Uniform expression of Notch1, suppressor of B-cell-specific gene expression, in plasmablastic lymphoma.

Context: Although the loss of B-lineage-specific gene expression is a distinctive feature of plasmablastic lymphoma, the underlying mechanism remains poorly understood. A candidate for this mechanism is Notch1 signaling, which interferes with the activity of B-cell-specific transcription factors E2A and early B-cell factor and positively regulates the mammalian target of rapamycin (mTOR) pathway.

Objective: To explore the mechanism of loss of B-cell phenotype by correlating expression of B-cell markers with that of Notch1 and downstream targets of the mTOR pathway in plasmablastic lymphoma.

Neuroanatomic profile of polyglutamine immunoreactivity in Huntington disease brains.

A pathologic hallmark of Huntington disease (HD) is the presence of intraneuronal aggregates of polyglutamine-containing huntingtin protein fragments. Monoclonal antibody 1C2 is a commercial antibody to normal human TATA-binding protein that detects long stretches of glutamine residues. Using 1C2 as a surrogate marker formutant huntingtin protein, we immunostained 19 HD cases, 10 normal controls, and 10 cases of frontotemporal degeneration with ubiquitinated inclusions as diseased controls.

Olfactory bulb alpha-synucleinopathy has high specificity and sensitivity for Lewy body disorders.

Involvement of the olfactory bulb by Lewy-type alpha-synucleinopathy (LTS) is known to occur at an early stage of Parkinson's disease (PD) and Lewy body disorders and is therefore of potential usefulness diagnostically. An accurate estimate of the specificity and sensitivity of this change has not previously been available. We performed immunohistochemical alpha-synuclein staining of the olfactory bulb in 328 deceased individuals.

Evaluation of alpha-synuclein immunohistochemical methods used by invited experts.

The use of alpha-synuclein immunohistochemistry has altered our concepts of the cellular pathology, anatomical distribution and prevalence of Lewy body disorders. However, the diversity of methodology between laboratories has led to some inconsistencies in the literature. Adoption of uniformly sensitive methods may resolve some of these differences.

TAR DNA-binding protein 43 immunohistochemistry reveals extensive neuritic pathology in FTLD-U: a midwest-southwest consortium for FTLD study.

TAR DNA-binding protein 43 (TDP-43) is a major component of the inclusions in frontotemporal lobar degeneration with ubiquitinated inclusions (FTLD-U). We studied TDP-43 pathology in the hippocampus and frontal cortex of autopsy brains from patients with FTLD-U (n = 68), dementia lacking distinctive histopathology (n = 4), other neurodegenerative diseases (n = 23), and controls (n = 12) using a sensitive immunohistochemistry protocol. Marked enhancement of staining of TDP-43-positive dystrophic neurites (DNs) was obtained, and we observed 2 previously unrecognized pathologic patterns (i.

Absence of expression of SMARCB1/INI1 in malignant rhabdoid tumors of the central nervous system, kidneys and soft tissue: an immunohistochemical study with implications for diagnosis.

Malignant rhabdoid tumors are high-grade neoplasms of the central nervous system (CNS), kidneys and soft tissue that usually occur in children. The histologic diagnosis of malignant rhabdoid tumor depends on identification of characteristic rhabdoid cells-large cells with eccentrically located nuclei and abundant, eosinophilic cytoplasm-and immunohistochemistry with antibodies to vimentin, keratin and epithelial membrane antigen. In most malignant rhabdoid tumors, the SMARCB1/INI1 gene, located in chromosome band 22q11.

The t(14;18) in diffuse large B-cell lymphoma: correlation with germinal center-associated markers and clinical features.

The clinical and biologic relevance of the t(14;18) and features of germinal center (GC) differentiation in diffuse large B-cell lymphoma (DLBCL) remain controversial. The authors examined the association of t(14;18) with GC-associated markers and clinical features in 44 de novo DLBCLs (22 nodal and 22 primary extranodal). CD10, bcl-2, and bcl-6 were expressed in 50%, 62%, and 54% of cases respectively.

Differences in ERK activation in squamous mucosa in patients who have gastroesophageal reflux disease with and without Barrett's esophagus.

Objectives: In some patients with gastroesophageal reflux disease (GERD), the reflux-damaged esophageal squamous epithelium heals through the process of intestinal metaplasia (resulting in Barrett's esophagus) rather than through the regeneration of more squamous cells. We hypothesized that squamous epithelium in Barrett's esophagus might have abnormalities in activation of the extracellular-regulated kinases 1 and 2 (ERK1/2) signaling pathway that may facilitate esophageal repair through metaplasia in response to acid-induced injury.

Methods: Endoscopic biopsies were taken from distal esophageal squamous mucosa in patients who had GERD with and without Barrett's esophagus and in controls, before and after esophageal perfusion with 0.

Alpha-synuclein expression in the developing human brain.

Alpha (alpha)-synuclein is a presynaptic protein, abnormal expression of which has been associated with neurodegenerative and neoplastic diseases. It is abundant in the developing vertebrate central nervous system (CNS), but less is known about its developmental expression in the human CNS. Immunohistochemical expression of alpha-synuclein was studied in 39 fetal, perinatal, pediatric, and adolescent brains.

Downregulation of protein phosphatase 2A carboxyl methylation and methyltransferase may contribute to Alzheimer disease pathogenesis.

ABalphaC, a major protein phosphatase 2A (PP2A) heterotrimeric enzyme, binds to and regulates the microtubule cytoskeleton and tau. We have shown that ABalphaC protein expression levels are selectively reduced in Alzheimer disease (AD). Notably, the carboxyl methylation of PP2A catalytic subunit (PP2A(C)) is critically required for ABalphaC holoenzyme assembly, and catalyzed by a specific methyltransferase (PPMT).

Percutaneous translumbar spinal cord compression injury in dogs from an angioplasty balloon: MR and histopathologic changes with balloon sizes and compression times.

Background And Purpose: Our previous model of spinal cord injury (SCI) included six dogs undergoing 30-minute compression with a balloon in the subarachnoid space. We determined whether various balloon sizes and compression times creates a gradation of injuries.

Methods: In 17 dogs (including our original six), angioplasty balloons 2, 4, or 7 mm in diameter (2 cm long) were inflated at T6 for 30, 120, or 240 minutes.

Altered expression levels of the protein phosphatase 2A ABalphaC enzyme are associated with Alzheimer disease pathology.

The formation of amyloid-containing senile plaques and tau-rich neurofibrillary tangles are central events in Alzheimer disease (AD) pathogenesis. Significantly, ABalphaC, a major protein phosphatase 2A (PP2A) holoenzyme, specifically binds to and dephosphorylates tau. Deregulation of PP2A results in tau hyperphosphorylation in vivo.

Beta-amyloid precursor protein immunohistochemistry in the evaluation of pediatric traumatic optic nerve injury.

Objective: The pathologic markers of nonaccidental injury (NAI) of the central nervous system (CNS) of infants and young children include subdural, subarachnoid, and retinal hemorrhages. Immunohistochemical staining for beta-amyloid precursor protein (betaAPP) has been used to investigate traumatic axonal injury of the brain, brain stem, and spinal cord injuries, and has potential as an additional indicator of traumatic head injury. A single study has reported that betaAPP immunostaining of the optic nerve in CNS NAI reveals axonal damage.

Beta-amyloid precursor protein staining of nonaccidental central nervous system injury in pediatric autopsies.

Immunohistochemical staining for beta-amyloid precursor protein (betaAPP) is a well-established marker of traumatic axonal injury in adults. Recent studies have used similar techniques to evaluate nonaccidental central nervous system injury (NAI) in infants and young children. In this prospective study, we report the results of betaAPP immunohistochemistry on the brain and spinal cord in 28 pediatric cases of NAI.

Beta-amyloid precursor protein staining in nonhomicidal pediatric medicolegal autopsies.

Immunohistochemical staining for beta-amyloid precursor protein (betaAPP) has been validated as a marker for axonal injury in adults surviving > or = 2 hours after white matter damage. The significance of betaAPP staining in pediatric brains and spinal cords is not as well established. We evaluated the white matter immunoreactivity for betaAPP from a variety of pediatric medicolegal autopsies: natural disease (non-Sudden Infant Death Syndrome [SIDS]), SIDS, motor vehicle accidents, drowning, near-drowning, overlay, carbon monoxide toxicity, miscellaneous trauma, and mechanical asphyxia.

Percutaneous translumbar spinal cord compression injury in a dog model that uses angioplasty balloons: MR imaging and histopathologic findings.

Background And Purpose: Previous animal models for spinal cord injury required laminectomy and exposure of the spinal cord to create direct trauma, compromising imaging by both surgical artifact and the nature of the production of the injury. Our purpose was to study a model that uses percutaneous intraspinal navigation with an angioplasty balloon, providing a controlled degree of spinal cord compression and allowing improved MR imaging of spinal cord injury.

Methods: Nine mongrel dogs were studied.

DNA polymerase kappa deficiency does not affect somatic hypermutation in mice.

Somatic hypermutation (SH) in B cells undergoing T cell-dependent immune responses generates high-affinity antibodies that provide protective immunity. Most current models of SH postulate the introduction of a nick into the DNA and subsequent replication-independent, error-prone short-patch synthesis by one or more DNA polymerases. The Pol kappa (DinB1) gene encodes a specialized mammalian DNA polymerase called DNA polymerase kappa (pol kappa), a member of the recently discovered Y family of DNA polymerases.

Constitutive and regulated expression of the mouse Dinb (Polkappa) gene encoding DNA polymerase kappa.

A recently discovered group of novel polymerases are characterized by significantly reduced fidelity of DNA synthesis in vitro. This feature is consistent with the relaxed fidelity required for the replicative bypass of various types of base damage that frequently block high fidelity replicative polymerases. The present studies demonstrate that the specialized DNA polymerase kappa (polkappa) is uniquely and preferentially expressed in the adrenal cortex and testis of the mouse, as well as in a variety of other tissues.