Moyamoya disease presenting to the ophthalmology clinic.
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Biomedical subjects
Publications and source records attributed to Naresh Sharma.
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Alzheimer's disease (AD) is the most common form of dementia in the elderly. AD is an invariably fatal neurodegenerative disorder with no effective treatment or definitive antemortem diagnostic test. Little is known about the changes in the brain preceding or accompanying initiation of the disease. Understanding the biological processes, which occur during AD onset and/or progression, will improve the diagnosis and treatment of the disease. As we will discuss in this review article, using high-throughput cDNA microarray we identified candidate genes whose expression is altered in the brain of cases at risk for AD dementia. However, it is possible that the use of the cDNA microarray technology alone may underestimate post-transcriptional modifications and therefore provides only a partial view of the biological problem of interest. As such, the combination of cDNA and protein arrays may provide a more global picture of the biological processes being studied. Based on this hypothesis, we initiated a series of high-throughput proteomic studies and found that the expressions of proteins involved in synaptic plasticity are selectively altered in the brain of cases at high risk to develop AD dementia (mild cognitive impairment; MCI). This is consistent with our cDNA microarray evidence showing that the expression of a-type synapsins is selectively altered in the brain of MCI cases. Collectively, these studies support the feasibility and usefulness of high-throughput cDNA microarray and proteomics techniques to study the sequential changes of distinctive gene expression patterns in the brain as a function of the progression of AD dementia.
The present study describes a novel and simple vaccination strategy that involves the culturing of live Mycobacterium tuberculosis and Salmonella typhimurium in syngeneic, allogeneic, and xenogeneic macrophages, followed by drug treatment and gamma irradiation, to kill the bacteria. Notable observations were that the lymphocytes obtained from the vaccinated mice proliferated and secreted mainly interferon- gamma and IgG2a, but not interleukin-4 and IgG1. The enumeration of viability of M. tuberculosis indicated a significant level of protection in the vaccinated mice after challenge with live M. tuberculosis. This vaccination strategy worked successfully for tuberculosis but also showed a significant decrease in mortality of mice challenged with live S. typhimurium.
OBJECTIVE: The objective of this six-week, examiner-blind clinical study was to assess the tooth whitening and extrinsic stain prevention efficacy of a new dentifrice delivering 1.0% hydrogen peroxide, 0.243% sodium fluoride, and sodium tripolyphosphate in a high-cleaning silica base (Test Dentifrice) relative to that of a commercially available hexametaphosphate-containing whitening dentifrice (Positive Control Dentifrice). METHODOLOGY: Following a baseline oral soft tissue examination and scoring of extrinsic tooth stain and tooth shade, qualifying adult male and female subjects from the Mississauga, Ontario, Canada area were randomized into either the Test or Positive Control Dentifrice group. The two groups were balanced for age, tobacco use, extrinsic tooth stain, and tooth shade scores. All subjects received a dental prophylaxis, and were provided with a supply of their assigned product and a soft-bristled adult toothbrush for use at home. Subjects were instructed to brush their teeth for two minutes twice daily (morning and evening) using only the dentifrice provided, and to refrain from using any other oral hygiene products for the entire six weeks of the study. There were no restrictions regarding diet or smoking habits during the course of the study. Oral soft tissue, extrinsic tooth stain and tooth shade assessments for each subject were repeated after two and six weeks of product use. All statistical tests were two-sided and employed a level of significance of alpha = 0.05. RESULTS: Seventy-six (76) subjects complied with the protocol and completed the entire study. At both the two-week and six-week examinations, the Test Dentifrice prevented statistically significant (p < 0.05) more tooth stain as compared to the Positive Control Dentifrice. Also, at the two-week and six-week examinations, the Test Dentifrice provided statistically significant (p < 0.05) greater tooth whitening as compared to the Positive Control Dentifrice (2.64 and 3.77 shade rank reductions, respectively). CONCLUSION: A new whitening dentifrice, delivering 1.0% hydrogen peroxide, 0.243% sodium fluoride, and sodium tripolyphosphate in a high-cleaning silica base provides a statistically significant greater level of efficacy for both tooth whitening and prevention of extrinsic tooth stain than the commercially available Positive Control Dentifrice.
The variation in sequence and length in the C-terminal region among members of the unique PE (Pro-Glu) and PPE (Pro-Pro-Glu) protein families of Mycobacterium tuberculosis is a likely source of antigenic variation, giving rise to the speculation that these protein families could be immunologically important. Based on in silico analysis, we selected a hypothetical open reading frame (ORF) encoding a protein belonging to the PPE family and having epitopes with predictably higher antigenic indexes. Reverse transcriptase PCR using total RNA extracted from in vitro-cultured M. tuberculosis H37Rv generated an mRNA product corresponding to this gene, indicating the expression of this ORF (Rv2430c) at the mRNA level. Recombinant protein expressed in Escherichia coli was used to screen the sera of M. tuberculosis-infected patients, as well as those of clinically healthy controls (n = 10), by enzyme-linked immunosorbent assay. The panel of patient sera comprised sera from fresh infection cases (category 1; n = 32), patients with relapsed tuberculosis (category 2; n = 30), and extrapulmonary cases (category 3; n = 30). Category 2 and 3 sera had strong antibody responses to the PPE antigen, equal to or higher than those to other well-known antigens, such as Hsp10 or purified protein derivative (PPD). However, a higher percentage of patients belonging to category 1, as opposed to clinically healthy controls, showed stronger antibody response against the PPE protein when probed with anti-immunoglobulin M (IgM) (71 versus 37.5%) or anti-IgG (62.5 versus 28.12%). Our results reveal that this PPE ORF induces a strong B-cell response compared to that generated by M. tuberculosis Hsp10 or PPD, pointing to the immunodominant nature of the protein.