Publications by authors named "Mohsin Maqbool"

7 Publications

  • Page 1 of 1

Cisplatin-Mediated Upregulation of APE2 Binding to MYH9 Provokes Mitochondrial Fragmentation and Acute Kidney Injury.

Cancer Res 2021 Feb 7;81(3):713-723. Epub 2020 Dec 7.

Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.

Cisplatin chemotherapy is standard care for many cancers but is toxic to the kidneys. How this toxicity occurs is uncertain. In this study, we identified apurinic/apyrimidinic endonuclease 2 (APE2) as a critical molecule upregulated in the proximal tubule cells (PTC) following cisplatin-induced nuclear DNA and mitochondrial DNA damage in cisplatin-treated C57B6J mice. The APE2 transgenic mouse phenotype recapitulated the pathophysiological features of C-AKI (acute kidney injury, AKI) in the absence of cisplatin treatment. APE2 pulldown-MS analysis revealed that APE2 binds myosin heavy-Chain 9 (MYH9) protein in mitochondria after cisplatin treatment. Human MYH9-related disorder is caused by mutations in MYH9 that eventually lead to nephritis, macrothrombocytopenia, and deafness, a constellation of symptoms similar to the toxicity profile of cisplatin. Moreover, cisplatin-induced C-AKI was attenuated in APE2-knockout mice. Taken together, these findings suggest that cisplatin promotes AKI development by upregulating APE2, which leads to subsequent MYH9 dysfunction in PTC mitochondria due to an unrelated role of APE2 in DNA damage repair. This postulated mechanism and the availability of an engineered transgenic mouse model based on the mechanism of C-AKI provides an opportunity to identify novel targets for prophylactic treatment of this serious disease. SIGNIFICANCE: These results reveal and highlight an unexpected role of APE2 via its interaction with MYH9 and suggest that APE2 has the potential to prevent acute kidney injury in patients with cisplatin-treated cancer. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/81/3/713/F1.large.jpg.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-1010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7869671PMC
February 2021

Deep cerebral vein expansion with metabolic and neurocognitive recovery in Sturge-Weber syndrome.

Ann Clin Transl Neurol 2018 Apr 12;5(4):502-506. Epub 2018 Mar 12.

Departments of Pediatrics and Neurology Wayne State University School of Medicine Children's Hospital of Michigan Detroit Medical Center Detroit Michigan.

We present longitudinal imaging data of a child with Sturge-Weber syndrome (SWS). At age 8 months, 3 weeks after initial seizures and prolonged motor deficit, MRI showed extensive right hemispheric SWS involvement with severe glucose hypometabolism on PET. She was treated with levetiracetam and aspirin. Follow-up imaging at age 29 months showed a robust interval expansion of enlarged deep medullary veins throughout the affected hemisphere along with a dramatic recovery of hemispheric metabolism and normalized neurocognitive functioning. These findings demonstrate a robust, multilobar hemispheric remodeling of deep venous collaterals that likely contributed to reversal of initial metabolic and neurocognitive deficits.
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http://dx.doi.org/10.1002/acn3.546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5899918PMC
April 2018

Brainstem disconnection in a patient with fetal alcohol syndrome.

Pediatr Neurol 2014 Aug 1;51(2):282-3. Epub 2014 Apr 1.

Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Detroit, Michigan; Department of Neurology, Children's Hospital of Michigan, Detroit, Michigan.

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http://dx.doi.org/10.1016/j.pediatrneurol.2014.03.026DOI Listing
August 2014

Novel FDG-PET findings in anti-NMDA receptor encephalitis: a case based report.

J Child Neurol 2011 Oct 19;26(10):1325-8. Epub 2011 May 19.

Department of Pediatrics and Neurology, Wayne State University School of Medicine, Detroit, Michigan, USA.

The clinical manifestation and nuclear imaging findings in a 15-year-old boy with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis are described in this case report. The previously healthy patient presented with new onset hallucinations, seizure, and within a week, his mental status rapidly deteriorated to nonverbal with oro-lingual-facial dyskinesias. An extensive laboratory work-up for encephalopathy was negative. Repeated brain magnetic resonance imaging (MRI) studies were normal. On day 26 of admission, nuclear imaging using fluorodeoxyglucose positron emission tomography (FDG-PET) showed global hypometobolism with a prominent focally intense hypermetabolic lesion in the right cerebellar cortex. Diagnosis of anti-NMDAR encephalitis was confirmed with quantitative serology. The patient showed clinical signs of improvement after 2 courses of intravenous immunoglobulin therapy over 4 weeks. On day 46, repeat brain FDG-PET showed overall improvement but in contrast to the previous, the right cerebellar cortex showed focal hypometabolism. This is the first reported case of such findings using FDG-PET in anti-NMDAR encephalitis.
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http://dx.doi.org/10.1177/0883073811405199DOI Listing
October 2011

The corticospinal tract in Sturge-Weber syndrome: a diffusion tensor tractography study.

Brain Dev 2008 Aug 4;30(7):447-53. Epub 2008 Mar 4.

Carman and Ann Adams Department of Pediatrics, Division of Pediatric Neurology, Children's Hospital of Michigan, Wayne State University, 3901 Beaubien Boulevard, Detroit, MI 48201, USA.

Objective: To utilize diffusion tensor tractography and evaluate the integrity of the corticospinal tract in children with unilateral Sturge-Weber syndrome (SWS).

Methods: Sixteen children (age: 1.5-12.3 years) with SWS involving one hemisphere and varying degrees of motor deficit, underwent magnetic resonance imaging (MRI) as part of a prospective clinical research study. Diffusion tensor imaging (DTI) was obtained and fiber tracking of the corticospinal tract was performed yielding average FA and ADC values along the pathway. These values were compared between the two hemispheres (affected vs. unaffected) and also correlated with the degree of motor deficits, after correction for age.

Results: Corticospinal tract FA values on the side of the affected hemisphere were lower (p=0.008) and ADC values were higher (p=0.011) compared to the normal side. Furthermore, FA and ADC values on the side of the angioma did not show the normal age-related variations, which the contralateral corticospinal pathway values did demonstrate. Although none of the patients had severe hemiparesis, those with moderate motor deficit had increased ADC values, as compared to those with mild (p=0.009) or no motor deficit (p=0.045).

Conclusion: MRI with DTI shows abnormalities of the corticospinal tract in children with SWS even before severe motor impairment develops. Thus, DTI can be a clinically useful method to evaluate the integrity of the corticospinal tract in young children who are at risk for progressive motor dysfunction.
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http://dx.doi.org/10.1016/j.braindev.2007.12.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2712285PMC
August 2008

Abnormal brain tryptophan metabolism and clinical correlates in Tourette syndrome.

Mov Disord 2007 Nov;22(15):2256-62

Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Wayne State University School of Medicine, Detroit, Michigan 48201, USA.

Symptoms in Tourette syndrome (TS) are likely related to abnormalities involving multiple neurotransmitter systems in striatal-thalamo-cortical circuitry. Although prior studies have found abnormal levels of tryptophan, serotonin, and their metabolites in blood, cerebrospinal fluid and brain tissue of TS patients, understanding of focal brain disturbances and their relationship to clinical phenotype remains poor. We used alpha-[(11)C]methyl-L-tryptophan (AMT) positron emission tomography (PET) to assess global and focal brain abnormalities of tryptophan metabolism and their relationship to behavioral phenotype in 26 children with TS and nine controls. Group comparisons on regional cortical and subcortical AMT uptake revealed decreased AMT uptake in bilateral dorsolateral prefrontal cortical and bilaterally increased uptake in the thalamus (P = 0.001) in TS children. The ratio of AMT uptake in subcortical structures to dorsolateral prefrontal cortex was significantly increased bilaterally (P < 0.01) in TS patients also. Behaviorally defined subgroups within the TS sample revealed differences in the pattern of AMT uptake in the fronto-striatal-thalamic circuit. This study demonstrates cortical and subcortical abnormalities of tryptophan metabolism in TS and provides neuroimaging evidence for a role of serotonergic mechanisms in the pathophysiology of TS.
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http://dx.doi.org/10.1002/mds.21712DOI Listing
November 2007

Abnormal brain connectivity in children after early severe socioemotional deprivation: a diffusion tensor imaging study.

Pediatrics 2006 Jun;117(6):2093-100

Carman and Ann Adams Department of Pediatrics, Children's Hospital of Michigan, Wayne State University, Detroit, Michigan, USA.

Objectives: We previously reported that children who were subjected to early socioemotional deprivation in Romanian orphanages showed glucose hypometabolism in limbic and paralimbic structures, including the orbital frontal gyrus, infralimbic prefrontal cortex, hippocampus/amygdala, lateral temporal cortex, and the brainstem. The present study used diffusion tensor imaging tractography to examine the integrity of white matter tracts that connect these brain regions.

Methods: Fractional anisotropy and apparent diffusion coefficient for uncinate fasciculus, stria terminalis, fornix, and cingulum were measured in 7 right-handed children (5 girls and 2 boys; mean age: 9.7 +/- 2.6 years) with a history of early severe socioemotional deprivation in Eastern European orphanages and compared with similar measurements in 7 right-handed normal children (4 girls and 3 boys; mean age: 10.7 +/- 2.8 years).

Results: Neuropsychological assessment of the orphans verified the relatively mild specific cognitive impairment and impulsivity consistent with previous studies of children who were adopted from Romanian orphanages. Fractional anisotropy values in the left uncinate fasciculus were decreased significantly in the early deprivation group compared with control subjects. Apparent diffusion coefficient values for the early deprivation group tended to be greater than that in control subjects in all of the tracts measured, without reaching statistical significance.

Conclusion: Our study demonstrates in children who experienced socioemotional deprivation a structural change in the left uncinate fasciculus that partly may underlie the cognitive, socioemotional, and behavioral difficulties that commonly are observed in these children.
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http://dx.doi.org/10.1542/peds.2005-1727DOI Listing
June 2006