To report a series of patients with no previous history of herpes simplex virus (HSV) infection who had new onset of herpetic keratitis after penetrating keratoplasty (PK).
Noncontrolled, ...retrospective case series.
We included in the study the patients who had new onset of herpetic keratitis after penetrating keratoplasty for corneal diseases unrelated to HSV infection who were seen at the Cornea Service at Wills Eye Hospital (Philadelphia, Pennsylvania) from January 1996 to December 2002. The diagnosis of HSV epithelial keratitis was based on clinical characteristics of either a classic herpetic dendrite, a geographic ulcer, or a nonhealing epithelial defect that responded only to antiviral therapy.
Fourteen patients were included in the study. Eight of these (57%) had presented with a geographic ulcer whereas six patients (43%) had a classic dendrite. The most common primary corneal disease that led to PK was pseudophakic bullous keratopathy (36%), followed by keratoconus (29%), Fuchs dystrophy (21%), and corneal scar unrelated to HSV (14%).
The ophthalmologist should be aware of the possibility of herpetic keratitis in eyes after PK, even in patients with no previous history of HSV infection.
The Antarctic planet interferometer
Proceedings of SPIE, the International Society for Optical Engineering/Proceedings of SPIE,
10/2004
Conference Proceeding
The complement system is a cascade of serum proteins and receptors which forms a vital arm of innate immunity and enhances the adaptive immune response. This work establishes the chromosomal ...localization of four key genes of the murine complement system. Mapping was performed using a novel and rapid PCR restriction length polymorphism method which was developed to exploit the murine expressed sequence tag (EST) database. This technique circumvents the laborious cDNA or genomic cloning steps of other mapping methods by relying on EST data and the prediction of exon–intron boundaries. This method can be easily applied to the genes of other systems, ranging from the interests of the individual researcher to large-scale gene localization projects. Here the complement system, probably one of the most well-characterized areas of immunology, was used as a model system. It was shown that the C3a receptor C1r and C1s genes form an unexpected complement gene cluster towards the telomeric end of chromosome 6. The second mannose binding lectin-associated serine protease gene was mapped to the telomeric end of chromosome 4, which is distinct from other complement-activating serine proteases. These results provide new insights into the evolution of this group of proteins.
Brain-derived neurotrophic factor (BDNF) plays an important role in the survival, differentiation, and outgrowth of select peripheral and central neurons throughout adulthood. Growing evidence ...suggests that BDNF is involved in the pathophysiology of mood disorders.
Ten single nucleotide polymorphisms (SNPs) across the BDNF gene were genotyped in a sample of 1749 Caucasian Americans from 250 multiplex bipolar families. Family-based association analysis was used with three hierarchical bipolar disorder models to test for an association between SNPs in BDNF and the risk of bipolar disorder. In addition, an exploratory analysis was performed to test for an association of the SNPs in BDNF and the phenotypes of rapid cycling and episode frequency.
Evidence of association (P<0.05) was found with several of the SNPs using multiple models of bipolar disorder; one of these SNPs also showed evidence of association (P<0.05) with rapid cycling.
These results provide further evidence that variation in BDNF affects the risk for bipolar disorder.
Lung surfactant protein (SP)-D belongs to the family of soluble collagenous C-type lectins, named collectins. SP-D participates in the local innate immune defense of the lung, eliciting various ...effector functions by acting as a pattern recognition receptor for the carbohydrate structures on inhaled microorganisms and particulate matter. This work describes the isolation and characterization of the mouse SP-D gene (Sftpd), which spans 8 exons over 14 kb of sequence and shows an overall organization similar to other collectin genes. The complete 5' untranslated region of the messenger RNA, absent from the published complementary DNA for mouse SP-D, was also cloned and is shown to be encoded by a single exon. Analysis of 3.5 kb of 5' flanking nucleotide sequence for Sftpd is described and reveals positional conservation of a number of transcription factor binding sites on comparison of Sftpd with the human SP-D gene and the bovine conglutinin gene. In addition, a single copy SP-D-like gene has been shown to be present in mammals, birds, and amphibians but is absent in fish. An atypical, rodent-specific, long terminal repeat of retroviral origin containing a minisatellite that has become inserted in Sftpd is described. Three new polymorphic microsatellites are also described, one of which is just 160 base pairs upstream of Sftpd. This microsatellite was used to map the gene to the central region of chromosome 14; fine-scale mapping indicates that it lies in a 5. 64-centimorgan area between D14Mit45 and D14Mit60. This will allow the easy identification of the collectin gene cluster and aid in the construction of a physical map over this region.
DIVISION IX: OPTICAL AND INFRARED TECHNIQUES Sterken, Christiaan L.; Hearnshaw, John B.; Landolt, Arlo U. ...
Proceedings of the International Astronomical Union,
12/2007, Letnik:
3, Številka:
T26B
Journal Article
Recenzirano
Odprti dostop
Division IX provides a forum for astronomers engaged in the innovation, development and calibration of optical instrumentation and observational procedures including data processing.
Somatic mutations drive the development of cancer and may contribute to ageing and other diseases
. Despite their importance, the difficulty of detecting mutations that are only present in single ...cells or small clones has limited our knowledge of somatic mutagenesis to a minority of tissues. Here, to overcome these limitations, we developed nanorate sequencing (NanoSeq), a duplex sequencing protocol with error rates of less than five errors per billion base pairs in single DNA molecules from cell populations. This rate is two orders of magnitude lower than typical somatic mutation loads, enabling the study of somatic mutations in any tissue independently of clonality. We used this single-molecule sensitivity to study somatic mutations in non-dividing cells across several tissues, comparing stem cells to differentiated cells and studying mutagenesis in the absence of cell division. Differentiated cells in blood and colon displayed remarkably similar mutation loads and signatures to their corresponding stem cells, despite mature blood cells having undergone considerably more divisions. We then characterized the mutational landscape of post-mitotic neurons and polyclonal smooth muscle, confirming that neurons accumulate somatic mutations at a constant rate throughout life without cell division, with similar rates to mitotically active tissues. Together, our results suggest that mutational processes that are independent of cell division are important contributors to somatic mutagenesis. We anticipate that the ability to reliably detect mutations in single DNA molecules could transform our understanding of somatic mutagenesis and enable non-invasive studies on large-scale cohorts.
Somatic mutations accumulate in healthy tissues as we age, giving rise to cancer and potentially contributing to ageing. To study somatic mutations in non-neoplastic tissues, we developed a series of ...protocols to sequence the genomes of small populations of cells isolated from histological sections. Here, we describe a complete workflow that combines laser-capture microdissection (LCM) with low-input genome sequencing, while circumventing the use of whole-genome amplification (WGA). The protocol is subdivided broadly into four steps: tissue processing, LCM, low-input library generation and mutation calling and filtering. The tissue processing and LCM steps are provided as general guidelines that might require tailoring based on the specific requirements of the study at hand. Our protocol for low-input library generation uses enzymatic rather than acoustic fragmentation to generate WGA-free whole-genome libraries. Finally, the mutation calling and filtering strategy has been adapted from previously published protocols to account for artifacts introduced via library creation. To date, we have used this workflow to perform targeted and whole-genome sequencing of small populations of cells (typically 100-1,000 cells) in thousands of microbiopsies from a wide range of human tissues. The low-input DNA protocol is designed to be compatible with liquid handling platforms and make use of equipment and expertise standard to any core sequencing facility. However, obtaining low-input DNA material via LCM requires specialized equipment and expertise. The entire protocol from tissue reception through whole-genome library generation can be accomplished in as little as 1 week, although 2-3 weeks would be a more typical turnaround time.
The extent to which cells in normal tissues accumulate mutations throughout life is poorly understood. Some mutant cells expand into clones that can be detected by genome sequencing. We mapped mutant ...clones in normal esophageal epithelium from nine donors (age range, 20 to 75 years). Somatic mutations accumulated with age and were caused mainly by intrinsic mutational processes. We found strong positive selection of clones carrying mutations in 14 cancer genes, with tens to hundreds of clones per square centimeter. In middle-aged and elderly donors, clones with cancer-associated mutations covered much of the epithelium, with
and
mutations affecting 12 to 80% and 2 to 37% of cells, respectively. Unexpectedly, the prevalence of
mutations in normal esophagus was several times higher than in esophageal cancers. These findings have implications for our understanding of cancer and aging.
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