Association of molecular subgroups with pathological parameters in endometrial carcinomas.

Background: The integration of molecular features into the already existing pathological classification of endometrial carcinomas will offer significant prognostic information. As the literature search reveals, there are no studies from India that have classified these carcinomas based on molecular subtypes. The aim of the study was to classify endometrial carcinomas into four subtypes based on their molecular and immunohistochemical features and to find out the association of each of these molecular subtypes with the other pathological parameters.

Pilot Nanostring PanCancer pathway analysis of colon adenocarcinoma in a tertiary healthcare centre in Kerala, India.

The prevalence of microsatellite instability and deoxyribonucleic acid mismatch repair deficiency in colorectal adenocarcinoma (CRC) cases is higher in India compared to western populations. No major study on the molecular pathogenesis is currently available in the Indian population. We conducted a pilot study to explore the differences in molecular pathogenesis of microsatellite stable (MSS) and microsatellite unstable CRC from a tertiary care centre in Kerala, South India.

Diagnostic accuracy of MicroRNA 208b level with respect to different types of atrial fibrillation.

MicroRNAs (miRNA) are prerequisite for cardiovascular functions. miRNA miR-208 b is a cardio-specific miRNA with tissue (atrial) levels elevated in atrial fibrillation (AFib) and blood levels significantly elevated in myocardial infarction. We calculated serum levels of miR-208 b in paroxysmal and persistent AFib, embolic cerebrovascular accident patients with AFib as possible etiology and controls.

Effects of Pyruvate Administration on Mitochondrial Enzymes, Neurological Behaviors, and Neurodegeneration after Traumatic Brain Injury.

Traumatic brain injury (TBI) is known to increase the susceptibility to various age-related neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). Although the role of damaged mitochondrial electron transport chain (ETC) in the progression of AD and PD has been identified, its relationship with altered expression of neurodegenerative proteins has not been examined before. This study aimed to investigate 1) how TBI could affect mitochondrial ETC and neurodegeneration in rat brain regions related to behavioral alteration, and 2) if administration of the key mitochondrial substrate pyruvate can improve the outcome of mild TBI (mTBI).

Somatic mutation detection efficiency in EGFR: a comparison between high resolution melting analysis and Sanger sequencing.

Background: High resolution melting curve analysis is a cost-effective rapid screening method for detection of somatic gene mutation. The performance characteristics of this technique has been explored previously, however, analytical parameters such as limit of detection of mutant allele fraction and total concentration of DNA, have not been addressed. The current study focuses on comparing the mutation detection efficiency of High-Resolution Melt Analysis (HRM) with Sanger Sequencing in somatic mutations of the EGFR gene in non-small cell lung cancer.

Cerebrospinal Fluid Hyaluronan and Neurofibromatosis Type 2.

Neurofibromatosis type 2 (NF-2) is associated with mainly three types of recurrent benign tumors restricted to the central nervous system: schwannoma, meningioma and ependymoma. The absence of the protein NF2/Merlin causes an uninterrupted cell proliferation cascade originating from an abnormal interaction between an extracellular mucopolysaccharide, hyaluronan (HA), and schwann cell surface CD44 receptor, which has been identified as one of the central causative factors for schwannoma. Most tumors in NF-2 have a predilection to originate from either arachnoid cap cells or schwann cells of the cisternal portion of nerve rootlets that share a continuous exposure to cerebrospinal fluid (CSF).

Metabolism and mechanisms of action of hyaluronan in human biology.

Hyaluronan is a ubiquitous high-molecular weight polymer of repeated disaccharides of glucuronic acid and N-acetylglucosamine. It is a membrane-bound, viscous material extruded into the extracellular matrix after being synthesized in the cytoplasm by hyaluronan synthases complex and a regulated degradation by a group of enzymes called hyaluronidases. Hyaluronan has varied biological roles on many vital organismal functions, such as cellular and tissue development, migration and repair after injury or inflammation and cancer genesis.

Efficacy of N-Acetylserotonin and Melatonin in the EAE Model of Multiple Sclerosis.

Melatonin and N-acetylserotonin (NAS) are tryptophan metabolites that have potent anti-oxidant, anti-inflammatory and neuroprotective properties in several animal models of neurological injury and disease including multiple sclerosis (MS). The therapeutic effect of NAS has not been reported previously in experimental autoimmune encephalomyelitis (EAE), a commonly used animal model of MS. Using a MOG-peptide induced EAE mouse model we examined the effects of melatonin and NAS on clinical score, inflammatory markers, free radical generation, and sparing of axons, oligodendrocytes and myelin.

Genotype-phenotype analysis of von Hippel-Lindau syndrome in fifteen Indian families.

The general prevalence of the familial multi-organ tumor disorder, von Hippel-Lindau syndrome (VHL), was estimated to be 1 in 25-40,000 in western studies two decades back. Few studies were done in Indian sub-continent, amidst a surge in clinical reports on VHL specific manifestations. The syndrome is correlated with mutations of the gene VHL (located in Chr 3p25.

N-Acetylaspartate reductions in brain injury: impact on post-injury neuroenergetics, lipid synthesis, and protein acetylation.

N-Acetylaspartate (NAA) is employed as a non-invasive marker for neuronal health using proton magnetic resonance spectroscopy (MRS). This utility is afforded by the fact that NAA is one of the most concentrated brain metabolites and that it produces the largest peak in MRS scans of the healthy human brain. NAA levels in the brain are reduced proportionately to the degree of tissue damage after traumatic brain injury (TBI) and the reductions parallel the reductions in ATP levels.

Do reductions in brain N-acetylaspartate levels contribute to the etiology of some neuropsychiatric disorders?

N-acetylaspartate (NAA) is recognized as a noninvasive diagnostic neuronal marker for a host of neuropsychiatric disorders using magnetic resonance spectroscopy (MRS). Numerous correlative clinical studies have found significant decreases in NAA levels in specific neuronal systems in an array of neuropsychiatric and substance-abuse disorders. We have recently identified the methamphetamine-induced neuronal protein known as "shati" as the NAA biosynthetic enzyme (aspartate N-acetyltransferase [Asp-NAT]; gene Nat8l).

Extensive aspartoacylase expression in the rat central nervous system.

Aspartoacylase (ASPA) catalyzes deacetylation of N-acetylaspartate (NAA) to generate acetate and aspartate. Mutations in the gene for ASPA lead to reduced acetate availability in the CNS during development resulting in the fatal leukodystrophy Canavan disease. Highly specific polyclonal antibodies to ASPA were used to examine CNS expression in adult rats.

Nuclear-cytoplasmic localization of acetyl coenzyme a synthetase-1 in the rat brain.

Acetyl coenzyme A synthetase-1 (AceCS1) catalyzes the synthesis of acetyl coenzyme A from acetate and coenzyme A and is thought to play diverse roles ranging from fatty acid synthesis to gene regulation. By using an affinity-purified antibody generated against an 18-mer peptide sequence of AceCS1 and a polyclonal antibody directed against recombinant AceCS1 protein, we examined the expression of AceCS1 in the rat brain. AceCS1 immunoreactivity in the adult rat brain was present predominantly in cell nuclei, with only light to moderate cytoplasmic staining in some neurons, axons, and oligodendrocytes.

Metabolic acetate therapy improves phenotype in the tremor rat model of Canavan disease.

Genetic mutations that severely diminish the activity of aspartoacylase (ASPA) result in the fatal brain dysmyelinating disorder, Canavan disease. There is no effective treatment. ASPA produces free acetate from the concentrated brain metabolite, N-acetylaspartate (NAA).

Methamphetamine-induced neuronal protein NAT8L is the NAA biosynthetic enzyme: implications for specialized acetyl coenzyme A metabolism in the CNS.

N-acetylaspartate (NAA) is a concentrated, neuron-specific brain metabolite routinely used as a magnetic resonance spectroscopy marker for brain injury and disease. Despite decades of research, the functional roles of NAA remain unclear. Biochemical investigations over several decades have associated NAA with myelin lipid synthesis and energy metabolism.

Metabolic acetate therapy for the treatment of traumatic brain injury.

Patients suffering from traumatic brain injury (TBI) have decreased markers of energy metabolism, including N-acetylaspartate (NAA) and ATP. In the nervous system, NAA-derived acetate provides acetyl-CoA required for myelin lipid synthesis. Acetate can also be oxidized in mitochondria for the derivation of metabolic energy.

N-acetylaspartate synthesis in the brain: mitochondria vs. microsomes.

Several reports during the last three decades have indicated that biosynthesis of N-acetylaspartate (NAA) occurs primarily in the mitochondria. But a recent report by Lu et al. in this journal [2004; 122: 71-78] and subsequent two reports that cited those data suggested a predominant microsomal localization of the NAA biosynthetic enzyme, which is surprising in view of what is known about the biological functions of NAA.