expression ratio transformation achieves lower CV and higher correlation to tissue phenotypes, a better classification of tissue type will follow. 2) the comparable classification accuracy achieved after data transformation suggested that pair-wise gene expression ratio between some pairs of genes can identify reliable markers for cancer.
CD155/PVR plays a key role in cell motility during tumor cell invasion and migration
Authors: Sloan Kevin E , Eustace Brenda K , Stewart Jean K , Zehetmeier Carol , Torella Claudia , Simeone Marina , Roy Jennifer E , Unger Christine , Louis David N , Ilag Leodevico L , Jay Daniel G
Published: October 2004

Background

Invasion is an important early step of cancer metastasis that is not well understood. Developing therapeutics to limit metastasis requires the identification and validation of candidate proteins necessary for invasion and migration.

Methods

We developed a functional proteomic screen to identify mediators of tumor cell invasion. This screen couples Fluorophore Assisted Light Inactivation (FALI) to a scFv antibody library to systematically inactivate surface proteins expressed by human fibrosarcoma cells followed by a high-throughput assessment of transwell invasion.

Results

Using this screen, we have identified CD155 (the poliovirus receptor) as a mediator of tumor cell invasion through its role in migration. Knockdown of CD155 by FALI or by RNAi resulted in a significant decrease in transwell migration of HT1080 fibrosarcoma cells towards a serum chemoattractant. CD155 was found to be highly expressed in multiple cancer cell lines and primary tumors including glioblastoma (GBM). Knockdown of CD155 also decreased migration of U87MG GBM cells. CD155 is recruited to the leading edge of migrating cells where it colocalizes with actin and αv-integrin, known mediators of motility and adhesion. Knockdown of CD155 also altered cellular morphology, resulting in cells that were larger and more elongated than controls when plated on a Matrigel substrate.

Conclusion

These results implicate a role for CD155 in mediating tumor cell invasion and migration and suggest that CD155 may contribute to tumorigenesis.