Long-term exposure to irinotecan reduces cell migration in glioma cells.

In spite of considerable research into the therapies for glioblastoma multiforme this tumour type remains very difficult to treat. As well as having a tendency to be inherently resistant to chemotherapy, glioblastoma multiforme also displays local invasion. Cell line studies have a continued and important role to play in understanding the mechanisms associated with both chemotherapy resistance and invasion. In the current study we have utilized the C6 glioma cell line to investigate the response to long-term, clinically relevant application of topoisomerase I and II inhibitors. Treatment with etoposide resulted in an increase in resistance to this topoisomerase II inhibitor. By contrast, the continuous exposure to a topoisomerase I inhibitor did not result in increased drug resistance, but was associated with a reduction in cell migration. This data supports further investigation of topoisomerase I inhibition as a means to inhibit glioma invasion without the development of parallel chemoresistance.

The role of the WNT/ß-catenin pathway in central nervous system primitive neuroectodermal tumours (CNS PNETs).

BACKGROUND: Central nervous system primitive neuroectodermal tumours (CNS PNETs) are embryonal tumours occurring predominantly in children. Current lack of knowledge regarding their underlying biology hinders development of more effective treatments. We previously identified WNT/ß-catenin pathway activation in one-third of CNS PNETs, which was potentially linked to a better prognosis. In this study, we have extended our cohort, achieving a statistically significant correlation with prognosis. We additionally investigated the biological effects of WNT/ß-catenin pathway activation in tumour pathogenesis. METHODS: A total of 42 primary and 8 recurrent CNS PNETs were analysed for WNT/ß-catenin pathway status using ß-catenin immunohistochemistry. Genomic copy number and mRNA expression data were analysed to identify a molecular profile linked to WNT/ß-catenin pathway activation. RESULTS: Pathway activation was seen in 26% of CNS PNETs and was significantly associated with longer overall survival. Genes displaying a significant difference in expression levels, between tumours with and without WNT/ß-catenin pathway activation, included several involved in normal CNS development suggesting aberrant pathway activation may be disrupting this process. CONCLUSION: We have identified WNT/ß-catenin pathway status as a marker, which could potentially be used to stratify disease risk for patients with CNS PNET. Gene expression data suggest pathway activation is disrupting normal differentiation in the CNS.

Pendred syndrome (goitre and sensorineural hearing loss) maps to chromosome 7 in the region containing the nonsyndromic deafness gene DFNB4.

Inherited causes account for about 50% of individuals presenting with childhood (prelingual) hearing loss, of which 70% are due to mutation in numerous single genes which impair auditory function alone (non-syndromic). The remainder are associated with other developmental anomalies termed syndromic deafness. Genes responsible for syndromic forms of hearing loss include the COL4A5 gene in Alport syndrome and the PAX3 and MITF genes in Waardenburg syndrome. Pendred syndrome is an autosomal recessive disorder associated with developmental abnormalities of the cochlea, sensorineural hearing loss and diffuse thyroid enlargement (goitre). Pendred syndrome is the most common syndromal form of deafness, yet the primary defect remains unknown. We have established a panel of 12 families with two or more affected individuals and used them to search for the location of the Pendred gene by linkage analysis. We excluded localization to four previously mapped nonsyndromic deafness loci but obtained conclusive evidence for linkage of the Pendred syndrome gene to microsatellite markers on chromosome 7q31 (D7S495 Zmax 7.32, Qmax = 0). This region contains a gene, DFNBL, for autosomal recessive non-syndromic sensorineural hearing loss. Multipoint analysis indicates that DFNB4 and Pendred syndrome co-localize to the same 5.5 centiMorgan (cM) interval flanked by D7S501 and D7S523. These data raise the possibility that Pendred syndrome is either allelic with DFNB4 or may represent an inherited contiguous gene disorder, not clinically manifest in the heterozygote.

WNT/ß-catenin pathway activation in Myc immortalised cerebellar progenitor cells inhibits neuronal differentiation and generates tumours resembling medulloblastoma.

BACKGROUND: Medulloblastoma is the most common malignant childhood brain tumour. Aberrant activation of the WNT/ß-catenin pathway occurs in approximately 25% of medulloblastomas. However, its role in medulloblastoma pathogenesis is not understood. METHODS: We have developed a model of WNT/ß-catenin pathway-activated medulloblastoma. Pathway activation was induced in a Myc immortalised cerebellar progenitor cell line through stable expression of Wnt1. In vitro and in vivo analysis was undertaken to understand the effect of pathway activation and identify the potential cell of origin. RESULTS: Tumours that histologically resembled classical medulloblastoma formed in vivo using cells overexpressing Wnt1, but not with the control cell line. Wnt1 overexpression inhibited neuronal differentiation in vitro, suggesting WNT/ß-catenin pathway activation prevents cells terminally differentiating, maintaining them in a more 'stem-like' state. Analysis of cerebellar progenitor cell markers demonstrated the cell line resembled cells from the cerebellar ventricular zone. CONCLUSION: We have developed a cell line with the means of orthotopically modelling WNT/ß-catenin pathway-activated medulloblastoma. We provide evidence of the role pathway activation is playing in tumour pathogenesis and suggest medulloblastomas can arise from cells other than granule cell progenitors. This cell line is a valuable resource to further understand the role of pathway activation in tumorigenesis and for investigation of targeted therapies.

An investigation of WNT pathway activation and association with survival in central nervous system primitive neuroectodermal tumours (CNS PNET).

Central nervous system primitive neuroectodermal tumours (CNS PNET) are high-grade, predominantly paediatric, brain tumours. Previously they have been grouped with medulloblastomas owing to their histological similarities. The WNT/beta-catenin pathway has been implicated in many tumour types, including medulloblastoma. On pathway activation beta-catenin (CTNNB1) translocates to the nucleus, where it induces transcription of target genes. It is commonly upregulated in tumours by mutations in the key pathway components APC and CTNNB1. WNT/beta-catenin pathway status was investigated by immunohistochemical analysis of CTNNB1 and the pathway target cyclin D1 (CCND1) in 49 CNS PNETs and 46 medulloblastomas. The mutational status of APC and CTNNB1 (beta-catenin) was investigated in 33 CNS PNETs and 22 medulloblastomas. CTNNB1 nuclear localisation was seen in 36% of CNS PNETs and 27% of medulloblastomas. A significant correlation was found between CTNNB1 nuclear localisation and CCND1 levels. Mutations in CTNNB1 were identified in 4% of CNS PNETs and 20% of medulloblastomas. No mutations were identified in APC. A potential link between the level of nuclear staining and a better prognosis was identified in the CNS PNETs, suggesting that the extent of pathway activation is linked to outcome. The results suggest that the WNT/beta-catenin pathway plays an important role in the pathogenesis of CNS PNETs. However, activation is not caused by mutations in CTNNB1 or APC in the majority of CNS PNET cases.

Antiprismatic Coordination about Xenon: The Structure of Nitrosonium Octafluoroxenate(VI).

The structure of nitrosonium octafluoroxenate(VI), 2NOF . XeF(6), has been determined by means of single-crystal x-ray counter methods (R-index = 0.046, weighted R-index = 0.042). The space group is Pnma, with a = 8.914(10) angstroms, b = 5.945(10) angstroms, and c = 12.83(2) angstroms (the numbers in parentheses are the standard deviations to the least significant digit or digits); the calculated density (rho) is 3.354 grams per cubic centimeter, and there are four formula units per unit cell. The material consists of well-separated NO(+) and (XeF(8))(2-) ions; the structural formula is thus (NO)(2) (XeF(8)). The anion configuration is that of a slightly distorted Archimedean antiprism. The observed distortion appears incompatible with a lone-pair repulsion model. Xenon-fluorine bond lengths of 1.971(7), 1.946(5), 1.958(7), 2.052(5), and 2.099(5) angstroms were found.

Investigation of chromosome 1q reveals differential expression of members of the S100 family in clinical subgroups of intracranial paediatric ependymoma.

Gain of 1q is one of the most common alterations in cancer and has been associated with adverse clinical behaviour in ependymoma. The aim of this study was to investigate this region to gain insight into the role of 1q genes in intracranial paediatric ependymoma. To address this issue we generated profiles of eleven ependymoma, including two relapse pairs and seven primary tumours, using comparative genome hybridisation and serial analysis of gene expression. Analysis of 656 SAGE tags mapping to 1q identified CHI3L1 and S100A10 as the most upregulated genes in the relapse pair with de novo 1q gain upon recurrence. Moreover, three more members of the S100 family had distinct gene expression profiles in ependymoma. Candidates (CHI3L1, S100A10, S100A4, S100A6 and S100A2) were validated using immunohistochemistry on a tissue microarray of 74 paediatric ependymoma. In necrotic cases, CHI3L1 demonstrated a distinct staining pattern in tumour cells adjacent to the areas of necrosis. S100A6 significantly correlated with supratentorial tumours (P<0.001) and S100A4 with patients under the age of 3 years at diagnosis (P=0.038). In conclusion, this study provides evidence that S100A6 and S100A4 are differentially expressed in clinically relevant subgroups, and also demonstrates a link between CHI3L1 protein expression and necrosis in intracranial paediatric ependymoma.

Data on the number and frequency of scientific literature citations for established medulloblastoma cell lines.

This article collates information about the number of scientific articles mentioning each of the established medulloblastoma cell lines, derived through a systematic search of Web of Science, Scopus and Google Scholar in 2016. The data for each cell line have been presented as raw number of citations, percentage share of the total citations for each search engine and as an average percentage between the three search engines. In order to correct for the time since each cell line has been in use, the raw citation data have also been divided by the number of years since the derivation of each cell line. This is a supporting article for a review of in vitro models of medulloblastoma published in "in vitro models of medulloblastoma: choosing the right tool for the job" (D.P. Ivanov, D.A. Walker, B. Coyle, A.M. Grabowska, 2016) [1].

Concurrence of Pendred syndrome, autoimmune thyroiditis, and simple goiter in one family.

Pendred syndrome is the autosomal recessively transmitted association of familial goiter and congenital deafness. There is no specific biochemical marker of this disease, and the diagnosis depends upon the demonstration of the triad of congenital sensorineural hearing loss, goiter, and abnormal perchlorate discharge test. Pendred syndrome is caused by mutations within the putative ion transporter gene (PDS gene), located on chromosome 7q. A wide variation in the clinical presentation of this condition, and its well documented phenotypic overlap with other thyroid disorders (such as Hashimoto's thyroiditis), can lead to diagnostic difficulties. The potential for misdiagnosis increases when these disorders occur coincidentally in the same family. We describe a kindred in which Pendred syndrome, autoimmune thyroiditis, and simple goiter coexisted, to highlight these diagnostic pitfalls and to illustrate the use of mutational analysis in resolving diagnostic confusion.

Genomic structure of the human congenital chloride diarrhea (CLD) gene.

Congenital chloride diarrhea (CLD) is caused by mutations in a gene which encodes an intestinal anion transporter. We report here the complete genomic organization of the human CLD gene which spans approximately 39kb, and comprises 21 exons. All exon/intron boundaries conform to the GT/AG rule. An analysis of the putative promoter region sequence shows a putative TATA box and predicts multiple transcription factor binding sites. The genomic structure was determined using DNA from several sources including multiple large-insert libaries and genomic DNA from Finnish CLD patients and controls. Exon-specific primers developed in this study will facilitate mutation screening studies of patients with the disease. Genomic sequencing of a BAC clone H_RG364P16 revealed the presence of another, highly homologous gene 3' of the CLD gene, with a similar genomic structure, recently identified as the Pendred syndrome gene (PDS).

Safety testing of needle free, jet injection devices to detect contamination with blood and other tissue fluids.

Needle free jet injection guns have been used extensively in both veterinary and human health to deliver both vaccine and drugs, but in recent years, concerns have mounted for their potential to transmit blood borne disease agents among consecutive vaccinates. A Ped-O-Jet type jet injection device was used to deliver serial subcutaneous injections of 0.5 mL saline (as a surrogate for vaccine) into calves and pigs, with intervening ejectates collected in vials to represent what the next vaccinate would have received. An enzyme linked immunosorbant assay was developed to detect species specific albumin as a marker for blood, using calibration standards from known dilutions of bovine or porcine blood. Assay sensitivity of 20 pL/mL corresponded to the estimated minimal chimpanzee infectious dose of 10 pL for hepatitis B virus. The methodology and available results for evaluating the safety of jet injector devices are reported.

The effects of patient characteristics and beliefs on responses to behavioral interventions for control of chronic diseases.

Tests of behavioral interventions seldom examine changes in health beliefs and behaviors thought to be prerequisites of improved outcome health states and they do not attempt to specify how patient characteristics or pretest measures influence responses to the intervention. In this study an experimental nursing intervention, its impact on hypertensive patients' beliefs about their disease, efficacy of medications and diet, as well as blood pressure and weight are described. Among patients from the experimental group, the ability of selected pretest variables to predict clinical outcomes and changes in clinical health states was evaluated. The intervention was successful in lowering diastolic blood pressure and altering certain beliefs held by the patients. The pretest characteristics were not successful in explaining hypertensive patients' responses to the intervention. Explanations for this are pursued through remarks from the content analysis of the intervention protocol. From these observations, the original health belief model was revised. The discussion concludes with a set of research questions that may prove promising for future research.

Patient literacy and the readability of written cancer educational materials.

PURPOSE/OBJECTIVES: The purpose of this study was to determine whether the reading level of educational materials for patients with cancer corresponds to the reading abilities of a sample of patients. A secondary aim was to describe what type of educational materials patients with cancer report as most helpful. DESIGN: Descriptive, cross-sectional. SETTING: Outpatient oncology clinics at an urban Veterans Affairs Medical Center. SAMPLE: A convenience sample of 63 outpatients with cancer. METHODS: Investigators used the Word Recognition Achievement Test-Revised Level (WRAT-R2) to measure patients' reading levels. They used the Flesch Index to analyze the reading levels of the booklets that the patients used (14 booklets developed by the American Cancer Society and 16 developed by the National Cancer Institute). Data were analyzed through descriptive statistics and a Wilcoxon signed rank test. MAIN RESEARCH VARIABLES: Patient and booklet reading levels. FINDINGS: The reading level of 27% of the sample was less than that of all 30 pamphlets (less than a sixth-grade reading level). Seventeen percent of the patients had a reading level between sixth and eighth grades (representing 47% of the pamphlets). Twenty-nine percent of the sample had WRAT scores between 9th and 12th grades (representing 80% of the pamphlets). Only 27% had WRAT scores of the 13th grade and above. Twenty-six percent of the patients preferred written educational materials alone, while 57% of patients desired more than one method of instruction. CONCLUSION: Written materials for the education of patients with cancer must be carefully matched to patient reading levels. Written materials may not be the only desirable mode of instruction. IMPLICATIONS FOR NURSING PRACTICE: Given the increasing complexity of cancer care, shorter hospital stays, and a shift toward busy ambulatory care centers, nurses need to develop creative, innovative, and comprehensive patient education programs that are understandable to patients and that use multiple types of instruction.

The prevalence of physical and sexual abuse in women veterans seeking care at a Veterans Affairs Medical Center.

Physical and sexual abuse are increasingly recognized as common harmful experiences for women. We surveyed 828 women veterans seeking care at the Baltimore Veterans Affairs Medical Center to determine the prevalence of physical and sexual abuse experiences, both during and outside of military service. Data were collected through an anonymous, mailed questionnaire, with a response rate of 52%. Sixty-eight percent of respondents reported at least one form of abuse, and 27% reported all three. Sexual abuse was most common (55%), followed by physical abuse (48%), and rape (41%). Enlisted women, women younger than 50, and single, separated, or divorced women were significantly more likely to report abusive experiences. Over 40% of the women reporting abuse were never victimized while on active duty, and these women were less likely to receive counseling. Physical and sexual abuse experiences are disturbingly common among women veterans and demonstrate the need for additional services to assist these women.

PIP: A survey to determine the prevalence of physical and sexual abuse experiences, during and outside of military service, was conducted among 828 women veterans at the Baltimore Veterans Affairs Medical Center. Data collection was through anonymous, mailed questionnaire. Three questions were used to elicit histories of physical abuse, sexual abuse, and rape. From the survey, 429 completed forms (52%) were returned. Most of the veterans had at least some college education and about 50% served 4 or more years on active duty. About 68% of the respondents reported at least one form of victimization, while 27% reported to have undergone all three forms, of which sexual abuse was the most common, followed by physical abuse and then rape. It was in adulthood that all three forms of abuse took place with one-third of the women reporting victimization during active duty. However, 50% of the women veterans reporting physical abuse, 44% reporting sexual abuse, and 52% reporting rape were never victimized during their military careers. Single women and divorced women were more likely to report victimization. In conclusion, physical and sexually abused veteran women were the ones more likely seeking care at the center.

Use of filters to treat visual-perception problem creates adherents and sceptics.

Patients who think they have a visual-perception dysfunction known as scotopic sensitivity-Irlen syndrome have trouble reading and may experience almost-constant headaches. Some find they are helped by coloured filters developed by a California researcher, Helen Irlen, who published a book on the subject called Reading by the Colors. Although Irlen has been criticized for not publishing scientific proof of the validity of her theories, her techniques have found some support, including some within the medical community.

Nuclear magnetic resonance: a review of principles and applications in medicine and chiropractic.

Nuclear Magnetic Resonance (NMR) has in principle been known since 1946 and has found many applications in the fields of physics and chemistry. However, although it has only been in recent years that it has found potential use in various fields of medicine, it is rapidly proceeding from research and development to the practical clinical stage. This paper seeks to provide a brief review of NMR principles and, applications current in medicine, and potential applications in the field of chiropractic.

A Review And Critique Of Analyses Of Multitrait-Multimethod Matrices.

Six methods of evaluating the degree to which multitrait-multimethod matrices meet the Campbell-Fiske criteria (1959) for construct validity are illustrated and evaluated. It is concluded that the path analytic method (Werts & Linn, 1970) provides the most detailed information regarding individual traits and methods as well as permitting the evaluation of alternate models of the data which involve rank reduction in methods, traits, or both. The analysis of variance technique (Kavanagh, et al, 1971) provides summary data based on the full matrix which can be useful for inter-matrix comparisons but does not assess the conformity of individual traits or methods to Campbell-Fiske criteria. The various factor analytically based approaches (Golding & Seidman, 1974; Jackson, 1975; Tucker, 1966) are most useful when one is interested in exploring the factor structure of a set of data across data collection methods.