PubMed Health⌕ Search

Biomedical subjects

J Curran

Publications and source records attributed to J Curran.

At least 19 recordsLinked to original sources
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↗
PubMed1996

Reexamination of the Sendai virus P protein domains required for RNA synthesis: a possible supplemental role for the P protein.

The Sendai virus P protein plays a central role in viral genome amplification and expression, forming complexes with the viral L protein to generate the polymerase (P-L) and unassembled N (P-N(o)). This latter complex prevents N from self-assembling illegitimately, i.e., independently of the concurrent assembly of a nascent viral genome, and is thought to represent the functional form of N in nucleocapsid assembly. Based upon earlier functional studies using an in vitro transcription/ replication system in which the P, L, and N proteins were coexpressed, we identified two regions of the P protein required for RNA synthesis, namely, the C-terminal 40% of the protein, and a second, apparently redundant domain near the N-terminus (either amino acids 1-77 or 78-145). The lack of sequence conservation in this second region, apart from overall negative charge, was reminiscent of the acidic activation domains of cellular transcription factors. However, we recently mapped a chaperone domain at the N-terminal of P (aa 33-41), which is required for stable complex formation with unassembled N(o) and, thus, for assembly and genome replication. In this present study we show that coexpression of N protein with P deletion mutants lacking this region (e.g., P delta 1-324) results in the sequestration of the mutant P by the illegitimately assembled form of N. As a consequence, P protein is unavailable for RNA synthesis from bona fide templates. We also find that in the absence of coexpressed N protein, the entire N-terminal 60% of the P protein is not required for mRNA synthesis. During these studies, a supplemental role for the P protein in viral RNA synthesis, independent of stable complex formation with L, was observed. This function involves, at least in part, the binding of additional copies of P to the N:RNA template.

Binding Sites↗
PubMed1996

Rescue of Sendai virus cDNA templates with cDNA clones expressing parainfluenza virus type 3 N, P and L proteins.

Several years ago, we reported that a Sendai virus (SeV) defective genome (DIH4UV) could be rescued in vivo with human parainfluenza virus type 1 (hPIV1) and bovine PIV3 but not by measles virus or vesicular stomatitis virus. It was concluded that the cis-acting RNA sequences were conserved within the SeV/PIV1/PIV3 group but that interactions between the polymerase complex (P-L) and the template protein N were unique for each virus. We have re-examined these conclusions using proteins expressed from cloned N, P and L genes for SeV and PIV3. The results demonstrate the specificity of the protein-protein interactions between polymerase and template, and confirm the prediction of the earlier work that PIV3 N, P and L proteins are capable of assembling and replicating SeV mini-genomes also expressed from a cDNA clone.

Animals↗
PubMed1996

Customization of a radiation management system to support in vivo patient dosimetry using diodes.

Considerable effort is generally made in the quality control of radiation therapy units and in patient chart checking to ensure accurate delivery of treatment to the patients. Record and verify (RV) systems have been implemented which will inhibit the beam from being turned ON if the parameters set on the medical linear accelerators do not match a preprogrammed file. It should be emphasized, however, that RV systems are designed only to ensure proper setup of parameters on the therapy units and bear no direct link with proper patient position. The only real link between treatment planning and delivery to the patient is in-vivo dosimetry. Diodes provide a convenient way of measuring the dose received by the patient in real time and, after the initial tedious calibrations, require very little additional effort. In order to facilitate diode use by the therapists in our institution, the radiation management system (RMS) database in use with our linear accelerators was interfaced with the output obtained from a commercially available diode dosimetry system. The chart printout format was altered to read this value from the RMS database allowing a near real-time recording of the actual dose received by the patient for up to three sites concurrently. This provides for an immediate additional check to the planned and received doses already recorded by the RMS RV software. This procedure, if carried out during the first treatment and subsequently on a weekly basis, would ensure that differences of the order of 5% or larger between planned and delivered dose would not go undetected.

Documentation↗
PubMed1996

The Sendai paramyxovirus accessory C proteins inhibit viral genome amplification in a promoter-specific fashion.

Many paramyxoviruses express small basic C proteins, from an alternate, overlapping open reading frame of the P gene mRNA, which were previously found to inhibit mRNA synthesis. During recent experiments in which infectious Sendai virus (SeV) was recovered from cDNA via the initial expression of the viral N, P, and L genes from plasmids, the abrogation of C protein expression from the plasmid P gene was found to be necessary for virus recovery. We have investigated the effect of C coexpression on the amplification of an internally deleted defective interfering (DI) genome directly in the transfected cell, for which, in contrast to virus recovery experiments, genome amplification is independent of mRNA synthesis carried out by the SeV polymerase. We find that C protein coexpression also strongly inhibits the amplification of this DI genome but has little or no effect on that of a copy-back DI genome (DI-H4). We have also characterized the C protein from a mutant SeV and found that (i) it had lost most of its inhibitory activity on internally deleted DI genome amplification and (ii) its coexpression no longer prevented the recovery of SeV from DNA. However, consistent with the insensitivity of copy-back DI genomes to C protein inhibition, C coexpression did not prevent the recovery of copy-back nondefective viruses from DNA. The inhibitory effects of C coexpression thus appear to be promoter specific.

Gene Amplification↗
PubMed1996

Orbit and optic nerve.

The optic nerve is a fiber tract of the brain, and is not a true cranial nerve. Primary pathologic processes seen in the central nervous system and its linings can therefore affect the optic nerve. Along their course the fibers of the visual pathways are also susceptible to secondary extrinsic processes. The MR appearance of many of the primary and secondary processes that affect the optic nerve are characteristic. Where the imaging features of a process are not characteristic, a fairly narrow differential diagnosis can be suggested depending on the imaging appearance and anatomic location of the pathologic entity. This article is a categorical overview of the disease entities that may affect the optic nerve and tracts. Pathologic processes are organized according to the typical sites of involvement along the visual pathways, from the retina to the occipital cortex. Medical imaging, pathologic, clinical, and epidemiological highlights are presented.

Brain Diseases↗
PubMed1995

A highly recombinogenic system for the recovery of infectious Sendai paramyxovirus from cDNA: generation of a novel copy-back nondefective interfering virus.

We have recovered infectious Sendai virus (SeV) from full-length cDNA (FL-3) by transfecting this cDNA and pGEM plasmids expressing the nucleocapsid protein (NP), phosphoprotein and large proteins into cells infected with a vaccinia virus which expresses T7 RNA polymerase. These cells were then injected into chicken eggs, in which SeV grows to very high titers. FL-3 was marked with a BglII site in the leader region and an NsiI site (ATGCAT) in the 5' nontranslated region of the NP gene, creating a new, out-of-frame, 5' proximal AUG. All the virus stocks generated eventually removed this impediment to NP expression, by either point mutation or recombination between FL-3 and pGEM-NP. The recovery system was found to be highly recombinogenic. Even in the absence of selective pressure, one in 20 of the recombinant SeV generated had exchanged the NP gene of FL-3 with that of pGEM-NP. When a fifth plasmid containing a new genomic 3' end without the presumably deleterious BglII site was included as another target for recombination, the new genomic 3' end was found in the recombinant SeV in 12 out of 12 recoveries. Using this approach, a novel copy-back nondefective virus was generated which interferes with wild-type virus replication.

Animals↗
PubMed1995

Paramyxovirus phosphoproteins form homotrimers as determined by an epitope dilution assay, via predicted coiled coils.

When HA epitope-tagged and untagged Sendai virus (SeV) P proteins are coexpressed and the products reacted with anti-HA, the untagged P protein is also selected because this protein is found as an oligomer. The oligomer was determined to be a homotrimer by coselection studies in which increasing amounts of untagged versus tagged protein were coexpressed, and these findings were extended to mumps virus, a member of the rubulavirus genus. The region of the SeV protein responsible for the oligomerization was localized to residues 344-411. Computer analysis of the 13 Paramyxovirus P proteins in the database revealed that all but one are predicted to form coiled coils in this region, the first of only two regions that can be aligned throughout the entire virus subfamily. The predicted coiled-coil region of the measles virus P protein, when grafted onto the C-terminus of the normally monomeric La protein, led to the efficient oligomerization of this reporter protein. The predicted coiled-coil region of these P proteins thus appears to be sufficient for oligomerization.

Amino Acid Sequence↗