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AB Chang NC Cox J Purcell JM Marchant PJ Lewindon GJ Cleghorn LC Ee GD Withers MK Patrick J Faoagali 《Respiratory research》2005,6(1):1-5
Background and methods
Human metapneumovirus (hMPV) is a recently discovered respiratory virus associated with bronchiolitis, pneumonia, croup and exacerbations of asthma. Since respiratory viruses are frequently detected in patients with acute exacerbations of COPD (AE-COPD) it was our aim to investigate the frequency of hMPV detection in a prospective cohort of hospitalized patients with AE-COPD compared to patients with stable COPD and to smokers without by means of quantitative real-time RT-PCR.Results
We analysed nasal lavage and induced sputum of 130 patients with AE-COPD, 65 patients with stable COPD and 34 smokers without COPD. HMPV was detected in 3/130 (2.3%) AE-COPD patients with a mean of 6.5 × 105 viral copies/ml in nasal lavage and 1.88 × 105 viral copies/ml in induced sputum. It was not found in patients with stable COPD or smokers without COPD.Conclusion
HMPV is only found in a very small number of patients with AE-COPD. However it should be considered as a further possible viral trigger of AE-COPD because asymptomatic carriage is unlikely. 相似文献13.
Woolford LB Southgate TD Margison GP Milsom MD Fairbairn LJ 《The journal of gene medicine》2006,8(1):29-34
The O(6)-methylguanine-DNA-methyltransferase (MGMT) inactivator O(6)-benzylguanine (O(6)-beG) is currently under clinical investigation as a potential tumour-sensitising agent. In clinical trials its use has been associated with increased myelotoxicity and a reduced maximum tolerated dose (MTD) for BCNU. Thus the concept of myeloprotection by gene therapy with an O(6)-beG-insensitive mutant of MGMT is soon to be tested. Recently, an alternative inactivator has been described (O(6)-(4-bromothenyl)guanine, PaTrin-2), which shows potential advantages over O(6)-beG in terms of higher activity against wild-type MGMT and oral formulation. The use of PaTrin-2 has also been associated with increased myelotoxicity in clinical trials and thus PaTrin-2 may also be a candidate for use in conjunction with mutant MGMT gene transfer in genetic chemoprotective strategies. However, its activity against mutant MGMTs has not been reported. We show here that the P(140)K mutant of MGMT is highly resistant to inactivation by PaTrin-2. Furthermore, we show that a human haemopoietic cell line (K562) transduced with a retroviral vector encoding MGMT(P140K) is highly resistant to the cytotoxic effects of PaTrin-2 in combination with the methylating agent temozolomide, and that cells expressing MGMT(P140K) can be effectively enriched in vitro following challenge with this drug combination. Finally, we show that animals reconstituted with bone marrow expressing MGMT(P140K) exhibit haemopoietic resistance to PaTrin-2/temozolomide, which results in in vivo selection of gene-modified cells. All of these effects were comparable to those also achieved using O(6)-beG/temozolomide. Thus our data show that MGMT(P140K) is a suitable candidate for chemoprotective gene therapy where PaTrin-2 is being used in conjunction with temozolomide. 相似文献
14.
Tattersall GJ de Andrade DV Brito SP Abe AS Milsom WK 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2006,176(2):125-138
In order to study the relative roles of receptors in the upper airways, lungs and systemic circulation in modulating the ventilatory
response of caiman (Caiman latirostris) to inhaled CO2, gas mixtures of varying concentrations of CO2 were administered to animals breathing through an intact respiratory system, via a tracheal cannula by-passing the upper
airways (before and after vagotomy), or via a cannula delivering gas to the upper airways alone. While increasing levels of
hypercarbia led to a progressive increase in tidal volume in animals with intact respiratory systems (Series I), breathing
frequency did not change until the CO2 level reached 7%, at which time it decreased. Despite this, at the higher levels of hypercarbia, the net effect was a large
and progressive increase in total ventilation. There were no associated changes in heart rate or arterial blood pressure.
On return to air, there was an immediate change in breathing pattern; breathing frequency increased above air-breathing values,
roughly to the same maximum level regardless of the level of CO2 the animal had been previously breathing, and tidal volume returned rapidly toward resting (baseline) values. Total ventilation
slowly returned to air breathing values. Administration of CO2 via different routes indicated that inhaled CO2 acted at both upper airway and pulmonary CO2-sensitive receptors to modify breathing pattern without inhibiting breathing overall. Our data suggest that in caiman, high
levels of inspired CO2 promote slow, deep breathing. This will decrease dead-space ventilation and may reduce stratification in the saccular portions
of the lung. 相似文献
15.
Background
Burkholderia pseudomallei is a saprophyte in tropical environments and an opportunistic human pathogen. This versatility requires a sensing mechanism that allows the bacterium to respond rapidly to altered environmental conditions. We characterized a two-component signal transduction locus from B. pseudomallei 204, mrgR and mrgS, encoding products with extensive homology with response regulators and histidine protein kinases of Escherichia coli, Bordetella pertussis, and Vibrio cholerae. 相似文献16.
We examined the magnitude of the hypoxic metabolic response in golden-mantled ground squirrels to determine whether the shift in thermoregulatory set point (T(set)) and subsequent fall in body temperature (T(b)) and metabolic rate observed in small mammals were greater in a species that routinely experiences hypoxic burrows and hibernates. We measured the effects of changing ambient temperature (T(a); 6--29 degrees C) on metabolism (O(2) consumption and CO(2) production), T(b), ventilation, and heart rate in normoxia and hypoxia (7% O(2)). The magnitude of the hypoxia-induced falls in T(b) and metabolism of the squirrels was larger than that of other rodents. Metabolic rate was not simply suppressed but was regulated to assist the initial fall in T(b) and then acted to slow this fall and stabilize T(b) at a new, lower level. When T(a) was reduced during 7% O(2), animals were able to maintain or elevate their metabolic rates, suggesting that O(2) was not limiting. The slope of the relationship between temperature-corrected O(2) consumption and T(a) extrapolated to a T(set) in hypoxia equals the actual T(b). The data suggest that T(set) was proportionately related to T(a) in hypoxia and that there was a shift from increasing ventilation to increasing O(2) extraction as the primary strategy employed to meet increasing metabolic demands under hypoxia. The animals were neither hypothermic nor hypometabolic, as T(b) and metabolic rate appeared to be tightly regulated at new but lower levels as a result of a coordinated hypoxic metabolic response. 相似文献
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Toledo LF Brito SP Milsom WK Abe AS Andrade DV 《Physiological and biochemical zoology : PBZ》2008,81(2):158-164
Abstract This study examined how the standard metabolic rate of tegu lizards, a species that undergoes large ontogenetic changes in body weight with associated changes in life-history traits, is affected by changes in body mass, body temperature, season, and life-history traits. We measured rates of oxygen consumption (Vo(2)) in 90 individuals ranging in body mass from 10.4 g to 3.75 kg at three experimental temperatures (17 degrees , 25 degrees , and 30 degrees C) over the four seasons. We found that standard metabolic rate scaled to the power of 0.84 of body mass at all experimental temperatures in all seasons and that thermal sensitivity of metabolism was relatively low (Q(10) approximately 2.0-2.5) over the range from 17 degrees to 30 degrees C regardless of body size or season. Metabolic rates did vary seasonally, being higher in spring and summer than in autumn and winter at the same temperatures, and this was true regardless of animal size. Finally, in this study, the changes in life-history traits that occurred ontogenetically were not accompanied by significant changes in metabolic rate. 相似文献
20.
Porteus C Hedrick MS Hicks JW Wang T Milsom WK 《Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology》2011,181(3):311-333
Over a decade has passed since Powell et al. (Respir Physiol 112:123–134, 1998) described and defined the time domains of the hypoxic ventilatory response (HVR) in adult mammals. These time domains, however,
have yet to receive much attention in other vertebrate groups. The initial, acute HVR of fish, amphibians and reptiles serves
to minimize the imbalance between oxygen supply and demand. If the hypoxia is sustained, a suite of secondary adjustments
occur giving rise to a more long-term balance (acclimatization) that allows the behaviors of normal life. These secondary
responses can change over time as a function of the nature of the stimulus (the pattern and intensity of the hypoxic exposure).
To add to the complexity of this process, hypoxia can also lead to metabolic suppression (the hypoxic metabolic response)
and the magnitude of this is also time dependent. Unlike the original review of Powell et al. (Respir Physiol 112:123–134,
1998) that only considered the HVR in adult animals, we also consider relevant developmental time points where information is
available. Finally, in amphibians and reptiles with incompletely divided hearts the magnitude of the ventilatory response
will be modulated by hypoxia-induced changes in intra-cardiac shunting that also improve the match between O2 supply and demand, and these too change in a time-dependent fashion. While the current literature on this topic is reviewed
here, it is noted that this area has received little attention. We attempt to redefine time domains in a more ‘holistic’ fashion
that better accommodates research on ectotherms. If we are to distinguish between the genetic, developmental and environmental
influences underlying the various ventilatory responses to hypoxia, however, we must design future experiments with time domains
in mind. 相似文献