• Asian Pacific Journal of Cancer Prevention
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• v.15 no.21
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• pp.9495-9498
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• 2014

Background: The difference in prognosis of adult and childhood acute lymphoblastic leukemia (ALL) can be attributed largely to variation in cytogenetic abnormalities with age groups. Cytogenetic analysis in acute leukemia is now routinely used to assist patient management, particularly in terms of diagnosis, disease monitoring, prognosis and risk stratification. Knowing about cytogenetic profile at the time of diagnosis is important in order to take critical decisions in management of the patients. Aim and Objectives: To determine the frequency of cytogenetic abnormalities in Pakistani adult patients with ALL in order to have insights regarding behavior of the disease. Materials and Methods: A retrospective analysis of all the cases of ALL (${\geq}15$years old) diagnosed at Aga Khan University from January 2006 to June 2014 was performed. Phenotype (B/T lineage) was confirmed in all cases by flow cytometry. Cytogenetic analysis was made for all cases using the trypsin-Giemsa banding technique. Karyotypes were interpreted using the International System for Human Cytogenetic Nomenclature (ISCN) criteria. Results: A total of 166 patients were diagnosed as ALL during the study period, of which 151 samples successfully yielded metaphase chromosomes. The male to female ratio was 3.4:1. The majority (n=120, 72.3%) had a B-cell phenotype. A normal karyotype was present in 51% (n=77) of the cases whereas 49% (n=74) had an abnormal karyotype. Of the abnormal cases, 10% showed Philadelphia chromosome; t(9;22)(q34;q11.2). Other poor prognostic cytogenetic subgroups were t(4;11)(q21;q23), hypodiploidy (35-45 chromosomes) and complex karyotype. Hyperdiploidy (47-57 chromosomes) occurred in 6.6%; all of whom were younger than 30 years. Conclusions: This study showed a relatively low prevalence of Philadelphia chromosome in Pakistani adults with ALL with an increase in frequency with age (p=0.003). The cumulative prevalence of Philadelphianegative poor cytogenetic aberrations in different age groups was not significant (p=0.6).

• KIEAE Journal
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• v.16 no.6
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• pp.159-166
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• 2016

Purpose: The architectural structures in the engineering field include more than one material, and the heat transfer through these multiple materials becomes complicated. More or less, the analytic solutions obtained by the hand calculation can provide the limited information of heat transfer phenomena. However, the engineers have generally been forced to obtain reliable results than those of the hand calculation. The numerical calculation such as a finite volume methods with the unstructured grid system is only the suitable means of the analysis for the complex and arbitrary domains that consists of multiple materials. In this study, a new numerical code is developed to provide temperature distributions in the multiple material domains, and the results of this code are compared with the validation cases in ISO10211. Method: Finite volume methods with an unstructured grid is employed. In terms of numerical methods, the heat transfer conduction coefficient is not defined on the surface of the cell between different material cells. The heat transfer coefficient is properly defined to accurately mimic the heat transfer through the surface. The boundary conditions of heat flux considering radiation or heat convection are also developed. Result: The comparison between numerical results and ISO 10211 cases. We are confirmed that the numerical method provides the proper temperature distributions, and the heat transfer equation and its boundary conditions are developed properly.

• Journal of Periodontal and Implant Science
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• v.25 no.2
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• pp.181-191
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• 1995

The ability of fibroblasts attach to teeth is of paramount imporance in re-establishing the lost connective tissue attachment after periodontal therapy. Tobacco contains a complex mixture of substances including nicotine. various nitrousamines, trace elements. and a variety of poorly characterized substances. The effects of nicotine on fibroblasts have reported an altered morphology and attachment of fibroblasts to substrates and disturbances in protein synthesis and secretion. This study examined the effect of nicotine, a major component of the particulate phase of tobacco smoke, on human gingival fibroblasts and periodontal ligament cells attachment to tissue culture surfaces and cellular activity of human gingival fibroblasts and periodontal ligament cells. Pooled human gingival fibroblasts made from extraction of 3rd molar were utilized between passage 4 and 5 and plated in 96 well plate at 20,000 cells per well. Cell number were determined using 3-(4,5-dimethylthiazole-2-y)2,5-diphenyltetrazolium bromide(MTI) , which is reflection of mitochondrial dehydrogenase activity. The concentration of nicotine used were 0.025, 0.05, 0.1, 0.2 and $0.4{\mu}M$, the average serum concentration for a smoker being approximately $0.1{\mu}M$. The results were as follows : 1. Attachment effects of nicotine on human gingival fibroblasts and periodontal ligament cells Excepts of $0.4{\mu}M$, the effects on attachment with increasing numbers of cells attaching with increasing nicotine concentrations, compared to control group. But over the 60min, return to control value. 2. The effect of cellular activity on human gingival fibroblasts and periodontal ligament cells. The cellular activity of human gingival fibroblasts and periodontal ligament cells were similar or decrease to control value at 1st incubation day. At 2nd incubation day, 0.05, 0.1, 0.2, $0.4{\mu}M$ concentrations were statistically different from control value on gingival fibroblasts group. But at 3rd incubation day, cellular activities of all experimental group were significantly decrease than control group.

• Journal of the Korean Society of Radiology
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• v.4 no.3
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• pp.31-37
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• 2010

In this paper, a photovoltaic system is designed with PWM(Pulse Width Modulation) voltage source inverter. Proposed synchronous signal and control signal was processed by 56F8323 microprocessor for stable modulation. The PWM voltage source inverter using inverter consists of complex type of electric power converter to compensate for the defect, that is solar cell cannot be developed continuously by connecting with the source of electric power for ordinary use. It can cause the effect of saving electric power, from 10 to 20[%]. The PWM voltage source inverter operates in situation that its output voltage is in same phase with the utility voltage. In addition, I connected extra power to the system through operation the system voltage and inverter power in a synchronized way by extracting the system voltage so that the phase of the system and PWM voltage inverter can be synchronized. In the system of this research showed good results after being controlled in order to provide stable power to the load and the system through maintaining and low output power of harmonics.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2001.11a
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• pp.100-100
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• 2001

Hypoxia is a pathophysiological condition that occurs during injury, ischemia, and stroke. Hypoxic stress induces the expression of genes associated with increased energy flux, including the glucose transporters Glutl and Glut3, several glycolytic enzymes, nitric oxide synthase, erythropoietin and vascular endothelial growth factor. Induction of these genes is mediated by a common basic helix-loop-helix PAS transcription complex, the hypoxia-inducible factor-l${\alpha}$ (HIF-1${\alpha}$)/ aryl hydrocarbon receptor nuclear translocator (ARNT). Insulin plays a central role in regulating metabolic pathways associated with energy storage and utilization. It triggers the conversion of glucose into glycogen and triglycerides and inhibits gluconeogenesis. Insulin also induced hypoxia-induced genes. However the underlying mechanism is unestablished. Here, we study the possibility that transcription factor HIF-1${\alpha}$ is involved in insulin-induced gene expression. We investigate the mechanism that regulates hypoxia-inducible gene expression In response to insulin We demonstrate that insulin increases the transcription of hypoxia- inducible gene. Insulin-induced transcription is not detected in Arnt defective cell lines. Under hypoxic condition, HIF- l${\alpha}$ stabilizes but does not under insulin treatment. Insulin-induced gene expression is inhibited by presence of PI-3 kinase inhibitor and Akt dominant negative mutant, whereas hypoxia-induced gene expression is not. ROS inhibitor differently affects insulin-induced gene expressions and hypoxia-induced gene expressions. Our results demonstrate that insulin also regulates hypoxia-inducible gene expression and this process is dependent on Arnt. However we suggest HIF-l${\alpha}$ is not involved insulin-induced gene expression and insulin- and hypoxia- induces same target genes via different signaling pathway.

• Molecular & Cellular Toxicology
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• v.5 no.2
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• pp.172-178
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• 2009

Nanoparticles are small-scale substances (<100 nm) with unique properties, complex exposure and health risk implications. Aluminum oxide ($Al_2O_3$) nanoparticles (NP) have been widely used as abrasives, wear-resistant coatings on propeller shafts of ships, to increase the specific impulse per weight of composite propellants used in solid rocket fuel and as drug delivery systems to increase solubility. However, recent studies have shown that nano-sized aluminum (10 nm in diameter) can generate adverse effects, such as pulmonary response. The cytotoxicity and genotoxicity of $Al_2O_3$ NP were investigated using the dye exclusion assay, the comet assay, and the mouse lymphoma thymidine kinase (tk$^{+/-}$) gene mutation assay (MLA). IC$_{20}$ values of $Al_2O_3$ NP in BEAS-2B cells were determined the concentration of 273.44 $\mu$g/mL and 390.63 $\mu$g/mL with and without S-9. However IC$_{20}$ values of $Al_2O_3$ NP were found nontoxic in L5178Y cells both of with and without S-9 fraction. In the comet assay, L5178Y cells and BEAS-2B cells were treated with $Al_2O_3$ NP which significantly increased 2-fold tail moment with and without S-9. Also, the mutant frequencies in the $Al_2O_3$ NP treated L5178Y cells were increased compared to the vehicle controls with S-9. The results of this study indicate that $Al_2O_3$ NP can cause primary DNA damage and cytotoxicity but not mutagenicity in cultured mammalian cells.

• Journal of Life Science
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• v.21 no.8
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• pp.1076-1082
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• 2011

Microtubule-based kinesin motor proteins are used for long-range vesicular transport. KIF5s (KIF5A, KIF5B and KIF5C) mediate the transport of various membranous vesicles along microtubules, but the mechanism behind how they recognize and bind to a specific cargo has not yet been completely elucidated. To identify the interaction protein for KIF5B, yeast two-hybrid screening was performed and a specific interaction with the unconventional myosin Myo9b, an actin-based vesicle transport motor, was found. The GTPase-activating protein (GAP) domain of Myo9s was essential for interaction with KIF5B in the yeast two-hybrid assay. Myo9b bound to the carboxyl-terminal region of KIF5B and to other KIF5 members. In addition, glutathione S-transferase (GST) pull-downs showed that Myo9s specifically interact to the complete Kinesin-I complex. An antibody to KIF5B specifically co-immunoprecipitated KIF5B associated with Myo9s from mouse brain extracts. These results suggest that kinesin-I motor protein interacts directly with actin-based motor proteins in the cell.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.9
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• pp.3817-3825
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• 2015

Background: The human protein methyl-transferase DOT1L catalyzes the methylation of histone H3 on lysine 79 (H3K79) at homeobox genes and is also involved in a number of significant processes ranging from gene expression to DNA-damage response and cell cycle progression. Inhibition of DOT1L activity by shRNA or small-molecule inhibitors has been established to prevent proliferation of various MLL-rearranged leukemia cells in vitro, establishing DOT1L an attractive therapeutic target for mixed lineage leukemia (MLL). Most of the drugs currently in use for the MLL treatment are reported to have low efficacy, hence this study focused on various natural compounds which exhibit minimal toxic effects and high efficacy for the target receptor. Materials and Methods: Structures of human protein methyl-transferase DOT1L and natural compound databases were downloaded from various sources. Virtual screening, molecular docking, dynamics simulation and drug likeness studies were performed for those natural compounds to evaluate and analyze their anti-cancer activity. Results: The top five screened compounds possessing good binding affinity were identified as potential high affinity inhibitors against DOT1L's active site. The top ranking molecule amongst the screened ligands had a Glide g-score of -10.940 kcal/mol and Glide e-model score of -86.011 with 5 hydrogen bonds and 12 hydrophobic contacts. This ligand's behaviour also showed consistency during the simulation of protein-ligand complex for 20000 ps, which is indicative of its stability in the receptor pocket. Conclusions: The ligand obtained out of this screening study can be considered as a potential inhibitor for DOT1L and further can be treated as a lead for the drug designing pipeline.

• Archives of Pharmacal Research
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• v.29 no.12
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• pp.1147-1153
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• 2006

Mizoribine (MZR) has been shown to possess immunosuppressive activity that selectively inhibits the proliferation of lymphocytes by interfering with inosine monophosphate dehydrogenase. The efficacy of MZR is not only in patients who have had renal transplantation, but also in patients with rheumatoid arthritis (RA), lupus nephritis, and primary nephritic syndrome. Because the exact mechanism of its immunosuppressive action is not clear, the object of this study was to examine the ability of MZR to regulate the antigen presenting cells (APCs), dendritic cells (DCs). In this work, we tested whether MZR ($1{\sim}10\;{\mu}g/mL$) could inhibit the cross-presentation of DCs. DC2.4 cells ($H-2K^{b}$) or bone marrow-derived DCs (BM-DCs) generated from BM cells of C57BL/6 mouse ($H-2K^{b}$) were cultured in the presence of MZR with OVA-microspheres, and the amount of OVA peptide-class I MHC complexes was measured by a T cell hybridoma, B3Z, that recognizes OVA (257-264 : SIINFEKL)-$H-2K^{b}$ complex and expresses-galactosidase. MZR profoundly inhibited the expression of SIINFEKL-$H-2K^{b}$ complexes. This inhibitory activity of MZR appeared to affect the phagocytic activity of DCs. MZR also decreased IL-2 production when we examined the effects of MZR on $CD4^{+}$ T cells. These results provide an understanding of the mechanism of immunosuppressive activity of MZR on the inhibition of MHC-restricted antigen presentation and phagocytic activity in relation to their actions on APCs.

• Geophysics and Geophysical Exploration
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• v.6 no.2
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• pp.95-100
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• 2003

In this study, we developed reflection tomography inversion algorithm using Straight Ray Technique (SRT) which can calculate travel time easily and fast for complex geological structure. The inversion process begins by setting the initial velocity model as a constant velocity model that hat only impedance boundaries. The inversion process searches a layer-interface structure model that is able to explain the given data satisfactorily by inverting to minimize data misfit. For getting optimal solution, we used Gauss-Newton method that needed constructing the approximate Hessian matrix. We also applied the Marquart-Levenberg regularization method to this inversion process to prevent solution diverging. The ability of the method to resolve typical target structures was tested in a synthetic salt dome inversion. Using the inverted velocity model, we obtained the migration image close to that of the true velocity model.