ABSTRACT
An intraluminal duodenal diverticulum (IDD) is a rare congenital anomaly that is the result of incomplete recanalization of the embryologic foregut leaving a fenestrated membrane within the lumen of the duodenum. Years of peristalsis acting on the membrane result in the formation of a diverticulum. Most patients are asymptomatic, while some may have abdominal pain, bloating, or fullness. Rare complications include gastrointestinal bleeding, obstruction, pancreatitis, and cholangitis. We present 2 cases with endoscopic findings consistent with partially obstructing symptomatic IDD.
ABSTRACT
BACKGROUND: Racial and ethnic disparities in hospital readmissions for several major illnesses and conditions are well-documented. However, due to the data typically used to assess readmission disparities little is known regarding the interplay between race/ethnicity and payer in fostering readmissions. This study used a statewide database of acute-care hospital admissions to examine 30-day readmission rates following hospitalization for chest pain and heart failure byrace/ethnicity and insurance status. METHODS: Connecticut hospital discharge data for patients admitted for Chest Pain-DRG 313 (n = 23,450) and Heart Failure and Shock-DRG 291 and 292 (n = 39,985) from 2008 - 2012 were analyzed using marginal logistic models for clustered data with generalized estimating equations. RESULTS: Results from logistic models indicated that Black patients were significantly more likely to be readmitted within 30 days of discharge following hospitalization for chest pain (OR = 1.19, CI = 1.04, 1.37) than were White patients. Hispanics, but not Blacks, were significantly more likely to be readmitted within 30 days of discharge following hospitalization for heart failure (OR = 1.30, CI = 1.15, 1.47). Rates of 30-day readmission across these conditions were between 50-100% higher among those covered by Medicaid compared to those covered by private payer. Controlling for patient socioeconomic status, patient comorbidities, and payer substantially reduced Black/White differences in the odds of readmission for chest pain but did not reduce Hispanic-White differences for heart failure. CONCLUSIONS: Racial and ethnic disparities were seen in hospital readmission rates for Chest Pain (DRG 313) and Heart Failure and Shock (DRG 291 and 292) when a statewide database that captures all acute care hospital admissions was analyzed. When controlling for patient socioeconomic status, comorbidities, and payer status, the difference in the odds of readmission for chest pain, but not heart failure, was reduced.
Subject(s)
Chest Pain/ethnology , Healthcare Disparities , Heart Failure/ethnology , Patient Readmission/statistics & numerical data , Aged , Connecticut , Ethnicity/statistics & numerical data , Female , Humans , Insurance, Health , Male , Medicaid , Medicare , Middle Aged , United StatesABSTRACT
Intestinal malrotation is an anomaly of fetal intestinal rotation that can present with symptoms after birth or in early childhood, but is rarely diagnosed in adults. Patients who have symptomatic presentations require surgery. Other entities may mimic intestinal malrotation and respond to non-surgical management. We present 2 adult cases with the radiological diagnosis of intestinal malrotation: one with true malrotation presenting as a duodenal mass, and another with "pseudo-malrotation" due to altered anatomy. These cases illustrate the importance of recognizing and differentiating these rare adult presentations of true malrotation from "pseudo-malrotation" in regards to their acute management.
ABSTRACT
INTRODUCTION: Isolated angioedema of the small intestine is a rare entity. The cases described have been related with angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or C1 esterase inhibitor deficiency. We present a case of small intestine angioedema caused by calcium channel blockers (CCBs) and a review of the literature. CASE REPORT: Over the course of approximately 2 years, a 56-year-old African American woman presented to our hospital with 8 similar episodes of diffuse, intermittent abdominal pain, nausea, vomiting, and diarrhea. The diagnostic workup was extensive and included normal stool studies, anticardiolipin antibodies, antinuclear antibodies, antineutrophil cytoplasmic antibodies, cryoglobulin studies, complement levels, urinary 5-hydroxyindoleacetic acid, and serum markers for inflammatory bowel diseases. A computed tomographic angiogram was normal. Abdominal computed tomographic scans showed prominent mural thickening of different intestinal segments, always involving the ileum. An esophagogastroduodenoscopy showed patchy edematous, violaceous folds in the second portion of the duodenum. Colonoscopy revealed a markedly edematous and erythematous distal ileum. The recurrences subsided after CCBs were discontinued in this patient and reoccurred when they were incidentally restarted. CONCLUSIONS: Our case demonstrates that CCBs can cause isolated intestinal angioedema with distinctive endoscopic findings. The discontinuation of the involved medication is the key for both diagnosis and treatment.
Subject(s)
Amlodipine/adverse effects , Angioedema/chemically induced , Calcium Channel Blockers/adverse effects , Intestine, Small , Abdominal Pain/diagnosis , Abdominal Pain/diagnostic imaging , Abdominal Pain/drug therapy , Angioedema/diagnostic imaging , Diarrhea/diagnosis , Diarrhea/diagnostic imaging , Diarrhea/drug therapy , Female , Humans , Intestinal Diseases/chemically induced , Intestinal Diseases/diagnostic imaging , Intestine, Small/diagnostic imaging , Intestine, Small/pathology , Middle Aged , RadiographyABSTRACT
DEK is an abundant and ubiquitous chromatin protein. Here we investigate whether DEK is regularly distributed in the chromatin of human HeLa cells. We show that DEK appears to be excluded from the heterochromatic compartment. However, DEK seems to colocalize with a subfraction of chromatin bearing acetylated histone H4. We examined certain DNA sequences in specifically immunoprecipitated chromatin for four selected human genes. We found that most of the investigated gene sequences were moderately enriched in immunoprecipitated chromatin. In contrast, a promoter-proximal element of the human TOP1 gene was highly enriched in the chromatin immunoprecipitates. This enrichment was lost when cells were treated with alpha-amanitin showing that DEK binds to this particular site only when the TOP1 gene is actively expressed. Our conclusion is that DEK could serve as an architectural protein at the promoter or enhancer sites of a subfraction of human genes.
Subject(s)
Chromatin/genetics , Chromatin/metabolism , Chromosomal Proteins, Non-Histone/genetics , Chromosomal Proteins, Non-Histone/metabolism , Oncogene Proteins/genetics , Oncogene Proteins/metabolism , Promoter Regions, Genetic/genetics , 3T3 Cells , Animals , Binding Sites , HeLa Cells , Humans , Mice , Poly-ADP-Ribose Binding Proteins , Protein BindingABSTRACT
DEK is an abundant and ubiquitous chromatin protein that has only recently attracted attention. DEK preferentially binds to cruciform and superhelical DNA and induces positive supercoils into closed circular DNA. It is quite likely therefore that DEK performs an important architectural function in chromatin. However, it is not known how DEK is distributed in chromatin. As the first study of its kind, we investigate the distribution of DEK at the CD21/complement receptor 2 gene regulatory regions in two B lymphocyte lines, namely Ramos, which expresses the CD21 gene, and Nalm-6, which does not. We use a chromatin immunoprecipitation approach and show that DEK appears to be distributed over various regions of the expressed and silent genes, but occurs in 2- to 3-fold higher amounts at a promoter-proximal site of the expressed gene. Moreover, induction of CD21 expression in Nalm-6 cells leads to accumulation of DEK at this site. We propose that the accumulation of DEK is functionally linked to gene expression.
Subject(s)
B-Lymphocytes/metabolism , Chromosomal Proteins, Non-Histone/metabolism , Oncogene Proteins/metabolism , Receptors, Complement 3d/metabolism , Azacitidine/analogs & derivatives , Azacitidine/pharmacology , B-Lymphocytes/drug effects , B-Lymphocytes/immunology , Cell Differentiation/immunology , Cell Line , Chromatin/metabolism , Chromosomal Proteins, Non-Histone/analysis , Decitabine , Gene Expression Regulation/immunology , Humans , Oncogene Proteins/analysis , Poly-ADP-Ribose Binding Proteins , Promoter Regions, Genetic , Receptors, Complement 3d/analysis , Receptors, Complement 3d/geneticsABSTRACT
Prothymosin alpha (ProTalpha) is a histone H1-binding protein that interacts with the transcription coactivator CREB-binding protein and potentiates transcription. Based on coimmunoprecipitation and mammalian two-hybrid assays, we show here that ProTalpha forms a complex with the oncoprotein SET. ProTalpha efficiently decondenses human sperm chromatin, while overexpression of GFP-ProTalpha in mammalian cells results in global chromatin decondensation. These results indicate that decondensation of compacted chromatin fibers is an important step in the mechanism of ProTalpha function.
Subject(s)
Chromatin/metabolism , Protein Precursors/metabolism , Proteins/metabolism , Thymosin/analogs & derivatives , Thymosin/metabolism , Amino Acid Sequence , Blotting, Western , CREB-Binding Protein , Cell Extracts , Chromosomal Proteins, Non-Histone , DNA-Binding Proteins , Green Fluorescent Proteins/metabolism , HeLa Cells , Histone Chaperones , Humans , Luciferases/metabolism , Male , Mass Spectrometry , Molecular Sequence Data , Molecular Weight , Nuclear Proteins/metabolism , Plasmids/metabolism , Precipitin Tests , Protein Binding , Protein Precursors/genetics , Proteins/chemistry , Recombinant Proteins/metabolism , Sequence Analysis, Protein , Silver Staining , Spermatozoa/metabolism , Thymosin/genetics , Trans-Activators/metabolism , Transcription Factors , Two-Hybrid System TechniquesABSTRACT
DEK was originally described as a proto-oncogene protein and is now known to be a major component of metazoan chromatin. DEK is able to modify the structure of DNA by introducing supercoils. In order to find interaction partners and functional domains of DEK, we performed yeast two-hybrid screens and mutational analyses. Two-hybrid screening yielded C-terminal fragments of DEK, suggesting that DEK is able to multimerize. We could localize the domain to amino acids 270 to 350 and show that multimerization is dependent on phosphorylation by CK2 kinase in vitro. We also found two DNA binding domains of DEK, one on a fragment including amino acids 87 to 187 and containing the SAF-box DNA binding motif, which is located between amino acids 149 and 187. This region is sufficient to introduce supercoils into DNA. The second DNA binding domain is located between amino acids 270 and 350 and thus overlaps the multimerization domain. We show that the two DNA-interacting domains differ in their binding properties and in their abilities to respond to CK2 phosphorylation.
Subject(s)
Chromosomal Proteins, Non-Histone/metabolism , Oncogene Proteins/metabolism , Amino Acid Sequence , Binding Sites , Casein Kinase II , Chromosomal Proteins, Non-Histone/chemistry , Chromosomal Proteins, Non-Histone/physiology , DNA, Superhelical/metabolism , Dimerization , HeLa Cells , Humans , Oncogene Proteins/chemistry , Oncogene Proteins/physiology , Phosphorylation , Poly-ADP-Ribose Binding Proteins , Protein Serine-Threonine Kinases/metabolism , Protein Structure, Tertiary/physiology , Proto-Oncogene Mas , Two-Hybrid System TechniquesABSTRACT
We have examined the posttranslational modification of the human chromatin protein DEK and found that DEK is phosphorylated by the protein kinase CK2 in vitro and in vivo. Phosphorylation sites were mapped by quadrupole ion trap mass spectrometry and found to be clustered in the C-terminal region of the DEK protein. Phosphorylation fluctuates during the cell cycle with a moderate peak during G(1) phase. Filter binding assays, as well as Southwestern analysis, demonstrate that phosphorylation weakens the binding of DEK to DNA. In vivo, however, phosphorylated DEK remains on chromatin. We present evidence that phosphorylated DEK is tethered to chromatin throughout the cell cycle by the un- or underphosphorylated form of DEK.
Subject(s)
Chromosomal Proteins, Non-Histone/metabolism , DNA-Binding Proteins/metabolism , Oncogene Proteins/metabolism , Protein Serine-Threonine Kinases/metabolism , Amino Acid Sequence , Binding Sites , Casein Kinase II , Cell Cycle , Chromatin/metabolism , DNA/metabolism , HeLa Cells , Humans , Mass Spectrometry , Phosphorylation , Poly-ADP-Ribose Binding Proteins , Protein Processing, Post-Translational , Resting Phase, Cell CycleABSTRACT
The ubiquitous proto-oncogene protein DEK has been found to be associated with chromatin during the entire cell cycle. It changes the topology of DNA in chromatin and protein-free DNA through the introduction of positive supercoils. The sequence and structure specificities of DEK-DNA interactions are not completely understood. The binding of DEK to DNA is not sequence specific, but we describe here that DEK has a clear preference for supercoiled and four-way junction DNA. In the presence of topoisomerase II, DEK stimulates intermolecular catenation of circular DNA molecules. DEK also increases the probability of intermolecular ligation of linear DNA molecules by DNA ligase. These binding properties qualify DEK as an architectural protein.
Subject(s)
DNA/chemistry , DNA/metabolism , Proto-Oncogene Proteins/metabolism , DNA/genetics , DNA, Catenated/chemistry , DNA, Catenated/metabolism , DNA, Concatenated/chemistry , DNA, Concatenated/metabolism , DNA, Cruciform/chemistry , DNA, Cruciform/metabolism , DNA, Superhelical/chemistry , DNA, Superhelical/metabolism , Protein Binding , Substrate SpecificityABSTRACT
Large T antigen is the replicative helicase of simian virus 40. Its specific binding to the origin of replication and oligomerization into a double hexamer distorts and unwinds dsDNA. In viral replication, T antigen acts as a functional homolog of the eukaryotic minichromosome maintenance factor MCM. T antigen is also an oncoprotein involved in transformation through interaction with p53 and pRb. We obtained the three-dimensional structure of the full-length T antigen double hexamer assembled at its origin of replication by cryoelectron microscopy and single-particle reconstruction techniques. The double hexamer shows different degrees of bending along the DNA axis. The two hexamers are differentiated entities rotated relative to each other. Isolated strands of density, putatively assigned to ssDNA, protrude from the hexamer-hexamer junction mainly at two opposite sites. The structure of the T antigen at the origin of replication can be understood as a snapshot of the dynamic events leading to DNA unwinding. Based on these results a model for the initiation of simian virus 40 DNA replication is proposed.
Subject(s)
Antigens, Viral, Tumor/chemistry , DNA, Viral/genetics , Replication Origin/genetics , Simian virus 40/immunology , Algorithms , Base Sequence , Crystallography, X-Ray , DNA Primers , DNA Replication , DNA, Viral/chemistry , Image Processing, Computer-Assisted , Molecular Sequence Data , Polymerase Chain Reaction , Protein Conformation , Simian virus 40/geneticsABSTRACT
We have investigated the molecular mechanism by which the proto-oncogene protein DEK, an abundant chromatin-associated protein, changes the topology of DNA in chromatin in vitro. Band-shift assays and electron microscopy revealed that DEK induces both intra- and intermolecular interactions between DNA molecules. Binding of the DEK protein introduces constrained positive supercoils both into protein-free DNA and into DNA in chromatin. The induced change in topology is reversible after removal of the DEK protein. As shown by sedimentation analysis and electron microscopy, the DEK-induced positive supercoiling causes distinct structural changes of DNA and chromatin. The observed direct effects of DEK on chromatin folding help to understand the function that this major chromatin protein performs in the nucleus.