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Biomedical subjects

Abhay Singh

Publications and source records attributed to Abhay Singh.

8 recordsLinked to original sources
PubMed2006

Modeling regulatory mechanisms in IL-6 signal transduction in hepatocytes.

Cytokines like interleukin-6 (IL-6) play an important role in triggering the acute phase response of the body to injury or inflammation. Signaling by IL-6 involves two pathways: Janus-associated kinases (JAK) and signal transducers and activators of transcription (STAT 3) are activated in the first pathway while the second pathway involves the activation of mitogen-activated protein kinases (MAPK). While it is recognized that both pathways play a major role in IL-6 signal transduction, a majority of studies have focused on signaling through either one of the pathways. However, simultaneous signaling through both JAK/STAT and MAPK pathways is still poorly understood. In this work, a mathematical model has been developed that integrates signaling through both the JAK/STAT and the MAPK pathway. The presented model is used to analyze the effect of three molecules that are involved in the regulation of IL-6 signaling-SHP-2 (domain containing tyrosine phosphatase 2), SOCS3 (suppressor of cytokine signaling 3), and a STAT3 nuclear phosphatase (PP2)-on the dynamics of IL-6 signal transduction in hepatocytes. The obtained results suggest that interactions between SHP-2 and SOCS3 influence signaling through the JAK/STAT and the MAPK pathways. It is shown that SHP-2 and SOCS3 do not just regulate the pathway that they are known to be associated with, (SHP-2 with MAPK and SOCS3 with JAK/STAT), but also have a strong effect on the other pathway. Several simulations with SOCS3, SHP-2, and PP2 knockout cells, that is, where the signaling pathway is unable to produce these proteins, have been performed to characterize the effect of these regulatory proteins on IL-6 signal transduction in hepatocytes.

Hepatocytes↗
PubMed2006

Mecamylamine (Targacept).

Targacept Inc, under license from the University of South Florida, is developing a low-dose, liquid gel capsule formulation of the nicotinic acetylcholine antagonist mecamylamine, as a potential treatment for various neuropsychiatric disorders.

Adolescent↗
PubMed2004

Effects of nicotinic stimulation on cognitive performance.

Recent advances in studies of nicotinic agents in humans have begun to more carefully define cognitive operations that can be influenced by nicotinic stimulation and/or blockade. Careful separation of the cognitive domains affected by nicotinic stimulation has identified attentional performance as the most likely candidate to be positively influenced by nicotinic receptor activation. Studies of the effects of nicotinic systems and/or nicotinic receptor stimulation in pathological disease states such as Alzheimer's disease, Parkinson's disease, attention deficit/hyperactivity disorder and schizophrenia show the potential for therapeutic utility of nicotinic drugs. In contrast to studies in pathological states, studies of nicotine in normal-non-smokers tend to show deleterious effects. This contradiction can be resolved by consideration of cognitive and biological baseline dependency differences between study populations in terms of the relationship of optimal cognitive performance to nicotinic receptor activity. Although normal individuals are unlikely to show cognitive benefits after nicotinic stimulation except under extreme task conditions, individuals with a variety of disease states can benefit from nicotinic drugs. Attentional function/dysfunction may serve as an endophenotypic therapeutic target for nicotinic drug development.

Attention↗
PubMed2004

Nicotine and nicotinic receptor involvement in neuropsychiatric disorders.

Advances in the understanding of the neurobiology of the nicotinic receptor have started to be matched by an appreciation of the potential role of these receptors in a variety of neuropsychiatric disorders. While alterations in nicotinic receptor number and/or function have been associated with such conditions as Alzheimer's disease for several years, there is increasing evidence that nicotinic receptor function may play a significant role in other disorders as well including schizophrenia, Parkinson's disease, anxiety disorders, and attention deficit-hyperactivity disorder (ADHD). Research in our laboratory and those of other investigators have utilized sophisticated psychopharmacological, cognitive, electrophysiological, neuroimaging and other techniques to assess the impact of nicotinic receptor modulation on the clinical expression of these disorders. This manuscript reviews data, both experimental and clinical, relating to the role of nicotine and/or nicotinic receptor function in a variety of neuropsychiatric disorders with the perspective of developing appropriate targets for therapeutic drug development.

Central Nervous System Diseases↗
PubMed2004

Nicotinic acetylcholine receptor system and neuropsychiatric disorders.

Investigations into the neurobiology, and biophysical and pharmacological properties of nicotinic receptors, also known as nicotinic acetylcholine receptors (nAChRs), have led to an improved understanding of their role in a variety of neuropsychiatric disorders. There is a growing body of evidence linking alterations in nicotinic receptor number and/or function to conditions such as schizophrenia, Alzheimer's disease, Parkinson's disease, anxiety disorders, mood disorders, and attention deficit-hyperactivity disorder. The implications of nicotine receptor modulation upon the clinical expression and progression of these disorders is currently under investigation, utilizing techniques that include psychopharmacological, cognitive, electrophysiological and neuroimaging analysis. This review attempts to outline evidence pertaining to the role of the nicotinic receptor system in various neuropsychiatric disorders in the context of understanding appropriate targets for therapeutic drug development.

Animals↗
PubMed2003

The construction and use of bacterial DNA microarrays based on an optimized two-stage PCR strategy.

BACKGROUND: DNA microarrays are a powerful tool with important applications such as global gene expression profiling. Construction of bacterial DNA microarrays from genomic sequence data using a two-stage PCR amplification approach for the production of arrayed DNA is attractive because it allows, in principal, the continued re-amplification of DNA fragments and facilitates further utilization of the DNA fragments for additional uses (e.g. over-expression of protein). We describe the successful construction and use of DNA microarrays by the two-stage amplification approach and discuss the technical challenges that were met and resolved during the project. RESULTS: Chimeric primers that contained both gene-specific and shared, universal sequence allowed the two-stage amplification of the 3,168 genes identified on the genome of Synechocystis sp. PCC6803, an important prokaryotic model organism for the study of oxygenic photosynthesis. The gene-specific component of the primer was of variable length to maintain uniform annealing temperatures during the 1st round of PCR synthesis, and situated to preserve full-length ORFs. Genes were truncated at 2 kb for efficient amplification, so that about 92% of the PCR fragments were full-length genes. The two-stage amplification had the additional advantage of normalizing the yield of PCR products and this improved the uniformity of DNA features robotically deposited onto the microarray surface. We also describe the techniques utilized to optimize hybridization conditions and signal-to-noise ratio of the transcription profile. The inter-lab transportability was demonstrated by the virtual error-free amplification of the entire genome complement of 3,168 genes using the universal primers in partner labs. The printed slides have been successfully used to identify differentially expressed genes in response to a number of environmental conditions, including salt stress. CONCLUSIONS: The technique detailed here minimizes the cost and effort to replicate a PCR-generated DNA gene fragment library and facilitates several downstream processes (e.g. directional cloning of fragments and gene expression as affinity-tagged fusion proteins) beyond the primary objective of producing DNA microarrays for global gene expression profiling.

Cyanobacteria↗
PubMed2002

Effects of cigarette smoking and nicotine nasal spray on psychiatric symptoms and cognition in schizophrenia.

Schizophrenic patients have among the highest rates of smoking of any group of patients. Previous studies have identified psychophysiological and potential nicotinic receptor abnormalities which may be associated with this phenomenon. The effects of acute smoking or acute administration of nicotine nasal spray, after smoking abstinence, on negative symptoms and neurocognitive function have been less extensively studied in experimental designs. This study investigated the effects of smoking of high nicotine or denicotinized cigarettes, and receiving active or placebo nicotine nasal sprays, on positive and negative symptoms and cognitive functions in schizophrenic patients. The study utilized a placebo controlled crossover experimental design with pre- and post-drug evaluations on each experimental day. Smoking high nicotine cigarettes decreased negative symptoms more than denicotinized cigarettes, but smoking neither cigarette changed scores of positive symptoms, anxiety, or depression. Active nicotine nasal spray did not differentially decrease negative symptoms compared with placebo, but did improve performance on a spatial organization task, and tended to improve some measures of verbal memory and two-choice reaction time in schizophrenic patients. Both high and denicotinized cigarettes improved performance on the spatial processing task, but there was no statistically significant differential drug (Cigarette type) effect. These results suggest that acute smoking of cigarettes may transiently decrease negative symptoms in patients with schizophrenia, but it is unclear whether this effect is attributable to nicotine, other components of cigarettes, or the act of smoking. Nicotine nasal spray may modestly improve some selected aspects of cognitive function in schizophrenia.

Administration, Intranasal↗