27 research outputs found
Physiological and morphological determinants of maximal expiratory flow in chronic obstructive lung disease
Maximal expiratory flow in chronic obstructive pulmonary disease (COPD)
could be reduced by three different mechanisms; loss of lung elastic
recoil, decreased airway conductance upstream of flow-limiting segments;
and increased collapsibility of airways. We hypothesized that decreased
upstream conductance would be related to inflammation and thickening of
the airway walls, increased collapsibility would be related to decreased
airway cartilage volume, and decreased collapsibility to inflammation and
thickening of the airway walls. Lung tissue was obtained from 72 patients
with different degrees of COPD, who were operated upon for a solitary
peripheral lung lesion. Maximal flow-static recoil (MFSR) plots to
estimate upstream resistance and airway collapsibility were derived in 59
patients from preoperatively measured maximal expiratory flow-volume and
pressure-volume curves. In 341 transversely cut airway sections, airway
size, airway wall dimensions and inflammatory changes were measured.
Airflow obstruction correlated with lung elastic recoil and the MFSR
estimate of airway conductance but not to airway collapsibility or to the
amount of airway cartilage. The upstream conductance decreased as the
inner wall became thicker. Airway collapsibility did not correlate with
the amount of airway cartilage, inflammation, or airway wall thickness. We
conclude that the maximal flow-static recoil model does not adequately
reflect the collapsibility of the flow-limiting segment
Progressive damage on high resolution computed tomography despite stable lung function in cystic fibrosis
For effective clinical management of cystic fibrosis (CF) lung disease it
is important to closely monitor the start and progression of lung damage.
The aim of this study was to investigate the ability of high-resolution
computed tomography (HRCT) scoring systems and pulmonary function tests
(PFT) to detect changes in lung disease. CF children (n=48) had two H
Cerebral ß-amyloid angiopathy in aged squirrel monkeys
Cerebral ß-amyloid angiopathy (CAA) is an
age-related disorder of the brain vasculature that is
involved in up to 20% of non-traumatic cerebral
hemorrhage in humans. CAA is a risk factor for
cognitive decline, and may exacerbate the dementia of
Alzheimer's disease. Progress in discovering the cause
and potential therapies for this disorder has been
hindered by the paucity of animal models, particularly
models of idiopathic CAA. The squirrel monkey
(Saimiri spp) develops significant CAA in the natural
course of aging. To evaluate the suitability of Saimiri as
a model of human CAA, we studied the distribution and
composition of Aß subtypes in CAA and parenchymal
(senile plaque) deposits in the brains of aged squirrel
monkeys, as well as the relationship between vascular ßamyloid
deposition and comorbid vasculopathies that
occur in aged humans. Our findings show that: 1) CAA
consists ultrastructurally of classical amyloid fibrils and is the principal type of cerebral ß-amyloidosis in squirrel
monkeys; 2) The two primary isoforms of Aß (Aß40 and
Aß42) coexist in most microvascular and parenchymal
lesions of Saimiri, although Aß40 tends to predominate
in larger arterioles; 3) CAA and parenchymal plaques
overlap to a considerable degree in most affected brain
areas, and are distributed symmetrically in the two
hemispheres; 4) Both CAA and plaques are particularly
abundant in rostral regions and comparatively sparse in
the occipital lobe; 5) Capillaries are especially
vulnerable to CAA in squirrel monkeys; and 6) When
CAA is severe, it is associated with a small, but
significant, increase in other vasculopathies, including
microhemorrhage, fibrinoid extravasation and focal
gliosis. These findings, in the context of genetic,
vascular and immunologic similarities between squirrel
monkeys and humans, support the squirrel monkey as a
biologically advantageous model for studying the basic
biology of idiopathic, age-related CAA, and for testing emerging therapies for human ß-amyloidoses such as
Alzheimer's disease
NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease
Sandford AJ, Malhotra D, Boezen HM, Siedlinski M, Postma DS, Wong V, Akhabir L, He JQ, Connett JE, Anthonisen NR, Pare PD, Biswal S. NFE2L2 pathway polymorphisms and lung function decline in chronic obstructive pulmonary disease. Physiol Genomics 44: 754-763, 2012. First published June 12, 2012; doi:10.1152/physiolgenomics.00027.2012.-An oxidant-antioxidant imbalance in the lung contributes to the development of chronic obstructive pulmonary disease (COPD) that is caused by a complex interaction of genetic and environmental risk factors. Nuclear erythroid 2-related factor 2 (NFE2L2 or NRF2) is a critical molecule in the lung's defense mechanism against oxidants. We investigated whether polymorphisms in the NFE2L2 pathway affected the rate of decline of lung function in smokers from the Lung Health Study (LHS)(n = 547) and in a replication set, the Vlagtwedde-Vlaardingen cohort (n = 533). We selected polymorphisms in NFE2L2 in genes that positively or negatively regulate NFE2L2 transcriptional activity and in genes that are regulated by NFE2L2. Polymorphisms in 11 genes were significantly associated with rate of lung function decline in the LHS. One of these polymorphisms, rs11085735 in the KEAP1 gene, was previously shown to be associated with the level of lung function in the Vlagtwedde-Vlaardingen cohort but not with decline of lung function. Of the 23 associated polymorphisms in the LHS, only rs634534 in the FOSL1 gene showed a significant association in the Vlagtwedde-Vlaardingen cohort with rate of lung function decline, but the direction of the association was not consistent with that in the LHS. In summary, despite finding several nominally significant polymorphisms in the LHS, none of these associations were replicated in the Vlagtwedde-Vlaardingen cohort, indicating lack of effect of polymorphisms in the NFE2L2 pathway on the rate of decline of lung function