Membrane proteins play key roles in the development and progression of cancer. We have studied differentially expressed membrane proteins in glioblastoma multiforme (GBM), the most common and aggressive type of primary brain tumor, by high resolution LC-MS/MS mass spectrometry and quantitation by iTRAQ. A total of 1834 membrane proteins were identified with high confidence, of which 356 proteins were found to be altered by 2-fold change or more (198 up-and 158 down-regulated); 56% of them are known membrane proteins associated with major cellular processes. Mass spectrometry results were confirmed for representative proteins on individual specimens by immunohistochemistry. On mapping of the differentially expressed proteins to cellular pathways and functional networks, we notably observed many calciumbinding proteins to be altered, implicating deregulation of calcium signaling and homeostasis in GBM, a pathway also found to be enriched in the report (
These three cases, in addition to others reported in the literature, point out an as yet poorly known etiology of occupational asthma to quaternary ammonium compounds in hospital employees. The exact mechanism of the action remains unexplained.
Fifty-six patients with cerebral zygomycosis (mucormycosis) were seen during the period 1971-2001 in two tertiary care hospitals located in south India with tropical climate and catering to neurological diseases. Forty-four patients had rhinocerebral and twelve patients had isolated central nervous system (CNS) zygomycosis. Of these, ten were culture proven (Rhizopus oryzae in eight and Mucor in two); 30 were diagnosed as probable and 16 were diagnosed possible; mixed infections were seen in three patients. Diabetes mellitus was the predisposing condition in a majority (31/44) of patients with the rhinocerebral form of zygomycosis. The tissue obtained at biopsy/autopsy in either form showed necrotic/infarcted tissue with neutrophilic infiltration with broad non-septate hyphae showing irregular branching. The outcome was poor despite surgical excision and antifungal therapy. The high concentration of spores in a mouldy environment, the bird population and improper disposal of hospital waste may facilitate healthy hosts presenting with primary CNS disease.
Glioblastomas (GBMs) are the most common and lethal primary tumors of the central nervous system with high level of recurrence despite aggressive therapy. Tumor-associated proteins/peptides may appear in the plasma of these patients as a result of disruption of the blood-brain barrier in them, raising the scope for development of plasma-based tests for diagnosis and monitoring the disease. With this objective, we analyzed the levels of proteins present in the plasma from GBM patients using an iTRAQ based LC-MS/MS approach. Analysis with pooled plasma specimens from the patient and healthy control samples revealed high confidence identification of 296 proteins, of which 61 exhibited a fold-change ≥1.5 in the patient group. Forty-eight of them contained signal sequence. A majority have been reported in the differentially expressed transcript or protein profile of GBM tissues; 6 have been previously studied as plasma biomarkers for GBM and 16 for other types of cancers. Altered levels of three representative proteins–ferritin light chain (FTL), S100A9, and carnosinase 1 (CNDP1)–were verified by ELISA in a test set of ten individual plasma specimens. FTL is an inflammation marker also implicated in cancer, S100A9 is an important member of the Ca2+ signaling cascade reported to be altered in GBM tissue, and CNDP1 has been reported for its role in the regulation of the levels of carnosine, implicated as a potential drug for GBM. These and other proteins in the dataset may form useful starting points for further clinical investigations for the development of plasma-based biomarker panels for GBM.
This is the largest series reported from India to the best of our knowledge. Squash smear technique is a very reliable and rapid method of intraoperative diagnosis. Knowledge of clinical and neuroimaging details helps the experienced neuropathologist to improve the diagnostic accuracy.
Intracranial abscesses are life-threatening infections that pose a diagnostic challenge not only to the neurosurgeon but also to the microbiologists. Detailed studies documenting the spectrum of infecting agents involved in brain abscesses are limited from India. Materials and Methods. This is a retrospective analysis of 352 samples from 1987 to 2010 analyzed at a tertiary care hospital in South India from 1987 to 2010, to document the changing trends with time. Results. The age of the patients ranged from 2 to 80 years, a larger number of males being affected. Otogenic infections were the most common cause while cryptogenic abscesses were 20%. Gram stain and culture positivity were 78% each. Gram-positive and negative facultative aerobes and obligate anaerobes were also on the rise. Unusual organisms, like Burkholderia pseudomallei, Salmonella typhi, Nocardia species, Cladosporium bantiana, Fonsecaea pedrosoi, Entamoeba histolytica, and Acanthamoeba were also isolated and/or detected from the brain abscesses aspirate or resected tissue. Summary. New and emerging pathogens associated with brain abscess, especially in immunosuppressed individuals, have renewed the necessity of an early detection, and it will be of great value in appropriate management of patients with brain abscess.
Of the 21 patients with aspergillosis of central nervous system seen during the years 1990-1997, 16 (76%) had aspergillosis of sino-cranial origin. The occupation in patients with sino-cranial aspergillosis was either agricultural or manual work and predisposing risk factors were present in only two (12.5%) patients. Skull-base syndromes were the presenting features in 13 patients and three patients presented with features of intracranial space-occupying lesion. Paranasal sinus mass lesions were seen in all the 16 patients. Computerized tomography showed intracranial extradural-enhancing mass lesions in the anterior, middle or posterior cranial fossa in nine (68%) patients, intracranial and orbital lesions in four and orbital lesions in three. Well-formed granuloma with dense fibrosis was the histological feature. Survival rates were not good even after surgical and antifungal chemotherapy. Surgical treatment was subradical in our series. The majority of cases of sinocranial aspergillosis are reported from countries with temperate climates and the high incidence in these regions is probably related to constant exposure to the high spore content of pathogenic Aspergillus species in the 'mouldy' work environment.
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