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31.
Samar Farha Daniel Laskowski Deepa George Margaret M Park WH Wilson Tang Raed A Dweik Serpil C Erzurum 《Respiratory research》2013,14(1):6
Background
Reduced gas transfer in patients with pulmonary arterial hypertension (PAH) is traditionally attributed to remodeling and progressive loss of pulmonary arterial vasculature that results in decreased capillary blood volume available for gas exchange.Methods
We tested this hypothesis by determination of lung diffusing capacity (DL) and its components, the alveolar capillary membrane diffusing capacity (Dm) and lung capillary blood volume (Vc) in 28 individuals with PAH in comparison to 41 healthy individuals, and in 19 PAH patients over time. Using single breath simultaneous measure of diffusion of carbon monoxide (DLCO) and nitric oxide (DLNO), DL and Dm were respectively determined, and Vc calculated. Dm and Vc were evaluated over time in relation to standard clinical indicators of disease severity, including brain natriuretic peptide (BNP), 6-minute walk distance (6MWD) and right ventricular systolic pressure (RVSP) by echocardiography.Results
Both DLCO and DLNO were reduced in PAH as compared to controls and the lower DL in PAH was due to loss of both Dm and Vc (all p < 0.01). While DLCO of PAH patients did not change over time, DLNO decreased by 24 ml/min/mmHg/year (p = 0.01). Consequently, Dm decreased and Vc tended to increase over time, which led to deterioration of the Dm/Vc ratio, a measure of alveolar-capillary membrane functional efficiency without changes in clinical markers.Conclusions
The findings indicate that lower than normal gas transfer in PAH is due to loss of both Dm and Vc, but that deterioration of Dm/Vc over time is related to worsening membrane diffusion. 相似文献32.
33.
MCW Chan CY Cheung WH Chui SW Tsao JM Nicholls YO Chan RWY Chan HT Long LLM Poon Y Guan JSM Peiris 《Respiratory research》2005,6(1):135
Background
Fatal human respiratory disease associated with influenza A subtype H5N1 has been documented in Hong Kong, and more recently in Vietnam, Thailand and Cambodia. We previously demonstrated that patients with H5N1 disease had unusually high serum levels of IP-10 (interferon-gamma-inducible protein-10). Furthermore, when compared with human influenza virus subtype H1N1, the H5N1 viruses in 1997 (A/Hong Kong/483/97) (H5N1/97) were more potent inducers of pro-inflammatory cytokines (e.g. tumor necrosis factor-a) and chemokines (e.g. IP-10) from primary human macrophages in vitro, which suggests that cytokines dysregulation may play a role in pathogenesis of H5N1 disease. Since respiratory epithelial cells are the primary target cell for replication of influenza viruses, it is pertinent to investigate the cytokine induction profile of H5N1 viruses in these cells.Methods
We used quantitative RT-PCR and ELISA to compare the profile of cytokine and chemokine gene expression induced by H5N1 viruses A/HK/483/97 (H5N1/97), A/Vietnam/1194/04 and A/Vietnam/3046/04 (both H5N1/04) with that of human H1N1 virus in human primary alveolar and bronchial epithelial cells in vitro.Results
We demonstrated that in comparison to human H1N1 viruses, H5N1/97 and H5N1/04 viruses were more potent inducers of IP-10, interferon beta, RANTES (regulated on activation, normal T cell expressed and secreted) and interleukin 6 (IL-6) in primary human alveolar and bronchial epithelial cells in vitro. Recent H5N1 viruses from Vietnam (H5N1/04) appeared to be even more potent at inducing IP-10 than H5N1/97 virus.Conclusion
The H5N1/97 and H5N1/04 subtype influenza A viruses are more potent inducers of proinflammatory cytokines and chemokines in primary human respiratory epithelial cells than subtype H1N1 virus. We suggest that this hyper-induction of cytokines may be relevant to the pathogenesis of human H5N1 disease. 相似文献34.
Rates and dates of divergence between AIDS virus nucleotide sequences 总被引:28,自引:3,他引:25
35.
Sequence variation in ZFX introns in human populations 总被引:3,自引:2,他引:1
DNA variation in human populations was studied by examining the last intron
of the ZFX gene (about 1, 151 bp) with a worldwide sample of 29
individuals. Only one polymorphic site was found, which is located in an
Alu sequence. This polymorphism is present at an intermediate frequency in
all populations studied, and could be a shared polymorphism or due to
migration among populations in Asia, Europe, and Africa. The nucleotide
diversity is 0.04%, supporting the view that the level of nucleotide
variation in nuclear DNA is very low in humans. From the sequence data, the
age (T) of the most recent common ancestor of the sampled sequences is
estimated: the mode of T is about 306,000 years, and the 95% confidence
interval of T is 162,000-952,000 years. This mode estimate is considerably
older than the estimates from Y- linked sequences.
相似文献
36.
Contrasting levels of DNA polymorphism at the autosomal and X-linked visual color pigment loci in humans and squirrel monkeys 总被引:1,自引:0,他引:1
The X-linked color pigment (opsin) locus is known to be highly polymorphic
in the squirrel monkey and other New World monkeys. To see whether this is
also the case for the autosomal (blue) opsin locus, we obtained 32 squirrel
monkey and 30 human blue opsin gene sequences. No amino acid polymorphism
was found in either the squirrel monkey sample or the human sample,
contrary to the situation at the X-linked opsin locus. This sharp contrast
in the level of polymorphism might be due to differences in gene expression
between the autosomal and the X-linked loci. At the X-linked locus,
heterozygote advantage can occur because, owing to X-inactivation, the two
alleles in a heterozygote are expressed in different cone cells, producing
two types of cone cell, whereas at the autosomal locus, heterozygote
advantage cannot occur because the two alleles in a heterozygote are
expressed in the same cone cells, producing only one type of cone cell
(i.e., phenotypically a homozygote). From the sequence data, the levels of
nucleotide diversity (pi, i.e., the number of nucleotide differences per
site) are estimated: for the human sample, pi = 0.00% per nondegenerate
site, 0.00% per twofold degenerate site, and 0.04% per fourfold degenerate
site in the coding regions and 0.01% per site in intron 4; for the squirrel
monkey sample, pi = 0.00% per nondegenerate site, 0.00% per twofold
degenerate site, and 0.15% per fourfold degenerate site in the coding
regions and 0.17% per site in intron 4. The blue opsin genes from the
common and pygmy chimpanzees, the gorilla, the capuchin, and the howler
monkey were also sequenced. Features critical to the function of the opsin
are well conserved in all known mammalian sequences. However, the
interhelical loops are, on average, actually more conservative than the
transmembrane helical regions. In addition, these sequence data and those
from some other genes indicate that the common and pygmy chimpanzees are
not closely related, their divergence data being from one third to one half
the date of the human-chimpanzee divergence.
相似文献
37.
The role of site-specific N-glycosylation in secretion of soluble forms of rabies virus glycoprotein 总被引:1,自引:1,他引:0
Wojczyk BS; Stwora-Wojczyk M; Shakin-Eshleman S; Wunner WH; Spitalnik SL 《Glycobiology》1998,8(2):121-130
Rabies virus glycoprotein is important in the biology and pathogenesis of
neurotropic rabies virus infection. This transmembrane glycoprotein is the
only viral protein on the surface of virus particles, is the viral
attachment protein that facilitates virus uptake by the infected cell, and
is the target of the host humoral immune response to infection. The
extracellular domain of this glycoprotein has N- glycosylation sequons at
Asn37, Asn247, and Asn319. Appropriate glycosylation of these sequons is
important in the expression of the glycoprotein. Soluble forms of rabies
virus glycoprotein were constructed by insertion of a stop codon just
external to the transmembrane domain. Using site-directed mutagenesis and
expression in transfected eukaryotic cells, it was possible to compare the
effects of site-specific glycosylation on the cell-surface expression and
secretion of transmembrane and soluble forms, respectively, of the same
glycoprotein. These studies yielded the surprising finding that although
any of the three sequons permitted cell surface expression of full-length
rabies virus glycoprotein, only the N-glycan at Asn319 permitted secretion
of soluble rabies virus glycoprotein. Despite its biological and medical
importance, it has not yet been possible to determine the crystal structure
of the full-length transmembrane form of rabies virus glycoprotein which
contains heterogeneous oligosaccharides. The current studies demonstrate
that a soluble form of rabies virus glycoprotein containing only one sequon
at Asn319 is efficiently secreted in the presence of the N-glycan
processing inhibitor 1-deoxymannojirimycin. Thus, it is possible to purify
a conformationally relevant form of rabies virus glycoprotein that contains
only one N-glycan with a substantial reduction in its microheterogeneity.
This form of the glycoprotein may be particularly useful for future studies
aimed at elucidating the three-dimensional structure of this important
glycoprotein.
相似文献
38.
39.
Background
The chondrichthyan or cartilaginous fish (chimeras, sharks, skates and rays) occupy an important phylogenetic position as the sister group to all other jawed vertebrates and as an early lineage to diverge from the vertebrate lineage following two whole genome duplication events in vertebrate evolution. There have been few comparative genomic analyses incorporating data from chondrichthyan fish and none comparing genomic information from within the group. We have sequenced the complete Hoxa cluster of the Little Skate (Leucoraja erinacea) and compared to the published Hoxa cluster of the Horn Shark (Heterodontus francisci) and to available data from the Elephant Shark (Callorhinchus milii) genome project. 相似文献40.
Gene conversion and natural selection in the evolution of X-linked color vision genes in higher primates 总被引:2,自引:1,他引:1
During higher primate evolution, gene conversion seems to have occurred
often between the red and green photo-pigment genes, which are tandemly
linked on the X chromosome. To understand this phenomenon better, intron 4
sequences of the red and green pigment genes of a male human (an Asian
Indian), a male chimpanzee, and a male baboon were amplified by PCR and
sequenced. The data show that the intron 4 sequences between the two genes
have been strongly or completely homogenized in the three species studied.
Apparently recent gene conversion events have occurred in introns 4 of the
red and green pigment genes in humans and chimpanzees. Two or more
conversion events may have occurred at different times in introns 4 of the
two pigment genes in baboons. The divergence between the two genes is
significantly lower in intron 4 than in exons 4 and 5 in each species,
contrary to the usual situation that introns evolve faster than exons. It
is most likely that strong natural selection for maintaining the distinct
functions of exons 4 and 5 of the red and green pigment genes has acted
against sequence homogenization of these exons.
相似文献