Defective radiation signal transduction in ataxia-telangiectasia cells

PURPOSE: The product of the gene ATM mutated in the human genetic disorder ataxia-telangiectasia (A-T) is predominantly present in the nucleus Compatible with a role in DNA-damage recognition and cell-cycle control. However, ATM is also present outside the nucleus in cytoplasmic and membrane associated vesicles, which may explain the more general signalling defect in A-T. This led us to investigate signalling events initiated by ionizing radiation, remote from the nucleus. MATERIALS AND METHODS: A-T and control lymphoblastoid cells were employed to study radiation-induced signalling at the level of protein activation using immunoprecipitation and immunoblotting. Flow cytometry was used to determine mobilization of intracellular Ca2+. RESULTS: Lymphoblastoid cells from A-T patients were found to be defective in the radiation-induced activation of protein tyrosine kinase p53/p56lyn. In control cells Ca2+ was mobilized in response to gamma-radiation largely from internal stores, and increased significantly over a 20 min period. This mobilization of Ca2+ was either absent or increased very slowly in A-T cells post-irradiation. The same pattern of release was observed after treatment with the radiometric agent, streptonigrin. In addition the phospatidylinositol 3-kinase (PI3-kinase) inhibitor wortmannin suppressed the release of Ca2+. CONCLUSION: These data demonstrate that ionizing radiation activates lyn kinase and leads to the release of Ca2+, and-for the first time-that these steps are ATM-dependent.     

Glutamatergic dysfunction in OCD.

The role of glutamatergic dysfunction in the pathophysiology of OCD has hardly been explored despite recent reports implicating glutamatergic dysfunction in OCD. We decided to investigate CSF glutamate levels in adult OCD probands compared to psychiatrically normal controls. In total, 21 consenting psychotropic drug-na?ve adult OCD patients, diagnosed using SCID-IV-CV, and 18 consenting psychiatrically normal controls with age within 10 years of age of the patients, who did not have any history of head injury or neurological illness, were included into the study. Aseptically collected and stored CSF samples obtained from the patients and control subjects were used for glutamate estimation, which was carried out by a modification of the procedure described by Lund (1986). CSF glutamate (micromol/l) level was found to be significantly higher [F(1,31)=6.846, p=0.014] in OCD patients (47.12+/-4.25) compared to control subjects (41.36+/-3.63) on analysis of covariance. There was no effect of gender, age, duration of illness, Y-BOCS score, or CGI-S score on CSF glutamate levels. Our study provides preliminary evidence implicating glutamatergic excess in the pathophysiology of OCD, which needs to be further explored by studies from other centers involving larger sample sets from different age groups.     

Isolated tuberculosis of testis.

Isolated epididymo-orchitis is an uncommon presentation of tuberculosis. We report a case of left sided epididymo-orchitis and scrotal involvement due to tuberculosis in a young male patient. The diagnosis was suspected on clinical examination of scrotum and confirmed by FNAC of scrotal and testis. Patient improved after taking antitubercular treatment. Key words: infection, scrotum, treatment.     

A Novel Supervised Approach for Segmentation of Lung Parenchyma from Chest CT for Computer-Aided Diagnosis

Segmentation of lung parenchyma from the chest computed tomography is an important task in analysis of chest computed tomography for diagnosis of lung disorders. It is a challenging task especially in the presence of peripherally placed pathology bearing regions. In this work, we propose a segmentation approach to segment lung parenchyma from chest. The first step is to segment the lungs using iterative thresholding followed by morphological operations. If the two lungs are not separated, the lung junction and its neighborhood are identified and local thresholding is applied. The second step is to extract shape features of the two lungs. The third step is to use a multilayer feed forward neural network to determine if the segmented lung parenchyma is complete, based on the extracted features. The final step is to reconstruct the two lungs in case of incomplete segmentation, by exploiting the fact that in majority of the cases, at least one of the two lungs would have been segmented correctly by the first step. Hence, the complete lung is determined based on the shape and region properties and the incomplete lung is reconstructed by applying graphical methods, namely, reflection and translation. The proposed approach has been tested in a computer-aided diagnosis system for diagnosis of lung disorders, namely, bronchiectasis, tuberculosis, and pneumonia. An accuracy of 97.37 % has been achieved by the proposed approach whereas the conventional thresholding approach was unable to detect peripheral pathology-bearing regions. The results obtained prove to be better than that achieved using conventional thresholding and morphological operations.     

Immunohistochemical and molecular genetic study on epithelioid glioblastoma: Series of seven cases with review of literature

Epithelioid glioblastoma (e-gbm) is a recently described variant of glioblastoma (GBM) which is associated with short survival and now added as a provisional entity to WHO 2016 classification of CNStumors. About half of these tumors show characteristic BRAF-V600E mutation. However, unlike conventional GBMs, e-gbm lack specific diagnostic and prognostic markers. Hence, we aimed to molecularly characterize these tumors. An extensive review of literature was performed.In a multi-institutional effort, all the cases of glioblastoma of year 2017 were reviewed. Cases with predominant epithelioid morphology were analysed. Seven cases of e-gbm (adults:4 and pediatric: 3) were identified. Duration of symptoms varied from 2 weeks to one month. Radiologically, all cases were supratentorial, contrast enhancing with solid and cystic appearance. Majority of the cases were immunopositive for GFAP (71%), EMA (71%), S100 (71%) and vimentin (85%). All the cases showed ATRX, INI-1 and H3K27me3 expression. BRAFV600Emutation was seen in 28% of cases. TERT mutation was seen in 40% cases, while one case showed EGFR amplification. H3F3A mutations and PTEN deletions were seen in none. Although e-gbms are rare, epithelioid morphology of a CNS tumor in a young adult or children with areas of necrosis needs thorough histomorphological and genetic workup.     

Laparoscopic total mesorectal excision

This article describes the operative technique that my colleagues and I apply to total mesorectal excision in patients with rectal cancer. A body of data support improvement of short-term outcomes over open resection. Although long-term data remain scarce, several ongoing trials may clarify this deficiency. The appropriateness of laparoscopy in the treatment for rectal cancer should be carefully weighed with consideration of patient preferences, surgeon experience, and available infrastructure.     

Adaptive optics imaging of the retina

Adaptive optics is a relatively new tool that is available to ophthalmologists for study of cellular level details. In addition to the axial resolution provided by the spectral-domain optical coherence tomography, adaptive optics provides an excellent lateral resolution, enabling visualization of the photoreceptors, blood vessels and details of the optic nerve head. We attempt a mini review of the current role of adaptive optics in retinal imaging. PubMed search was performed with key words Adaptive optics OR Retina OR Retinal imaging. Conference abstracts were searched from the Association for Research in Vision and Ophthalmology (ARVO) and American Academy of Ophthalmology (AAO) meetings. In total, 261 relevant publications and 389 conference abstracts were identified.