Bilal Malik - Academia.edu (original) (raw)

Papers by Bilal Malik

Human Molecular Genetics, 2015

Mutations in VPS35 (PARK17) cause autosomal dominant, late onset Parkinson&am... more Mutations in VPS35 (PARK17) cause autosomal dominant, late onset Parkinson's disease (PD). VPS35 forms a core component of the retromer complex that mediates the retrieval of membrane proteins from endosomes back to either the Golgi or plasma membrane. While aberrant endosomal protein sorting has been linked to several neurodegenerative diseases, the mechanisms by which VPS35 mutations and retromer function contribute to PD pathogenesis are not clear. To address this, we generated transgenic Drosophila that express variant forms of human VPS35 found in PD cases and the corresponding variants of the Drosophila ortholog. We did not find evidence of dominant toxicity from any variant form including the pathogenic D620N mutation, even with aging. However, assessing the ability of Vps35 variants to rescue multiple vps35-mutant phenotypes, we found that the D620N mutation confers a partial loss of function. Recently, VPS35 has been linked to the formation of mitochondria-derived vesicles, which mediate the degradation of mitochondrial proteins and contribute to mitochondrial quality control. This process is also promoted by two other PD-lined genes parkin (PARK2) and PINK1 (PARK6). We demonstrate here that vps35 genetically interacts with parkin but interestingly not with pink1. Strikingly, Vps35 overexpression is able to rescue several parkin-mutant phenotypes. Together these findings provide in vivo evidence that the D620N mutation likely confers pathogenicity through a partial loss of function mechanism and that this may be linked to other known pathogenic mechanisms such as mitochondrial dysfunction.

2015 Second International Conference on Advances in Computing and Communication Engineering, 2015

... 5. Report Date September 30, 2009 6. Performing Organization Code 7. Author(s) Richard W. Lyl... more ... 5. Report Date September 30, 2009 6. Performing Organization Code 7. Author(s) Richard W. Lyles, PhD, PE, Bilal Z. Malik, Amna Chaudhry, Ghassan Abu-Lebdeh, PhD, PE, M. Abrar Siddiqui 8. Performing Org. Report No. ...

Assessment of perceived gaps in transportation service from various perspectives is critical for ... more Assessment of perceived gaps in transportation service from various perspectives is critical for service providers in developing strategies for improved performance. A methodology is proposed for: assessment of the perceived gaps in transportation services from the consumers' ...

JPMA. The Journal of the Pakistan Medical Association, 2016

To evaluate the accuracy of intra-operative frozen section in the diagnosis of various pelvic neo... more To evaluate the accuracy of intra-operative frozen section in the diagnosis of various pelvic neoplasms, including ovarian tumours. The retrospective study was conducted at Shifa International Hospital and comprised records of all patients with lesions of female genital tract who underwent frozen section between January 2010 and December 2012. Comparison was made with the final diagnosis after histopathology was performed on examining permanent paraffin sections. The mean age of the 54 patients was 43.70+/-14.8 years (range: 19-75 years). The frozen section was accurate in 51(92.6%) cases. It had a moderately high sensitivity of 75%, high specificity of 97.6%, high positive predictive value of 90% and high negative predictive value of 93.2%. Lack of agreement was found in cases of ovarian tumours of the mucinous and borderline variety. Frozen section showed a considerable level of accuracy when dealing with suspected pelvic neoplasms.

Renal Failure, 2014

Phenazopyridine is a urinary analgesic; commonly seen side-effects of this drug include, orange d... more Phenazopyridine is a urinary analgesic; commonly seen side-effects of this drug include, orange discoloration of urine, methemoglobinemia, yellowish skin discoloration, hepatitis and acute renal failure. Various case reports with phenazopyridine associated acute renal failure secondary to acute tubular necrosis have been reported in the literature. Acute kidney injury in these patients is caused by either direct injury to renal tubular epithelial cells or secondary to pigment induced nephropathy from hemolytic anemia. Hypoxic injury from phenazopyridine-induced methemoglobinemia has been well documented. We report a case of biopsy proven acute interstitial nephritis, associated with therapeutic doses of phenazopyridine without any evidence of methemoglobinemia or other mechanism of renal injury. Clinicians should be aware of the toxicity of this commonly used drug and should look closely for signs of renal insufficiency. Identifying and stopping the offending medication stays as the first step, but recent studies indicate that early steroid administration improves renal recovery, as well as decreasing the risk of progression to chronic kidney disease with fibrosis and consequent permanent renal damage.

Japanese Journal of Ophthalmology, 2011

Journal of Neurogenetics, 2010

The American Heart Hospital Journal, 2011

Coronary perforation during percutaneous coronary intervention is a rare but dreaded complication... more Coronary perforation during percutaneous coronary intervention is a rare but dreaded complication. The risk factors, optimal management, and outcome remain obscure. To determine the predisposing factors, optimal management, and preventive strategies. We retrospectively looked at coronary perforations at our catheterization laboratory over the last 10 years. We reviewed patient charts and reports. Two independent operators, in a blinded approach, reviewed all procedural cineangiograms. Data were analyzed by simple statistical methodology. Nine patients were treated conservatively and six patients were treated with prolonged balloon inflation. Six patients were treated with polytetrafluoroethylene (PTFE)-covered stents. One patient required emergency coronary artery bypass graft. No deaths were reported. Subjects with perforations also had a significantly higher total white blood cell count (means 12,134 versus 6,155, 95 % confidence interval [CI], p< 0.0001, n=22), total absolute neutrophil count (means 74.2 % versus 57.1 %, 95 % CI, p<0.0001, n=22), and neutrophil:lymphocyte ratio (means 3.65 versus 1.50, 95% CI, p<0.0001, n=22). Coronary perforations are rare but potentially fatal events. Hypertension, small vessel diameter, high balloon:artery ratio, use of hydrophilic wires, and presence of myocardial bridging appear to be possible risk factors. Most perforations can be treated conservatively or with prolonged balloon inflation using perfusion balloons. Use of PTFE-covered stents could be a life-saving measure in cases of large perforations. Subjects with perforations also had greater systemic inflammation as indicated by elevated white cell counts.

Brain a Journal of Neurology, Jun 4, 2014

Journal of molecular neuroscience : MN, Jan 17, 2015

Spinal and bulbar muscular atrophy (SBMA) is a late-onset neuromuscular disease caused by a polyg... more Spinal and bulbar muscular atrophy (SBMA) is a late-onset neuromuscular disease caused by a polyglutamine expansion in the androgen receptor gene which results in progressive spinal and bulbar motor neuron degeneration, resulting in muscle atrophy and weakness. Although the causative genetic defect is known, until recently, the molecular pathogenesis of the disease was unclear, resulting in few, if any, targets for therapy development. As a result, there is currently no effective treatment for SBMA. However, over the past decade, our understanding of the pathomechanisms that play a role in SBMA has increased dramatically, and several of these pathways and mechanisms have now been investigated as possible therapeutic targets. In this review, we discuss some of the key pathomechanisms implicated in SBMA and describe some of the therapeutic strategies that have been tested in SBMA to date, which fall into four main categories: (i) gene silencing; (ii) protein quality control and/or inc...

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 2015

Several imaging techniques have been advocated as clinical adjuncts to improve identification of ... more Several imaging techniques have been advocated as clinical adjuncts to improve identification of suspicious oral lesions. However, these have not yet shown superior sensitivity or specificity over conventional oral examination techniques. We developed a multimodal, multi-scale optical imaging system that combines macroscopic biochemical imaging of fluorescence lifetime imaging with subcellular morphologic imaging of reflectance confocal microscopy for early detection of oral cancer. We tested our system on excised human oral tissues. In total, 4 tissue specimens were imaged. These specimens were diagnosed as either clinically normal, oral lichen planus, gingival hyperplasia, or superficially invasive squamous cell carcinoma. The optical and fluorescence lifetime properties of each specimen were recorded. Both quantitative and qualitative differences among normal, benign, and squamous cell carcinoma lesions can be resolved with fluorescence lifetime imaging reflectance confocal microscopy. The results demonstrate that an integrated approach based on these two methods can potentially enable rapid screening and evaluation of large areas of oral epithelial tissue. Early results from ongoing studies of imaging human oral cavity illustrate the synergistic combination of the 2 modalities. An adjunct device based on such optical characterization of oral mucosa can potentially be used to detect oral carcinogenesis in early stages.

The Journal of invasive cardiology

Spontaneous coronary artery dissection as a cause of acute myocardial ischemia is a rare entity t... more Spontaneous coronary artery dissection as a cause of acute myocardial ischemia is a rare entity that has been associated with several different clinical profiles and precipitating events. The recognition of this entity as the cause of acute ischemia is important because the therapeutic considerations may be different than that for ischemia due to a ruptured atherosclerotic plaque. We report a case of spontaneous coronary artery dissection in a 31-year-old female that was induced by prolonged, forceful retching. To our knowledge, this is the first reported case of such an association. Prolonged retching should be added to the list of causes of spontaneous coronary artery dissection.

PloS one, 2015

Automatic segmentation of nuclei in reflectance confocal microscopy images is critical for visual... more Automatic segmentation of nuclei in reflectance confocal microscopy images is critical for visualization and rapid quantification of nuclear-to-cytoplasmic ratio, a useful indicator of epithelial precancer. Reflectance confocal microscopy can provide three-dimensional imaging of epithelial tissue in vivo with sub-cellular resolution. Changes in nuclear density or nuclear-to-cytoplasmic ratio as a function of depth obtained from confocal images can be used to determine the presence or stage of epithelial cancers. However, low nuclear to background contrast, low resolution at greater imaging depths, and significant variation in reflectance signal of nuclei complicate segmentation required for quantification of nuclear-to-cytoplasmic ratio. Here, we present an automated segmentation method to segment nuclei in reflectance confocal images using a pulse coupled neural network algorithm, specifically a spiking cortical model, and an artificial neural network classifier. The segmentation a...

Proper treatment of diabetes includes maintenance of near normal blood glucose levels, which can ... more Proper treatment of diabetes includes maintenance of near normal blood glucose levels, which can only be achieved with frequent blood glucose monitoring. Current blood finger-stick methods for glucose sensing are invasive, often resulting in low patient compliance and poor disease control. The development of a noninvasive glucose sensor has the potential to provide optimal management of diabetes. Our proposed noninvasive approach is based on an optical polarimetry system for probing the anterior chamber of the eye. The sensor would eventually be used to measure the aqueous humor glucose concentration as a means to determine the blood glucose concentration. In this report, we present the development of a near real-time (less than 1 second) dual wavelength closed-loop polarimetric system to minimize glucose prediction error in the presence of varying birefringence due to motion artifact. The new dual wavelength polarimetric system and in vitro glucose measurement results will be prese...

Human Molecular Genetics, 2015

Mutations in VPS35 (PARK17) cause autosomal dominant, late onset Parkinson&am... more Mutations in VPS35 (PARK17) cause autosomal dominant, late onset Parkinson's disease (PD). VPS35 forms a core component of the retromer complex that mediates the retrieval of membrane proteins from endosomes back to either the Golgi or plasma membrane. While aberrant endosomal protein sorting has been linked to several neurodegenerative diseases, the mechanisms by which VPS35 mutations and retromer function contribute to PD pathogenesis are not clear. To address this, we generated transgenic Drosophila that express variant forms of human VPS35 found in PD cases and the corresponding variants of the Drosophila ortholog. We did not find evidence of dominant toxicity from any variant form including the pathogenic D620N mutation, even with aging. However, assessing the ability of Vps35 variants to rescue multiple vps35-mutant phenotypes, we found that the D620N mutation confers a partial loss of function. Recently, VPS35 has been linked to the formation of mitochondria-derived vesicles, which mediate the degradation of mitochondrial proteins and contribute to mitochondrial quality control. This process is also promoted by two other PD-lined genes parkin (PARK2) and PINK1 (PARK6). We demonstrate here that vps35 genetically interacts with parkin but interestingly not with pink1. Strikingly, Vps35 overexpression is able to rescue several parkin-mutant phenotypes. Together these findings provide in vivo evidence that the D620N mutation likely confers pathogenicity through a partial loss of function mechanism and that this may be linked to other known pathogenic mechanisms such as mitochondrial dysfunction.

2015 Second International Conference on Advances in Computing and Communication Engineering, 2015

... 5. Report Date September 30, 2009 6. Performing Organization Code 7. Author(s) Richard W. Lyl... more ... 5. Report Date September 30, 2009 6. Performing Organization Code 7. Author(s) Richard W. Lyles, PhD, PE, Bilal Z. Malik, Amna Chaudhry, Ghassan Abu-Lebdeh, PhD, PE, M. Abrar Siddiqui 8. Performing Org. Report No. ...

Assessment of perceived gaps in transportation service from various perspectives is critical for ... more Assessment of perceived gaps in transportation service from various perspectives is critical for service providers in developing strategies for improved performance. A methodology is proposed for: assessment of the perceived gaps in transportation services from the consumers' ...

JPMA. The Journal of the Pakistan Medical Association, 2016

To evaluate the accuracy of intra-operative frozen section in the diagnosis of various pelvic neo... more To evaluate the accuracy of intra-operative frozen section in the diagnosis of various pelvic neoplasms, including ovarian tumours. The retrospective study was conducted at Shifa International Hospital and comprised records of all patients with lesions of female genital tract who underwent frozen section between January 2010 and December 2012. Comparison was made with the final diagnosis after histopathology was performed on examining permanent paraffin sections. The mean age of the 54 patients was 43.70+/-14.8 years (range: 19-75 years). The frozen section was accurate in 51(92.6%) cases. It had a moderately high sensitivity of 75%, high specificity of 97.6%, high positive predictive value of 90% and high negative predictive value of 93.2%. Lack of agreement was found in cases of ovarian tumours of the mucinous and borderline variety. Frozen section showed a considerable level of accuracy when dealing with suspected pelvic neoplasms.

Renal Failure, 2014

Phenazopyridine is a urinary analgesic; commonly seen side-effects of this drug include, orange d... more Phenazopyridine is a urinary analgesic; commonly seen side-effects of this drug include, orange discoloration of urine, methemoglobinemia, yellowish skin discoloration, hepatitis and acute renal failure. Various case reports with phenazopyridine associated acute renal failure secondary to acute tubular necrosis have been reported in the literature. Acute kidney injury in these patients is caused by either direct injury to renal tubular epithelial cells or secondary to pigment induced nephropathy from hemolytic anemia. Hypoxic injury from phenazopyridine-induced methemoglobinemia has been well documented. We report a case of biopsy proven acute interstitial nephritis, associated with therapeutic doses of phenazopyridine without any evidence of methemoglobinemia or other mechanism of renal injury. Clinicians should be aware of the toxicity of this commonly used drug and should look closely for signs of renal insufficiency. Identifying and stopping the offending medication stays as the first step, but recent studies indicate that early steroid administration improves renal recovery, as well as decreasing the risk of progression to chronic kidney disease with fibrosis and consequent permanent renal damage.

Japanese Journal of Ophthalmology, 2011

Journal of Neurogenetics, 2010

The American Heart Hospital Journal, 2011

Coronary perforation during percutaneous coronary intervention is a rare but dreaded complication... more Coronary perforation during percutaneous coronary intervention is a rare but dreaded complication. The risk factors, optimal management, and outcome remain obscure. To determine the predisposing factors, optimal management, and preventive strategies. We retrospectively looked at coronary perforations at our catheterization laboratory over the last 10 years. We reviewed patient charts and reports. Two independent operators, in a blinded approach, reviewed all procedural cineangiograms. Data were analyzed by simple statistical methodology. Nine patients were treated conservatively and six patients were treated with prolonged balloon inflation. Six patients were treated with polytetrafluoroethylene (PTFE)-covered stents. One patient required emergency coronary artery bypass graft. No deaths were reported. Subjects with perforations also had a significantly higher total white blood cell count (means 12,134 versus 6,155, 95 % confidence interval [CI], p< 0.0001, n=22), total absolute neutrophil count (means 74.2 % versus 57.1 %, 95 % CI, p<0.0001, n=22), and neutrophil:lymphocyte ratio (means 3.65 versus 1.50, 95% CI, p<0.0001, n=22). Coronary perforations are rare but potentially fatal events. Hypertension, small vessel diameter, high balloon:artery ratio, use of hydrophilic wires, and presence of myocardial bridging appear to be possible risk factors. Most perforations can be treated conservatively or with prolonged balloon inflation using perfusion balloons. Use of PTFE-covered stents could be a life-saving measure in cases of large perforations. Subjects with perforations also had greater systemic inflammation as indicated by elevated white cell counts.

Brain a Journal of Neurology, Jun 4, 2014

Journal of molecular neuroscience : MN, Jan 17, 2015

Spinal and bulbar muscular atrophy (SBMA) is a late-onset neuromuscular disease caused by a polyg... more Spinal and bulbar muscular atrophy (SBMA) is a late-onset neuromuscular disease caused by a polyglutamine expansion in the androgen receptor gene which results in progressive spinal and bulbar motor neuron degeneration, resulting in muscle atrophy and weakness. Although the causative genetic defect is known, until recently, the molecular pathogenesis of the disease was unclear, resulting in few, if any, targets for therapy development. As a result, there is currently no effective treatment for SBMA. However, over the past decade, our understanding of the pathomechanisms that play a role in SBMA has increased dramatically, and several of these pathways and mechanisms have now been investigated as possible therapeutic targets. In this review, we discuss some of the key pathomechanisms implicated in SBMA and describe some of the therapeutic strategies that have been tested in SBMA to date, which fall into four main categories: (i) gene silencing; (ii) protein quality control and/or inc...

Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 2015

Several imaging techniques have been advocated as clinical adjuncts to improve identification of ... more Several imaging techniques have been advocated as clinical adjuncts to improve identification of suspicious oral lesions. However, these have not yet shown superior sensitivity or specificity over conventional oral examination techniques. We developed a multimodal, multi-scale optical imaging system that combines macroscopic biochemical imaging of fluorescence lifetime imaging with subcellular morphologic imaging of reflectance confocal microscopy for early detection of oral cancer. We tested our system on excised human oral tissues. In total, 4 tissue specimens were imaged. These specimens were diagnosed as either clinically normal, oral lichen planus, gingival hyperplasia, or superficially invasive squamous cell carcinoma. The optical and fluorescence lifetime properties of each specimen were recorded. Both quantitative and qualitative differences among normal, benign, and squamous cell carcinoma lesions can be resolved with fluorescence lifetime imaging reflectance confocal microscopy. The results demonstrate that an integrated approach based on these two methods can potentially enable rapid screening and evaluation of large areas of oral epithelial tissue. Early results from ongoing studies of imaging human oral cavity illustrate the synergistic combination of the 2 modalities. An adjunct device based on such optical characterization of oral mucosa can potentially be used to detect oral carcinogenesis in early stages.

The Journal of invasive cardiology

Spontaneous coronary artery dissection as a cause of acute myocardial ischemia is a rare entity t... more Spontaneous coronary artery dissection as a cause of acute myocardial ischemia is a rare entity that has been associated with several different clinical profiles and precipitating events. The recognition of this entity as the cause of acute ischemia is important because the therapeutic considerations may be different than that for ischemia due to a ruptured atherosclerotic plaque. We report a case of spontaneous coronary artery dissection in a 31-year-old female that was induced by prolonged, forceful retching. To our knowledge, this is the first reported case of such an association. Prolonged retching should be added to the list of causes of spontaneous coronary artery dissection.

PloS one, 2015

Automatic segmentation of nuclei in reflectance confocal microscopy images is critical for visual... more Automatic segmentation of nuclei in reflectance confocal microscopy images is critical for visualization and rapid quantification of nuclear-to-cytoplasmic ratio, a useful indicator of epithelial precancer. Reflectance confocal microscopy can provide three-dimensional imaging of epithelial tissue in vivo with sub-cellular resolution. Changes in nuclear density or nuclear-to-cytoplasmic ratio as a function of depth obtained from confocal images can be used to determine the presence or stage of epithelial cancers. However, low nuclear to background contrast, low resolution at greater imaging depths, and significant variation in reflectance signal of nuclei complicate segmentation required for quantification of nuclear-to-cytoplasmic ratio. Here, we present an automated segmentation method to segment nuclei in reflectance confocal images using a pulse coupled neural network algorithm, specifically a spiking cortical model, and an artificial neural network classifier. The segmentation a...

Proper treatment of diabetes includes maintenance of near normal blood glucose levels, which can ... more Proper treatment of diabetes includes maintenance of near normal blood glucose levels, which can only be achieved with frequent blood glucose monitoring. Current blood finger-stick methods for glucose sensing are invasive, often resulting in low patient compliance and poor disease control. The development of a noninvasive glucose sensor has the potential to provide optimal management of diabetes. Our proposed noninvasive approach is based on an optical polarimetry system for probing the anterior chamber of the eye. The sensor would eventually be used to measure the aqueous humor glucose concentration as a means to determine the blood glucose concentration. In this report, we present the development of a near real-time (less than 1 second) dual wavelength closed-loop polarimetric system to minimize glucose prediction error in the presence of varying birefringence due to motion artifact. The new dual wavelength polarimetric system and in vitro glucose measurement results will be prese...