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1.
Med J Armed Forces India ; 79(Suppl 1): S189-S195, 2023 Dec.
Article in English | MEDLINE | ID: mdl-38144611

ABSTRACT

Background: Power Doppler ultrasound (PDUS) is an established non-invasive modalities for quantification of inflammation, which has a bearing on the assessment of disease activity in rheumatoid arthritis (RA). However, PDUS has several disadvantages including cost of equipment, steep learning curve and inter-observer variability. Thermal imaging has emerged as a simple, powerful tool for mapping the heat distribution pattern and has the potential to document and quantify disease activity in RA. The objective was to study the thermal imaging pattern of inflamed knee joints in cases of RA and its correlation with PDUS. Methods: This pilot case-control study was carried out at the rheumatology centre in India including 100 subjects (50 controls and 50 RA patients). All participants underwent thermal imaging and PDUS for the knee joints. The mean temperatures in area of interest in knee, thigh and knee-thigh differential were analysed in comparison with PDUS findings. Results: RA subjects had significantly higher mean knee temperature and mean knee-thigh temperature differential compared with controls (p value < 0.00001). PDUS documented inflammation strongly correlated with knee-thigh temperature differential. Conclusion: There was a statistically significant difference in mean knee temperature as well as mean knee-thigh temperature differential of inflamed versus control knees. Thermal imaging has the potential to become simple, objective, cost-effective and reliable tool for diagnosis and assessment of disease activity in inflammatory arthritis.

2.
J Assoc Physicians India ; 70(4): 11-12, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35443434

ABSTRACT

Antiphospholipid anti body syndrome is an autoimmune disorder characterized by arterial or venous thrombosis and/or pregnancy morbidity with foetal deaths or abortions in the presence of antiphospholipid antibodies. Catastrophic antiphospholipid antibody syndrome (CAPS) is an accelerated form of disease with rapid involvement of multiple organ systems often posing a diagnostic challenge. There is a paucity of literature on the presentations of CAPS owing to the orphan nature of the disease. MATERIAL: We present three cases of CAPS in patients with systemic lupus erythematosus (SLE). OBSERVATION: Case 1 - A 22-year-old lady with SLE presented with anasarca, abnormal mentation, anaemia, thrombocytopenia, ANA (IIF) 4+ speckled, positive lupus anticoagulant with pulmonary thromboembolism involving right middle and left lower lobes. While in hospital, she developed infarct in left middle cerebral artery territory; was managed with IVIg, anticoagulation, pulse methylprednisolone and cyclophosphamide. She had a refractory course with cytokine storm syndrome, neutropenic sepsis and eventually succumbed to her illness. Case 2 - A 23-year-old lady presented with a history of oral ulcers, alopecia, photosensitive malar rash, polyarthritis of small joints of hands, Raynaud's phenomenon, intermittent fever with headache and arterial thrombosis resulting in gangrene of the right thumb. She had ANA (IIF) 3+ speckled, raised anti-ds-DNA, positive for lupus anticoagulant; was managed as SLE with hydroxychloroquine and prednisolone. She returned to hospital with generalized tonic-clonic seizures, papilledema but no focal neurological deficit. MRI brain showed superior sagittal sinus thrombosis; was managed with pulse methylprednisolone, anti-coagulation, anti-epileptic drugs, cyclophosphamide and hydroxychloroquine; patient survived. Case 3 - A 47- year-old lady with SLE and Lupus Nephritis Class IV on Euro-Lupus regime presented with paraparesis, cold and clammy left lower limb with absent femoral, popliteal, anterior tibial and dorsalis pedis pulses. CT angiography showed thrombosis infra-renal abdominal aorta and in the left popliteal artery; was positive for high titre ß2-GPI IgM. She was managed with pulse methylprednisolone, anti-coagulation, broad-spectrum antibiotics but developed sudden haemodynamic deterioration after the first cycle of plasmapheresis and was switched to IVIg. However, she developed cardiac arrest and succumbed before MR angiography for suspected anterior spinal artery thrombosis and amputation for left lower limb. CONCLUSION: In our cases, timely diagnoses were made based on a high index of suspicion and were managed with a combination of IVIg, systemic glucocorticoids, plasmapheresis and other supportive measures. However, despite providing the standard of care, we encountered poor outcome in two patients, highlighting the high mortality associated with CAPS.


Subject(s)
Antiphospholipid Syndrome , Lupus Erythematosus, Systemic , Thrombosis , Adult , Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis , Cyclophosphamide , Female , Humans , Hydroxychloroquine , Immunoglobulins, Intravenous , Lupus Coagulation Inhibitor , Lupus Erythematosus, Systemic/complications , Lupus Erythematosus, Systemic/diagnosis , Methylprednisolone , Middle Aged , Pregnancy , Thrombosis/complications , Young Adult
3.
Med J Armed Forces India ; 78(1): 54-60, 2022 Jan.
Article in English | MEDLINE | ID: mdl-35035044

ABSTRACT

BACKGROUND: Time and cost constraints lead to majority of clinical laboratories deviating away from an ideal practice of checking for antinuclear antibodies (ANAs) by indirect immunofluorescence (IIF) at multiple dilutions. Usage of screening dilution of 1:40 recommended by most manufacturers of commercial ANA kits results in numerous false positive-tests and misdiagnosis of connective tissue disorders (CTDs). We sought to study the ideal screening dilution for ANA by IIF for a diagnosis of ANA-related CTDs. METHODS: Serum samples of patients with ANA-related conditions (n = 233) and healthy controls (n = 154) were evaluated by IIF using Immuno Concepts Hep-2000 ® ANA kits at dilutions from 1:40 to 1:640. Accuracy for diagnosis of CTDs for each serum dilution was assessed by receiver operating curve (ROC) analysis. RESULTS: Antinuclear antibodies (ANA) positivity was observed in 19.5%, 10.4%, 4.55%, 0.65%, and 0% of healthy controls at dilutions of 1:40, 1:80, 1:160, 1:320, and 1:640, respectively. ANA positivity at 1:40 dilution was observed among 26.4% cases with mimics of CTDs. Prevalence of ANA positivity in ANA-related CTDs was 97.3%, 96.4%, 89.3%, 83.9%, and 71.4% at dilutions of 1:40, 1:80, 1:160, 1:320, and 1:640, respectively. ROC analysis revealed best test performance for distinction between healthy and ANA-related CTD populations at a serum dilution of 1 in 80. CONCLUSIONS: Antinuclear antibodies (ANA) positivity at low titers (1:40) is highly prevalent in healthy population (19.5%) as well as amongst mimics of CTD (26.4%). Our study suggests a higher screening dilution of 1:80 for ANA by IIF for diagnosis of CTD maybe better. Combination of 1:80 and 1:160 dilutions provides optimum sensitivity and specificity for diagnosis of ANA-related disorders.

5.
ESMO Open ; 6(4): 100172, 2021 08.
Article in English | MEDLINE | ID: mdl-34242968

ABSTRACT

BACKGROUND: More than 80% of anaplastic lymphoma kinase (ALK)-positive anaplastic large cell lymphoma (ALCL) patients harbor the (nucleophosmin) NPM1-ALK fusion gene t(2;5) chromosomal translocation. We evaluated the preclinical and clinical efficacy of ceritinib treatment of this aggressive lymphoma. MATERIALS AND METHODS: We studied the effects of ceritinib treatment in NPM1-ALK+ T-cell lymphoma cell lines in vitro and on tumor size and survival advantage in vivo utilizing tumor xenografts. We treated an NPM1-ALK+ ALCL patient with ceritinib. We reviewed all hematologic malignancies profiled by a large hybrid-capture next-generation sequencing (NGS)-based comprehensive genomic profiling assay for ALK alterations. RESULTS: In our in vitro experiments, ceritinib inhibited constitutive activation of the fusion kinase NPM1-ALK and downstream effector molecules STAT3, AKT, and ERK1/2, and induced apoptosis of these lymphoma cell lines. Cell cycle analysis following ceritinib treatment showed G0/G1 arrest with a concomitant decrease in the percentage of cells in S and G2/M phases. Further, treatment with ceritinib in the NPM1-ALK+ ALCL xenograft model resulted in tumor regression and improved survival. Of 19 272 patients with hematopoietic diseases sequenced, 58 patients (0.30%) harbored ALK fusions that include histiocytic disorders, multiple myeloma, B-cell neoplasms, Castleman's disease, and juvenile xanthogranuloma. A multiple relapsed NPM1-ALK+ ALCL patient treated with ceritinib achieved complete remission with ongoing clinical benefit to date, 5 years after initiation of therapy. CONCLUSIONS: This ceritinib translational study in NPM1-ALK+ ALCL provides a strong rationale for a prospective study of ceritinib in ALK+ T-cell lymphomas and other ALK+ hematologic malignancies.


Subject(s)
Lymphoma, Large-Cell, Anaplastic , Anaplastic Lymphoma Kinase/genetics , Humans , Lymphoma, Large-Cell, Anaplastic/drug therapy , Lymphoma, Large-Cell, Anaplastic/genetics , Nucleophosmin , Prospective Studies , Pyrimidines , Receptor Protein-Tyrosine Kinases/genetics , Sulfones
6.
Dalton Trans ; 48(33): 12684-12698, 2019 Sep 07.
Article in English | MEDLINE | ID: mdl-31384875

ABSTRACT

Producing pure H2 and O2 to sustain the renewable energy sources with minimal environmental damage is a key objective of photo/electrochemical water-splitting research. Metallic Ni-based electrocatalysts are expensive and eco-hazardous. This has rendered the replacement or reduction of Ni content in Ni-based electrocatalysts a decisive criterion in the development of bifunctional electrocatalytic materials. In the current study, spinel/ilmenite composite nickel titanate (NTO) nanofibers were synthesised using sol-gel assisted electrospinning followed by pyrolysis at different soaking temperatures (viz., 773, 973, and 1173 K). The presence of a defective spinel NTO phase (SNTO) distributed uniformly along the nanofibers was confirmed by X-ray photoelectron and Raman spectroscopy. The electron micrographs revealed the morphological change of NTO nanofibers from a mosaic to bamboo structure with an increase in pyrolysis soaking temperature. The electrocatalytic activity of NTO nanofibers obtained at different pyrolysis soaking temperatures for alkaline water-splitting was studied. The highly defective SNTO manifests properties similar to metallic Ni and favours H2 evolution through the hydrogen evolution reaction (HER) by adsorbing more H+ ions on active sites. In contrast, the ilmenite NTO favours O2 discharge. These results are explained based on the morphology of the NTO nanofibers. The mosaic structure which has higher porosity and greater SNTO content shows excellent HER performance. In contrast, the large bamboo structured NTO nanofibers which have lesser porosity and SNTO content cage the bigger (OH)ads ions at their catalytic sites to facilitate OER performance.

7.
Sci Rep ; 9(1): 2749, 2019 02 26.
Article in English | MEDLINE | ID: mdl-30808902

ABSTRACT

Despite advances in biology and treatment modalities, the prognosis of glioblastoma (GBM) remains poor. Serum reflects disease macroenvironment and thus provides a less invasive means to diagnose and monitor a diseased condition. By employing 4-plex iTRAQ methodology, we identified 40 proteins with differential abundance in GBM sera. The high abundance of serum S100A8/S100A9 was verified by multiple reaction monitoring (MRM). ELISA and MRM-based quantitation showed a significant positive correlation. Further, an integrated investigation using stromal, tumor purity and cell type scores demonstrated an enrichment of myeloid cell lineage in the GBM tumor microenvironment. Transcript levels of S100A8/S100A9 were found to be independent poor prognostic indicators in GBM. Medium levels of pre-operative and three-month post-operative follow-up serum S100A8 levels predicted poor prognosis in GBM patients who lived beyond median survival. In vitro experiments showed that recombinant S100A8/S100A9 proteins promoted integrin signalling dependent glioma cell migration and invasion up to a threshold level of concentrations. Thus, we have discovered GBM serum marker by iTRAQ and verified by MRM. We also demonstrate interplay between tumor micro and macroenvironment and identified S100A8 as a potential marker with diagnostic and prognostic value in GBM.


Subject(s)
Biomarkers, Tumor/blood , Calgranulin A/blood , Calgranulin B/blood , Glioblastoma/pathology , Mass Spectrometry/methods , Tumor Microenvironment , Apoptosis , Case-Control Studies , Cell Movement , Cell Proliferation , Follow-Up Studies , Glioblastoma/blood , Humans , Prognosis , Prospective Studies , Survival Rate , Tumor Cells, Cultured
8.
J Craniovertebr Junction Spine ; 9(3): 209-211, 2018.
Article in English | MEDLINE | ID: mdl-30443143

ABSTRACT

Cervical granulomatous infections of the posterior elements are very rare, it is often difficult to diagnose due to rarity and variable presentation of symptoms. Any cervical surgical procedure carries a certain morbid risk to the patient. We present a case of cervical 2-3 facet joint lesion which was managed by a minimally invasive technique with a favorable outcome.

9.
Australas Phys Eng Sci Med ; 41(4): 1047-1055, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30338494

ABSTRACT

A long-term multichannel electroencephalogram recording plays a crucial role in recognizing the epileptic seizure activities from the brain lobes. This research study investigates the automated detection of epileptic seizures from multichannel electroencephalogram recordings using Teager energy feature. A supervised back-propagation neural network model was implemented to classify the inter-ictal seizures. The study was conducted on multichannel electroencephalogram data that was obtained from Institute of Neuroscience, Ramaiah Memorial Hospital, Bengaluru, India, after ethical clearance from the from the Institutional Ethics Board. Initially, notch filter was applied to remove the 50 Hz power line noise from raw electroencephalogram followed by independent component analysis to remove eye blinks and muscular activities. A time domain feature called Teager energy was estimated which detects the rapid changes in the given electroencephalogram time series. A 1 s windowing was introduced to ensure stationarity for estimation of Teager energy. The descriptive and box plot analysis ensures the suitability of the Teager energy for the seizure detection. The performance of the multilayer perceptron neural network classifier was evaluated using sensitivity, specificity, and false detection rate. Simulation results showed the highest sensitivity, specificity and false detection rate of 96.66%, 99.15%, and 0.30 per hour respectively. It can be concluded that procedure can be applied for real-time seizure detection.


Subject(s)
Electroencephalography/methods , Seizures/diagnosis , Signal Processing, Computer-Assisted , Algorithms , Humans , Neural Networks, Computer , Sensitivity and Specificity
10.
Brain Inform ; 5(2): 10, 2018 Sep 03.
Article in English | MEDLINE | ID: mdl-30175391

ABSTRACT

Detection of epileptic seizure activities from long-term multi-channel electroencephalogram (EEG) signals plays a significant role in the timely treatment of the patients with epilepsy. Visual identification of epileptic seizure in long-term EEG is cumbersome and tedious for neurologists, which might also lead to human error. Therefore, an automated tool for accurate detection of seizures in a long-term multi-channel EEG is essential for the clinical diagnosis. This study proposes an algorithm using multi-features and multilayer perceptron neural network (MLPNN) classifier. After appropriate approval from the ethical committee, recordings of EEG data were collected from the Institute of Neurosciences, Ramaiah Memorial College and Hospital, Bengaluru. Initially, preprocessing was performed to remove the power-line noise and motion artifacts. Four features, namely power spectral density (Yule-Walker), entropy (Shannon and Renyi), and Teager energy, were extracted. The Wilcoxon rank-sum test and descriptive analysis ensure the suitability of the proposed features for pattern classification. Single and multi-features were fed to the MLPNN classifier to evaluate the performance of the study. The simulation results showed sensitivity, specificity, and false detection rate of 97.1%, 97.8%, and 1 h-1, respectively, using multi-features. Further, the results indicate the proposed study is suitable for real-time seizure recognition from multi-channel EEG recording. The graphical user interface was developed in MATLAB to provide an automated biomarker for normal and epileptic EEG signals.

11.
Oncogene ; 37(4): 522-533, 2018 01 25.
Article in English | MEDLINE | ID: mdl-28991227

ABSTRACT

Despite advances in biology and therapeutic modalities, existence of highly tumorigenic glioma stem-like cells (GSCs) makes glioblastomas (GBMs) invincible. N6-methyl adenosine (m6A), one of the abundant mRNA modifications catalyzed by methyltransferase-like 3 and 14 (METTL3/14), influences various events in RNA metabolism. Here, we report the crucial role of METTL3-mediated m6A modification in GSC (neurosphere) maintenance and dedifferentiation of glioma cells. METTL3 expression is elevated in GSC and attenuated during differentiation. RNA immunoprecipitation studies identified SOX2 as a bonafide m6A target of METTL3 and the m6A modification of SOX2 mRNA by METTL3 enhanced its stability. The exogenous overexpression of 3'UTR-less SOX2 significantly alleviated the inhibition of neurosphere formation observed in METTL3 silenced GSCs. METTL3 binding and m6A modification in vivo required intact three METTL3/m6A sites present in the SOX2-3'UTR. Further, we found that the recruitment of Human antigen R (HuR) to m6A-modified RNA is essential for SOX2 mRNA stabilization by METTL3. In addition, we found a preferential binding by HuR to the m6A-modified transcripts globally. METTL3 silenced GSCs showed enhanced sensitivity to γ-irradiation and reduced DNA repair as evidenced from the accumulation of γ-H2AX. Exogenous overexpression of 3'UTR-less SOX2 in METTL3 silenced GSCs showed efficient DNA repair and also resulted in the significant rescue of neurosphere formation from METTL3 silencing induced radiosensitivity. Silencing METTL3 inhibited RasV12 mediated transformation of mouse immortalized astrocytes. GBM tumors have elevated levels of METTL3 transcripts and silencing METTL3 in U87/TIC inhibited tumor growth in an intracranial orthotopic mouse model with prolonged mice survival. METTL3 transcript levels predicted poor survival in GBMs which are enriched for GSC-specific signature. Thus our study reports the importance of m6A modification in GSCs and uncovers METTL3 as a potential molecular target in GBM therapy.


Subject(s)
Brain Neoplasms/genetics , Glioblastoma/genetics , Methyltransferases/metabolism , Neoplastic Stem Cells/pathology , SOXB1 Transcription Factors/genetics , 3' Untranslated Regions/genetics , Adenosine/analogs & derivatives , Adenosine/metabolism , Animals , Brain/cytology , Brain/pathology , Brain/surgery , Brain Neoplasms/pathology , Brain Neoplasms/radiotherapy , Brain Neoplasms/surgery , Carcinogenesis/genetics , Cell Dedifferentiation/genetics , Cell Dedifferentiation/radiation effects , Cell Line, Tumor , Cell Proliferation/genetics , DNA Repair/radiation effects , ELAV-Like Protein 1/metabolism , Female , Gene Expression Regulation, Neoplastic , Glioblastoma/pathology , Glioblastoma/radiotherapy , Glioblastoma/surgery , Humans , Methyltransferases/genetics , Mice , Mice, Nude , Mutagenesis, Site-Directed , Neoplastic Stem Cells/radiation effects , RNA, Messenger/metabolism , Radiation Tolerance/genetics , SOXB1 Transcription Factors/metabolism , Spheroids, Cellular/radiation effects , Xenograft Model Antitumor Assays
12.
Bone Marrow Transplant ; 53(1): 3-10, 2018 01.
Article in English | MEDLINE | ID: mdl-29084201

ABSTRACT

Hematopoietic stem cell transplantation (HSCT) represents a curative option for those afflicted with numerous hematologic malignancies and bone marrow failure syndromes. Advances and refinement of the HSCT process have resulted in increasing number of transplants performed on older patients in the recent years. Pre-transplant assessments (PTA) function to risk stratify patients prior to undergoing HSCT in an effort to predict those at higher risk of treatment-related toxicity, to inform risk/benefit assessments and to aid clinical decision making. Traditionally used risk stratification parameters such as chronologic age, comorbidity and performance status may not fully capture physical function, physiologic fitness, highlighting a need for improvement in PTA. Incorporation of frailty measurements in pre-HSCT assessments, particularly in elderly transplant candidates, may result in improving predictive ability of existing tools such as the Hematopoietic Cell Transplantation Comorbidity Index and Karnofsky performance status. Here, we review existing pre-HSCT assessment tools, measures of frailty that may aid in risk stratification for patients undergoing HSCT and directions for future research using frailty in the pre-HSCT setting.


Subject(s)
Hematopoietic Stem Cell Transplantation/methods , Transplantation Conditioning/methods , Female , Frailty , Humans , Male
13.
J Clin Neurosci ; 42: 97-101, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28457859

ABSTRACT

OBJECTIVES: To find the correlation between radiologically proven improvement in cerebral hemodynamics with clinical improvement in patients undergoing cranioplasty. MATERIAL AND METHODS: The study is a prospective observational study of 10 cases, in M S Ramaiah Institute of Neurosciences, involving patients treated by a decompressive craniectomy for intractable intra cranial hypertension either due to trauma or stroke and afterwards underwent cranioplasty. RESULTS: Of the 10 patients, 70% patients showing significant improvement in motor functions on Barthel index scale, 60% patients showed improvement in speech, mean duration from date of decompressive craniectomy to cranioplasty being 122.4days. Cerebral perfusion was remarkably better after cranioplasty, as demonstrated decrease in the Pulsatility index on the ipsilateral side of decompression on Trans cranial Doppler (<0.73 mean). This data also favored improved cerebral blood flow and permeability on the CT perfusion with increase in cerebral blood flow (CBF), Cerebral Blood Volume (CBV) and decrease in Time to Peak (TTP) and a positive outcome when correlated with Barthel index with P-values of 0.093, 0.017 and 0.001 respectively. CONCLUSION: Cranioplasty influences the cerebral hemodynamics after cranioplasty and has a positive correlation on the functional outcome and cerebral blood flow in the MCA territory.


Subject(s)
Bone Transplantation/adverse effects , Decompressive Craniectomy , Hemodynamics/physiology , Intracranial Hypertension/physiopathology , Intracranial Hypertension/surgery , Plastic Surgery Procedures/adverse effects , Skull/surgery , Cerebrovascular Circulation/physiology , Female , Humans , Intracranial Hypertension/diagnostic imaging , Male , Prospective Studies , Treatment Outcome
14.
Neurol India ; 65(1): 99-102, 2017.
Article in English | MEDLINE | ID: mdl-28084249

ABSTRACT

INTRODUCTION: Tourette's syndrome (TS) is a complex neuropsychiatric disorder characterized by the presence of multiple motor and vocal tics. Here, we report the case of a young man with severe TS refractory to multiple medications who underwent deep brain stimulation (DBS), which was successful in substantially ameliorating his tics. To our knowledge, this is the first such report from India and South Asia. CASE REPORT: An 18-year-old right-handed male patient was diagnosed with TS at the age of 10 years. He had facial and ocular tics. He was also hitting his fist against his chest and shouting obscenities. The manifestations would be present in every waking hour with a maximum tic free interval of 15-20 minutes. They would often result in self-injury or damage to objects. He would have frequent crying spells, anger outbursts, and death wishes. As tics became highly conspicuous and socially inappropriate, he dropped out of school and remained almost completely house-bound for the preceding year. On evaluation, he scored 96 (46 on tic-severity subscale and 50 on impairment subscale) of a maximum of 100 on the Yale Global Tic Severity Scale. (YGTSS). MANAGEMENT: After failure of multiple combinations of medicines, repetitive transcranial magnetic stimulation, and behavioural therapies, he successfully underwent DBS to bilateral anteromedial globus pallidus interna. CONCLUSION: Tic severity reduced substantially post-surgery, with the YGTSS score improving by more than 72%. These improvements were sustained on follow-up visits with the patient successfully returning to join college. To our knowledge, this is the first such report from India and South Asia.


Subject(s)
Deep Brain Stimulation/methods , Globus Pallidus , Tourette Syndrome/therapy , Adolescent , Globus Pallidus/surgery , Humans , Male , Tourette Syndrome/surgery
15.
Oncogene ; 36(1): 71-83, 2017 01 05.
Article in English | MEDLINE | ID: mdl-27212030

ABSTRACT

An integrative functional genomics study of multiple forms of data are vital for discovering molecular drivers of cancer development and progression. Here, we present an integrated genomic strategy utilizing DNA methylation and transcriptome profile data to discover epigenetically regulated genes implicated in cancer development and invasive progression. More specifically, this analysis identified fibromodulin (FMOD) as a glioblastoma (GBM) upregulated gene because of the loss of promoter methylation. Secreted FMOD promotes glioma cell migration through its ability to induce filamentous actin stress fiber formation. Treatment with cytochalasin D, an actin polymerization inhibitor, significantly reduced the FMOD-induced glioma cell migration. Small interfering RNA and small molecule inhibitor-based studies identified that FMOD-induced glioma cell migration is dependent on integrin-FAK-Src-Rho-ROCK signaling pathway. FMOD lacking C-terminus LRR11 domain (ΔFMOD), which does not bind collagen type I, failed to induce integrin and promote glioma cell migration. Further, FMOD-induced integrin activation and migration was abrogated by a 9-mer wild-type peptide from the FMOD C-terminus. However, the same peptide with mutation in two residues essential for FMOD interaction with collagen type I failed to compete with FMOD, thus signifying the importance of collagen type I-FMOD interaction in integrin activation. Chromatin immunoprecipitation-PCR experiments revealed that transforming growth factor beta-1 (TGF-ß1) regulates FMOD expression through epigenetic remodeling of FMOD promoter that involved demethylation and gain of active histone marks with a simultaneous loss of DNMT3A and EZH2 occupancy, but enrichment of Sma- and Mad-related protein-2 (SMAD2) and CBP. FMOD silencing inhibited the TGF-ß1-mediated glioma cell migration significantly. In univariate and multivariate Cox regression analysis, both FMOD promoter methylation and transcript levels predicted prognosis in GBM. Thus, this study identified several epigenetically regulated alterations responsible for cancer development and progression. Specifically, we found that secreted FMOD as an important regulator of glioma cell migration downstream of TGF-ß1 pathway and forms a potential basis for therapeutic intervention in GBM.


Subject(s)
Epigenesis, Genetic , Epigenomics , Fibromodulin/genetics , Gene Expression Regulation, Neoplastic , Genes, Essential , Glioma/genetics , Cell Line, Tumor , Cell Movement/drug effects , Chromatin Assembly and Disassembly , Collagen Type I/metabolism , Cytoskeleton/metabolism , DNA Methylation , Epigenomics/methods , Focal Adhesion Protein-Tyrosine Kinases/metabolism , Gene Expression Profiling , Genome-Wide Association Study , Glioma/metabolism , Glioma/mortality , Humans , Kaplan-Meier Estimate , Models, Biological , Prognosis , Promoter Regions, Genetic , Signal Transduction/drug effects , Transcription, Genetic , Transcriptome , Transforming Growth Factor beta1/metabolism , rho-Associated Kinases/metabolism , src-Family Kinases/metabolism
16.
Acta Neurochir (Wien) ; 158(10): 1973-5, 2016 10.
Article in English | MEDLINE | ID: mdl-27517688

ABSTRACT

Infarction in the artery of Percheron territory is a rare phenomenon in which occlusion of an unpaired perforating artery arising from the P1 segment on one side results in infarcts in the bilateral paramedian thalami with or without midbrain infarcts. We describe the case of a 40-year-old male who developed this complication following re-exploratory trans-sphenoidal surgery for a pituitary adenoma. In this first report of its kind in endoscopic pituitary surgery, the pathogenesis and clinico-radiological features of this rare vascular event are discussed.


Subject(s)
Arteries/pathology , Infarction/etiology , Natural Orifice Endoscopic Surgery/adverse effects , Neurosurgical Procedures/adverse effects , Pituitary Gland/surgery , Pituitary Neoplasms/surgery , Postoperative Complications/pathology , Thalamus/diagnostic imaging , Adult , Humans , Infarction/diagnostic imaging , Male , Thalamus/blood supply , Thalamus/pathology
17.
Clin Radiol ; 71(6): 602-9, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27038652

ABSTRACT

Lymphoma may arise within the central nervous system (CNS), known as primary CNS lymphoma (PCNSL) or may involve the CNS secondary to systemic disease. Clinical features are non-specific. A provisional diagnosis of PCNSL can be made on imaging, potentially changing the management algorithm from neurosurgical resection to biopsy. PCNSL in immunocompetent patients generally presents late, is solid, is bright on diffusion weighted imaging and shows uniform enhancement. Contiguity with a cerebrospinal fluid (CSF) surface and perivascular enhancement are useful clues. Immunocompromised patients, on the other hand, present earlier and often have multiple, necrotic, haemorrhagic lesions with irregular or rim enhancement. Secondary CNS involvement predominantly affects the leptomeninges. This review illustrates the varied imaging features of CNS lymphoma, atypical presentations, and differential diagnoses.


Subject(s)
Brain Neoplasms/diagnostic imaging , Brain Neoplasms/pathology , Lymphoma/diagnostic imaging , Lymphoma/pathology , Magnetic Resonance Imaging/methods , Tomography, X-Ray Computed/methods , Humans , Image Enhancement/methods
18.
J Clin Neurosci ; 26: 147-9, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26732285

ABSTRACT

Intracranial hemangiopericytomas are uncommon tumors, and their intraventricular occurrence is even rarer. We report a 40-year-old man who presented with raised intracranial pressure. His MRI showed a 3.3 × 3.2 × 3.2 cm heterogeneously enhancing lesion in the left frontal horn obstructing the foramen of Monro and causing hydrocephalus. The tumor was excised through an anterior interhemispheric, transcallosal approach, and histopathology revealed an anaplastic hemangiopericytoma (World Health Organization grade III). To our knowledge this is the first report of this rare pathology being located within the frontal horn of the lateral ventricle.


Subject(s)
Cerebral Ventricle Neoplasms/pathology , Hemangiopericytoma/pathology , Lateral Ventricles/pathology , Adult , Cerebral Ventricle Neoplasms/complications , Hemangiopericytoma/complications , Humans , Hydrocephalus/etiology , Intracranial Hypertension/etiology , Magnetic Resonance Imaging , Male
19.
Ann Med Health Sci Res ; 5(4): 241-6, 2015.
Article in English | MEDLINE | ID: mdl-26229711

ABSTRACT

BACKGROUND: Escherichia coli strains mainly fall into four phylogenetic groups (A, B1, B2, and D) and that virulent extra-intestinal strains mainly belong to groups B2 and D. AIM: The aim was to determine the association between phylogenetic groups of E. coli causing extraintestinal infections (ExPEC) regarding the site of infection, expression of virulence factors, antimicrobial resistance patterns, and clinical outcome. This descriptive study was carried out in a multi-specialty Tertiary Care Hospital. MATERIALS AND METHODS: A total of 300 E. coli causing ExPEC were studied. Triplex polymerase chain reaction was used to classify the phylogenetic groups; hemolysin production was assessed on sheep blood agar and biofilm production in a microtiter plate assay. Production of extended spectrum of beta-lactamase (ESBLs) was detected by combination disk method; AmpC was detected by AmpC disk test, Carbapenemase production was detected by modified Hodge test and metallo-ß-lactamase by metallo-beta-lactamases (MBL) E-test. RESULTS: Of 300 isolates, 61/300 (20%) belonged to phylogroup A, 27/300 (9%) to phylogroup B1, 104/300 (35%) were B2 and 108/300 (36%) belonged to group D, respectively. Phylogroups B2 and D were the most predominant groups in urinary tract infection and sepsis. Prognoses were better in infections with group A and B1 isolates, and relapses and death were common in infections with B2 and D. Expression of biofilm was greatest in B1 and hemolysin in group B2. Group A and B1 showed higher resistance to ciprofloxacin and were most frequent ß-lactamase (ESBL, AmpC, Carbapenemase and MBL) producers. CONCLUSIONS: Phylogenetic group B2 and D were predominant in ExPEC and exhibited least antimicrobial resistance among the groups. Resistance to multiple antibiotics was most prevalent in group A and B1. Regular monitoring of antimicrobial susceptibility in commensal strains is essential as they might transfer the property of antimicrobial resistance to pathogenic strains.

20.
J Clin Pediatr Dent ; 39(2): 128-32, 2015.
Article in English | MEDLINE | ID: mdl-25823482

ABSTRACT

UNLABELLED: The aim of the study was to estimate the diurnal variations of salivary cortisol in children with autism and healthy children and it's implication on behavior during non-invasive dental procedures. STUDY DESIGN: 50 children with autism and 50 healthy children in the age group between 6 to 12 years of both genders with the need for dental treatment were included in the study. Whole unstimulated saliva was collected from them during early hours of the day and during evenings for 2 consecutive days . The collected saliva was then subjected to electrochemiluminescence assay . Minimum invasive dental procedures like hand scaling, pit and fissure sealants and glass ionomer cement restorations were performed for the participants each time after the saliva sample collection and their behavior during the procedures was rated using Frankl's Behavior Rating Scale. RESULTS: Significant correlation was seen between cortisol levels and behavior in children with autism. As cortisol levels increased in children with autism, behavior worsened and as the cortisol levels decreased they showed positive behaviour. CONCLUSION: Cortisol acts as a stress marker and studying the diurnal variations of salivary cortisol can help us in attaining better knowledge about the behavior pattern and thereby assist us in modifying the behavior modification procedures and treatment planning in this group of special children.


Subject(s)
Autistic Disorder/metabolism , Child Behavior , Dental Care for Children , Dental Care for Disabled , Hydrocortisone/analysis , Saliva/chemistry , Autistic Disorder/psychology , Child , Circadian Rhythm , Dental Atraumatic Restorative Treatment/psychology , Dental Care for Children/psychology , Dental Care for Disabled/psychology , Dental Scaling/psychology , Female , Glass Ionomer Cements/chemistry , Humans , Male , Pit and Fissure Sealants/therapeutic use , Stress, Physiological/physiology
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