Dileep Kumar - Academia.edu (original) (raw)
Papers by Dileep Kumar
Histology and histopathology, 2014
HIV-associated nephropathy (HIVAN) is a common complication of HIV-1 infection in patients with A... more HIV-associated nephropathy (HIVAN) is a common complication of HIV-1 infection in patients with African ancestry in general and with APOL1 gene risk variants in particular. Although collapsing glomerulopathy is considered a hallmark of HIVAN, significant numbers of glomeruli in patients with HIVAN also display other variants of focal segmental glomerulosclerosis (FSGS). We propose that collapsed glomeruli as well as glomeruli with other variants of FSGS are manifestations of HIVAN and their prevalence depends on associated host factors. We explored the role of the renin-angiotensin system (RAS) in the manifestation of any specific glomerular phenotype in HIVAN. To evaluate the role of the RAS we have used a genetically engineered mouse model of HIVAN (Tg26) with two and four copies of angiotensinogen (Agt) gene (Tg26/Agt2 and Tg26/Agt4). In Tg26/Agt2, 1 out of 6 glomeruli exhibited sclerosed phenotype, whereas 1 out of 25 glomeruli displayed collapsed phenotype; on the other hand, i...
Cellular signalling, Jan 24, 2014
In the present study, we evaluated the effect of short term hyperglycemia on renal lesions in a m... more In the present study, we evaluated the effect of short term hyperglycemia on renal lesions in a mouse model (Tg26) of HIV-associated nephropathy (HIVAN). Control and Tg26 mice in groups (n=6) were administered either normal saline (FVBN or Tg) or streptozotocin (FVBN+STZ or Tg26+STZ). After two weeks, biomarkers were collected and kidneys were harvested. FVBN+ STZ and Tg26+STZ displayed elevated serum glucose levels when compared to FVBN and Tg26 respectively. Tg26+STZ displayed elevated (P<0.05) blood urea nitrogen (BUN) levels (P<0.05) and enhanced…
Renal Failure, 2009
Renal biopsy data indicate that tubular epithelial cells serve as a reservoir for HIV-1 infection... more Renal biopsy data indicate that tubular epithelial cells serve as a reservoir for HIV-1 infection. We studied the effect of HIV-1 gp120 envelope gene expression on tubular cell apoptosis. HIV-1 gp120 was expressed in a lentiviral vector pHR-CMV-IRES2-EGFP-DeltaB. This plasmid construct was used to produce pseudotyped virus using VSV-G envelope to enhance the tropism for efficient viral transduction. Human proximal tubular (HK-2) cells were transduced and assayed for cellular injury by trypan blue exclusion, Hoechst and PI staining, TUNEL, and cell cycle staging. HIV-1 gp120-transduced HK-2 cells showed cellular injury in a time-dependent manner. Gp120-transduced cells showed 2.5-fold greater apoptosis when compared with vector-transduced cells. Cell cycle analysis did not reveal any alteration between gp120-transduced cells and vector-transduced cells. Gp120-transduced cells showed higher expression of both Fas and FasL, whereas pretreatment with anti-FasL antibody partially inhibited gp120-induced tubular cell apoptosis. Similarly, pretreatment with caspase-8 inhibitor attenuated gp120-induced HK2 cell apoptosis. Moreover, gp120-transduced cells showed activation of caspase 8. These results suggest that HIV-1 gp120 expression induces tubular cell apoptosis through the extrinsic pathway by enhancing Fas and FasL expression and activation of caspase-8.
Cellular Signalling, 2012
Journal of Biological Chemistry, 2009
Experimental and Molecular Pathology, 2013
Experimental and Molecular Pathology, 2013
Experimental and Molecular Pathology, 2012
Experimental and Molecular Pathology, 2013
Cellular Signalling, 2012
AJP: Renal Physiology, 2011
Human immunodeficiency virus (HIV)-1 has been reported to cause tubular cell injury both in in vi... more Human immunodeficiency virus (HIV)-1 has been reported to cause tubular cell injury both in in vivo and in vitro studies. In the present study, we evaluated the role of oxidative stress in the induction of apoptosis in HIV gene expressing mouse tubular cells in in vivo (Tg26, a transgenic mouse model of HIV-associated nephropathy) and in vitro (tubular cells were transduced with pNL4-3: ΔG/P-GFP, VSV.G psueudo typed virus) studies. Although Tg26 mice showed enhanced tubular cell reactive oxygen species (ROS) generation and apoptosis, renal tissue did not display a robust antioxidant response in the form of enhanced free radical scavenger (MnSOD/catalase) expression. Tg26 mice not only showed enhanced tubular cell expression of phospho-p66ShcA but also displayed nuclear Foxo3a translocation to the cytoplasm. These findings indicated deactivation of tubular cell Foxo3A-dependent redox-sensitive stress response program (RSSRP) in Tg26 mice. In in vitro studies, NL4-3 (pNL4-3: ΔG/P-GFP,...
The American Journal of Pathology, 2011
AJP: Renal Physiology, 2012
In the present study, we evaluated the effect of inhibition of renin activity (aliskiren) on the ... more In the present study, we evaluated the effect of inhibition of renin activity (aliskiren) on the progression of renal lesions in two different mouse models (Vpr and Tg26) of human immunodeficiency virus (HIV)-associated nephropathy (HIVAN). In protocol A, Vpr mice were fed either water (C-VprA) or doxycycline [Doxy (D-VprA)] in their drinking water for 6 wk. In protocols B and C, Vpr mice received either normal saline (C-VprB/C), Doxy + normal saline (D-VprB/C), or Doxy + aliskiren (AD-VprB/C) for 6 wk ( protocol B) or 12 wk ( protocol C). In protocols D and E, Vpr mice were fed Doxy for 6 wk followed by kidney biopsy. Subsequently, half of the mice were administered either normal saline (D-VprD/E) or aliskiren (AD-VprD/E) for 4 wk ( protocol D) or 8 ( protocol E) wk. All D-VprA mice showed renal lesions in the form of focal segmental glomerular sclerosis and dilatation of tubules. In protocols B and C, aliskiren diminished both progression of renal lesions and proteinuria. In proto...
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2009
American Journal of Psychiatry, Oct 27, 2014
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2008
British Journal of Medicine and Medical Research, 2014
ABSTRACT Objective: To observe the demographic characteristics of the patients, substance abused,... more ABSTRACT Objective: To observe the demographic characteristics of the patients, substance abused, intention and precipitating factors for self-poisoning presenting to Accident& Emergency department of Liaquat University Hospital Hyderabad, Sindh, Pakistan. Patients and Methodology: A prospective observational study was carried out for a period of 6 months from (March 2013 to August 2013).100 patients more than >12years with a definite history of self-poisoning were included. Details regarding patients demographic characteristics e.g. age, sex, maritalstatus, academic status, socioeconomic standing etc. and substance abused for self-poisoning were recorded on a specifically designed proforma. Results: During the study period 100 patients of DSP were included. Of 100 patients 40% (n=40) were male age ranges from (15-50) and 60% (n=60) were female age ranges from (17-50). Mean age of the patients was 23.63±8.370 (mean±SD). Out of hundred patients 57% (F=31, M=26) were uneducated, 56% (F=34, M=22) were unmarried, those who were unmarried had statistically significant relationship with the use of organophosphorous compounds/Rat killer for self-poisoning (p= 0.0281). 85% of the total patients belonged to lower socioeconomic class. Occupation wise mostly female were household/house wife and male were farmer/labour. (49%) of the studied group used organo-phosphorous containing compound insecticide/pesticides, 29% used Rat killer. 11% of the patients consumed benzodiazepine for self-poisoning.60% of the total patients had suicidal intention, use of organophosphorous compound/Rat killer is significantly associated with the intention to suicide (p=0.0001), 33%of the patients wanted to draw attention and 7% committed DSP to show anger, or to punish themselves because of guilt Table 4. (46%) committed the act of DSP after having conflict with parents other had interpersonal conflicts with husband/wife, girlfriend/boyfriend and close relatives. Conclusion: Use of organophosphorous containing compound/Rat killer are associated with an intention to suicide (p=0.0001) and these are preferred substances used for self-poisoning among unmarried population (p=0.0281).Demographic characteristics of patients do not vary greatly with relation to their orientation to urban or rural areas as well as choice of substance for self-poisoning were also independent to location (p=1.0000 - See more at: http://www.sciencedomain.org/abstract.php?iid=311&id=12&aid=2427#sthash.ChauDIzB.dpuf
Nuclear Medicine and Biology, Dec 1, 2006
Excessive activation via the metabotropic glutamate receptor subtype 5 (mGluR(5)) has been implic... more Excessive activation via the metabotropic glutamate receptor subtype 5 (mGluR(5)) has been implicated in depression, neuropathic pain and other psychiatric, neurological and neurodegenerative diseases. A mGluR(5) radioligand for in vivo quantification by positron emission tomography (PET) would facilitate studies of the role of this receptor in disease and treatment. 3-Methoxy-5-pyridin-2-ylethynylpyridine (MPEPy), a selective and high-affinity antagonist at the mGluR(5) receptor was selected as a candidate ligand; a recent publication by Yu et al. [Nucl Med Biol 32 (2005) 631-640] presented initial micro-PET results for [(11)C]MPEPy with enthusiasm. Building on their efforts, we report as unique contributions (1) an improved chemical synthesis method, (2) the first data using human tissue, (3) phosphor images for rat brain preparations, (4) a novel comparison of anesthetic agents and (5) in vivo data in baboon. In vitro phosphor imaging studies of this ligand using human and rat brain tissue demonstrated high specific binding in the hippocampus, striatum and cortex with minimal specific binding in the cerebellum. In contrast, in vivo micro-PET studies in rats using urethane anesthesia, PET studies in baboons using isoflurane anesthesia and ex vivo micro-PET studies in unanesthetized rats each showed little specific binding in the brain. Despite the promising in vitro results, the low signal-to-noise ratio found in vivo does not justify the use of [(11)C]MPEPy as a PET radiotracer in humans.
Histology and histopathology, 2014
HIV-associated nephropathy (HIVAN) is a common complication of HIV-1 infection in patients with A... more HIV-associated nephropathy (HIVAN) is a common complication of HIV-1 infection in patients with African ancestry in general and with APOL1 gene risk variants in particular. Although collapsing glomerulopathy is considered a hallmark of HIVAN, significant numbers of glomeruli in patients with HIVAN also display other variants of focal segmental glomerulosclerosis (FSGS). We propose that collapsed glomeruli as well as glomeruli with other variants of FSGS are manifestations of HIVAN and their prevalence depends on associated host factors. We explored the role of the renin-angiotensin system (RAS) in the manifestation of any specific glomerular phenotype in HIVAN. To evaluate the role of the RAS we have used a genetically engineered mouse model of HIVAN (Tg26) with two and four copies of angiotensinogen (Agt) gene (Tg26/Agt2 and Tg26/Agt4). In Tg26/Agt2, 1 out of 6 glomeruli exhibited sclerosed phenotype, whereas 1 out of 25 glomeruli displayed collapsed phenotype; on the other hand, i...
Cellular signalling, Jan 24, 2014
In the present study, we evaluated the effect of short term hyperglycemia on renal lesions in a m... more In the present study, we evaluated the effect of short term hyperglycemia on renal lesions in a mouse model (Tg26) of HIV-associated nephropathy (HIVAN). Control and Tg26 mice in groups (n=6) were administered either normal saline (FVBN or Tg) or streptozotocin (FVBN+STZ or Tg26+STZ). After two weeks, biomarkers were collected and kidneys were harvested. FVBN+ STZ and Tg26+STZ displayed elevated serum glucose levels when compared to FVBN and Tg26 respectively. Tg26+STZ displayed elevated (P<0.05) blood urea nitrogen (BUN) levels (P<0.05) and enhanced…
Renal Failure, 2009
Renal biopsy data indicate that tubular epithelial cells serve as a reservoir for HIV-1 infection... more Renal biopsy data indicate that tubular epithelial cells serve as a reservoir for HIV-1 infection. We studied the effect of HIV-1 gp120 envelope gene expression on tubular cell apoptosis. HIV-1 gp120 was expressed in a lentiviral vector pHR-CMV-IRES2-EGFP-DeltaB. This plasmid construct was used to produce pseudotyped virus using VSV-G envelope to enhance the tropism for efficient viral transduction. Human proximal tubular (HK-2) cells were transduced and assayed for cellular injury by trypan blue exclusion, Hoechst and PI staining, TUNEL, and cell cycle staging. HIV-1 gp120-transduced HK-2 cells showed cellular injury in a time-dependent manner. Gp120-transduced cells showed 2.5-fold greater apoptosis when compared with vector-transduced cells. Cell cycle analysis did not reveal any alteration between gp120-transduced cells and vector-transduced cells. Gp120-transduced cells showed higher expression of both Fas and FasL, whereas pretreatment with anti-FasL antibody partially inhibited gp120-induced tubular cell apoptosis. Similarly, pretreatment with caspase-8 inhibitor attenuated gp120-induced HK2 cell apoptosis. Moreover, gp120-transduced cells showed activation of caspase 8. These results suggest that HIV-1 gp120 expression induces tubular cell apoptosis through the extrinsic pathway by enhancing Fas and FasL expression and activation of caspase-8.
Cellular Signalling, 2012
Journal of Biological Chemistry, 2009
Experimental and Molecular Pathology, 2013
Experimental and Molecular Pathology, 2013
Experimental and Molecular Pathology, 2012
Experimental and Molecular Pathology, 2013
Cellular Signalling, 2012
AJP: Renal Physiology, 2011
Human immunodeficiency virus (HIV)-1 has been reported to cause tubular cell injury both in in vi... more Human immunodeficiency virus (HIV)-1 has been reported to cause tubular cell injury both in in vivo and in vitro studies. In the present study, we evaluated the role of oxidative stress in the induction of apoptosis in HIV gene expressing mouse tubular cells in in vivo (Tg26, a transgenic mouse model of HIV-associated nephropathy) and in vitro (tubular cells were transduced with pNL4-3: ΔG/P-GFP, VSV.G psueudo typed virus) studies. Although Tg26 mice showed enhanced tubular cell reactive oxygen species (ROS) generation and apoptosis, renal tissue did not display a robust antioxidant response in the form of enhanced free radical scavenger (MnSOD/catalase) expression. Tg26 mice not only showed enhanced tubular cell expression of phospho-p66ShcA but also displayed nuclear Foxo3a translocation to the cytoplasm. These findings indicated deactivation of tubular cell Foxo3A-dependent redox-sensitive stress response program (RSSRP) in Tg26 mice. In in vitro studies, NL4-3 (pNL4-3: ΔG/P-GFP,...
The American Journal of Pathology, 2011
AJP: Renal Physiology, 2012
In the present study, we evaluated the effect of inhibition of renin activity (aliskiren) on the ... more In the present study, we evaluated the effect of inhibition of renin activity (aliskiren) on the progression of renal lesions in two different mouse models (Vpr and Tg26) of human immunodeficiency virus (HIV)-associated nephropathy (HIVAN). In protocol A, Vpr mice were fed either water (C-VprA) or doxycycline [Doxy (D-VprA)] in their drinking water for 6 wk. In protocols B and C, Vpr mice received either normal saline (C-VprB/C), Doxy + normal saline (D-VprB/C), or Doxy + aliskiren (AD-VprB/C) for 6 wk ( protocol B) or 12 wk ( protocol C). In protocols D and E, Vpr mice were fed Doxy for 6 wk followed by kidney biopsy. Subsequently, half of the mice were administered either normal saline (D-VprD/E) or aliskiren (AD-VprD/E) for 4 wk ( protocol D) or 8 ( protocol E) wk. All D-VprA mice showed renal lesions in the form of focal segmental glomerular sclerosis and dilatation of tubules. In protocols B and C, aliskiren diminished both progression of renal lesions and proteinuria. In proto...
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2009
American Journal of Psychiatry, Oct 27, 2014
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2008
British Journal of Medicine and Medical Research, 2014
ABSTRACT Objective: To observe the demographic characteristics of the patients, substance abused,... more ABSTRACT Objective: To observe the demographic characteristics of the patients, substance abused, intention and precipitating factors for self-poisoning presenting to Accident& Emergency department of Liaquat University Hospital Hyderabad, Sindh, Pakistan. Patients and Methodology: A prospective observational study was carried out for a period of 6 months from (March 2013 to August 2013).100 patients more than >12years with a definite history of self-poisoning were included. Details regarding patients demographic characteristics e.g. age, sex, maritalstatus, academic status, socioeconomic standing etc. and substance abused for self-poisoning were recorded on a specifically designed proforma. Results: During the study period 100 patients of DSP were included. Of 100 patients 40% (n=40) were male age ranges from (15-50) and 60% (n=60) were female age ranges from (17-50). Mean age of the patients was 23.63±8.370 (mean±SD). Out of hundred patients 57% (F=31, M=26) were uneducated, 56% (F=34, M=22) were unmarried, those who were unmarried had statistically significant relationship with the use of organophosphorous compounds/Rat killer for self-poisoning (p= 0.0281). 85% of the total patients belonged to lower socioeconomic class. Occupation wise mostly female were household/house wife and male were farmer/labour. (49%) of the studied group used organo-phosphorous containing compound insecticide/pesticides, 29% used Rat killer. 11% of the patients consumed benzodiazepine for self-poisoning.60% of the total patients had suicidal intention, use of organophosphorous compound/Rat killer is significantly associated with the intention to suicide (p=0.0001), 33%of the patients wanted to draw attention and 7% committed DSP to show anger, or to punish themselves because of guilt Table 4. (46%) committed the act of DSP after having conflict with parents other had interpersonal conflicts with husband/wife, girlfriend/boyfriend and close relatives. Conclusion: Use of organophosphorous containing compound/Rat killer are associated with an intention to suicide (p=0.0001) and these are preferred substances used for self-poisoning among unmarried population (p=0.0281).Demographic characteristics of patients do not vary greatly with relation to their orientation to urban or rural areas as well as choice of substance for self-poisoning were also independent to location (p=1.0000 - See more at: http://www.sciencedomain.org/abstract.php?iid=311&id=12&aid=2427#sthash.ChauDIzB.dpuf
Nuclear Medicine and Biology, Dec 1, 2006
Excessive activation via the metabotropic glutamate receptor subtype 5 (mGluR(5)) has been implic... more Excessive activation via the metabotropic glutamate receptor subtype 5 (mGluR(5)) has been implicated in depression, neuropathic pain and other psychiatric, neurological and neurodegenerative diseases. A mGluR(5) radioligand for in vivo quantification by positron emission tomography (PET) would facilitate studies of the role of this receptor in disease and treatment. 3-Methoxy-5-pyridin-2-ylethynylpyridine (MPEPy), a selective and high-affinity antagonist at the mGluR(5) receptor was selected as a candidate ligand; a recent publication by Yu et al. [Nucl Med Biol 32 (2005) 631-640] presented initial micro-PET results for [(11)C]MPEPy with enthusiasm. Building on their efforts, we report as unique contributions (1) an improved chemical synthesis method, (2) the first data using human tissue, (3) phosphor images for rat brain preparations, (4) a novel comparison of anesthetic agents and (5) in vivo data in baboon. In vitro phosphor imaging studies of this ligand using human and rat brain tissue demonstrated high specific binding in the hippocampus, striatum and cortex with minimal specific binding in the cerebellum. In contrast, in vivo micro-PET studies in rats using urethane anesthesia, PET studies in baboons using isoflurane anesthesia and ex vivo micro-PET studies in unanesthetized rats each showed little specific binding in the brain. Despite the promising in vitro results, the low signal-to-noise ratio found in vivo does not justify the use of [(11)C]MPEPy as a PET radiotracer in humans.