Tumor angiogenic switch determines sustained proliferative malignant transformation in tumorigenesis and overlaps with para-inflammatory phenomena

Contextual BCR-ABL tyrosine kinase over-activity determines in formulated fashion the emergence of proliferation and anti-apoptosis that arise largely as derived phenomena of otherwise homeostatic mechanisms of the c-ABL gene within hematopoietic stem cells and hemangioblasts in the bone marrow. The ability to suppress almost completely, both in terms of phenotype and cytogenetically, the myeloid cell line expansion by imatinib mesylate is indicative of a phenomenon that depends strictly on the transformed status of the cell of origin in the chronic myeloid leukemia process. It is with relevance to complex participation of the dynamics of the fused BCR- ABL protein product that contextual conditioning of the cells of origin of the gene translocation further motivates the dimensional expansion of the transformed myeloid cell clones to increasing proliferative rates, thus leading to blast crisis as eventual loss of differentiating potential.peer-reviewe

A dual origin for Bcr-Abl gene translocation/fusion as dynamics of synergism of the hematopoietic stem cell and hemangioblast in chronic myeloid leukemia

Contextual BCR-ABL tyrosine kinase over-activity determines in formulated fashion the emergence of proliferation and anti-apoptosis that arise largely as derived phenomena of otherwise homeostatic mechanisms of the c-ABL gene within hematopoietic stem cells and hemangioblasts in the bone marrow. The ability to suppress almost completely, both in terms of phenotype and cytogenetically, the myeloid cell line expansion by imatinib mesylate is indicative of a phenomenon that depends strictly on the transformed status of the cell of origin in the chronic myeloid leukemia process. It is with relevance to complex participation of the dynamics of the fused BCR- ABL protein product that contextual conditioning of the cells of origin of the gene translocation further motivates the dimensional expansion of the transformed myeloid cell clones to increasing proliferative rates, thus leading to blast crisis as eventual loss of differentiating potential.peer-reviewe

ANTI-NMDA ENCEPHALITIS IN THE ACUTE SETTING

Background: Encephalitis associated with antibodies targeted against the N-methyl-D-aspartate (NMDA) receptor is increasingly recognised as a major cause of an acute presentation of organic psychosis. Misdiagnosis and subsequent inappropriate referral to psychiatric services is common and avoidable. This review focuses on addressing this issue in the acute setting. Methods: The authors present a review of existing literature relating to the pathophysiology and presentation of anti-NMDA receptor encephalitis, prior to proposing a management pathway avoiding delays to treatment incurred through misdiagnosis or inappropriate referral. Conclusions: Acute care physicians should have a low threshold for suspecting anti-NMDA receptor encephalitis in any patient presenting with acute psychosis in the context of non-specific coryzal and constitutional symptoms in whom infective causes have been excluded. The presence of pleocytosis and reduced protein in routine CSF analysis should further raise suspicion, and samples should be sent for immunohistochemical testing. Availability and efficiency of this testing is currently suboptimal

ANTI-NMDA ENCEPHALITIS IN THE ACUTE SETTING

Background: Encephalitis associated with antibodies targeted against the N-methyl-D-aspartate (NMDA) receptor is increasingly recognised as a major cause of an acute presentation of organic psychosis. Misdiagnosis and subsequent inappropriate referral to psychiatric services is common and avoidable. This review focuses on addressing this issue in the acute setting. Methods: The authors present a review of existing literature relating to the pathophysiology and presentation of anti-NMDA receptor encephalitis, prior to proposing a management pathway avoiding delays to treatment incurred through misdiagnosis or inappropriate referral. Conclusions: Acute care physicians should have a low threshold for suspecting anti-NMDA receptor encephalitis in any patient presenting with acute psychosis in the context of non-specific coryzal and constitutional symptoms in whom infective causes have been excluded. The presence of pleocytosis and reduced protein in routine CSF analysis should further raise suspicion, and samples should be sent for immunohistochemical testing. Availability and efficiency of this testing is currently suboptimal

NEUROPSYCHIATRIC MANIFESTATIONS OF COLLOID CYSTS: A REVIEW OF THE LITERATURE

Colloid cysts account for approximately 2% of primary brain tumours and the majority of cases are identified in the fourth and fifth decade. They are small, gelatinous neoplasms lined by a single layer of mucin-secreting columnar epithelium that are thought to arise from errors in folding of the primitive neuroepithelium. They develop in the rostral aspect of the third ventricle in the foramen of Monro in 99% of cases and despite their benign histology carry a poor prognosis, with a mortality greater than 10% in symptomatic cases. The location of colloid cysts within the ventricular system results in obstruction of the foramen of Monro as the cyst grows, disrupting the circulation of cerebrospinal fluid (CSF) and causing hydrocephalus. This is the mechanism behind the most common presenting symptoms of postural headache, nausea and vomiting - a clinical picture synonymous with hydrocephalus and intracranial pathology. In addition to these classical neurological symptoms, there is a high prevalence of psychiatric symptoms in the patient population, with symptoms ranging from anterograde amnesia to gustatory hallucination. These symptoms can occur with or without the presence of hydrocephalus, and are thought to be secondary to compression of connecting pathways between the mesocortices and subcortical limbic regions. These symptoms have been shown to be comparative in frequency to the classical symptoms, yet are rarely the reason for referral to a neurological or neurosurgical service for investigation

Radiation therapy combined with intracerebral administration of carboplatin for the treatment of brain tumors

Background: In this study we determined if treatment combining radiation therapy (RT) with intracerebral (i.c.) administration of carboplatin to F98 glioma bearing rats could improve survival over that previously reported by us with a 15 Gy dose (5 Gy × 3) of 6 MV photons.Methods: First, in order to reduce tumor interstitial pressure, a biodistribution study was carried out to determine if pretreatment with dexamethasone alone or in combination with mannitol and furosemide (DMF) would increase carboplatin uptake following convection enhanced delivery (CED). Next, therapy studies were carried out in rats that had received carboplatin either by CED over 30 min (20 μg) or by Alzet pumps over 7 d (84 μg), followed by RT using a LINAC to deliver either 20 Gy (5 Gy × 4) or 15 Gy (7.5 Gy × 2) dose at 6 or 24 hrs after drug administration. Finally, a study was carried out to determine if efficacy could be improved by decreasing the time interval between drug administration and RT.Results: Tumor carboplatin values for D and DMF-treated rats were 9.4 ±4.4 and 12.4 ±3.2 μg/g, respectively, which were not significantly different (P = 0.14). The best survival data were obtained by combining pump delivery with 5 Gy × 4 of X-irradiation with a mean survival time (MST) of 107.7 d and a 43% cure rate vs. 83.6 d with CED vs. 30-35 d for RT alone and 24.6 d for untreated controls. Treatment-related mortality was observed when RT was initiated 6 h after CED of carboplatin and RT was started 7 d after tumor implantation. Dividing carboplatin into two 10 μg doses and RT into two 7.5 Gy fractions, administered 24 hrs later, yielded survival data (MST 82.1 d with a 25% cure rate) equivalent to that previously reported with 5 Gy × 3 and 20 μg of carboplatin.Conclusions: Although the best survival data were obtained by pump delivery, CED was highly effective in combination with 20 Gy, or as previously reported, 15 Gy, and the latter would be preferable since it would produce less late tissue effects.peer-reviewe

Changes in Global Gene Expression in Response to Chemical and Genetic Perturbation of Chromatin Structure

DNA methylation is important for controlling gene expression in all eukaryotes. Microarray analysis of mutant and chemically-treated Arabidopsis thaliana seedlings with reduced DNA methylation revealed an altered gene expression profile after treatment with the DNA methylation inhibitor 5-aza-2′ deoxycytidine (5-AC), which included the upregulation of expression of many transposable elements. DNA damage-response genes were also coordinately upregulated by 5-AC treatment. In the ddm1 mutant, more specific changes in gene expression were observed, in particular for genes predicted to encode transposable elements in centromeric and pericentromeric locations. These results confirm that DDM1 has a very specific role in maintaining transcriptional silence of transposable elements, while chemical inhibitors of DNA methylation can affect gene expression at a global level