Akash Mirza - Academia.edu (original) (raw)

Papers by Akash Mirza

Cancer Research, 2010

The p53 protein is a primary regulator of the cellular response to DNA damage and is a critical t... more The p53 protein is a primary regulator of the cellular response to DNA damage and is a critical tumor suppressor. Restoration of p53 function in soft tissue sarcomas and hepatocellular carcinomas in mice was reported to cause tumor regressions associated with cellular senescence. These findings led us to investigate the ability of HDM2 antagonism to induce cellular senescence as well as apoptosis in a broad panel of wild-type p53 cell lines derived from human solid tumors. Here we report that the small molecule HDM2 antagonist Nutlin-3a activates p53 and induces cellular senescence in 10 out of 12 human tumor cell lines tested. Only two of these tumor cell lines also demonstrated an apoptotic response to Nutlin-3a. The kinetics of senescence induction by Nutlin-3a was slower than that of the apoptotic response, suggesting that apoptosis may be the first-line response, while senescence may be triggered as a back-up program when the apoptotic response fails to execute. A distinct expression profile of p53 target genes associated with apoptosis, cell cycle and senescence was observed and corresponded with the distinct phenotypic responses in this panel of cell lines. Depletion of p53 protein expression using shRNA blocked cellular senescence induced by HDM2 antagonism demonstrating the critical role for p53 in this process. The pronounced effects of Nutlin-3a on senescence in multiple wild-type p53 tumor cell lines underscores the unique anti-tumor mechanisms of HDM2 antagonism. This approach may provide a novel therapeutic strategy for future cancer treatment. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3197.

Mechanisms …, 1999

Every year more than 17 million deaths worldwide are caused by infectious diseases. The great maj... more Every year more than 17 million deaths worldwide are caused by infectious diseases. The great majority of these deaths occur in underdeveloped countries and are attributed to diseases preventable by existing vaccines, or diseases that could potentially be prevented with new vaccines. The fact that most human and veterinary pathogens establish infection in the host by initiating contact at a mucosal surface, provide the rationale for the development of mucosal vaccines. An increasing number of strategies have been proposed to facilitate mucosal immunization. Among the most widely investigated strategies are the use of attenuated microorganisms; the inclusion of immunizing antigens in lipid-based carriers, the genetic creation of transgenic plants and the use of mucosal adjuvants derived from bacterial toxins. This review provides a brief summary of the most recent advances in the field of mucosal immunization with an special emphasis on a promising genetically detoxified mucosal adjuvant, LT(R192G), derived from the heat-labile toxin of enterotoxigenic E. coli. We present evidence regarding the safety, immunogenicity, and efficacy of LT(R192G) for the development of a new generation of mucosal vaccines.

bibliotecavirtual.clacso.org.ar

... Encontramos en la década de los setenta, cuando los movimien-tos sociales son planteados dent... more ... Encontramos en la década de los setenta, cuando los movimien-tos sociales son planteados dentro de la arena política, los aportes de Alain Touraine en Actores sociales y sistemas políticos en América Lati-na, de 1987, y en la primera edición en ... Mirza, Christian Adel. ...

The British Accounting Review, 1991

This study was undertaken to use agency theory to test for a relationship between environment-rel... more This study was undertaken to use agency theory to test for a relationship between environment-related disclosure and the oil industry. A review of social disclosure in 1984 annual reports of 131 leading UK companies indicated that a positive relationship existed between the oil industry and environment-related disclosure. This result was found to be consistent with agency theory which dictates that social information is disclosed to increase the welfare of management. There is evidence of a renewed interest in the social performance of companies. Consequently, corporate social disclosure provides a fertile area for research. Agency theory can be used for developing and testing hypotheses to explain corporate social disclosure. University of North Queensland for his helpful comments. Thanks are also due to an anonymous referee for the helpful comments and suggestions on an earlier version of this paper.

Pakistan Cottons, 1980

... Document details. Title The currently recognised species of Gossypium, their relationship and... more ... Document details. Title The currently recognised species of Gossypium, their relationship and description. Authors Mirza, A.; Shaikh, AL Journal Pakistan Cottons 1980 Vol. 24 No. 4 pp. 283-298 Record Number 19810720411. Abstract. ...

Asian Cardiovascular and Thoracic Annals, 2011

Data of 401 patients who underwent mitral valve replacement with the Carpentier-Edwards Perimount... more Data of 401 patients who underwent mitral valve replacement with the Carpentier-Edwards Perimount bioprosthesis between 1984 and 2009 were evaluated. Their mean age was 68.1 ± 10.4 years (range, 22–90 years) and 54.9% were female. The most common etiology was degenerative disease (33.2%) and 62.1% of patients had mitral insufficiency. Follow-up was 3,178 patient-years, and 96.8% complete; the mean follow-up was 8.9 ± 3.1 years. Overall survival at 25 years was 10.2% ± 3%. Late mortality was 2.48% per patient-year, and valve-related deaths occurred at 1.62% per patient-year. The actuarial freedom from reoperation due to structural valve deterioration at 20 years was 24.3% ± 2% for degenerative disease and 15% ± 1.4% for non-degenerative disease. For degenerative valve disease, the freedom from structural valve deterioration at 18-years was 39% ± 1% for recipients <60-years old and 66% ± 2% for those ≥60-years old. Our data confirm the excellent durability and low mortality associa...

European journal of …, 1998

We have defined conditions for generating large numbers of dendritic cells (DC) in marrow culture... more We have defined conditions for generating large numbers of dendritic cells (DC) in marrow cultures from 10-12-week-old ACI or WF rats. The combination of granulocyte-macrophage colony-stimulating factor (GM-CSF) and TNF-alpha, known to induce DC from human CD34+ progenitors, was not effective with rat. In contrast, GM-CSF plus IL-4 generated DC in high yield, corresponding to 30-40% of the initial number of plated marrow cells. The DC proliferated in distinctive aggregates, in which most cells had an immature phenotype marked by undetectable surface B7 and high levels of MHC class II products within intracellular lysosomes. When dislodged and dispersed, the aggregates gave rise to mature stellate DC with abundant surface MHC class II and B7, sparse MHC class II- lysosomes, and strong T cell-stimulating capacity. Therefore, rat marrow progenitors can generate large numbers of immature DC, with abundant intracellular MHC class II compartments, and potent, stimulatory, mature DC.

Nature, 1997

Figure 1 MHC class II distribution defines three distinct stages in the developmental maturation ... more Figure 1 MHC class II distribution defines three distinct stages in the developmental maturation of bone-marrow-derived dendritic cells in vitro. DCs from bone marrow cultures were collected, plated on glass coverslips, and processed for immunofluorescence and ...

Virology, 1999

Recent evidence suggests that the attachment (HN) and fusion (F) glycoproteins of Newcastle disea... more Recent evidence suggests that the attachment (HN) and fusion (F) glycoproteins of Newcastle disease virus interact at the cell surface in a virus-specific manner to promote syncytium formation. Consistent with the existence of such an interaction, we have shown that it is ...

American Journal of …, 1997

This study was undertaken to delineate a possible role for tissue transglutaminase (tTG), an enzy... more This study was undertaken to delineate a possible role for tissue transglutaminase (tTG), an enzyme that catalyzes protein cross-linking, in hepatic fibrogenesis. Rats were treated with CCl4 solution and then killed at different stages of liver injury and fibrogenesis. Liver tTG mRNA levels were markedly increased as early as 6 h after the first injection, peaked at 4 days and 1 wk, and remained increased for 8 wk. The enzymatic activity of tTG was increased in livers of rats treated with CCl4, in a fashion that paralleled the Northern blot results. Cell isolation experiments indicated that all hepatic cell types synthesize tTG mRNA. Increased binding to the nuclear factor-kappaB (NF-kappaB) motif of the tTG promoter was found in the nuclear extracts prepared from CCl4-treated samples. These data demonstrate an increase in tTG gene expression during hepatic injury and fibrosis, suggesting a possible role for this enzyme in stabilizing the fibrotic bands during hepatic fibrogenesis. Moreover, increased NF-kappaB binding to the tTG promoter may represent one of the mechanisms by which cell injury induces tTG transcription and thus potentiates the process of fibrogenesis.

The major problem in oral drug formulations is low and erratic bioavailability, which mainly resu... more The major problem in oral drug formulations is low and erratic bioavailability, which mainly results from poor aqueous solubility. This may lead to high inter-and intra subject variability, lack of dose proportionality and therapeutic failure. The improvement of bioavailability of drugs with such properties presents one of the greatest challenges in drug formulations. Oral lipid based formulations are attracting considerable attention due to their capacity to increase the solubility, facilitating gastrointestinal absorption and reduce or eliminate the effect of food on the absorption of poorly water soluble, lipophilic drug and thus increasing the bioavailability. The present review outlines the recent findings on selfemulsifying drug delivery system (SEDDS), self-micro/nanoemulsifying drug delivery system (SMEDDS/SNEDDS) and evaluation of these formulations published over the past decade. The application of lipid based formulations as a promising system for the oral delivery of many therapeutic agents including traditional medicine (TM) has also been examined in the current review.

Clinical …, 1997

This study examined the palatability of 22 antimicrobial suspensions by using five independent ca... more This study examined the palatability of 22 antimicrobial suspensions by using five independent categories for scoring: appearance, smell, texture, taste, and aftertaste. The likely overall influence on patient compliance was also evaluated. Drugs were compared within their respective ...

Proceedings of …, 1998

345-GHz facility SIS receiver for the JCMT. [Proceedings of SPIE 3357, 620 (1998)]. Charles T. Cu... more 345-GHz facility SIS receiver for the JCMT. [Proceedings of SPIE 3357, 620 (1998)]. Charles T. Cunningham, Lorne Avery, CR Bergeron, Stephane Claude, PA Feldman, JR Fletcher, Jianrong Gao, Robert H. Hayward, JB Jegers ...

Infection and …, 1993

INFECTION AND IMMUNITY, Dec. 1993, p. 5326-5332 0019-9567/93/125326-07$02.00/0 Copyright ©) 1993,... more INFECTION AND IMMUNITY, Dec. 1993, p. 5326-5332 0019-9567/93/125326-07$02.00/0 Copyright ©) 1993, American Society for Microbiology ... Presentation of Mycobacterial Antigens by Human Dendritic ... Cells: Lack of Transfer from Infected Macrophages

Oncogene, 2002

Survivin is an inhibitor of apoptosis protein, which is over-expressed in most tumors. Aberrant e... more Survivin is an inhibitor of apoptosis protein, which is over-expressed in most tumors. Aberrant expression of survivin and loss of wild-type p53 in many tumors prompted us to investigate a possible link between these two events. Here we show that wild-type p53 represses ...

Archives of Virology, 1988

Summary Adenovirus type 12 transcriptional complexes were isolated from cells during the early ph... more Summary Adenovirus type 12 transcriptional complexes were isolated from cells during the early phase of infection. Sedimentation analysis identified a fast sedimenting complex type I and a slow sedimenting complex type II. Both complexes made virus specific RNA complementary to all the early genes and both contained viral DNA, which in type II but not in type I had nucleosome

ABSTRACT We apply a particle code (Direct Simulation Monte Carlo, DSMC) to a nozzleflowexpansion ... more ABSTRACT We apply a particle code (Direct Simulation Monte Carlo, DSMC) to a nozzleflowexpansion set-up which is typical for thermal plasma spray systems. Although those systems tend to have a pressure level which is too high to be treated with DSMC we obtain good results with respect to Pitot pressure measurement based Mach number estimations at different axial distances from the nozzle exit plane. Precisely, we compare the Mach numbers at 0, 30, 60, and 90 mm distance from the nozzle exit plane which was chosen as inflow boundary. The relative deviation of the simulated Mach numbers (Ma) from the measured is mostly about 10%. An influence of theflowfield upstream due to a static boundary condition downstream is also observed. The vital code extensions which allowed this simulation with DSMC are briefly discussed. Further code extensions for future research activities are outlined.

Oncogene, 2003

Oncogene is one of the world's leading cancer journals. It is published weekly and covers al... more Oncogene is one of the world's leading cancer journals. It is published weekly and covers all aspects of the structure and function of Oncogenes. Oncogene also publishes 8 Reviews issues a year, on a broad range of topics.

For the past many years, it has been observed that many terrorist activities are taking place aro... more For the past many years, it has been observed that many terrorist activities are taking place around the globe. It has become a hideous task in making proper identification of ones identity. Tracking the person through Identification Card is not the liable answer of getting to the right person at the right time. In humans, mitochondrial DNA spans 16,569 DNA building blocks (base pairs), [1] representing a fraction of the total DNA in cells. Nuclear and mitochondrial DNA are thought to be of separate evolutionary origin, with the mtDNA being derived from the circular genomes of the bacteria that were engulfed by the early ancestors of today's eukaryotic cells. Each mitochondrion is estimated to contain 2-10 mtDNA copies [2]. Unlike nuclear DNA, which is inherited from both parents and in which genes are rearranged in the process of recombination, there is usually no change in mtDNA from parent to offspring. Although mtDNA also recombines, it does so with copies of itself within the same mitochondrion. Because of this and because the mutation rate of animal mtDNA is higher than that of nuclear DNA,[3] mtDNA is a powerful tool for tracking ancestry through females (matrilineage) and has been used in this role to track the ancestry of many species back hundreds of generations. Human mtDNA can also be used to help identify individuals. [4] Forensic tests that are carried out in laboratories occasionally use mtDNA comparison form the human remains, and especially to identify older unidentified skeletal remains. Although unlike nuclear DNA mtDNA is not specific to one individual, it can be used in combination with other evidence (anthropological evidence, circumstantial evidence, and the like) to establish identification. mtDNA is also used to exclude possible matches between missing persons and unidentified remains.[5] In this research project we have suggested and planned out a way through which countering terrorism would be made Regenerating Human Mitochondrial Genome from a Programmed Microchip 267 easy and definite. We have come up with a plan to save human mitochondrial genome in a programmable chip, on an experimental basis initially. This genome sequence on the chip would serve as pivotal part of one's identity in their ID cards.