TDP-43 and Alzheimer's Disease Pathology in the Brain of a Harbor Porpoise Exposed to the Cyanobacterial Toxin BMAA.

Cetaceans are well-regarded as sentinels for toxin exposure. Emerging studies suggest that cetaceans can also develop neuropathological changes associated with neurodegenerative disease. The occurrence of neuropathology makes cetaceans an ideal species for examining the impact of marine toxins on the brain across the lifespan.

BMAA, Methylmercury, and Mechanisms of Neurodegeneration in Dolphins: A Natural Model of Toxin Exposure.

Dolphins are well-regarded sentinels for toxin exposure and can bioaccumulate a cyanotoxin called β--methylamino-l-alanine (BMAA) that has been linked to human neurodegenerative disease. The same dolphins also possessed hallmarks of Alzheimer's disease (AD), suggesting a possible association between toxin exposure and neuropathology. However, the mechanisms of neurodegeneration in dolphins and the impact cyanotoxins have on these processes are unknown.

Cyanobacterial neurotoxin BMAA and brain pathology in stranded dolphins.

Dolphin stranding events occur frequently in Florida and Massachusetts. Dolphins are an excellent sentinel species for toxin exposures in the marine environment. In this report we examine whether cyanobacterial neurotoxin, β-methylamino-L-alanine (BMAA), is present in stranded dolphins.

Progressive multifocal leukoencephalopathy associated with brentuximab vedotin therapy: a report of 5 cases from the Southern Network on Adverse Reactions (SONAR) project.

Background: Brentuximab vedotin (BV) is an anti-CD30 monoclonal antibody-drug conjugate that was approved in 2011 for the treatment of patients with anaplastic large cell and Hodgkin lymphomas. The product label indicates that 3 patients who were treated with BV developed progressive multifocal leukoencephalopathy (PML), a frequently fatal JC virus-induced central nervous system infection. Prior immunosuppressive therapy and compromised immune systems were postulated risk factors.

Leukostasis in an Adult with AML Presenting as Multiple High Attenuation Brain Masses on CT.

Acute myeloid leukemia (AML) is a hematologic malignancy that can present with central nervous system (CNS) symptoms. Neurological symptoms may result from the local accumulation of malignant cells in or near the brain (chloroma), infection, hemorrhage, or infarcts from leukostasis. Leukostasisis a syndrome that can include brain infarction due hyperviscosity of blood with vascular occlusion but CNS involvement is rarely encountered in adults.

Histone 3 lysine 9 trimethylation is differentially associated with isocitrate dehydrogenase mutations in oligodendrogliomas and high-grade astrocytomas.

Trimethylation of histone 3 lysine 9 (H3K9me3) is a marker of repressed transcription. Cells transfected with mutant isocitrate dehydrogenase (IDH) show increased methylation of histone lysine residues, including H3K9me3, because of inhibition of histone demethylases by 2-hydroxyglutarate. Here, we evaluated H3K9me3 and its association with IDH mutations in 284 gliomas.

Intramedullary spinal sarcoidosis masquerading as cervical stenosis.

Objective: Intramedullary spinal sarcoidosis is a difficult diagnosis to make because of its nonspecific clinical and imaging features and its imitation of other common spine disorders. We present a patient with intramedullary spinal sarcoidosis that mimicked spinal cord injury from a cervical disk herniation.

Methods: Relevant information was extracted from the patient's medical and imaging records.

Hybrid peripheral nerve sheath tumor.

In recent literature, there have been case reports of an extremely rare entity characterized by hybrid peripheral nerve tumors consisting of elements of neurofibroma, schwannoma, and/or perineurioma. The authors present a unique case of a patient with multiple painful hybrid tumors with negative genetic testing for neurofibromatosis Type 1 and no clinical evidence of neurofibromatosis Type 2 or schwannomatosis. A 28-year-old woman presented with tentatively diagnosed schwannomatosis.

IgG4-related inflammatory pseudotumor of the central nervous system responsive to mycophenolate mofetil.

Orbital apex and skull base masses often present with neuro-ophthalmic signs and symptoms. Though the localization of these syndromes and visualization of the responsible lesion on imaging is typically straightforward, definitive diagnosis usually relies on biopsy. Immunohistochemistry is important for categorization and treatment planning.

Fecal incontinence: prevalence, severity, and quality of life data from an outpatient gastroenterology practice.

Background. The prevalence of fecal incontinence varies tremendously as a result of inadequate data collection methods. Few office-based studies have assessed the prevalence of fecal incontinence and none have looked at modifiable risk factors or effect on quality of life.

Mycoplasmal cerebral vasculopathy in a lymphoma patient: presumptive evidence of Mycoplasma pneumoniae microvascular endothelial cell invasion in a brain biopsy.

A 73-year-old man had episodic encephalopathy, ataxia and neuropathy. Symptoms largely resolved but adenopathy later lead to the diagnosis of a low-grade follicular lymphoma. The neurological symptoms soon recurred with new pontine calcifications identified by computed tomography.

Efficient method for generating nuclear fractions from marrow stromal cells.

Stem cells have received significant attention for their envisioned potential to treat currently unapproachable diseases. No less important is the utility of stem cells to serve as model systems of differentiation. Analyses at the transcriptome, miRNA and proteome levels have yielded valuable insights into events underlying stem cell differentiation.

Genetic variation in the urea cycle: a model resource for investigating key candidate genes for common diseases.

The urea cycle is the primary means of nitrogen metabolism in humans and other ureotelic organisms. There are five key enzymes in the urea cycle: carbamoyl-phosphate synthetase 1 (CPS1), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS1), argininosuccinate lyase (ASL), and arginase 1 (ARG1). Additionally, a sixth enzyme, N-acetylglutamate synthase (NAGS), is critical for urea cycle function, providing CPS1 with its necessary cofactor.

Base-pair neutral homozygotes can be discriminated by calibrated high-resolution melting of small amplicons.

Genotyping by high-resolution melting analysis of small amplicons is homogeneous and simple. However, this approach can be limited by physical and chemical components of the system that contribute to intersample melting variation. It is challenging for this method to distinguish homozygous G::C from C::G or A::T from T::A base-pair neutral variants, which comprise approximately 16% of all human single nucleotide polymorphisms (SNPs).

Disparate host response and donor survival after the transplantation of mesenchymal or neuroectodermal cells to the intact rodent brain.

Background: To circumvent ethical and legal complications associated with embryonic cell sources, investigators have proposed the use of nonneural donor sources for use in neural transplantation strategies. Leading candidate sources include autologous marrow stromal cells (MSCs) and fibroblasts, which are mesodermal derivatives. However, we recently reported that MSCs transplanted to the adult brain are rapidly rejected by an inflammatory response.

Isolation, characterization, and differentiation of stem cells derived from the rat amniotic membrane.

Stem-cell-based therapies may offer treatments for a variety of intractable diseases. A fundamental goal in stem-cell biology concerns the characterization of diverse populations that exhibit different potentials, growth capabilities, and therapeutic utilities. We report the characterization of a stem-cell population isolated from tissue explants of rat amniotic membrane.

Mutations in the phenylalanine hydroxylase gene identified in 95 patients with phenylketonuria using novel systems of mutation scanning and specific genotyping based upon thermal melt profiles.

Phenylketonuria (PKU, MIM 261600; EC 1.14.16.

Marrow stromal cells transplanted to the adult brain are rejected by an inflammatory response and transfer donor labels to host neurons and glia.

Abstract The remarkable plasticity of marrow stromal cells (MSCs) after transplantation to models of neurological disease and injury has been described. In this report, we investigated the plasticity and long-term survival of MSCs transplanted into the normal brain. MSCs were isolated from green fluorescent protein (GFP) transgenic rats and double-labeled with 5-bromo-2-deoxyuridine (BrdU) and bis benzamide (BBZ) prior to transplantation into the adult hippocampus or striatum.

Adult bone marrow stromal cells in the embryonic brain: engraftment, migration, differentiation, and long-term survival.

We recently differentiated adult rat and human bone marrow stromal cells (MSCs) into presumptive neurons in cell culture. To determine whether the MSCs assume neuronal functions in vivo, we now characterize for the first time engraftment, migration, phenotypic expression, and long-term survival after infusion into embryonic day 15.5 (E15.