Simultaneous presence of t(10;11)(p12;q23) and t(11;19)(q23;p13.1) in an infantile acute myeloid leukemia.
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Biomedical subjects
Publications and source records attributed to John Quinn.
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A panel of hybridomas was produced using intact Listeria monocytogenes serotype 1/2a cells as the immunogen. An IgG2a monoclonal antibody (mAb) 'mAb2B3' was isolated that reacted with L. monocytogenes but not with a representative panel of related Listeria spp. and non-Listeria spp. Binding activity was greatest against L. monocytogenes serotype 1/2a and was significantly enhanced when cells were prepared in Listeria enrichment broth (LEB). The reactive epitope was deduced, by immunoblot analysis, to be a surface localised protein of approximately 80 kilodaltons (kDa), putatively assumed to be internalin A (InlA). Recombinant InlA protein was subsequently expressed in Escherischia coli. When crude E. coli cell lysates were subjected to immunoblot analysis, it was demonstrated that the mAb bound specifically to the heterologously expressed recombinant InlA protein, thus confirming the specificity of the mAb. The mAb was further evaluated in a series of enzyme-linked-immunosorbent assay (ELISA)-based formats and in a surface plasmon resonance (SPR)-based biosensor platform. Both configurations were capable of differential identification of virulent L. monocytogenes at concentrations greater than or equal to 1x10(7) cells/ml. Notwithstanding the apparent insensitivity, the results indicate that InlA could be exploited as a marker for highly specific confirmatory identification of pathogenic L. monocytogenes following primary enrichment of suspect food samples, using the anti-InlA antibody 'mAb2B3', described herein.
Psychological trauma is a major public-health problem, and trauma victims frequently turn to the Internet for medical information related to trauma. The Internet has many advantages for trauma victims, including low cost, privacy, use of access, and reduced direct social interactions. However, there are no regulations on what is posted on the Internet, or by whom, and little is known about the quality of information currently available related to the topic of psychological trauma. The purpose of this study was to evaluate the quality of Internet sites related to the topic of psychological trauma. The top 20 hits for searches on Google, AllTheWeb, and Yahoo were tabulated, using search words of 'psychological trauma', 'stress', 'PTSD', and 'trauma'. From these searches, a list of 94 unique unsponsored hits that represented accessible websites was generated. Fourteen sites were unrelated or only peripherally related, and eight were related but were not comprehensively evaluated because they represented brochures, online book sales, etc. Seventy-two websites underwent evaluation of the content, design, disclosure, ease of use, and other factors based on published guidelines for medical information sites. Forty-two per cent of sites had inaccurate information, 82% did not provide a source of their information, and 41% did not use a mental-health professional in the development of the content. Ratings of content (e.g. accuracy, reliability, etc.) were 4 (2 SD) on a scale of 1 - 10, with 10 being the best. There were similar ratings for the other variables assessed. These findings suggest that although abundant, websites providing information about psychological trauma are often not useful, and can sometimes provide inaccurate and potentially harmful information to consumers of medical information.
Imipenem-resistant Serratia marcescens isolates were cultured from a lung transplant patient given multiple antibiotics over several months. The strains expressed SME-3, a beta-lactamase of the rare SME carbapenem-hydrolyzing family. SME-3 differed from SME-1 by a single amino acid substitution of tyrosine for histidine at position 105, but the two beta-lactamases displayed similar hydrolytic profiles.
We performed an extensive genetic association study of the six known apolipoprotein-L (APOL) genes and schizophrenia (SZ) using a novel DNA pooling strategy. The APOL genes are both positional and functional candidate genes for SZ. This gene family maps to chromosome 22q12.3, a region implicated by SZ linkage studies as likely to contain one or more SZ susceptibility genes. A recent gene expression study demonstrated up-regulation of APOL1, 2, and 4 in post-mortem brain samples from SZ patients compared to controls in two independent samples. To test for genetic association with SZ, we analyzed 143 SNPs from dbSNP from across the APOL genes in an Irish sample of 219 cases and 231 controls. Of these 143 SNPs, 51 (36%) were polymorphic in our Irish sample and were genotyped using a novel three-stage DNA pooling strategy. This strategy does not require the identification of a heterozygous individual for DNA pooling association analysis and is therefore very efficient when using public database SNPs. We found no evidence to support the hypothesis that genetic variation at the APOL genes contributes to SZ susceptibility in our sample.
We describe a case of blood transfusion-dependent myelodysplastic syndrome (refractory anaemia), associated with macrocytosis and elevated percentage of hypochromic cells. Following an acute hospital admission with a respiratory tract infection, the patient entered a complete and sustained remission.
The NO-cGMP pathway has emerged as a neuroprotective signaling system involved in communication between neurons and glia. We have previously shown that axotomy or nerve growth factor (NGF)-deprivation of dorsal root ganglion (DRG) neurons leads to increased production of NO and at the same time an increase in cGMP production in their satellite glia cells. Blockade of NO or its receptor, the cGMP synthesizing enzyme soluble guanylate cyclase (sGC), results in apoptosis of neurons and glia. We now show that co-culture of neonatal DRG neurons with either Schwann cells pre-treated with an NO donor or a membrane-permeant cGMP analogue; or neurons maintained in the medium from Schwann cell cultures treated in the same way, prevents neuronal apoptosis. Both NO donor and cGMP treatment of Schwann cells results in synthesis of NGF and NT3. Furthermore, if the Schwann cells are previously infected with adenoviral vectors expressing a dominant negative sGC mutant transgene, treatment of these Schwann cells with an NO donor now fails to prevent neuronal apoptosis. Schwann cells treated in this way also fail to express neither cGMP nor neurotrophins. These findings suggest NO-sGC-cGMP-mediated NGF and NT3 synthesis by Schwann cells protect neurons.
OBJECTIVE: To compare expert-generated textual summaries of physiological data with trend graphs, in terms of their ability to support neonatal Intensive Care Unit (ICU) staff in making decisions when presented with medical scenarios. METHODS: Forty neonatal ICU staff were recruited for the experiment, eight from each of five groups--junior, intermediate and senior nurses, junior and senior doctors. The participants were presented with medical scenarios on a computer screen, and asked to choose from a list of 18 possible actions those they thought were appropriate. Half of the scenarios were presented as trend graphs, while the other half were presented as passages of text. The textual summaries had been generated by two human experts and were intended to describe the physiological state of the patient over a short period of time (around 40 minutes) but not to interpret it. RESULTS: In terms of the content of responses there was a clear advantage for the Text condition, with participants tending to choose more of the appropriate actions when the information was presented as text rather than as graphs. In terms of the speed of response there was no difference between the Graphs and Text conditions. There was no significant difference between the staff groups in terms of speed or content of responses. In contrast to the objective measures of performance, the majority of participants reported a subjective preference for the Graphs condition. CONCLUSIONS: In this experimental task, participants performed better when presented with a textual summary of the medical scenario than when it was presented as a set of trend graphs. If the necessary algorithms could be developed that would allow computers automatically to generate descriptive summaries of physiological data, this could potentially be a useful feature of decision support tools in the intensive care unit.
A polyclonal antibody was produced against Internalin B (InlB)-enriched extract and used to develop an inhibition assay to detect Listeria monocytogenes cells in solution using surface plasmon resonance. The gene sequence encoding for the InlB protein was cloned into a Qiagen pQE-60 vector, expressed in Escherichia coli, and purified by immobilized metal affinity chromatography. Protein G-purified anti-InlB-enriched extract polyclonal antibody was incubated with various concentrations of L. monocytogenes cells and subsequently injected over a purified-recombinant InlB (rInlB)-immobilized CM5 sensor chip surface. A decrease in antibody binding response was observed with increasing L. monocytogenes cell concentrations. Intraday and interday assay variability studies were carried out to evaluate precision and reproducibility. The assay had a limit of detection of less than 2 x 10(5) cells per ml and could be successfully reproduced with coefficients of variation of between 2.5 and 7.7%.
During early embryonic (E12) development almost all dorsal root ganglion (DRG) neurons express the neuronal isoform of nitric oxide synthase (nNOS). At this stage, the axons of these neurons are rudimentary and have not made contact with peripheral tissue targets. As their axons establish contact with peripheral targets such as the skin, the number of neurons expressing nNOS decrease that correspond to increased immunoreactivity for nerve growth factor (NGF) in the skin, and its high affinity receptor, tyrosine kinase A (trkA) in both skin and DRG neurons. During late postnatal development, very few DRG neurons express nNOS; however, axotomy or NGF deprivation of cultured DRG neurons induce nNOS and NOS blockade causes neuronal death. In contrast, NGF-deprived embryonic and neonatal DRG neurons die by apoptosis, while NOS blockade has no effect. Overall, these observations suggest that NGF and nitric oxide (NO) interact during embryonic and postnatal development to facilitate neuronal selection and survival. The roles of NO, NGF and its receptor trkA in DRG neurons during different stages of development are discussed.
The opportunistic food pathogen Listeria monocytogenes is of great concern to the food industry and its rapid detection is of major importance. This paper describes the detection of L. monocytogenes with a polyclonal antibody by means of a new subtractive inhibition assay using a BIAcore 3000 biosensor. Incubating L. monocytogenes cells and antibody for a short period of time, followed by subsequent separation of free unbound antibody with a stepwise centrifugation process, allowed the detection of 1 x 10(5) L. monocytogenes cells/ml in less than 30 min. Free antibody was passed over an anti-Fab ligand-coated sensor chip surface with the generated response being inversely proportional to the inhibiting cell concentration. The method was simple, rapid and needed minimum sample preparation. This assay format has the potential for the quick and sensitive detection of pathogens with limited sample handling and preparation.
A recent study identified a putative association between variants in the regulator of G-protein signalling 4 (RGS4) and schizophrenia, Chowdari et al. [2002: Hum Mol Genet 11: 1373-1380]. RGS4 is both a positional and functional candidate gene for schizophrenia. Chowdari and colleagues identified association at this locus in a number of distinct and ethnically diverse samples, although the pattern of association was not the same in all the samples. Our study attempted to replicate this association in an independent Irish sample of schizophrenia cases and controls. We succeeded in detecting evidence of association at the RGS4 locus. The signal comes from a four-marker haplotype that is in significant excess in our case sample. The same haplotype is in excess in the Caucasian schizophrenia sample used by Chowdari et al. [2002: Hum Mol Genet 11: 1373-1380]. This study provides further support for the contribution of RGS4 to schizophrenia susceptibility.
A recent family-based association study identified a putative association between variants in the dystrobrevin binding protein 1 (dysbindin) gene (DTNBP1) and schizophrenia. This study used a sample of 270 Irish pedigrees multiply affected with schizophrenia. We attempted to replicate these findings in an independent Irish sample of 219 schizophrenia cases and 231 controls. No evidence was found to suggest an association between the DTNBP1 gene and schizophrenia in our sample. Possible reasons for these findings are discussed.
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We have produced a yeast artificial chromosome (YAC) transgenic model containing the human preprotachykinin-A gene (hPPTA) that can drive appropriate expression of beta-galactosidase within the adult mouse brain. Here, we investigate its embryonic expression to assess the transcriptional regulation of the PPTA gene during the development of several neural pathways later affected by disease in humans. We demonstrate that the human PPTA gene regulatory region is active in appropriate areas of the developing brain at significantly earlier time points than has been previously reported. Furthermore, despite replacement of most of the 3' untranslated region by the marker gene cassette, the modified human YAC is able to express substance P (SP) on a murine SP/NKA(-/-) background. This transgenic model, in addition to being valuable in examining the hPPTA regulatory region, will also prove to be important in exploring the downstream function of the gene in the adult and the embryo brain.
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A challenge faced by the Center for Drug Evaluation and Research (CDER) in effectively carrying out its mission requires it to integrate the disciplines of science, medicine, law, and public policy. One way to do that is by ensuring a highly trained multidisciplinary staff. The CDER has been able to meet this requirement by identifying the core competencies needed to accomplish its mission. The use of a competency-based training model in the planning, development, and delivery of its advanced scientific education program allows CDER staff to maintain current knowledge as well as prepare for future scientific education needs. The CDER educational model could be readily adapted to meet the educational needs of other organizations.
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