Absent in melanoma 2 regulates tumor cell proliferation in glioblastoma multiforme.

INTRODUCTION: Inflammation is a key aspect of glioblastoma multiforme (GBM) although it remains unclear how it contributes to GBM pathogenesis. Inflammasomes are intracellular multi-protein complexes that are involved in innate immunity and are activated by cellular stress, principally in macrophages. This study examined the expression of inflammasome-associated genes in GBM, particularly absent in melanoma 2 (AIM2). METHODS: Tissue samples from surgically-resected GBM tumors (n = 10) were compared to resected brain specimens from patients with epilepsy (age- and sex-matched Other Disease Controls (ODC, n=5)) by qRT-PCR, western blotting and immunofluorescence. Gene expression studies in human astrocytoma U251 cells were performed and the effects of deleting the absent in melanoma 2 (AIM2) gene using the CRISPR-Cas9 system were analyzed. RESULTS: GBM tissues showed significantly elevated expression of multiple immune (CD3E, CD163, CD68, MX1, ARG1) and inflammasome (AIM2, NLRP1, IL18, CASP1, and IL-33) genes compared to ODC tissues, without induction of IL1B, IFNG or TNFA. An insert-containing AIM2 variant transcript was highly expressed in GBM tissues and in U251 cells. AIM2 immunoreactivity was concentrated in the tumor core in the absence of PCNA immunodetection and showed a predominant 52 kDa immunoreactive band on western blot. Deletion of AIM2 resulted in significantly enhanced proliferation of U251 cells, which also displayed increased resistance to temozolomide treatment. CONCLUSIONS: GBM tumors express a distinct profile of inflammasome-associated genes in a tumor-specific manner. AIM2 expression in tumor cells suppressed cell proliferation while also conferring increased susceptibility to contemporary GBM therapy.

The Role of Flaviviral Proteins in the Induction of Innate Immunity.

Flaviviruses are positive, single-stranded, enveloped cytoplasmic sense RNA viruses that cause a variety of important diseases worldwide. Among them, Zika virus, West Nile virus, Japanese encephalitis virus, and Dengue virus have the potential to cause severe disease. Extensive studies have been performed to elucidate the structure and replication strategies of flaviviruses, and current studies are aiming to unravel the complex molecular interactions between the virus and host during the very early stages of infection. The outcomes of viral infection and rapid establishment of the antiviral state, depends on viral detection by pathogen recognition receptors and rapid initiation of signalling cascades to induce an effective innate immune response. Extracellular and intracellular pathogen recognition receptors play a crucial role in detecting flavivirus infection and inducing a robust antiviral response. One of the main hallmarks of flaviviral nonstructural proteins is their multiple strategies to antagonise the interferon system. In this chapter, we summarize the molecular characteristics of flaviviral proteins and discuss how viral proteins target different components of the interferon signalling pathway by blocking phosphorylation, enhancing degradation, and downregulating the expression of major components of the Janus kinase/signal transducer and activator of transcription pathway. We also discuss how the interactions of viral proteins with host proteins facilitate viral pathogenesis. Due to the lack of antivirals or prophylactic treatments for many flaviviral infections, it is necessary to fully elucidate how these viruses disrupt cellular processes to influence pathogenesis and disease outcomes.

Penile incarceration with encircling metallic objects: a study of successful removal.

OBJECTIVE: This article aimed to study the various treatment options according to the grading scale for penile incarceration. MATERIALS AND METHODS: A retrospective review, of all the case files of patients presented with penile incarceration with encircling metallic object was performed. The patients were analyzed for age, marital status, motive, object used, who applied it, trauma grade, duration of incarceration, removal technique, removal time, anesthesia used and recovery time. RESULT: A total of seven patients were identified. The average age was 46.71 years. Self-sexual gratification was the most common motive (five patients). Six patients presented within 24 hours. Grade II of injury was commonest type of injury seen in five patients.The technique of removal chosen was according to grade of penile injury, duration of incarceration and type of object used. Spinal anesthesia was used in most of the cases (five patients). CONCLUSION: Penile incarceration with encircling metallic objects is a rare presentation and requires urgent intervention according to trauma grade to prevent complications.

Microbiological profile of lower respiratory tract infections in neurological intensive care unit of a tertiary care center from Central India.

BACKGROUND: Lower respiratory tract infections (LRTI's) are the most frequent infections among patients in intensive care units. The consequences of increased drug resistance are far reaching since bacterial infection of the lower respiratory tract (LRT) is a major cause of death from infectious disease. OBJECTIVE: The study was conducted with the aim of determining the bacterial etiology of LRTI in the neuro intensive care unit (NICU) as well as to update the clinicians with the various antimicrobial alternatives available in the treatment of LRTI. SUBJECTS AND METHODS: The study was conducted for the period of 3 years from January 2010 to December 2012 in the Microbiology Department of a Teaching Tertiary Care Hospital. The LRT specimens from 230 patients admitted in a NICU during the study period were processed. Following culture, the isolated organisms were identified and antimicrobial sensitivity was performed by standard methods. RESULTS: Out of the 230 LRT specimens evaluated, 198 (86.08%) were culture positive. A total of 254 pathogens were recovered with a predominance of Gram-negative isolates (n = 243; 96.05%) Pseudomonas aeruginosa was the most dominant pathogen followed by Klebsiella pneumoniae. Alarmingly high percentage of extended spectrum beta-lactamase and methicillin resistant Staphylococcus aureus isolates were detected. The resistance to cephalosporins, aminoglycosides and carbapenem were remarkable. CONCLUSIONS: Therefore, we can conclude that for effective management of LRTI's, an ultimate and detailed bacteriological diagnosis and susceptible testing is required to overcome global problem of antibiotic resistance.

Maroteaux-Lamy syndrome.

Mucopolysaccharidoses are a type of lysosomal storage disorders characterized by defect in the degradation of Mucopolysaccharides due to deficiency of specific lysosomal enzymes leading to their accumulation in various tissues. MPS -VI (Maroteaux-Lamy Syndrome) is an autosomal recessive syndrome due to deficiency of enzyme Aryl- Sulfatase -B, and is characterized by characteristic facies, normal intelligence, Dysostosis multiplex, organomegaly, joint stiffness, corneal clouding and striking inclusions in peripheral blood leucocytes. We present an 8-year-old male child with MPS-VI syndrome, confirmed by enzyme assay.

Properties of glutamine aminohydrolases in subcellular fractions of liver of tumour bearing mice.

Glutamine aminohydrolase is found to be present in microsomal and soluble supernatant in liver of EAC-bearing mice. Enzymes obtained from these two sources were characterized and found to behave differently from the mitochondrial glutaminase of both normal and tumour-bearing mice.

Glutamine aminotransferase and glutamine aminohydrolase ratio as a possible test for antitumour compounds.

Three known antitumour drugs have been tested for their effect on the GAT/GNase ratio of Ehrlich Ascites cells and host plasma. It was observed that all these drugs had changed the ratio of the 2 types of glutaminases from below 1.0 to the normal value of 1.0, this was accompanied with an increase in the survival time of the tumour-bearing animals. There was, however, no effect on the plasma GAT/GNase ratio of normal animals in the presence of the 3 antitumour compounds tested.