Anatomy and histology of the transverse humeral ligament.

The classic literature describes the transverse humeral ligament (THL) as a distinct anatomic structure with a role in biceps tendon stability; however, recent literature suggests that it is not a distinct anatomic structure. The purpose of this study was to evaluate the gross and microscopic anatomy of the THL, including a specific investigation of the histology of this ligament. Thirty frozen, embalmed cadaveric specimens were dissected to determine the gross anatomy of the THL.

IFN-γ signaling to astrocytes protects from autoimmune mediated neurological disability.

Demyelination and axonal degeneration are determinants of progressive neurological disability in patients with multiple sclerosis (MS). Cells resident within the central nervous system (CNS) are active participants in development, progression and subsequent control of autoimmune disease; however, their individual contributions are not well understood. Astrocytes, the most abundant CNS cell type, are highly sensitive to environmental cues and are implicated in both detrimental and protective outcomes during autoimmune demyelination.

Characterisation and classification of the neural anatomy in the human hip joint.

Hip arthroscopy remains a useful surgical intervention for labral injuries. The literature has predominantly focused on structural and vascular considerations of the hip joint, with few studies examining the neurohistology of the surrounding periarticular tissues. We mapped and identified the periarticular neural anatomy, to identify the presence of sensory nerve fibres and mechanoreceptors within the hip joint.

Role of differentiation of liver sinusoidal endothelial cells in progression and regression of hepatic fibrosis in rats.

Background & Aims: Capillarization, characterized by loss of differentiation of liver sinusoidal endothelial cells (LSECs), precedes the onset of hepatic fibrosis. We investigated whether restoration of LSEC differentiation would normalize crosstalk with activated hepatic stellate cells (HSC) and thereby promote quiescence of HSC and regression of fibrosis.

Methods: Rat LSECs were cultured with inhibitors and/or agonists and examined by scanning electron microscopy for fenestrae in sieve plates.

Human breast cancer histoid: an in vitro 3-dimensional co-culture model that mimics breast cancer tissue.

Progress in our understanding of heterotypic cellular interaction in the tumor microenvironment, which is recognized to play major roles in cancer progression, has been hampered due to unavailability of an appropriate in vitro co-culture model. The aim of this study was to generate an in vitro 3-dimensional human breast cancer model, which consists of cancer cells and fibroblasts. Breast cancer cells (UACC-893) and fibroblasts at various densities were co-cultured in a rotating suspension culture system to establish co-culture parameters.

Effects of the change in cutoff values for human epidermal growth factor receptor 2 status by immunohistochemistry and fluorescence in situ hybridization: a study comparing conventional brightfield microscopy, image analysis-assisted microscopy, and interobserver variation.

Context: New guidelines for HER2 testing have been introduced.

Objectives: To evaluate the difference in HER2 assessment after introduction of new cutoff levels for both immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) and to compare interobserver agreement and time to score between image analysis and conventional microscopy.

Design: Samples from 150 patients with breast cancer were scored by 7 pathologists using conventional microscopy, with a cutoff of both 10% and 30% IHC-stained cells, and using automated microscopy with image analysis.

Enhanced antiviral T cell function in the absence of B7-H1 is insufficient to prevent persistence but exacerbates axonal bystander damage during viral encephalomyelitis.

The T cell inhibitory ligand B7-H1 hinders T cell-mediated virus control, but also ameliorates clinical disease during autoimmune and virus-induced CNS disease. In mice infected with gliatropic demyelinating coronavirus, B7-H1 expression on oligodendroglia delays virus control, but also dampens clinical disease. To define the mechanisms by which B7-H1 alters pathogenic outcome, virus-infected B7-H1-deficient (B7-H1(-/-)) mice were analyzed for altered peripheral and CNS immune responses.

Monocytes regulate T cell migration through the glia limitans during acute viral encephalitis.

Leukocyte access into the central nervous system (CNS) parenchyma is tightly regulated by the blood-brain barrier (BBB). Leukocyte migration through the endothelial cell wall into the perivascular space is well characterized; however, mechanisms regulating their penetration through the glia limitans into the parenchyma are less well studied, and the role of monocytes relative to neutrophils is poorly defined. Acute viral encephalitis was thus induced in CCL2-deficient (CCL2(-/-)) mice to specifically abrogate monocyte recruitment.

Gamma interferon signaling in oligodendrocytes is critical for protection from neurotropic coronavirus infection.

Neurotropic coronavirus induces acute encephalomyelitis and demyelination in mice. Infection of BALB/c (H-2(d)) mice expressing a dominant negative gamma interferon (IFN-gamma) receptor specifically in oligodendrocytes was examined to determine the influence of IFN-gamma signaling on pathogenesis. Inhibition of IFN-gamma signaling in oligodendrocytes increased viral load, infection of oligodendrocytes, oligodendrocyte loss, demyelination, and axonal damage resulting in increased mortality.

RNase L mediated protection from virus induced demyelination.

IFN-alpha/beta plays a critical role in limiting viral spread, restricting viral tropism and protecting mice from neurotropic coronavirus infection. However, the IFN-alpha/beta dependent mechanisms underlying innate anti-viral functions within the CNS are poorly understood. The role of RNase L in viral encephalomyelitis was explored based on its functions in inhibiting translation, inducing apoptosis, and propagating the IFN-alpha/beta pathway through RNA degradation intermediates.

Target-dependent B7-H1 regulation contributes to clearance of central nervous system infection and dampens morbidity.

The neurotropic coronavirus JHM strain of mouse hepatitis virus persists in oligodendroglia despite the presence of virus-specific CD8 T cells. Expression of programmed death 1 (PD-1) and B7-H1 were studied during acute and persistent infection to examine whether this negative regulatory mechanism contributes to CNS viral persistence. The majority of CNS-infiltrating CD8 T cells expressed PD-1, with the highest levels on virus-specific CD8 T cells.

Interleukin-12 (IL-12), but not IL-23, deficiency ameliorates viral encephalitis without affecting viral control.

The relative contributions of interleukin-12 (IL-12) and IL-23 to viral pathogenesis have not been extensively studied. IL-12p40 mRNA rapidly increases after neurotropic coronavirus infection. Infection of mice defective in both IL-12 and IL-23 (p40(-/-)), in IL-12 alone (p35(-/-)), and in IL-23 alone (p19(-/-)) revealed that the symptoms of coronavirus-induced encephalitis are regulated by IL-12.

Prevention of hepatic fibrosis in a murine model of metabolic syndrome with nonalcoholic steatohepatitis.

The endocannabinoid pathway plays an important role in the regulation of appetite and body weight, hepatic lipid metabolism, and fibrosis. Blockade of the endocannabinoid receptor CB1 with SR141716 promotes weight loss, reduces hepatocyte fatty acid synthesis, and is antifibrotic. D-4F, an apolipoprotein A-1 mimetic with antioxidant properties, is currently in clinical trials for the treatment of atherosclerosis.

CD4 T cells contribute to virus control and pathology following central nervous system infection with neurotropic mouse hepatitis virus.

Replication of the neurotropic mouse hepatitis virus strain JHM (JHMV) is controlled primarily by CD8(+) T-cell effectors utilizing gamma interferon (IFN-gamma) and perforin-mediated cytotoxicity. CD4(+) T cells provide an auxiliary function(s) for CD8(+) T-cell survival; however, their direct contribution to control of virus replication and pathology is unclear. To examine a direct role of CD4(+) T cells in viral clearance and pathology, pathogenesis was compared in mice deficient in both perforin and IFN-gamma that were selectively reconstituted for these functions via transfer of virus-specific memory CD4(+) T cells.

Review of meningioma histopathology.

The histological appearance of a meningioma is an important predictor of tumor behavior and is frequently a factor in decisions concerning therapy. The relationship between histological features and prognosis is formalized in grading schemes such as those published by the World Health Organization (WHO), most recently in 2007. Although the latest edition is an improvement over previous grading schemes, the WHO scheme still fails to fully address a variety of important issues regarding the relationship between meningioma histological characteristics and behavior.

Primary intraosseous meningioma.

Primary intraosseous meningiomas are a subtype of primary extradural meningiomas and constitute fewer than 2% of meningiomas overall, but they represent approximately two thirds of all extradural meningiomas. These types of meningiomas originate within the bones of the skull and thus can have a clinical presentation and radiographic differential diagnosis that is different from those for intradural meningiomas. Primary intraosseous meningiomas are classified based on their location and histopathological characteristics.

Type I interferons are essential in controlling neurotropic coronavirus infection irrespective of functional CD8 T cells.

Neurotropic coronavirus infection induces expression of both beta interferon (IFN-beta) RNA and protein in the infected rodent central nervous system (CNS). However, the relative contributions of type I IFN (IFN-I) to direct, cell-type-specific virus control or CD8 T-cell-mediated effectors in the CNS are unclear. IFN-I receptor-deficient (IFNAR(-/-)) mice infected with a sublethal and demyelinating neurotropic virus variant and those infected with a nonpathogenic neurotropic virus variant both succumbed to infection within 9 days.

Telomerase and markers of cellular proliferation are associated with the progression of cervical intraepithelial neoplasia lesions.

The expression of the catalytic subunit of telomerase protein (human telomerase reverse transcriptase [hTERT]), which is associated with telomerase activity, was evaluated as a potential marker of the high-grade premalignant cervical intraepithelial neoplasia (CIN 2/3) lesions. For comparison, cases of normal cervical squamous mucosa, low-grade CIN1 lesion, and cervical squamous cell carcinoma were included. The hTERT expression was also compared with Ki-67 and topoisomerase II-alpha (TPII-alpha) to determine the proliferative activity of the hTERT-positive dysplastic cells by a quantitative immunohistochemical staining method and was classified as follows: negative, 5% or less; moderate, 6% to 50%; or high, greater than 50% of the positive cells.

Liver X receptor activation decreases the severity of experimental autoimmune encephalomyelitis.

Agonists of liver X receptors (LXR), members of the nuclear hormone receptor superfamily, alter secretion of proinflammatory cytokines, suggesting potential antiinflammatory effects. A synthetic LXR agonist inhibited T-cell proliferation and cytokine release in a dose-dependent manner. Treatment of mice during induction of experimental autoimmune encephalomyelitis reduced clinical symptoms, central nervous system cellular inflammation, and major histocompatibility class II expression on microglia, as well as demyelination.

Mouse hepatitis virus pathogenesis in the central nervous system is independent of IL-15 and natural killer cells.

Infection by the neurotropic JHM strain of mouse hepatitis virus (JHMV) results in an acute encephalomyelitis associated with demyelination. T cells are critical in controlling viral replication, but also contribute to central nervous system (CNS) pathogenesis. To reveal a role for innate effectors in anti-viral immunity and neurological disease, JHMV pathogenesis was studied in mice deficient in interleukin-15 (IL-15-/-) and natural killer (NK) cells.

Inhibition of interferon-gamma signaling in oligodendroglia delays coronavirus clearance without altering demyelination.

Infection of the central nervous system (CNS) by the neurotropic JHM strain of mouse hepatitis virus (JHMV) induces an acute encephalomyelitis associated with demyelination. To examine the anti-viral and/or regulatory role of interferon-gamma (IFN-gamma) signaling in the cell that synthesizes and maintains the myelin sheath, we analyzed JHMV pathogenesis in transgenic mice expressing a dominant-negative IFN-gamma receptor on oligodendroglia. Defective IFN-gamma signaling was associated with enhanced oligodendroglial tropism and delayed virus clearance.

Vaccine-induced memory CD8+ T cells cannot prevent central nervous system virus reactivation.

Noncytopathic viruses use multiple strategies to evade immune detection, challenging a role for vaccine induced CTL in preventing microbial persistence. Recrudescence of neurotropic coronavirus due to loss of T cell-mediated immune control provided an experimental model to test T cell vaccination efficacy in the absence of Ab. Challenge virus was rapidly controlled in vaccinated Ab-deficient mice coincident with accelerated recruitment of memory CD8+ T cells and enhanced effector function compared with primary CD8+ T cell responses.

CNS viral infection diverts homing of antibody-secreting cells from lymphoid organs to the CNS.

Neurotropic coronavirus infection of mice results in acute encephalomyelitis followed by viral persistence. Whereas cellular immunity controls acute infection, humoral immunity regulates central nervous system (CNS) persistence. Maintenance of serum Ab was correlated with tissue distribution of virus-specific Ab-secreting cells (ASC).

Astrocyte expression of a dominant-negative interferon-gamma receptor.

Interferon-gamma (IFN-gamma) is a major proinflammatory cytokine, and binding to its nearly ubiquitous receptor induces a wide variety of biological functions. To explore the role(s) of IFN-gamma signaling in astrocytes, transgenic mice (GFAP/IFN-gammaR1DeltaIC) expressing a dominant-negative IFN-gamma receptor alpha chain under control of the astrocyte-specific glial fibrillary acid protein (GFAP) promoter were generated. Transgenic mice developed normally, had normal astrocyte numbers and distribution, and exhibited no clinically overt phenotype.

The peroxisome proliferator-activated receptor gamma ligand rosiglitazone delays the onset of inflammatory bowel disease in mice with interleukin 10 deficiency.

Aims: To test whether the peroxisome proliferator-activated receptor gamma (PPARgamma) ligand rosiglitazone (Ro) has therapeutic activity in the IL-10(-/-) mouse model of inflammatory bowel disease (IBD), and to identify the cellular targets and molecular mechanisms of Ro action.

Methods: The progression of spontaneous chronic colitis in IL-10(-/-) mice was compared in 5-week-old mice fed a standard diet with or without Ro for 12 weeks. The possible therapeutic effect of Ro was also tested over a 6-week interval in older IL-10(-/-) mice with established IBD.