60 research outputs found
Footprint of Positive Selection in Treponema pallidum subsp. pallidum Genome Sequences Suggests Adaptive Microevolution of the Syphilis Pathogen
In the rabbit model of syphilis, infection phenotypes associated with the Nichols and Chicago strains of Treponema pallidum (T. pallidum), though similar, are not identical. Between these strains, significant differences are found in expression of, and antibody responses to some candidate virulence factors, suggesting the existence of functional genetic differences between isolates. The Chicago strain genome was therefore sequenced and compared to the Nichols genome, available since 1998. Initial comparative analysis suggested the presence of 44 single nucleotide polymorphisms (SNPs), 103 small (≤3 nucleotides) indels, and 1 large (1204 bp) insertion in the Chicago genome with respect to the Nichols genome. To confirm the above findings, Sanger sequencing was performed on most loci carrying differences using DNA from Chicago and the Nichols strain used in the original T. pallidum genome project. A majority of the previously identified differences were found to be due to errors in the published Nichols genome, while the accuracy of the Chicago genome was confirmed. However, 20 SNPs were confirmed between the two genomes, and 16 (80.0%) were found in coding regions, with all being of non-synonymous nature, strongly indicating action of positive selection. Sequencing of 16 genomic loci harboring SNPs in 12 additional T. pallidum strains, (SS14, Bal 3, Bal 7, Bal 9, Sea 81-3, Sea 81-8, Sea 86-1, Sea 87-1, Mexico A, UW231B, UW236B, and UW249C), was used to identify “Chicago-“ or “Nichols -specific” differences. All but one of the 16 SNPs were “Nichols-specific”, with Chicago having identical sequences at these positions to almost all of the additional strains examined. These mutations could reflect differential adaptation of the Nichols strain to the rabbit host or pathoadaptive mutations acquired during human infection. Our findings indicate that SNPs among T. pallidum strains emerge under positive selection and, therefore, are likely to be functional in nature
Prevalence of pulmonary tuberculosis in young adult patients with Type 1 diabetes mellitus in India
Decreased expression of antioxidant enzymes in the conjunctival epithelium of dry eye (Sjogren s syndrome) and its possible contribution to the development of ocular surface oxidative injuries
Previous studies have described elevated
lipid peroxidase, myeloperoxidase and xanthine
oxidoreductase/xanthine oxidase levels on the ocular
surface of patients suffering from autoimmune dry eye
(Sjögren’s syndrome, SS). Reactive oxygen species
generated by various enzymatic systems may be
dangerous to the eye if they are not sufficiently cleaved
by antioxidants. Because antioxidants have not been
investigated in dry eye, the aim of this study was to
examine the expression of antioxidant enzymes that
cleave reactive oxygen species and play a key role in
antioxidant protection. Conjunctival epithelial cells of
dry eye (SS) patients were obtained by the method of
impression cytology using Millicell membranes. Normal
eyes served as controls. In the conjunctival epithelium
superoxide dismutase, catalase and glutathione
peroxidase were examined immunohistochemically. The
enzyme expression levels were determined by image
analysis and statistical evaluation. In contrast to normal
eyes, where antioxidant enzymes were highly expressed
in the conjunctival epithelium, in dry eye their
expression was much less pronounced in correlation with the increasing severity of dry eye symptoms. Our
study suggests that the decreased expression of
antioxidant enzymes in dry eye disease (SS) contributes
to the development of anterior eye surface oxidative
injuries
Ocular surface injuries in autoimmune dry eye. The severity of microscopical disturbances goes parallel with the severity of symptoms of dryness
Autoimmune dry eye (Sjögren’s syndrome,
SS) is a chronic systemic disease characterized by
salivary and lacrimal gland inflammation and tissue
damage leading to keratoconjunctivitis sicca and
xerostomia. In this review attention has been devoted to
the cause of the development of oxidative injuries of the
ocular surface of patients suffering from SS. It was
shown that lacrimal glands and diseased conjunctival
epithelium reveal increased expression of proinflammatory
cytokines which are released into the tear
fluid. A high amount of pro-inflammatory cytokines
highly induce the elevated expression and activity of
enzymatic systems that generate reactive oxygen and
nitrogen species. An abundant amount of these toxic
products leads to a decrease in antioxidants and to the
formation of cytotoxic related oxidants, such as
peroxynitrite. All these factors, together with reactive
oxygen species from polymorphonuclear leukocytes,
contribute to the development of oxidative injuries at the
ocular surface. From the clinical point of view it is
important that the level of severity of the above
described microscopical disturbances found in
conjunctival epithelial cells goes parallel with the level
of severity of dry eye symptoms
The role of conjunctival epithelial cell xanthine oxidoreductase/xanthine oxidase in oxidative reactions on the ocular surface of dry eye patients with sjögren`s syndrome
Previous papers examined lipid peroxidase
levels and myeloperoxidase activity as products of
oxidative and inflammatory reactions in the tear fluid of
patients suffering from dry eye. The aim of the present
paper was to investigate whether the enzymes xanthine
oxidoreductase/xanthine oxidase known to generate
reactive oxygen species contribute to oxidative reactions
on the ocular surface. Xanthine oxidoreductase/xanthine
oxidase were examined immunohistochemically as well
as histochemically in conjunctival epithelial cells of
patients suffering from dry eye. Patients with verified
autoimmune dry eye (Sjögren’s syndrome) participated
in our study; normal eyes served as controls.
Conjunctival epithelial cells were obtained by the
method of impression cytology using Millicell
membranes. The results revealed a pronounced
expression, as well as activity of xanthine
oxidoreductase/xanthine oxidase in the conjunctival
epithelium of dry eye. It is suggested that reactive
oxygen species which are generated by this enzymatic
system, contribute to oxidative reactions on the eye
surface of patients with ocular manifestations of
autoimmune disease (Sjögren’s syndrome)
UVB light regulates expression of antioxidants and inflammatory mediators in human corneal epithelial cells
Autoimmune Diabetes Mellitus with Adult Onset and Type 1 Diabetes Mellitus in Children Have Different Genetic Predispositions
A study of the morphology, fine structure and histochemistry of the foot of the pediveliger of Mytilus edulis
Prolactin is associated with metabolic risk and cortisol in 1007 women with polycystic ovary syndrome
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