Aging in heterozygous Dnmt1-deficient mice: effects on survival, the DNA methylation genes, and the development of amyloidosis.

We previously reported that heterozygous DNA methyltransferase 1-deficient (Dnmt1(+/-)) mice maintain T-cell immune function and DNA methylation levels with aging, whereas controls develop autoimmunity, immune senescence, and DNA hypomethylation. We therefore compared survival, cause of death, and T-cell DNA methylation gene expression during aging in Dnmt1(+/-) mice and controls. No difference in longevity was observed, but greater numbers of Dnmt1(+/-) mice developed jejunal apolipoprotein AII amyloidosis.

An in vitro model of Fabry disease.

Fabry disease is an X-linked inherited loss of alpha-galactosidase A (alpha-Gal A). Affected patients experience complications that include neuropathy, renal failure, and cardiovascular disease. Although the genetic and biochemical basis of this sphingolipidosis is well studied, the basis for the vascular disease remains poorly understood.

Well-circumscribed, minimally enhancing glioblastoma multiforme of the trigone: a case report and review of the literature.

Glioblastoma multiforme (GBM) is known to present within the lateral ventricle but is relatively infrequent and predominantly found in the frontal horn or body of the ventricle. A GBM located within the trigone is rare, and one that appears well-circumscribed, homogeneous, and minimally contrast enhancing, as demonstrated in this patient, is highly unusual.

Estrogen regulates CCR gene expression and function in T lymphocytes.

Estrogen has been implicated in the observed female bias in autoimmune diseases. However, the mechanisms behind this gender dimorphism are poorly defined. We have previously reported that in vivo T cell trafficking is gender- and estrogen-dependent.

Learning to improve safety: false-positive pathology report results in wrongful surgery.

Background: A patient experienced a wrongful surgical resection, specifically, a radical retropubic prostatectomy because of a false-positive pathology report.

Findings From The Root Cause Analysis (rca): The RCA team identified three antecedent events that contributed to this medical error: (1) a second (concurring) pathologist did not provide a written opinion, (2) a single pathologist who reviewed and signed the final report, and (3) a pathologist who did not review the case and reconfirm the diagnosis immediately prior to the surgical resection.

Recommendations: The RCA team recommended that the concurring pathologist write his or her diagnostic findings on the referral form, two pathologists review and sign the final typed report, and a pathologist rereview the slides on the business day prior to a surgical resection.

Benign paratesticular Schwannoma.

Scrotal masses are common findings on genitourinary exam. The majority of these masses are benign and can be identified via history and physical exam alone. Question as to the origin of these masses merits additional evaluation that typically consists of an imaging study (e.

Tissue-specific effect of estradiol on endothelial cell-dependent lymphocyte recruitment.

Estrogen profoundly affects onset and severity of many immune-mediated diseases. In our murine model of drug-induced autoimmunity, female-specific, estrogen-dependent increase in splenic lymphocyte homing was directly implicated in increased disease severity. The present study evaluated the effect of estradiol on microvascular endothelial cells from the spleen compared to endothelial cells from the dermis, which has no disease manifestation in this model.

Tracheal reconstruction using tissue-engineered cartilage.

Objectives: To determine whether rabbit cartilage can be tissue engineered using a polyglycolic acid (PGA) construct composed of PGA mesh, autologous chondrocytes, and alginate covalently linked with the cell adhesion sequence arginine-glycine-aspartic acid (RGD), and to investigate the feasibility of reconstructing tracheal defects using the PGA construct in conjunction with a bioabsorbable intratracheal stent.

Methods: Nineteen New Zealand White rabbits were used. Nine rabbits underwent subcutaneous implantation of 3 different PGA construct combinations: (1) PGA, autologous chondrocytes, and RGD-modified alginate; (2) PGA, autologous chondrocytes, and unmodified alginate; and (3) PGA and RGD-modified alginate.

Marasmius oreades lectin induces renal thrombotic microangiopathic lesions.

The present studies demonstrate that infusion of a type B specific lectin derived from the mushroom Marasmius oreades (MOA) into mice binds selectively to the glomerular endothelial cells via surface carbohydrate moieties resulting in cell injury and death associated with platelet-fibrin thrombi. This selective MOA binding to the endothelial cells can be abrogated by a sugar specific for the carbohydrate sequence. Hemolytic-Uremic Syndrome (HUS) and the closely associated Thrombotic Thrombocytopenic Purpura (TTP) are diseases associated with widespread microvascular injury in various organs.

A stepwise method for the isolation of endothelial cells and smooth muscle cells from individual canine coronary arteries.

Methods for the stepwise isolation of endothelial cells and smooth muscle cells from individual canine coronary arteries are described. Both cell types can be isolated in pure culture with high yields. Dogs are a common species used in the study of atherosclerosis and coronary artery disease.

Regulatory effects of iNOS on acute lung inflammatory responses in mice.

The role of endogenous NO in the regulation of acute lung injury is not well defined. We investigated the effects of inducible nitric oxide synthase (iNOS) and endothelial NOS (eNOS) on the acute inflammatory response in mouse lungs. Acute lung injury was induced by intratracheal instillation of bacterial lipopolysaccharide (LPS) into wild-type (WT) mice and mice deficient in iNOS (iNOS(-/-)) or eNOS (eNOS(-/-)).

Vascular expression of matrix metalloproteinase-13 (collagenase-3) in basal cell carcinoma.

Matrix metalloproteinase-13 (MMP-13; collagenase-3) was detected in the vasculature from 17 of 20 human basal cell carcinomas as assessed by immunohistology immediately after surgery. In contrast, MMP-1 (interstitial collagenase) was detected in the vasculature of only two of the same specimens. MMP-13 reactivity was also observed in the capillaries of normal human skin taken from the wound margin.

Expression and function of C5a receptor in mouse microvascular endothelial cells.

The complement-derived anaphylatoxin, C5a, is a potent phlogistic molecule that mediates its effects by binding to C5a receptor (C5aR; CD88). We now demonstrate specific binding of radiolabeled recombinant mouse C5a to mouse dermal microvascular endothelial cells (MDMEC) with a K(d50) of 3.6 nM and to approximately 15,000-20,000 receptors/cell.

Eosinophil recruitment in type-2 hypersensitivity pulmonary granulomas: source and contribution of monocyte chemotactic protein-3 (CCL7).

Monocyte chemotactic protein-3 (MCP-3/CCL7) has potent eosinophil chemoattractant properties. The present study determined its relative contribution to the formation of Th2 cytokine-mediated (type-2) eosinophil-rich interstitial lung granulomas induced by antigens of Schistosoma mansoni eggs. Both MCP-3 transcripts and protein levels were more strongly expressed in lungs with type-2 than with type-1 (mycobacterial antigen-elicited Th1-mediated) granulomas.