Sandeep Mahajan - Academia.edu (original) (raw)
Papers by Sandeep Mahajan
In the present study we have prepared ferroelectric BaZrxTi1-xO3 (0 ≤x ≤0.10) ceramic by conventi... more In the present study we have prepared ferroelectric BaZrxTi1-xO3 (0 ≤x ≤0.10) ceramic by conventional and microwave sintering (MWS) method. Phase formation was confirmed by XRD, and SEM analysis was done to get microstructural information of the samples. A dense microstructure in the MWS ceramics processed under 4 h of cycle time (including heating, cooling, and holding time) in comparison
Peritoneal Dialysis International, 2004
Objectives: Factors such as limited health-care budget allotment and poor accessibility of the ma... more Objectives: Factors such as limited health-care budget allotment and poor accessibility of the majority of the population to hemodialysis (HD) facilities should favor the use of peritoneal dialysis (PD) in India. However, only 6% of end-stage renal disease patients undergoing dialysis in India are on PD. We undertook this prospective study to evaluate various factors that could contribute to this low rate of use of PD at a tertiary-care state-run hospital in Northern India. ♦ ♦ ♦ ♦ ♦ Methods: All the patients who entered our HD or PD program from August 2001 to December 2003 were interviewed using a preset questionnaire. The questionnaire recorded their basic disease and comorbidity, social and demographic characteristics, awareness of the various modalities of renal replacement therapy (RRT), and the reasons for choosing their present modality of therapy. Treating nephrologists were also interviewed with respect to the factors that, in their opinion, were responsible for the limited use of PD at our institute. ♦ ♦ ♦ ♦ ♦ Results: In total, 342 patients on HD, 66 patients on PD,
International Urology and Nephrology, Feb 1, 2005
This review focuses on the association between renal insufficiency and cardiovascular disease and... more This review focuses on the association between renal insufficiency and cardiovascular disease and discusses therapeutic options. Although the association of chronic renal insufficiency and cardiovascular risk was first shown in patients with end-stage renal disease, even minor renal dysfunction has now been established as an independent risk for atherosclerotic cardiovascular disease. Treatment with angiotensinconverting enzyme inhibitors and statins can reduce cardiovascular morbidity and mortality in patients with renal insufficiency. Coronary revascularization improves the prognosis in patients with renal dysfunction, but there is still an underutilization of coronary revascularization procedures in patients with renal insufficiency. There is enough data that shows high mortality after percutaneous transluminal coronary angioplasty in patients with reduced renal function and that slight renal dysfunction exposes the patient with a cardiac event to an excessive cardiac mortality. Further investigation should focus on the cause of and possible preventive interventions, for the staggering cardiovascular risk in the ever-increasing number of people with renal dysfunction.
Molecular and Cellular Biology, Oct 1, 1995
Bruton's tyrosine kinase (Btk) is tyrosine phosphorylated and enzymatically activated following l... more Bruton's tyrosine kinase (Btk) is tyrosine phosphorylated and enzymatically activated following ligation of the B-cell antigen receptor. These events are temporally regulated, and Btk activation follows that of various members of the Src family of protein tyrosine kinases, thus raising the possibility that Src kinases participate in the Btk activation process. We have evaluated the mechanism underlying Btk enzyme activation and have explored the potential regulatory relationship between Btk and Src protein kinases. We demonstrate in COS transient-expression assays that Btk can be activated through intramolecular autophosphorylation at tyrosine 551 and that Btk autophosphorylation is required for Btk catalytic functions. Coexpression of Btk with members of the Src family of protein tyrosine kinases, but not Syk, led to Btk tyrosine phosphorylation and activation. Using a series of point mutations in Blk (a representative Src protein kinase) and Btk, we show that Src kinases activate Btk through an indirect mechanism that requires membrane association of the Src enzymes as well as functional Btk SH3 and SH2 domains. Our results are compatible with the idea that Src protein tyrosine kinases contribute to Btk activation by indirectly stimulating Btk intramolecular autophosphorylation.
Saudi Journal of Kidney Diseases and Transplantation, May 1, 2011
... 5. Sakhuja V, Sud K. End-stage renal disease in India and Pakistan: burden of disease and man... more ... 5. Sakhuja V, Sud K. End-stage renal disease in India and Pakistan: burden of disease and management issues. ... Top Correspondence Address: Ankur Gupta Department of Nephrology, All India Institute of Medical Sciences (AIIMS), New Delhi India Login to access the Email id. ...
Susceptibility to infections is a major cause of high morbidity and mortality in patients with ch... more Susceptibility to infections is a major cause of high morbidity and mortality in patients with chronic kidney disease (CKD). Polymorphonuclear leukocytes (PMNs) play a major role in the host defense against various infections. Although the phagocytic function of PMNs in uremic patients has been subjected to repeated evaluation, results have been inconsistent. Also, the effects of progressive uremia and acute hemodialysis (HD) on polymorphonuclear function have been scarcely evaluated. In this study, we assessed the phagocytic index (PI) of PMNs following their uptake of IgG-coated sheep erythrocytes in patients with varying severity of CKD and in healthy controls. In patients with advanced renal failure, the effects of acute HD on PI pre- and post-HD were also studied. A total of 30 patients with CKD and 15 healthy controls were studied. Patients with CKD were categorized into two groups: mild to moderate renal failure (S. Creatinine 2-6 mg/dL) and advanced renal failure (S. Creatinine >6 mg/dL) (n=15 for each). All three groups were age and sex matched. Patients with advanced renal failure had significantly impaired PI (4.03 +/- 1.15) as compared to patients with mild to moderate renal failure (7.17 +/- 2.62) and normal controls (8.13 +/- 3.31) (p < 0.001 for both). There was a statistically insignificant decline in the PI in patients with mild to moderate RF when compared to controls (7.17 +/- 2.62 versus 8.13 +/- 3.31). In patients with advanced renal failure, acute HD led to a significant improvement in PI (5.52 +/- 1.55 versus 4.03 +/- 1.15, p < 0.01). In patients with CKD, there is a progressive decline in the phagocytic index of the PMNs with increasing severity of uremia. Significant improvement in the phagocytic index following acute hemodialysis suggests the role of a circulating uremic toxin in this PMN dysfunction.
Clinical Cancer Research an Official Journal of the American Association For Cancer Research, Jun 1, 1999
A novel homology model of the kinase domain of Janus kinase (JAK) 3 was used for the structure-ba... more A novel homology model of the kinase domain of Janus kinase (JAK) 3 was used for the structure-based design of dimethoxyquinazoline compounds with potent and specific inhibitory activity against JAK3. The active site of JAK3 in this homology model measures roughly 8 Å ؋ 11 Å ؋ 20 Å, with a volume of ϳ530 Å 3 available for inhibitor binding. Modeling studies indicated that 4-(phenyl)-amino-6,7-dimethoxyquinazoline (parent compound WHI-258) would likely fit into the catalytic site of JAK3 and that derivatives of this compound that contain an OH group at the 4 position of the phenyl ring would more strongly bind to JAK3 because of added interactions with Asp-967, a key residue in the catalytic site of JAK3. These predictions were consistent with docking studies indicating that compounds containing a
Saudi Journal of Kidney Diseases and Transplantation, May 1, 2011
Peritoneal Dialysis International, 2007
During the 4 years of PD treatment, our patient did not experience peritonitis, severe malnutriti... more During the 4 years of PD treatment, our patient did not experience peritonitis, severe malnutrition, or systemic inflammation. Such good maintenance of PD might also be responsible for the preservation of the peritoneum (12).
Himalayas is a byproduct of the continent-to-continent collision due to the convergent movement o... more Himalayas is a byproduct of the continent-to-continent collision due to the convergent movement of the Indian plate towards Eurasian plate. Dharamsala area of NW Himalayas falls on the southern slope of the Dhauladhar range. The area is seismically active and falls in the High Seismic Zone V of the Seismic Map of India. Diverse lithology within a short span of distance makes the study area tectonically significant. A geochemical soil-gas survey has been conducted in the Dharamsala region. Transverse profiles have been taken across the Main Boundary Thrust 2 (MBT2) and some lineaments in Dharamsala and surrounding areas. To carry out the present investigation soil-gas samples were collected in sample bags at depth of about 0.7-1.0 m by using hollow steel probe. The collected soil-gas sample bags are analyzed for radon and helium. The radon concentration varies from 37 to 754 kBq/m3 and that of helium varies from 5.24 to 5.46 ppm. Anomalous values are found on MBT-2 and other tectonic features present in the area. The data analysis clearly reveals anomalous values of subsurface gases along the fault and lineaments.
Journal of Dentistry of Tehran University of Medical Sciences, Mar 1, 2013
Objectives: Comparative evaluation of the reinforcing effect of different post systems in the res... more Objectives: Comparative evaluation of the reinforcing effect of different post systems in the restoration of endodontically treated human anterior teeth at two different lengths of post space preparation-an in vitro study Materials and Methods: 135 extracted human incisors were endodontically treated, out of which 120 teeth were decoronated 2mm above the cementoenamel junction and divided into four experimental groups based on the post system to be used: Glass fiber post (GFP) and stainless steel post (SSP), titanium post (TTP), cast metal post (CMP). Each group was divided into two sub-groups according to the length of post space preparation: 5mm and 10mm. All the samples were restored with metal crowns. The fracture resistance was measured by applying loads at an angle of 135º to the long axis of teeth in an instron universal testing machine. Fracture mode was analyzed for all the samples. Results from the four test groups were compared and analysed using one-way ANOVA test and the Post-hoc Bonferroni test to demonstrate differences between pairs of groups. Results: The results revealed that SSP group at 10mm post space length showed the significantly ("P-value< 0.05") highest fracture resistance (793.7787 N). Decrease in post length resulted in the decrease in fracture resistance in all the groups reduced to values even lesser than the control (437.8733N).
![Research paper thumbnail of Specificity of α-Cyano-β-Hydroxy-β-Methyl-N-[4-(Trifluoromethoxy)Phenyl]-Propenamide as an Inhibitor of the Epidermal Growth Factor Receptor Tyrosine Kinase](https://attachments.academia-assets.com/65220251/thumbnails/1.jpg)
](Clinical Cancer Research, Dec 1, 1999
The epidermal growth factor receptor (EGFR) tyrosine kinase has an essential function for the sur... more The epidermal growth factor receptor (EGFR) tyrosine kinase has an essential function for the survival of human breast cancer cells. In a systematic effort to design potent and specific inhibitors of this receptor family protein tyrosine kinase (PTK) as antibreast cancer agents, we recently reported the construction of a three-dimensional homology model of the EGFR kinase domain. In this model, the catalytic site is defined by two -sheets that form an interface at the cleft between the NH 2 -terminal and COOH-terminal lobes of the kinase domain. Our modeling studies revealed a distinct, remarkably planar triangular binding pocket within the kinase domain with approximate dimensions of 15 Å ؋ 12 Å ؋ 12 Å, and the thickness of the binding pocket is ϳ7 Å with an estimated volume of ϳ600 Å 3 available for inhibitor binding. Molecular docking studies had identified ␣-cyano--hydroxy--methyl-N-[4-(trifluoromethoxy)phenyl]-propenamide (LFM-A12) as our lead inhibitor, with an estimated binding constant of 13 M, which subsequently inhibited EGFR kinase in vitro with an IC 50 value of 1.7 M. LFM-A12 was also discovered to be a highly specific inhibitor of the EGFR. Even at very high concentrations ranging from 175-350 M, this inhibitor did not affect the enzymatic activity of other PTKs, including the Janus kinases JAK1 and JAK3, the Src family kinase HCK, the Tec family member Bruton's tyrosine kinase, SYK kinase, and the receptor family PTK insulin receptor kinase. This observation is in contrast to the activity of a quinazoline inhibitor tested as a control, 4-(3bromo, 4-hydroxyanilino)-6,7-dimethoxyquinazoline, which was shown to inhibit EGFR and other tyrosine kinases such as HCK, JAK3, and SYK.
Indian Journal of Transplantation, 2014
Developments in Psychiatry in India, 2015
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis
Factors such as limited health-care budget allotment and poor accessibility of the majority of th... more Factors such as limited health-care budget allotment and poor accessibility of the majority of the population to hemodialysis (HD) facilities should favor the use of peritoneal dialysis (PD) in India. However, only 6% of end-stage renal disease patients undergoing dialysis in India are on PD. We undertook this prospective study to evaluate various factors that could contribute to this low rate of use of PD at a tertiary-care state-run hospital in Northern India. All the patients who entered our HD or PD program from August 2001 to December 2003 were interviewed using a preset questionnaire. The questionnaire recorded their basic disease and comorbidity, social and demographic characteristics, awareness of the various modalities of renal replacement therapy (RRT), and the reasons for choosing their present modality of therapy. Treating nephrologists were also interviewed with respect to the factors that, in their opinion, were responsible for the limited use of PD at our institute. I...
Leukemia & lymphoma, 2003
The leflunomide metabolite analog alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl)-prop... more The leflunomide metabolite analog alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl)-propenamide (LFM-A13) is a rationally-designed specific inhibitor of the TEC family protein tyrosine kinase, Bruton's tyrosine kinase (BTK) which plays an important role in platelet physiology by regulating the glycoprotein GPVI-FcRgamma-coupled collagen receptor signaling pathway. At low micromolar concentrations, LFM-A13 inhibited collagen-induced ultrastructural changes indicative of activation. LFM-A13 inhibited collagen (but not thrombin, TRAP-6, or ADP)-induced platelet aggregation in a concentration-dependent fashion with an IC50 value of 2.8 microM. LFM-A13 was not toxic to mice when administered systemically at dose levels ranging from 1 to 100 mg/kg. At nontoxic dose levels, LFM-A13 prolonged the tail bleeding times of mice and improved event-free survival in two mouse models of agonist-induced invariably fatal pulmonary thromboembolism. To our knowledge, LFM-A13 is the first a...
Advances in experimental medicine and biology, 1994
1. Adv Exp Med Biol. 1994;365:131-41. Involvement of nonreceptor protein tyrosine kinases in mult... more 1. Adv Exp Med Biol. 1994;365:131-41. Involvement of nonreceptor protein tyrosine kinases in multichain immune recognition receptor signal transduction. Burkhardt AL, Saouaf SJ, Mahajan S, Bolen JB. Department of Molecular ...
Molecular and cellular biology, 1995
Bruton's tyrosine kinase (Btk) is tyrosine phosphorylated and enzymatically activated followi... more Bruton's tyrosine kinase (Btk) is tyrosine phosphorylated and enzymatically activated following ligation of the B-cell antigen receptor. These events are temporally regulated, and Btk activation follows that of various members of the Src family of protein tyrosine kinases, thus raising the possibility that Src kinases participate in the Btk activation process. We have evaluated the mechanism underlying Btk enzyme activation and have explored the potential regulatory relationship between Btk and Src protein kinases. We demonstrate in COS transient-expression assays that Btk can be activated through intramolecular autophosphorylation at tyrosine 551 and that Btk autophosphorylation is required for Btk catalytic functions. Coexpression of Btk with members of the Src family of protein tyrosine kinases, but not Syk, led to Btk tyrosine phosphorylation and activation. Using a series of point mutations in Blk (a representative Src protein kinase) and Btk, we show that Src kinases activ...
In the present study we have prepared ferroelectric BaZrxTi1-xO3 (0 ≤x ≤0.10) ceramic by conventi... more In the present study we have prepared ferroelectric BaZrxTi1-xO3 (0 ≤x ≤0.10) ceramic by conventional and microwave sintering (MWS) method. Phase formation was confirmed by XRD, and SEM analysis was done to get microstructural information of the samples. A dense microstructure in the MWS ceramics processed under 4 h of cycle time (including heating, cooling, and holding time) in comparison
Peritoneal Dialysis International, 2004
Objectives: Factors such as limited health-care budget allotment and poor accessibility of the ma... more Objectives: Factors such as limited health-care budget allotment and poor accessibility of the majority of the population to hemodialysis (HD) facilities should favor the use of peritoneal dialysis (PD) in India. However, only 6% of end-stage renal disease patients undergoing dialysis in India are on PD. We undertook this prospective study to evaluate various factors that could contribute to this low rate of use of PD at a tertiary-care state-run hospital in Northern India. ♦ ♦ ♦ ♦ ♦ Methods: All the patients who entered our HD or PD program from August 2001 to December 2003 were interviewed using a preset questionnaire. The questionnaire recorded their basic disease and comorbidity, social and demographic characteristics, awareness of the various modalities of renal replacement therapy (RRT), and the reasons for choosing their present modality of therapy. Treating nephrologists were also interviewed with respect to the factors that, in their opinion, were responsible for the limited use of PD at our institute. ♦ ♦ ♦ ♦ ♦ Results: In total, 342 patients on HD, 66 patients on PD,
International Urology and Nephrology, Feb 1, 2005
This review focuses on the association between renal insufficiency and cardiovascular disease and... more This review focuses on the association between renal insufficiency and cardiovascular disease and discusses therapeutic options. Although the association of chronic renal insufficiency and cardiovascular risk was first shown in patients with end-stage renal disease, even minor renal dysfunction has now been established as an independent risk for atherosclerotic cardiovascular disease. Treatment with angiotensinconverting enzyme inhibitors and statins can reduce cardiovascular morbidity and mortality in patients with renal insufficiency. Coronary revascularization improves the prognosis in patients with renal dysfunction, but there is still an underutilization of coronary revascularization procedures in patients with renal insufficiency. There is enough data that shows high mortality after percutaneous transluminal coronary angioplasty in patients with reduced renal function and that slight renal dysfunction exposes the patient with a cardiac event to an excessive cardiac mortality. Further investigation should focus on the cause of and possible preventive interventions, for the staggering cardiovascular risk in the ever-increasing number of people with renal dysfunction.
Molecular and Cellular Biology, Oct 1, 1995
Bruton's tyrosine kinase (Btk) is tyrosine phosphorylated and enzymatically activated following l... more Bruton's tyrosine kinase (Btk) is tyrosine phosphorylated and enzymatically activated following ligation of the B-cell antigen receptor. These events are temporally regulated, and Btk activation follows that of various members of the Src family of protein tyrosine kinases, thus raising the possibility that Src kinases participate in the Btk activation process. We have evaluated the mechanism underlying Btk enzyme activation and have explored the potential regulatory relationship between Btk and Src protein kinases. We demonstrate in COS transient-expression assays that Btk can be activated through intramolecular autophosphorylation at tyrosine 551 and that Btk autophosphorylation is required for Btk catalytic functions. Coexpression of Btk with members of the Src family of protein tyrosine kinases, but not Syk, led to Btk tyrosine phosphorylation and activation. Using a series of point mutations in Blk (a representative Src protein kinase) and Btk, we show that Src kinases activate Btk through an indirect mechanism that requires membrane association of the Src enzymes as well as functional Btk SH3 and SH2 domains. Our results are compatible with the idea that Src protein tyrosine kinases contribute to Btk activation by indirectly stimulating Btk intramolecular autophosphorylation.
Saudi Journal of Kidney Diseases and Transplantation, May 1, 2011
... 5. Sakhuja V, Sud K. End-stage renal disease in India and Pakistan: burden of disease and man... more ... 5. Sakhuja V, Sud K. End-stage renal disease in India and Pakistan: burden of disease and management issues. ... Top Correspondence Address: Ankur Gupta Department of Nephrology, All India Institute of Medical Sciences (AIIMS), New Delhi India Login to access the Email id. ...
Susceptibility to infections is a major cause of high morbidity and mortality in patients with ch... more Susceptibility to infections is a major cause of high morbidity and mortality in patients with chronic kidney disease (CKD). Polymorphonuclear leukocytes (PMNs) play a major role in the host defense against various infections. Although the phagocytic function of PMNs in uremic patients has been subjected to repeated evaluation, results have been inconsistent. Also, the effects of progressive uremia and acute hemodialysis (HD) on polymorphonuclear function have been scarcely evaluated. In this study, we assessed the phagocytic index (PI) of PMNs following their uptake of IgG-coated sheep erythrocytes in patients with varying severity of CKD and in healthy controls. In patients with advanced renal failure, the effects of acute HD on PI pre- and post-HD were also studied. A total of 30 patients with CKD and 15 healthy controls were studied. Patients with CKD were categorized into two groups: mild to moderate renal failure (S. Creatinine 2-6 mg/dL) and advanced renal failure (S. Creatinine &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;6 mg/dL) (n=15 for each). All three groups were age and sex matched. Patients with advanced renal failure had significantly impaired PI (4.03 +/- 1.15) as compared to patients with mild to moderate renal failure (7.17 +/- 2.62) and normal controls (8.13 +/- 3.31) (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001 for both). There was a statistically insignificant decline in the PI in patients with mild to moderate RF when compared to controls (7.17 +/- 2.62 versus 8.13 +/- 3.31). In patients with advanced renal failure, acute HD led to a significant improvement in PI (5.52 +/- 1.55 versus 4.03 +/- 1.15, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). In patients with CKD, there is a progressive decline in the phagocytic index of the PMNs with increasing severity of uremia. Significant improvement in the phagocytic index following acute hemodialysis suggests the role of a circulating uremic toxin in this PMN dysfunction.
Clinical Cancer Research an Official Journal of the American Association For Cancer Research, Jun 1, 1999
A novel homology model of the kinase domain of Janus kinase (JAK) 3 was used for the structure-ba... more A novel homology model of the kinase domain of Janus kinase (JAK) 3 was used for the structure-based design of dimethoxyquinazoline compounds with potent and specific inhibitory activity against JAK3. The active site of JAK3 in this homology model measures roughly 8 Å ؋ 11 Å ؋ 20 Å, with a volume of ϳ530 Å 3 available for inhibitor binding. Modeling studies indicated that 4-(phenyl)-amino-6,7-dimethoxyquinazoline (parent compound WHI-258) would likely fit into the catalytic site of JAK3 and that derivatives of this compound that contain an OH group at the 4 position of the phenyl ring would more strongly bind to JAK3 because of added interactions with Asp-967, a key residue in the catalytic site of JAK3. These predictions were consistent with docking studies indicating that compounds containing a
Saudi Journal of Kidney Diseases and Transplantation, May 1, 2011
Peritoneal Dialysis International, 2007
During the 4 years of PD treatment, our patient did not experience peritonitis, severe malnutriti... more During the 4 years of PD treatment, our patient did not experience peritonitis, severe malnutrition, or systemic inflammation. Such good maintenance of PD might also be responsible for the preservation of the peritoneum (12).
Himalayas is a byproduct of the continent-to-continent collision due to the convergent movement o... more Himalayas is a byproduct of the continent-to-continent collision due to the convergent movement of the Indian plate towards Eurasian plate. Dharamsala area of NW Himalayas falls on the southern slope of the Dhauladhar range. The area is seismically active and falls in the High Seismic Zone V of the Seismic Map of India. Diverse lithology within a short span of distance makes the study area tectonically significant. A geochemical soil-gas survey has been conducted in the Dharamsala region. Transverse profiles have been taken across the Main Boundary Thrust 2 (MBT2) and some lineaments in Dharamsala and surrounding areas. To carry out the present investigation soil-gas samples were collected in sample bags at depth of about 0.7-1.0 m by using hollow steel probe. The collected soil-gas sample bags are analyzed for radon and helium. The radon concentration varies from 37 to 754 kBq/m3 and that of helium varies from 5.24 to 5.46 ppm. Anomalous values are found on MBT-2 and other tectonic features present in the area. The data analysis clearly reveals anomalous values of subsurface gases along the fault and lineaments.
Journal of Dentistry of Tehran University of Medical Sciences, Mar 1, 2013
Objectives: Comparative evaluation of the reinforcing effect of different post systems in the res... more Objectives: Comparative evaluation of the reinforcing effect of different post systems in the restoration of endodontically treated human anterior teeth at two different lengths of post space preparation-an in vitro study Materials and Methods: 135 extracted human incisors were endodontically treated, out of which 120 teeth were decoronated 2mm above the cementoenamel junction and divided into four experimental groups based on the post system to be used: Glass fiber post (GFP) and stainless steel post (SSP), titanium post (TTP), cast metal post (CMP). Each group was divided into two sub-groups according to the length of post space preparation: 5mm and 10mm. All the samples were restored with metal crowns. The fracture resistance was measured by applying loads at an angle of 135º to the long axis of teeth in an instron universal testing machine. Fracture mode was analyzed for all the samples. Results from the four test groups were compared and analysed using one-way ANOVA test and the Post-hoc Bonferroni test to demonstrate differences between pairs of groups. Results: The results revealed that SSP group at 10mm post space length showed the significantly ("P-value< 0.05") highest fracture resistance (793.7787 N). Decrease in post length resulted in the decrease in fracture resistance in all the groups reduced to values even lesser than the control (437.8733N).
Clinical Cancer Research, Dec 1, 1999
The epidermal growth factor receptor (EGFR) tyrosine kinase has an essential function for the sur... more The epidermal growth factor receptor (EGFR) tyrosine kinase has an essential function for the survival of human breast cancer cells. In a systematic effort to design potent and specific inhibitors of this receptor family protein tyrosine kinase (PTK) as antibreast cancer agents, we recently reported the construction of a three-dimensional homology model of the EGFR kinase domain. In this model, the catalytic site is defined by two -sheets that form an interface at the cleft between the NH 2 -terminal and COOH-terminal lobes of the kinase domain. Our modeling studies revealed a distinct, remarkably planar triangular binding pocket within the kinase domain with approximate dimensions of 15 Å ؋ 12 Å ؋ 12 Å, and the thickness of the binding pocket is ϳ7 Å with an estimated volume of ϳ600 Å 3 available for inhibitor binding. Molecular docking studies had identified ␣-cyano--hydroxy--methyl-N-[4-(trifluoromethoxy)phenyl]-propenamide (LFM-A12) as our lead inhibitor, with an estimated binding constant of 13 M, which subsequently inhibited EGFR kinase in vitro with an IC 50 value of 1.7 M. LFM-A12 was also discovered to be a highly specific inhibitor of the EGFR. Even at very high concentrations ranging from 175-350 M, this inhibitor did not affect the enzymatic activity of other PTKs, including the Janus kinases JAK1 and JAK3, the Src family kinase HCK, the Tec family member Bruton's tyrosine kinase, SYK kinase, and the receptor family PTK insulin receptor kinase. This observation is in contrast to the activity of a quinazoline inhibitor tested as a control, 4-(3bromo, 4-hydroxyanilino)-6,7-dimethoxyquinazoline, which was shown to inhibit EGFR and other tyrosine kinases such as HCK, JAK3, and SYK.
Indian Journal of Transplantation, 2014
Developments in Psychiatry in India, 2015
Peritoneal dialysis international : journal of the International Society for Peritoneal Dialysis
Factors such as limited health-care budget allotment and poor accessibility of the majority of th... more Factors such as limited health-care budget allotment and poor accessibility of the majority of the population to hemodialysis (HD) facilities should favor the use of peritoneal dialysis (PD) in India. However, only 6% of end-stage renal disease patients undergoing dialysis in India are on PD. We undertook this prospective study to evaluate various factors that could contribute to this low rate of use of PD at a tertiary-care state-run hospital in Northern India. All the patients who entered our HD or PD program from August 2001 to December 2003 were interviewed using a preset questionnaire. The questionnaire recorded their basic disease and comorbidity, social and demographic characteristics, awareness of the various modalities of renal replacement therapy (RRT), and the reasons for choosing their present modality of therapy. Treating nephrologists were also interviewed with respect to the factors that, in their opinion, were responsible for the limited use of PD at our institute. I...
Leukemia & lymphoma, 2003
The leflunomide metabolite analog alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl)-prop... more The leflunomide metabolite analog alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl)-propenamide (LFM-A13) is a rationally-designed specific inhibitor of the TEC family protein tyrosine kinase, Bruton's tyrosine kinase (BTK) which plays an important role in platelet physiology by regulating the glycoprotein GPVI-FcRgamma-coupled collagen receptor signaling pathway. At low micromolar concentrations, LFM-A13 inhibited collagen-induced ultrastructural changes indicative of activation. LFM-A13 inhibited collagen (but not thrombin, TRAP-6, or ADP)-induced platelet aggregation in a concentration-dependent fashion with an IC50 value of 2.8 microM. LFM-A13 was not toxic to mice when administered systemically at dose levels ranging from 1 to 100 mg/kg. At nontoxic dose levels, LFM-A13 prolonged the tail bleeding times of mice and improved event-free survival in two mouse models of agonist-induced invariably fatal pulmonary thromboembolism. To our knowledge, LFM-A13 is the first a...
Advances in experimental medicine and biology, 1994
1. Adv Exp Med Biol. 1994;365:131-41. Involvement of nonreceptor protein tyrosine kinases in mult... more 1. Adv Exp Med Biol. 1994;365:131-41. Involvement of nonreceptor protein tyrosine kinases in multichain immune recognition receptor signal transduction. Burkhardt AL, Saouaf SJ, Mahajan S, Bolen JB. Department of Molecular ...
Molecular and cellular biology, 1995
Bruton's tyrosine kinase (Btk) is tyrosine phosphorylated and enzymatically activated followi... more Bruton's tyrosine kinase (Btk) is tyrosine phosphorylated and enzymatically activated following ligation of the B-cell antigen receptor. These events are temporally regulated, and Btk activation follows that of various members of the Src family of protein tyrosine kinases, thus raising the possibility that Src kinases participate in the Btk activation process. We have evaluated the mechanism underlying Btk enzyme activation and have explored the potential regulatory relationship between Btk and Src protein kinases. We demonstrate in COS transient-expression assays that Btk can be activated through intramolecular autophosphorylation at tyrosine 551 and that Btk autophosphorylation is required for Btk catalytic functions. Coexpression of Btk with members of the Src family of protein tyrosine kinases, but not Syk, led to Btk tyrosine phosphorylation and activation. Using a series of point mutations in Blk (a representative Src protein kinase) and Btk, we show that Src kinases activ...