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Biomedical subjects

J McAllister

Publications and source records attributed to J McAllister.

At least 19 recordsLinked to original sources
PubMed2001

The effect of production variables in monolog and dialog on comprehension by novel listeners.

Prior research has identified a number of dimensions along which speakers modify referring expressions. The present study aimed to determine and describe the actual relationship existing between these production characteristics and corresponding measures of listener comprehension. Spoken descriptions were elicited from eight speakers during monolog and dialog conditions of the tangram task. In a subsequent listening experiment, 163 new subjects listened to the referring expressions from the speech corpus, and were asked to select, from an array of tangram figures, the one that was being described in the referring expression. Results revealed that the production variables most commonly documented by previous researchers collectively contributed to listener comprehension to a surprisingly small, but consistently significant, degree. Furthermore, the communicative context in which referring expressions were produced did not substantially influence their overall comprehensibility; instead, communicative context, as well as the individual characteristics of the speaker who produced the referring expression, appeared to affect which variables listeners found most useful when inferring what the speaker meant.

Adult↗
PubMed2000

HIV-1-associated central nervous system dysfunction.

Despite more than 15 years of extensive investigative efforts, a complete understanding of the neurological consequences of HIV-1 CNS infection remains elusive. Although the resources of numerous investigators have been focused on studies of HIV-1-associated CNS disease, the complex nature of the disease processes that underlie the clinical, pathological, and cellular manifestations of HIV-1 CNS infection have required a larger volume of studies than was initially envisioned. Several major areas remain as the focus of current research efforts. One of the more pressing issues facing researchers and clinicians alike is the search for correlates to the development of HIV-1-associated CNS neuropathology and the onset of HIVD. Although numerous parameters have been studied, none have been shown to be absolute predictors or markers of HIV-1-related CNS dysfunction. The identification of solid correlates of HIVD is an important goal that would permit clinical identification of individuals at risk for developing potentially crippling, life-threatening CNS abnormalities and would facilitate early treatment of nascent neurological problems. A more complete comprehension of the cellular foundations of CNS dysfunction and HIVD is also a fundamental part of strategies designed to treat or prevent HIV-1-associated CNS disease. Future investigations will strive to expand the body of knowledge concerning the complex interactions between infected and uninfected neuroglial cells and the roles of numerous cytokines, chemokines, and other soluble agents that are deregulated during HIV-1 CNS infection. In particular, a thorough understanding of the mechanisms of neurotoxicity may facilitate the development of new therapies that alleviate or eliminate the clinical consequences of CNS infection. Finally, investigators will continue to study HIVD within the context of single and combination drug therapies used in the treatment of HIV-1 infection and AIDS. As newer and more effective systemic treatments for HIV-1 infection and AIDS are introduced, the effects of these treatments on the onset, incidence, and severity of HIVD will also require intensive study. The impact of drug therapies on the ability of the CNS to act as an HIV-1 reservoir will also need to be addressed. Introduction of each new drug or drug combination will necessitate studies of drug penetration into the CNS and efficacy against the development of CNS abnormalities. Furthermore, as more effective treatments prolong the lifespan of individuals infected with HIV-1, the impact of extended survival on the occurrence and severity of HIVD will also require further investigations. The quest for answers to these and other questions will be complicated by the diversity of experimental systems used to study different aspects of HIV-1 CNS infection and HIVD. Each system has its own unique strengths and weaknesses. Clinical observations provide a continuous spectrum of symptomatic findings but reveal little about the underlying mechanisms of disease. In vivo imaging techniques, such as CT and MRI, also provide a continuum of observations, but the images are limited in their resolution. Neuropathological examinations of postmortem HIV-1-infected brains offer gross, cellular, and molecular views (including phenotypic and genotypic analyses of CNS viral isolates) of the diseased brain, but only provide a snapshot of the end-stage neurologic dysfunction. Studies that rely on animal surrogates for HIV-1, including SIV, simian-HIV (SHIV), feline immunodeficiency virus (FIV), visna virus, and HIV-1 SCID-hu models, permit experimental protocols that cannot be carried out in humans, but are limited by the fidelity with which each virus and animal model emulates the conditions and events observed in the human host. Finally, in vitro techniques, which include the use of primary cells and cell lines, adult or fetal human cell cultures, and BBB barrier model systems, are also convenient means by which aspe

AIDS Dementia Complex↗
PubMed1999

Does botulinum toxin injection make esophagomyotomy a more difficult operation?

BACKGROUND: Some patients with achalasia treated by botulinum toxin injection still require an esophagomyotomy. In this study, we analyzed the impact of botulinum toxin injection on the technical aspects and outcome of esophagomyotomy. METHODS: We studied 57 patients, with a mean age of 46 years (range, 12-97) who were treated between January 1995 and March 1998 by esophagomyotomy performed via minimally invasive techniques by one team. Operative reports, videotapes, and clinical outcome were analyzed to define the technical difficulties, perforations, and outcome. RESULTS: Fifteen of the 57 patients had received one or more injections of botulinum toxin (botox group) preoperatively. Difficulties in dissection of the submucosal plane were encountered in eight of the 15 cases (53.3%), and a mucosal laceration (perforation) occurred in two cases (13.3%). Forty-two of the 57 patients had not received any injections (non-botox group). In three patients (7%), difficulties in identifying or following the submucosal plane were encountered, although 29 patients had one or more previous dilations, and perforation occurred in one case (2.4%). All mucosal injuries were repaired laparoscopically, and the patients recovered without obvious sequelae. Dysphagia improved significantly after the operation in both groups (botox group, from preoperative score of 3. 8 to a postoperative score of 0.7; non-botox, from a score of 3.4 preoperatively to 0.5 postoperatively). Regurgitation also improved in both groups (botox, 2.7 preoperatively, 0.92 postoperatively; non-botox group, 2.0 preoperatively, 0.56 postoperatively). CONCLUSIONS: Injection of botulinum toxin significantly increases the technical difficulties and thus the potential risk of esophagomyotomy. The immediate results were equally good for both groups in our series, but the long-term sequelae of repeated injections are unknown. Laparoscopic Heller myotomy is a safe and effective procedure even after unsuccessful treatment with botulinum toxin.

Anti-Dyskinesia Agents↗
PubMed1999

Variation of hepatitis C virus following serial transmission: multiple mechanisms of diversification of the hypervariable region and evidence for convergent genome evolution.

We have studied the evolution of hepatitis C virus (HCV) from a common source following serial transmission from contaminated batches of anti-D immunoglobulin. Six secondary recipients were each infected with virus from identifiable primary recipients of HCV-contaminated anti-D immunoglobulin. Phylogenetic analysis of virus E1/E2 gene sequences [including the hypervariable region (HVR)] and part of NS5B confirmed their common origin, but failed to reproduce the known epidemiological relationships between pairs of viruses, probably because of the frequent occurrence of convergent substitutions at both synonymous and nonsynonymous sites. There was no evidence that the rate at which the HCV genome evolves is affected by transmission events. Three different mechanisms appear to have been involved in generating variation of the hypervariable region; nucleotide substitution, insertion/deletion of nucleotide triplets at the E1/E2 boundary and insertion of a duplicated segment replacing almost the entire HVR. These observations have important implications for the phylogenetic analysis of HCV sequences from epidemiologically linked isolates.

Adolescent↗
PubMed1999

Estimation of the retinal nerve fibre layer thickness in the papillomacular area of long standing stage IV macular holes.

AIM: To compare the thickness of the retinal nerve fibre layer (RNFL) in the papillomacular area of patients with long standing stage IV macular holes with age matched controls, using a scanning laser polarimeter. METHODS: The nerve fibre analyser (NFA) was used to measure the mean thickness of the RNFL around the optic nerve head, the thickness values of temporal and nasal 45 degrees sectors and the integral values in 10 patients with macular holes and in 10 age matched controls. RESULTS: The mean RNFL thickness around the optic nerve head was 79.71 (SD 15.06) microm in the macular hole group and 75.1 (10.8) microm in the control group (p = 0.44). The mean thickness in the temporal sector was 63.69 (12.08) microm in the macular hole group and 58.65 (8.9) microm in the control group (p = 0.3). The mean ratio between the temporal and nasal sector thickness values was 0.8441 in the macular hole group and 0.7819 in the controls (p = 0.42). CONCLUSIONS: There was no significant difference in the thickness of the RNFL in the papillomacular area in the two groups. This suggests that there may be no changes in the thickness of the RNFL in patients with long standing macular holes.

Adult↗
PubMed1999

Correlation of histological findings with gadolinium enhanced MRI scans during healing of a PHEMA orbital implant in rabbits.

BACKGROUND/AIMS: To investigate a poly(2-hydroxyethyl methacrylate) (PHEMA) orbital implant with a spongy anterior hemisphere and a smooth gel posterior hemisphere, by histology correlated with magnetic resonance images. METHODS: Following enucleation, eight rabbits received PHEMA implants to which the muscles were directly sutured, and underwent gadolinium enhanced magnetic resonance imaging (MRI) from 3 to 52 weeks. After the rabbits were killed, the implants were removed, cut in a plane corresponding to the scan, and processed for light and electron microscopy. RESULTS: All eight rabbits retained their implant to the end of the study period without complications. The scans demonstrated muscle attachment to the anterior half of the implant, and enhancement was seen on injection of gadolinium chelate. Histology confirmed muscle attachment, and cellular and vascular ingrowth. Over time, a transformation from reactive inflammatory to relatively non-vascular scar tissue was seen within the implant. Calcium deposits in one implant were detected by imaging and histology. CONCLUSION: The implants are readily visualised on MRI. Muscle attachment and fibrovascular ingrowth into the anterior hemisphere are seen, while encapsulation of the posterior hemisphere is minimal. Histological findings confirm the progress of the healing response, with initial inflammation and marked vascularisation, developing later into quiescent scar tissue predominantly of fibroblasts.

Animals↗
PubMed1999

A second outbreak of hepatitis C virus infection from anti-D immunoglobulin in Ireland.

OBJECTIVE: To investigate the infectivity for hepatitis C virus (HCV) of intravenous anti-D immunoglobulin batches manufactured in Ireland between 1991 and 1994. METHODS: Women who had received anti-D manufactured between 1991 and 1994 were screened for serological markers of HCV infection and for the presence of HCV RNA by RT-PCR amplification and virus genotyping. RESULTS: 44 women exposed to anti-D manufactured between 1991 and 1994 were polymerase chain reaction positive for HCV RNA, 19 of whom were infected with genotype 3a virus shown by phylogenetic analysis of the NS5B gene to be closely related to that from the single implicated donor. CONCLUSIONS: Anti-D manufactured in 1991-1994 transmitted infection of HCV genotype 3a. The prevalence of HCV-specific antibody in anti-D recipients was relatively low (0.59%), consistent with the low level of virus RNA in these anti-D batches.

Disease Outbreaks↗
PubMed1998

Is the single use of intraoperative 5-fluorouracil in filtering surgery for high-risk cases enough?

PURPOSE: To study the efficacy of the adjunctive use of a single intraoperative application of 5-fluorouracil (5FU) in eyes with poor prognoses for a successful outcome with a trabeculectomy. METHOD: Twenty-four patients (25 eyes) with a mean age of 63.7 +/- 14.7 years (range 27-86 years) and a history of one or more risk factors (age < 50 years, more than 3 years on topical medication, a previous failed filter, previous cataract surgery, uveitis, neovascular glaucoma) underwent trabeculectomy with the intraoperative application of 5FU on a sponge (25 mg/ml) for 5 min. The average follow-up was 10.1 +/- 5.5 months. RESULTS: The mean pre-operative intraocular pressure (IOP) was 24.7 +/- 6.2 mmHg and the mean post-operative IOP was 13.9 +/- 3.5 mmHg. Success, defined as an IOP within desired target levels for a particular eye, in the presence of a functioning filter, without supplementary medical therapy, was achieved in 56.5% of cases. CONCLUSIONS: Our results of successful filters in this group of patients with moderate- to high-risk characteristics approach similar figures quoted for trabeculectomies without the adjunctive use of intraoperative 5FU in eyes with poor prognoses with a similar length of follow-up. Though the numbers are small there is a trend that indicates that the intraoperative application of a single dose of 5FU alone may not be sufficient in eyes with moderate- to high-risk characteristics of failure of a trabeculectomy.

Adult↗
PubMed1998

Long-term evolution of the hypervariable region of hepatitis C virus in a common-source-infected cohort.

The long-term evolution of the hepatitis C virus hypervariable region (HVR) and flanking regions of the E1 and E2 envelope proteins have been studied in a cohort of women infected from a common source of anti-D immunoglobulin. Whereas virus sequences in the infectious source were relatively homogeneous, distinct HVR variants were observed in each anti-D recipient, indicating that this region can evolve in multiple directions from the same point. Where HVR variants with dissimilar sequences were present in a single individual, the frequency of synonymous substitution in the flanking regions suggested that the lineages diverged more than a decade previously. Even where a single major HVR variant was present in an infected individual, this lineage was usually several years old. Multiple lineages can therefore coexist during long periods of chronic infection without replacement. The characteristics of amino acid substitution in the HVR were not consistent with the random accumulation of mutations and imply that amino acid replacement in the HVR was strongly constrained. Another variable region of E2 centered on codon 60 shows similar constraints, while HVR2 was relatively unconstrained. Several of these features are difficult to explain if a neutralizing immune response against the HVR is the only selective force operating on E2. The impact of PCR artifacts such as nucleotide misincorporation and the shuffling of dissimilar templates is discussed.

Amino Acid Sequence↗
PubMed1995

An upstream stimulatory factor (USF) binding motif is critical for rat preprotachykinin-A promoter activity in PC12 cells.

We demonstrate the presence of a functional E box motif in the proximal rat preprotachykinin-A (rPPT) promoter. This element (spanning nucleotides -67 to -47) exhibits the sequence 5'-CACGTG-3' which is recognized and bound by the basic helix-loop-helix family of regulatory proteins. We also show that at least one of the factors bound to this rPPT promoter element in both HeLa and PC12 nuclear extract is the ubiquitously expressed transcription factor, the upstream stimulatory factor (USF). Mutation of this element by insertion of a 10 bp linker into the E box motif, in an rPPT promoter fragment spanning -865 to +92, destroys the ability of this promoter fragment to support reporter gene expression in a PC12 cell model of rPPT promoter activity. The data indicate that this rPPT E box element is likely to function as an important cis-regulatory domain in the rPPT promoter.

Animals↗
PubMed1995

Multiple protein complexes, including AP2 and Sp1, interact with a specific site within the rat preprotachykinin-A promoter.

We demonstrate that there is a unique AP2 binding site in the rat preprotachykinin-A promoter (rPPT) spanning -865 to -47. AP2 is a transcription factor whose expression in sensory neurons has been correlated with rPPT expression in these cells. This binding site is adjacent to an element we previously identified as binding a single stranded DNA binding protein which was also present in sensory neurons. These two complexes encompass a region which we had proposed might form a stem-loop structure, allowing binding of the single stranded DNA binding protein to the DNA. Here using electrophoretic mobility shift analysis we demonstrate that the DNA region corresponding to the putative stem-loop structure is bound by a variety of transcription factors, including in addition to AP2 the ubiquitous Sp1. DNase 1 footprint analysis demonstrates that binding to this domain by the proteins recognising the double-stranded form of the cis acting element is mutually exclusive. A promoter fragment containing this domain demonstrated a DNase 1 footprint over the 5' region of the stem-loop structure. Competition of the binding for this element by an oligonucleotide corresponding to the stem-loop structure removed the 5' footprint and exposed a new footprint over the 3' region of the stem-loop structure and extending for several base pairs. This change in protection observed with DNase 1 digestion also correlated with changes of the DNase 1 pattern at specific locations 3' of the proposed stem-loop structure. These changes correlated with two DNA sequences which were homologous to one another and to a region within the proposed stem-loop structure. Our results indicate that AP2 could regulate rPPT gene expression by a variety of mechanisms.

Animals↗
PubMed1995

Cell-specific activation of the glial-specific JC virus early promoter by large T antigen.

JC virus causes the human demyelinating disease progressive multifocal leukoencephalopathy by selective infection of glial cells. This cell specificity results from glial-specific expression of viral early genes (large and small T antigens). Analysis of transcriptional regulation by the MH1 JC virus early promoter demonstrates that glial specificity is directed by the basal promoter. Because T antigen regulates the basal region of several viral and cellular promoters, we investigated whether it controls the JC virus basal promoter in a glial-specific manner. A JC virus T antigen expression plasmid generated a 95-kDa protein which exhibited nuclear localization and physical association with p53. T antigen repressed the JC virus and SV40 early promoters 4- to 5-fold in glioma cells. Conversely, T antigen induced 100- to 200-fold activation of the JC virus early promoter in nonglial cells, whereas the SV40 promoter was repressed. Activation required the JC virus TATA box sequence and a pentanucleotide repeat immediately upstream of the TATA box, but was independent of the upstream enhancer region. These data demonstrate that the JC virus basal promoter is responsible for glial-specific gene expression and suggest a mechanism for this regulation.

Antigens, Polyomavirus Transforming↗
PubMed1995

Characterisation of a functional E box motif in the proximal rat preprotachykinin-A promoter.

Three E box motifs, which are upstream of the major transcriptional start site, have previously been characterised in the rat preprotachykinin-A (rPPT) promoter. Only one of these, in the proximal promoter spanning nucleotides -67 to -47, has been demonstrated to support reporter gene expression in clonal cell lines under basal growth conditions. Here we demonstrate that the reporter gene expression can be further induced by the action of phorbol 12-myristate 13-acetate (TPA) and nerve growth factor (NGF), respectively, in both HeLa and the neuronally derived PC12 cells. This response is due to the E box motif and not an overlapping consensus sequence for a putative AP1 element, a class of element previously demonstrated to respond to both TPA and NGF in these cell lines. Finally, we demonstrate that this E box motif can support similar levels of reporter gene expression in primary cultures of dorsal root ganglion neurons as observed in clonal cell lines, demonstrating that E box binding complexes can (1) function as a transcriptional regulator in dorsal root ganglion neurons and (2) bind to and therefore presumably regulate rPPT promoter activity.

Animals↗