Glioblastoma multiforme (GBM) remains refractory to conventional therapy. CD133+ GBM cells have been recently isolated and characterized as chemo-/radio-resistant tumor-initiating cells and are hypothesized to be responsible for post-treatment recurrence. In order to explore the molecular properties of tumorigenic CD133+ GBM cells that resist treatment, we isolated CD133+ GBM cells from tumors that are recurrent and have previously received chemo-/radio-therapy. We found that the purified CD133+ GBM cells sorted from the CD133+ GBM spheres express SOX2 and CD44 and are capable of clonal self-renewal and dividing to produce fast-growing CD133− progeny, which form the major cell population within GBM spheres. Intracranial injection of purified CD133+, not CD133− GBM daughter cells, can lead to the development of YKL-40+ infiltrating tumors that display hypervascularity and pseudopalisading necrosis-like features in mouse brain. The molecular profile of purified CD133+ GBM cells revealed characteristics of neuroectoderm-like cells, expressing both radial glial and neural crest cell developmental genes, and portraying a slow-growing, non-differentiated, polarized/migratory, astrogliogenic, and chondrogenic phenotype. These data suggest that at least a subset of treated and recurrent GBM tumors may be seeded by CD133+ GBM cells with neural and mesenchymal properties. The data also imply that CD133+ GBM cells may be clinically indolent/quiescent prior to undergoing proliferative cell division (PCD) to produce CD133− GBM effector progeny. Identifying intrinsic and extrinsic cues, which promote CD133+ GBM cell self-renewal and PCD to support ongoing tumor regeneration may highlight novel therapeutic strategies to greatly diminish the recurrence rate of GBM.Electronic supplementary materialThe online version of this article (doi:10.1007/s11060-009-9919-z) contains supplementary material, which is available to authorized users.

Background Unbalanced translocations can cause developmental delay (DD), intellectual disability (ID), growth problems, dysmorphic features, and congenital anomalies. They may arise de novo or may be inherited from a parent carrying a balanced rearrangement. It is estimated that 1/500 people is a balanced translocation carrier. The outcomes of different chromosomal rearrangements have the potential to reveal the functional consequences of partial trisomy or partial monosomy and can help guide genetic counseling for balanced carriers, and other young patients diagnosed with similar imbalances. Methods We performed clinical phenotyping and cytogenetic analyses of two siblings with a history of developmental delay (DD), intellectual disability (ID) and dysmorphic features. Results The proband, a 38-year-old female, has a history of short stature, dysmorphic features and aortic coarctation. She underwent chromosomal microarray analysis, which identified partial monosomy of 4q and partial trisomy of 10p. Her brother, a 37-year-old male, has a history of more severe DD, behavioral problems, dysmorphic features, and congenital anomalies. Subsequently, karyotype confirmed two different unbalanced translocations in the siblings: 46,XX,der(4)t(4;10)(q33;p15.1) and 46,XY,der(10)t(4;10)(q33;p15.1), respectively. These chromosomal rearrangements represent two possible outcomes from a parent who is a carrier for a balanced translocation 46,XX,t(4;10)(q33;p15.1). Conclusion To our knowledge, this 4q and 10p translocation has not been described in literature. In this report we compare clinical features due to the composite effects of partial monosomy 4q with partial trisomy 10p and partial trisomy 4q with partial monosomy 10p. These findings speak to the relevance of old and new genomic testing, the viability of these segregation outcomes, and need for genetic counseling.

BackgroundApproximately 4% of the African-American population possess a valine-to-isoleucine (V122I) substitution within the transthyretin protein that results in a tendency for a normally tetrameric protein to dissociate into misfolded, monomeric subunits. These misfolded proteins can then accumulate pathologically and cause an autosomal dominant amyloid cardiomyopathy. Homozygous patients are infrequently documented in case reports, and though there are larger studies among heterozygous patients, there is a lack of studies or reports comparing disease within a family.Case summaryIn this case series, we discuss a 61-year-old African-American male who succumbed to heart failure secondary to cardiac amyloidosis while awaiting orthotopic heart transplantation. We compare his case with that of his sister, a 65-year-old African-American woman with a history of recurrent supraventricular tachycardia requiring radiofrequency ablation, and intermittent chest pain with chronically elevated troponin despite no evidence of coronary artery disease. The sister in question was found to be homozygous for the transthyretin (TTR) V122I mutation with evidence of infiltrative process on cardiac magnetic resonance imaging, while clinical testing verified a heterozygous genotype in the brother. Here, we compare the clinical course and imaging data for the aforementioned brother–sister pair in the context of the amyloidogenic transthyretin V122I gene variant.DiscussionThrough this familial report, we aim to highlight the variations in expression both within this family and in comparison, to the population. We also hope to emphasize the importance of genetic testing of families at risk for this specific transthyretin variant within the African-American community especially as novel therapies begin to emerge.

West Nile virus (WNV) is a mosquito-borne infectious disease that can produce potentially life-threatening meningoencephalitis in immunocompromised individuals. In 2017, there were 536 human cases of WNV in California, with 43 fatalities reported to the California Department of Public Health. Peak mosquito transmission periods are in the late summer and early fall when mosquitoes are maximally viremic. In addition to risk factors such as advanced age, malignancy, or prior organ transplantation, the probability of progression to severe, neuroinvasive disease has been reported to be significantly higher in individuals suffering from lymphoma receiving rituximab in addition to other oncologic treatments. Here, we describe the case of a patient who recently received chemotherapy with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone for diffuse large B-cell lymphoma, complicated by meningoencephalitis due to seronegative neuroinvasive WNV infection, ultimately resulting in death.