The role of oncogenes, tumour suppressor genes and growth factors in oral squamous cell carcinoma: a case of apoptosis versus proliferation

Mutation, deactivation and disregulated expression of oncogenes and tumour-suppressor genes may be involved in the pathogenesis of oral squamous cell carcinoma (SCC). Deactivation of the p53 tumour-suppressor gene allows cell proliferation and blocks apoptosis of malignant oral keratinocytes. Mutation in the ras oncog-ene results in persistent mitogenic signalling. Upregul-ated c-Myc expression, in the presence of growth factors, provides an additional proliferative signal. Loss of retino-blastoma tumour-suppressor gene (Rb) function may contribute to oral keratinocyte hyperproliferation and recent evidence suggests that simultaneous deactivation of both p53 and Rb is required for tumourigenesis. Enhanced Bcl-2 and reduced Fas expression inhibit tumour cell apoptosis and may convey resistance to cyto-toxic drugs and T cell-mediated cytotoxicity, respectively. Exogenous mutagens such as tobacco, alcohol and viral oncogenes may cause altered expression of oncogenes and tumour-suppressor genes in some cases of oral SCC. The impact of these mechanisms on future therapies for oral SCC is highlighted.     

A Review on Joint Carotid Intima-Media Thickness and Plaque Area Measurement in Ultrasound for Cardiovascular/Stroke Risk Monitoring: Artificial Intelligence Framework

Journal of Digital Imaging - Cardiovascular diseases (CVDs) are the top ten leading causes of death worldwide. Atherosclerosis disease in the arteries is the main cause of the CVD, leading to...     

Elucidating the protective and pathologic T cell species in the virus-induced corneal immunoinflammatory condition herpetic stromal keratitis

Herpetic stromal keratitis (HSK) results in postinfection with Herpes simplex virus type 1 (HSV-1). The pathogenesis involves tissue damage by the host immune system, classifying HSK as an immunopathological disease. The crucial disease orchestrating cells is thought to be the T lymphocytes. The present study elucidates pathogenic and protective T cell subsets involved in the development of HSK using the gBT mice, which possess a monoclonal population of CD8+ T cells reactive to a HSV immunodominant epitope. Results show that HSV-reactive CD8+ T cells enter infected corneas during the acute but not the chronic phase of the disease during which the predominant population is CD4+ T cells. Adoptive transfer experiments in T and B cell-deficient recombination-activating gene knockout mice revealed that HSV-reactive CD8+ T cells are capable of ocular virus clearance, possibly through a combination of corneal and peripheral nervous system antiviral effects, but are not involved in lesion development. CD4+ T cells of the virus-specific or nonspecific species emerged as the pathogenic T cells capable of precipitating disease. These observations have the potential to yield important treatment strategies by targeting specific cell types in HSK.     

Impact of Solvent on Electrospinning of Zein and Analysis of Resulting Fibers

Zein fibers have been produced by electrospinning from acetic acid, aqueous methanol, ethanol and isopropyl alcohol. Alcohol solutions produced fibers that were predominantly ribbons. Fibers spun from acetic acid solution have a round morphology with a narrower distribution of diameters when spun under suitable conditions. The IR spectra of electrospun fibers display increased absorbance at 1 650 cm^?1 relative to starting material, indicative of increased α‐helical structure. Raman spectra of fibers spun from acetic acid solution had spectral differences, having increased absorbance at 680, 750 and 860 cm^?1, versus fibers spun from alcoholic solvents suggesting different tertiary structure within the fiber, which may result from different structures in solution. Polarized Raman spectroscopy taken parallel and perpendicular to the fiber axis displayed no differences, suggesting similar secondary and tertiary structures in these directions. All of the fibers had some degree of birefringence demonstrating the presence of orientation. The smaller fibers were highly birefringent throughout the fiber, while the larger fibers had orientation at the surface only. Quality fibers could not be produced from N,N‐dimethylformamide, acetone/water, acetic acid/water, 8 M urea/water or 10% NaOH/water zein solutions.

     

Molecular analysis of Cryptococcus neoformans mitochondrial cytochrome b gene sequences

Mitochondrial cytochrome b genes (cyt b) of 40 strains of Cryptococcus neoformans were partially sequenced to determine the genetic relations. With the exception of the type strain of C. neoformans var. neoformans, all strains contained introns in their sequences. Analysis of 386 bp of coding sequence from each strain under investigation revealed a total of 27 (6.99%) variable nucleotide sites and categorized isolates of C. neoformans into nine cyt b types. C. neoformans var. gattii included cyt b types I to V, and C. neoformans var. neoformans comprised types VI to IX. cyt b types were correlated with serotypes. All strains with cyt b types I, IV, and V were serotype B. All other strains except IFM 5878 (serotype B) with cyt b types II and III were serotype C. Serotype D strains had cyt b types VI and IX, and serotype A strains were cyt b type VIII. Of four serotype AD strains, one was cyt b type VII and the remaining three were type VIII. The phylogenetic tree based on deduced amino acid sequences divided the strains only into C. neoformans var. neoformans and C. neoformans var. gattii. These results indicate that cyt b sequences are effective for DNA typing as well as phylogenetic analysis of C. neoformans.     

Nef-specific CD45RA+ CD8+ T cells secreting MIP-1β but not IFN-γ are associated with nonprogressive HIV-1 infection

Background

Long-term survival of HIV-1 infected individuals is usually achieved by continuous administration of combination antiretroviral therapy (ART). An exception to this scenario is represented by HIV-1 infected nonprogressors (NP) which maintain relatively high circulating CD4+ T cells without clinical symptoms for several years in the absence of ART. Several lines of evidence indicate an important role of the T-cell response in the modulation of HIV-1 infection during the acute and chronic phase of the disease.

Results

We analyzed the functional and the differentiation phenotype of Nef- and Tat-specific CD8+ T cells in a cohort of HIV-1 infected NP in comparison to progressors, ART-treated seropositive individuals and individuals undergoing a single cycle of ART interruption. We observed that a distinctive feature of NP is the presence of Nef-specific CD45RA+ CD8+ T cells secreting MIP-1beta but not IFN-gamma. This population was present in 7 out of 11 NP. CD45RA+ IFN-gamma^neg MIP-1beta+ CD8+ T cells were not detected in HIV-1 infected individuals under ART or withdrawing from ART and experiencing a rebounding viral replication. In addition, we detected Nef-specific CD45RA+ IFN-gamma^neg MIP-1beta+ CD8+ T cells in only 1 out of 10 HIV-1 infected individuals with untreated progressive disease.

Conclusion

The novel antigen-specific CD45RA+ IFN-gamma^neg MIP-1beta+ CD8+ T cell population represents a new candidate marker of long-term natural control of HIV-1 disease progression and a relevant functional T-cell subset in the evaluation of the immune responses induced by candidate HIV-1 vaccines.     

Segment-2 sequence analysis and cross-neutralization studies on some Indian bluetongue viruses suggest isolates are VP2-variants of serotype 23

Sequence analysis of segment 2 (seg-2) of three Indian bluetongue virus (BTV) isolates, Dehradun, Rahuri and Bangalore revealed 99% nucleotide identity amongst them and 96% with the reference BTV 23. Phylogenetic analysis grouped the isolates in ‘nucleotype D’. The deduced amino acid (aa) sequence of the Bangalore isolate showed a high variability in a few places compared to other isolates. B-cell epitope analyses predicted an epitope that is present exclusively in the Bangalore isolate. Two-way cross serum neutralization confirmed that Bangalore isolate is antigenically different from the other two isolates. The results of this study suggest that these three isolates are VP2 variants of BTV 23. This signifies that non-cross-neutralizing variants of the same BTV serotype should be included in vaccine preparation.