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J Curran

Publications and source records attributed to J Curran.

At least 37 records · Page 2Linked to original sources
PubMed2000

Conditional genotypic probabilities for microsatellite loci.

Modern forensic DNA profiles are constructed using microsatellites, short tandem repeats of 2-5 bases. In the absence of genetic data on a crime-specific subpopulation, one tool for evaluating profile evidence is the match probability. The match probability is the conditional probability that a random person would have the profile of interest given that the suspect has it and that these people are different members of the same subpopulation. One issue in evaluating the match probability is population differentiation, which can induce coancestry among subpopulation members. Forensic assessments that ignore coancestry typically overstate the strength of evidence against the suspect. Theory has been developed to account for coancestry; assumptions include a steady-state population and a mutation model in which the allelic state after a mutation event is independent of the prior state. Under these assumptions, the joint allelic probabilities within a subpopulation may be approximated by the moments of a Dirichlet distribution. We investigate the adequacy of this approximation for profiled loci that mutate according to a generalized stepwise model. Simulations suggest that the Dirichlet theory can still overstate the evidence against a suspect with a common microsatellite genotype. However, Dirichlet-based estimators were less biased than the product-rule estimator, which ignores coancestry.

Alleles↗
PubMed2000

Sendai virus C proteins must interact directly with cellular components to interfere with interferon action.

Sendai virus (SeV) infection of interferon (IFN)-competent cells is one of the most efficient ways of inducing IFN production. Virus replication is nevertheless largely unaffected, since SeV infection also interfers with IFN action, a prerequisite for the establishment of an antiviral state. This property has been mapped by reverse genetics to the viral C gene, which is also known to act as a promoter-specific inhibitor of viral RNA synthesis. Using luciferase reporter plasmids containing IFN-responsive promoters, we have found that all four C proteins effectively interdict IFN signaling when expressed independently of SeV infection. The C proteins must therefore interact directly with cellular components to carry this out. The C gene in the context of an SeV infection was also found to induce STAT1 instability in some cells, whereas in other cells it apparently acts to prevent the synthesis of STAT1 in response to the virus infection or IFN treatment. The SeV C proteins appear to act in at least two ways to counteract the IFN induced by SeV infection.

Animals↗
PubMed1999

Replication of paramyxoviruses.

Molecular studies on the replication of paramyxoviruses have undergone a revolution in recent years due to the development of techniques that permit the manipulation of their genomes as cDNA. This has led to new information on the structure-function organization of the viral proteins involved in genome expression, as well as dissection of the cis-acting template sequences that regulate transcription and replication. Studies using recombinant viruses have also provided new insights into the role of the accessory proteins (V, C, M1/M2) in both for virus growth in cultured cells and pathogenesis in animals.

Paramyxoviridae↗
PubMed1999

Smokers and haemodynamic responses to desflurane.

Changes in basic haemodynamic variables following a sudden increase in the concentration of inspired desflurane administered during anaesthesia were compared in 30 female smokers and 30 nonsmokers. Smokers had significantly greater percentage increases in heart rate (p = 0.02), systolic and diastolic blood pressure (p < 0.005 and = 0.01, respectively) and rate-pressure product (p < 0.005). Such increases were reached faster by smokers for both systolic and diastolic blood pressures (p < 0.01) and for rate-pressure product (p = 0.02). The peak values of rate pressure product reached were sufficient to warrant caution when using desflurane for anaesthesia in smokers.

Adult↗
PubMed1999

Comparison of ondansetron and cyclizine for prevention of nausea and vomiting after day-case gynaecological laparoscopy.

We have compared ondansetron 4 mg i.v. and cyclizine 50 mg i.v., in a double-blind, randomized, placebo-controlled study for the prevention of postoperative nausea and vomiting (PONV) for 24 h after day-case gynaecological laparoscopy. Compared with placebo (n = 58), ondansetron (n = 60) and cyclizine (n = 57) reduced significantly the incidence of moderate or severe nausea (30% and 23% vs 52%; P = 0.02 and P = 0.001, respectively) and requirement for escape antiemetic (28% and 16% vs 47%; P = 0.04 and P < 0.001, respectively) before discharge from hospital. There were no significant differences in PONV after discharge. Significantly more patients suffered no PONV before and after discharge after ondansetron and cyclizine compared with placebo (31% and 33% vs 12%; P = 0.02 and P < 0.01, respectively). For diagnostic laparoscopy (n = 74), fewer patients received escape antiemetic after cyclizine than after ondansetron (4% vs 37%; P < 0.01); for laparoscopic sterilization (n = 101), both antiemetics were equally effective. Ondansetron and cyclizine both reduced severe and moderate nausea and the need for antiemetic therapy after day-case gynaecological laparoscopy.

Adult↗
PubMed1999

The influence of breathing system filters on paediatric capnography.

Breathing system filters are in common use during paediatric anaesthesia. Expired gas sampling from the patient side of these filters may contaminate and saturate the sampling line, while sampling from the machine side may cause underestimation of end-tidal carbon dioxide (PECO 2). The aim of this investigation was to elucidate the degree of underestimation of PECO 2 induced by sampling from the machine side of a breathing system filter. Ten spontaneously breathing children and ten children receiving mechanical ventilation under general anaesthesia were studied. PECO 2 was higher at the patient side of the filter in both ventilated and spontaneously breathing groups (P<0.002 for each). The bias in measuring at the machine side of the filter was significantly greater in the spontaneously breathing children as compared with the mechanically ventilated children (-1.8 vs -0.7 kPa; P<0.004).

Anesthesia, General↗
PubMed1998

Reliability of medial temporal lobe volume measurements using reformatted 3D images.

The study assessed whether standardizing the angle of image display and controlling for head position in three planes affects the scan-rescan reliability of medial temporal lobe volume measures when very thin (1.5 mm) slices are used. Five volunteers were scanned two times on consecutive days. A three-dimensional MRI sequence acquired whole brain data in 1.4 mm thick coronal slices. The data were displayed as 1.5 mm thick images and were rated both in the originally acquired coronal plane, and after reformatting to correct for head tilt and display the brain in the coronal plane perpendicular to the long axis of the left anterior hippocampus. One rater measured five brain regions (temporal lobe, anterior and posterior hippocampus, amygdala, and temporal horn) on the left and right sides of the two non-reformatted and two reformatted scans to obtain inter-scan variance. Furthermore, most scans were remeasured, to obtain 'reread' variances. All data were log-transformed in order to produce comparable variability across brain regions of different sizes. For all the regions, except the temporal horn, the non-reformatted scans showed significantly larger scan-rescan variability than the reformatted scans. A typical standard deviation for a non-reformatted pair of scans was 0.10, corresponding to 26% error, while a typical value for a reformatted pair of scans was 0.04, corresponding to 10% error. For all the regions, the reread data (intra-rater reliability) gave similar results for both reformatted and non-reformatted images with similar standard deviations (typical value for reread standard deviation was 0.020, corresponding to 5% error). The data suggest that, even when very thin slices are acquired, volume measurement accuracy of gray matter structures in the temporal lobe is considerably improved by controlling for image orientation in three planes. For these structures, the sample size needed to detect a small (5%) within-subject volume change would be halved if reformatted images were used. Image contrast is an additional important factor since the reformatted T1 weighted images used in this study, which have suboptimal CSF/brain contrast, worsened measurement accuracy in the temporal horn.

Adult↗
PubMed1998

Pediatric low-grade gliomas: prognosis with proton magnetic resonance spectroscopic imaging.

OBJECTIVE: Our aim was to assess the correlation between the low-grade glioma (LGG) metabolic profile and tumor progression. Using in vivo proton magnetic resonance spectroscopic imaging, we specifically asked whether and which metabolic features are associated with tumor regrowth or recurrence. METHODS: Eleven pediatric patients with histologically proven partially resected (<20% resection) midline LGG were treated and followed up for a period of 2 years. All patients underwent proton magnetic resonance spectroscopic imaging studies before any management was determined. Tumor progression was defined as radiological evidence of mass enlargement (>25%) during the follow-up period. Proton magnetic resonance spectroscopic imaging was performed using a PRESS-CSI sequence on a General Electric 1.5-tesla scanner (General Electric Medical System, Waukesha, WI). The signal intensities of N-acetylaspartate, choline (CHO), and creatine from the tumor and the normal brain were used to calculate normalized metabolite intensities and metabolite ratios. RESULTS: Tumors that progressed during a 2-year period displayed higher normalized CHO than those that remained stable (Mann-Whitney test, P < 0.03). The majority (five of six) of the rapidly growing LGG showed values of normalized CHO of at least 1, whereas the nonprogressors had a normalized CHO value of less than 1. CONCLUSION: In association with pediatric LGG, high normalized CHO values seem to herald the potential for rapid tumor growth. These observations may be valuable for defining subsets of patients with LGG who may benefit from early therapeutic interventions.

Adolescent↗
PubMed1998

A role for the Sendai virus P protein trimer in RNA synthesis.

The SeV P protein is found as a homotrimer (P3) when it is expressed in mammalian cells, and trimerization is mediated by a predicted coiled-coil motif which maps within amino acids (aa) 344 to 411 (the BoxA region). The bacterially expressed protein also appears to be trimeric, apparently precluding a role for phosphorylation in the association of the P monomers. I have examined the role of P trimerization both in the protein's interaction with the nucleocapsid (N:RNA) template and in the protein's function on the template during RNA synthesis. As with the results of earlier experiments (32), I found that both the BoxA and BoxC (aa 479 to 568) regions were required for stable binding of P to the N:RNA. Binding was also observed with P proteins containing less than three BoxC regions, suggesting that trimerization may be required to permit contacts between multiple BoxC regions and the N:RNA. However, these heterologous trimers failed to function in viral RNA synthesis, indicating that the third C-terminal leg of the trimer plays an essential role in P function on the template. We speculate that this function may involve the movement of P (and possibly the polymerase complex) on the template and the maintenance of processivity.

HeLa Cells↗
PubMed1998

The various Sendai virus C proteins are not functionally equivalent and exert both positive and negative effects on viral RNA accumulation during the course of infection.

Recombinant Sendai viruses were prepared which cannot express their Cprime, C, or Cprime plus C proteins due to mutation of their respective start codons ([Cprime-minus], [C-minus] and [double mutant], respectively). The [Cprime-minus] and [C-minus] stocks were similar to that of wild-type (wt) virus in virus titer and plaque formation, whereas the double-mutant stock had a much-reduced PFU or 50% egg infective dose/particle ratio and produced very small plaques. Relative to the wt virus infection, the [Cprime-minus] and [C-minus] infections of BHK cells resulted in significantly greater accumulation of viral RNAs, consistent with the known inhibitory effects of the Cprime and C proteins. The double-mutant infection, in contrast, was delayed in its accumulation of viral RNAs; however, once accumulation started, overaccumulation quickly occurred, as in the single-mutant infections. Our results suggest that the Cprime and C proteins both provide a common positive function early in infection, so that only the double mutant undergoes delayed RNA accumulation and exhibits the highly debilitated phenotype. Later in infection, the same proteins appear to act as inhibitors of RNA accumulation. In infections of mice, [Cprime-minus] was found to be as virulent as wt virus whereas [C-minus] was highly attenuated. These results suggest that the Cprime and C proteins cannot be functionally equivalent, since C can replace Cprime for virulence in mice whereas Cprime cannot replace C.

Animals↗
PubMed1998

Sendai virus Y proteins are initiated by a ribosomal shunt.

The Sendai virus P/C mRNA expresses eight primary translation products by using a combination of ribosomal choice and cotranscriptional mRNA editing. The longest open reading frame (ORF) of the mRNA starts at AUG104 (the second initiation site) and encodes the 568-amino-acid P protein, an essential subunit of the viral polymerase. The first (ACG81), third (ATG114), fourth (ATG183), and fifth (ATG201) initiation sites are used to express a C-terminal nested set of polypeptides (collectively named the C proteins) in the +1 ORF relative to P, namely, C', C, Y1, and Y2, respectively. Leaky scanning accounts for translational initiation at the first three start sites (a non-ATG followed by ATGs in progressively stronger contexts). Consistent with this, changing ACG81/C' to ATG (GCCATG81G) abrogates expression from the downstream ATG104/P and ATG114/C initiation codons. However, expression of the Y1 and Y2 proteins remains normal in this background. We now have evidence that initiation from ATG183/Y1 and ATG201/Y2 takes place via a ribosomal shunt or discontinuous scanning. Scanning complexes appear to assemble at the 5' cap and then scan ca. 50 nucleotides (nt) of the 5' untranslated region before being translocated to an acceptor site at or close to the Y initiation codons. No specific donor site sequences are required, and translation of the Y proteins continues even when their start codons are changed to ACG. Curiously, ATG codons (in good contexts) in the P ORF, placed either 16 nt upstream of Y1, 29 nt downstream of Y2, or between the Y1 and Y2 codons, are not expressed even in the ACGY1/ACGY2 background. This indicates that ATG183/Y1 and ATG201/Y2 are privileged start sites within the acceptor site. Our observations suggest that the shunt delivers the scanning complex directly to the Y start codons.

Base Sequence↗
PubMed1998

Cerebral 1H MR spectroscopy and neuropsychologic status of patients with hepatic encephalopathy.

OBJECTIVE: Our objective was to assess the metabolite levels (myo-inositol [ml], choline [Cho], creatine [Cr], glutamate or glutamine [Glx], and N-acetyl-L-aspartate [NAA]) visible on 1H MR spectroscopy in patients with subclinical and mild hepatic encephalopathy before and after liver transplantation and to correlate these data with the results of neuropsychiatric tests and related clinical findings. SUBJECTS AND METHODS: A stimulated-echo sequence was used to localize a single voxel in the parietal region. Seventeen patients and 13 healthy volunteers were investigated. Nine of the 17 patients also were investigated after liver transplantation. A battery of neuropsychologic tests also was administered to patients to assess frontal, memory, and motor functions. RESULTS: Before liver transplantation, significant reductions in mI:Cr (51%) and Cho:Cr (11%) and a significant increase in Glx:Cr (20%) were observed in patients compared with the respective ratios in healthy subjects. Patients also were significantly impaired on neuropsychologic tests measuring frontal and motor performance, but not memory. Impairment on the frontal index showed a significant correlation with mI:Cr levels; likewise, performance on the motor index showed a significant correlation with serum ammonia levels before transplantation. MR spectroscopy after liver transplantation showed changes in the metabolite ratios compared with the pretransplantation status. Even though the Glx:Cr ratios decreased after transplantation, the mI:Cr ratio remained lower than those of healthy subjects. CONCLUSION: The relationship of changes in the metabolite ratios recorded from a voxel in the posteromedial parietal lobe to the neuropsychologic findings before and after liver transplantation is a major finding.

Adult↗
PubMed1998

Proton MR spectroscopy in Lesch-Nyhan disease.

In vivo proton spectra for four patients with Lesch-Nyhan disease and four control subjects matched for age and sex were acquired from voxels (1.5 x 1.5 x 1.5 cm3) placed in the prefrontal cortex and striatum. The patients with Lesch-Nyhan disease had decreased metabolites, especially N-acetylaspartate and glutamate/glutamine, only in the prefrontal cortex as compared with the control group. These findings suggest axonal loss in the prefrontal area of this population. The cortical glutamate/glutamine peak decrement does not confirm cytopathologic studies of Lesch-Nyhan disease and deserves further investigation.

Adolescent↗
PubMed1997

End-tidal carbon dioxide measurement and breathing system filters.

Breathing system filters are recommended for use during general anaesthesia. Manufacturers of gas sampling equipment recommend that gas is sampled from the 'machine side' of these filters, thereby avoiding contamination of the sampling line and waterlogging in the case of heat and moisture exchangers. The aim of this study was to investigate differences between the measured end-tidal carbon dioxide values at either side of the filter. Fifteen adults were studied during mechanical ventilation and 15 during spontaneous ventilation under general anaesthesia. End-tidal carbon dioxide values were significantly lower at the machine side of the filter in both groups (p = 0.00001). The measurement error induced by the inclusion of the breathing system filter was significantly greater in the spontaneously breathing group (p = 0.0004).

Adult↗
PubMed1997

Inhibition of Sendai virus genome replication due to promoter-increased selectivity: a possible role for the accessory C proteins.

The role of the negative-stranded virus accessory C proteins is difficult to assess because they appear sometimes as nonessential and thereby of no function. On the other hand, when a function is found, as in the case of Sendai virus, it represents an enigma, in that the C proteins inhibit replication under conditions where the infection follows an exponential course. Furthermore, this inhibitory function is exerted differentially: in contrast to the replication of internal deletion defective interfering (DI) RNAs, that of copy-back DI RNAs appears to escape inhibition, under certain experimental conditions (in vivo assay). In a reexamination of the C effect by the reverse genetics approach, it was found that copy-back RNA replication is inhibited by C in vivo as well, under conditions where the ratio of C to copy-back template is increased. This effect can be reversed by an increase in P but not L protein. The "rule of six" was differentially observed in the presence or absence of C. Finally, a difference in the ability of the replicating complex to tolerate promoter modifications in RNA synthesis initiation was shown to occur in the presence or the absence of C as well. We propose that C acts by increasing the selectivity of the replicating complex for the promoter cis-acting elements governing its activity. The inhibitory effect of C becomes the price to pay for this increased selectivity.

DNA-Directed RNA Polymerases↗