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Biomedical subjects

J Bear

Publications and source records attributed to J Bear.

At least 19 recordsLinked to original sources
PubMed2001

Non-aqueous-phase-liquid breakthrough during evaporative drying of clay barriers.

In this study, an attempt has been made to model a real field scenario, whereby an initially almost saturated clay liner in a waste site is gradually drying, due to evaporation at its lower boundary. A detailed conceptual model that deals with the penetration and breakthrough of non-aqueous-phase-liquid (NAPL) in clay liners is introduced. Water content of clay samples was monitored during ambient evaporation through apertures at the base of sample holders. Clay drying rate served as the primary parameter for the NAPL breakthrough study. The interconnection between drying rates, structural damage formation (cracks and suction) and NAPL penetration is especially addressed. The processes taking place in the clay samples during drying appear to be associated with the capillary effects between the different fluid phases in the vicinity of either the NAPL-clay or the clay-air boundaries. A conceptual model of NAPL penetration and breakthrough of the clay layer has been considered, based on both indirect and direct observations of structural damages produced on either clay boundaries. A mutual interaction between these two boundaries is suggested and discussed. NAPL breakthrough is suggested to take place through cracks initiated on the upper soil surface.

Aluminum Silicates↗
PubMed2001

Rotavirus encephalopathy: pathogenesis reviewed.

Two cases of rotavirus gastroenteritis associated with neurological involvement, one with encephalitis (defined by abnormal neurological signs, cerebrospinal fluid (CSF) pleocytosis and detection of rotavirus genomic nucleic acid in the CSF) and one with a non-inflammatory encephalopathy (defined by abnormal neurological signs, an entirely normal CSF and detection of rotavirus genomic nucleic acid in the CSF), are presented and used as a basis to review and explore potential pathogenetic mechanisms, including direct viral replication within neurons and indirect effects of the newly described rotavirus 'enterotoxin'.

Acyclovir↗
PubMed2001

Identification of a novel posttranscriptional regulatory element by using a rev- and RRE-mutated human immunodeficiency virus type 1 DNA proviral clone as a molecular trap.

Human immunodeficiency virus (HIV) and all other lentiviruses utilize the essential viral protein Rev, which binds to RRE RNA, to export their unspliced and partially spliced mRNAs from the nucleus. We used a rev- and RRE-defective HIV type 1 (HIV-1) molecular clone in complementation experiments to establish a method for the rapid isolation of posttranscriptional regulatory elements from the mammalian genome by selecting for rescue of virus replication. Viruses rescued by this method contained a novel element with homology to rodent intracisternal A-particle (IAP) retroelements. A functional element was contained within a 247-nucleotide fragment named RNA transport element (RTE), which was able to promote replication of the Rev- and RRE-defective HIV-1 in both human lymphoid cell lines and primary lymphocytes, demonstrating its potent posttranscriptional function. RTE was functional in many cell types, indicating that the cellular factors that recognize RTE are widely expressed and evolutionarily conserved. RTE also promoted RNA export from Xenopus oocyte nuclei. RTE-mediated RNA transport was CRM1 independent, and RTE did not show high affinity for binding to mRNA export factor TAP/NXF1. Since CRM1 and TAP/NXF1 are critical export receptors associated with the two recognized mRNA export pathways, these results suggest that RTE functions via a distinct export mechanism. Taken together, our results identify a novel posttranscriptional control element that uses a conserved cellular export mechanism.

Active Transport, Cell Nucleus↗
PubMed2000

Unusual CD4+CD8+ phenotype in a greek patient diagnosed with adult T-cell leukemia positive for human T-cell leukemia virus type I (HTLV-I).

We describe the first Greek patient diagnosed with Adult T cell leukemia (ATL) characterized by an expansion of CD4+CD8+ double positive lymphocytes. Low levels of plasma antibodies against HTLV-I Env and Gag proteins were detected. Analysis of the the patient's DNA revealed that she was infected by a cosmopolitan strain of HTLV-I. Since HTLV-I usually leads to the expansion of CD4+ cells, this patient illustrates a rare immunophenotype, which suggests that the HTLV-I-induced proliferative response may occur in a pre-T cell stage.

Base Sequence↗
PubMed2000

The mRNA export in Caenorhabditis elegans is mediated by Ce-NXF-1, an ortholog of human TAP/NXF and Saccharomyces cerevisiae Mex67p.

Human TAP and Saccharomyces cerevisiae Mex67p belong to a family of proteins that mediate mRNA export. Computer searches identified previously two Caenorhabditis elegans genes, C15H11.3 and C115H11.6, that encode putative homologs of hTAP and Mex67p (Segref et al., EMBO J, 1997, 16:3256-3271). Using RNA interference experiments in C. elegans, we found that functional knockout of C15H11.3 resulted in nuclear accumulation of poly(A)-containing RNAs and was lethal for both embryos and adult nematodes. No embryonic or progeny abnormality was observed in functional knockout of C15H11.6. Taken together, these data established that the C15H11.3 gene product is an ortholog of hTAP and Mex67p; thus, it was named Ce-NXF-1. Ce-NXF-1 binds RNA directly and is a nucleocytoplasmic shuttle protein accumulating in the nucleoplasm and at the nuclear rim. The rim association is mediated via unique signals present in the C-terminal portion of all TAP/NXF and Mex67p proteins. This region was shown to interact with the FG-repeat domains of nucleoporins Nup98, Nup153, and Nup214, indicating that the rim association occurs through components of the nuclear pore complex. In summary, Ce-NXF-1 belongs together with hTAP and Mex67p to a family of proteins that participate in mRNA export and can provide a direct molecular link between mRNAs and components of the nuclear pore complex. Therefore, despite differences in mRNA metabolism between these species, they utilize a conserved mRNA transport mechanism.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1999

Do acute mucosal reactions lead to consequential late reactions in patients with head and neck cancer?

BACKGROUND AND PURPOSE: The relationship between acute and late mucosal reactions remains ill defined but is of considerable relevance to efforts to produce therapeutic gains through the use of altered fractionation schemes and concurrent chemotherapy. We therefore investigated whether acute mucosal reactions in patients treated with an accelerated and a conventionally fractionated radiotherapy regime predicted the severity of late mucosal reactions. PATIENTS AND METHODS: The study population consisted of 191 patients randomised on a prospective trial comparing conventional fractionation at 2 Gy/fraction per day, 70 Gy over 47 days with an accelerated regimen of 59.4 Gy, 1.8 Gy b.i.d over 24 days for Stage III-IV carcinoma of the head and neck. Acute and late mucosal reactions were scored according to RTOG/EORTC criteria and analyzed using multiple regression techniques. RESULTS: The duration of time spent by patients at the acute confluent mucositis grade 3 level was inversely related to the time to onset of the reaction for both fractionation schedules. Time to onset was more rapid for patients treated on the accelerated schedule but time spent at the reaction grade did not differ significantly between the schedules. After correction for treatment and patient related factors, anatomical site (oral cavity/oropharynx versus hypopharynx/larynx) and increasing duration of confluent mucositis emerged as independent predictors of the hazard of late mucosal reactions with the latter effect being more pronounced in the accelerated treatment arm. The expected reduction in late mucosal effects in the accelerated fractionation arm, predicted by the LQ model for late effects was identified only in patients whose acute confluent mucosal reactions lasted less than 20 days. CONCLUSIONS: The presence of individual patient susceptibility factors that determine the severity of acute mucosal reactions is suggested. A link between severe and prolonged acute reactions and the risk of developing late mucosal reactions that is independent of biological dose, has also been found. Purpose designed prospective studies of these issues are necessary.

Acute Disease↗
PubMed1999

Identification of novel import and export signals of human TAP, the protein that binds to the constitutive transport element of the type D retrovirus mRNAs.

The nuclear export of the unspliced type D retrovirus mRNA depends on the cis-acting constitutive transport RNA element (CTE) that has been shown to interact with the human TAP (hTAP) protein promoting the export of the CTE-containing mRNAs. We report here that hTAP is a 619-amino-acid protein extending the previously identified protein by another 60 residues at the N terminus and that hTAP shares high homology with the predicted rat and mouse TAP proteins. We found that hTAP is a nuclear protein that accumulates in the nuclear rim and the nucleoplasm. We further demonstrated that hTAP is able to shuttle between the nucleus and the cytoplasm. Identification of the signals responsible for nuclear import (NLS) and export (NES) revealed that they are distinct but partially overlapping. NLS and NES of hTAP are active transferable signals that do not share similarities with known elements. The C-terminal portion contributes further to hTAP's nuclear retention and contains a signal(s) for nuclear rim association. Taken together, our data show that hTAP is a dynamic protein capable of bidirectional trafficking across the nuclear envelope. These data further support hTAP's role as an export factor of the CTE-containing mRNAs.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1998

Responses of deep entorhinal cortex are epileptiform in an electrogenic rat model of chronic temporal lobe epilepsy.

We investigated whether entorhinal cortex (EC) layer IV neurons are hyperexcitable in the post-selfsustaining limbic status epilepticus (post-SSLSE) animal model of temporal lobe epilepsy. We studied naive rats (n = 44), epileptic rats that had experienced SSLSE resulting in spontaneous seizures (n = 45), and electrode controls (n = 7). There were no differences between electrode control and naive groups, which were pooled into a single control group. Intracellular and extracellular recordings were made from deep layers of EC, targeting layer IV, which was activated by stimulation of the superficial layers of EC or the angular bundle. There were no differences between epileptic and control neurons in basic cellular characteristics, and all neurons were quiescent under resting conditions. In control tissue, 77% of evoked intracellular responses consisted of a short-duration [8.6 +/- 1.3 (SE) ms] excitatory postsynaptic potential and a single action potential followed by gamma-aminobutyric acid-A (GABAA) and GABAB inhibitory post synaptic potentials (IPSPs). Ten percent of controls did not contain IPSPs. In chronically epileptic tissue, evoked intracellular responses demonstrated prolonged depolarizing potentials (256 +/- 39 ms), multiple action potentials (13 +/- 4), and no IPSPs. Ten percent of epileptic responses were followed by rhythmic "clonic" depolarizations. Epileptic responses exhibited an all-or-none response to progressive increases in stimulus intensity and required less stimulation to elicit action potentials. In both epileptic and control animals, intracellular responses correlated precisely in morphology and duration with extracellular field potentials. Severing the hippocampus from the EC did not alter the responses. Duration of intracellular epileptic responses was reduced 22% by the N-methyl--aspartate (NMDA) antagonist (-)-2-amino-5-phosphonovaleric acid (APV), but they did not return to normal and IPSPs were not restored. Epileptic and control responses were abolished by the non-NMDA antagonist 6, 7-dinitroquinoxaline-2-3-dione (DNQX). A monosynaptic IPSP protocol was used to test connectivity of inhibitory interneurons to primary cells by direct activation of interneurons with a stimulating electrode placed near the recording electrode in the presence of APV and DNQX. Using this protocol, IPSPs similar to control (P > 0.05) were seen in epileptic cells. The findings demonstrate that deep layer EC cells are hyperexcitable or "epileptiform" in this model. Hyperexcitability is not due to interactions with the hippocampus. It is due partially to augmented NMDA-mediated excitation. The lack of IPSPs in epileptic neurons may suggest inhibition is impaired, but we found evidence that inhibitory interneurons are connected to their target cells and are capable of inducing IPSPs.

Action Potentials↗
PubMed1997

The clinical impact of echocardiography on antibiotic prophylaxis use in patients with suspected mitral valve prolapse.

PURPOSE: To determine the impact of echocardiography on the use of antibiotic prophylaxis in patients with suspected mitral valve prolapse (MVP). PATIENTS AND METHODS: We evaluated 147 consecutive patients who were referred for "rule out mitral valve prolapse" to a university hospital echocardiography laboratory. Chart review and phone contact were used to determine the demographic characteristics of the patients; past diagnosis of MVP, symptoms, and exam at referral; practice specialty of referring MD; echocardiographic findings; and change in prophylaxis usage as a result of the echocardiogram (ECHO). Prophylaxis was considered to be indicated if the echocardiogram demonstrated MVP with at least mild regurgitation or abnormal thickening of at least one mitral leaflet. RESULTS: Based on the ECHO a change in antibiotic prophylaxis was indicated in 20 of 147 (14%) patients including initiation of prophylaxis in 6, and discontinuation of prophylaxis in 14. However, only 4 of 20 patients (20%) actually changed their prophylaxis habits leading to an actual yield of 4 management changes per 131 ECHOs ordered (3%). This corresponded to 1 change in management per $36,250 in hospital and physician costs. Younger age, female gender, and presence of symptoms were associated with a benign ECHO. Indications for a change in management were not significantly different between physician specialities: 18% for generalists (internal medicine and family practice), 12% for cardiologists, and 7% for other specialists, P = 0.3. CONCLUSIONS: In patients referred for evaluation of MVP, echocardiography infrequently resulted in changes in antibiotic prophylaxis management and was associated with significant expense.

Adult↗
PubMed1997

Identification of an RNA sequence within an intracisternal-A particle element able to replace Rev-mediated posttranscriptional regulation of human immunodeficiency virus type 1.

Human immunodeficiency virus type 1 (HIV-1) replication depends on the posttranscriptional regulation by the viral Rev protein and can be replaced with the posttranscriptional RNA control element (CTE) of the type D simian retroviruses. We have identified a sequence which shares only nucleotide sequences of the internal loops and secondary structure with the CTE and which is part of a novel murine intracisternal-A particle (IAP) retroelement, inserted within the transcribed mouse osteocalcin-related gene. This sequence, named CTE(IAP), can replace the Rev-mediated regulation of HIV-1, hence it is a posttranscriptional regulatory element. Related elements have been identified in other IAPs. These results suggest that insertional mutagenesis can affect gene expression by providing a functional posttranscriptional control element. The CTE(IAP) and CTEs of the type D simian retroviruses represent a novel class of RNA elements characterized by unique sequences within the internal loops which are predicted to represent the interaction site with cellular factor(s). These findings suggest that such elements may be involved in posttranscriptional regulation of cellular mRNAs.

Amino Acid Sequence↗
PubMed1996

Neurological outcome of severe cystic periventricular leukomalacia.

OBJECTIVE: To determine the neurological outcome of a cohort of premature babies having ultrasound diagnoses of severe cystic periventricular leukomalacia. METHODOLOGY: All neonatal intensive care unit admissions born at less than 35 weeks gestation or weighing less than 1500 g underwent serial cranial ultrasounds. Those developing severe bilateral cystic periventricular leukomalacia (12 patients) were then followed clinically to a mean age of 27.3 months. RESULTS: Ten of the 12 patients fulfilling strict ultrasound criteria survived. All had a major neurological handicap, all having spastic quadriparesis and visual impairments, with most suffering global developmental delay and epilepsy. CONCLUSIONS: Severe bilateral cystic periventricular leukomalacia results in major permanent handicap. It is currently impossible to identify most patients with this condition while they are being ventilated. Non-ultrasound techniques are needed to diagnose the condition earlier, and to give guidance to management.

Developmental Disabilities↗
PubMed1996

Responses of the superficial entorhinal cortex in vitro in slices from naive and chronically epileptic rats.

1. The main purposes of this study are to characterize the intracellular and extracellular responses of cells in superficial layers of entorhinal cortex (EC) in chronically epileptic animals, determine whether their altered physiology is dependent on being connected to hippocampus, and investigate whether there is evidence of augmented excitation and inhibitory interneuron disconnection. 2. Functional connectivity was maintained between the hippocampal area and the EC in vitro in a combined rat hippocampal-parahippocampal slice preparation by slicing with a vibratome at a 30-deg angle to the base of the brain. Three groups of animals were studied: naive animals, animals that had experienced a previous episode of (nonconvulsive) self-sustaining limbic system status epilepticus (SSLSE) induced by electrical stimulation resulting in a chronically epileptic state, and animals in an electrode control group. In chronically epileptic rats and the electrode control group, studies were done on tissue contralateral to the side of electrode implantation. 3. Extracellular and intracellular recordings were made from the superficial layers of EC. Neurons in the superficial layers of the EC were activated by stimulation of the deep layers within the EC or the angular bundle adjacent to the EC, which contains axons from EC neurons. Responses could be elicited by antidromic and synaptic mechanisms by stimulation at either site. In addition, a monosynaptic protocol was used that involved direct activation of interneurons with a stimulating electrode placed near the recording electrode in the presence of the ionotropic glutamate blockers D(-)-2-amino-5-phosphonovaleric acid (APV) and 6,7-dinitroquinoxaline-2-3-dione (DNQX). 4. Responses were collected over a range of stimulus intensities, from very low to high intensities, to construct input/output function (I/O) curves. Amplitudes and durations were measured at the lowest stimulus intensity that elicited a maximum responses. 5. Extracellular field potential responses from electrode controls did not differ from naives qualitatively with respect to morphology of field potential responses or quantitatively with respect to response duration and amplitude. Field potential responses in tissue from post-SSLSE rats differed markedly in morphology from naive and electrode controls, being more complex, significantly longer in duration, and decreased in amplitude. These epileptiform responses were shortened markedly by blockade of N-methyl-D-aspartate (NMDA) receptors with APV, but this manipulation did not convert responses to a normal morphology. These responses were abolished by blockade of non-NMDA mediated ionotropic glutamate receptors with DNQX. 6. During intracellular recordings of neurons in slices from both control and epileptic animals, neurons were quiescent under resting conditions in the absence of electrical stimulation. 7. Intracellular responses in electrode controls were identical to naive, and together were considered "controls." In control tissue, evoked intracellular responses were similar to those previously described and most commonly consisted of an excitatory postsynaptic potential (EPSP) that was blocked partially by the NMDA-receptor antagonist APV, followed by hyperpolarizing potentials, which were identified electrophysiologically and pharmacologically as gamma-aminobuturic acid-A (GABAA)- and GABAB-receptor-mediated inhibitory postsynaptic potentials (IPSPs). EPSPs were blocked completely by DNQX. 8. In chronically epileptic tissue, evoked intracellular responses differed markedly from responses in control animals, exhibiting all-or-none prolonged paroxysmal depolarizing events with multiple superimposed action potentials in response to a single shock. These depolarizing events were reduced in duration and amplitude, but not abolished, in APV. IPSPs were not seen or markedly reduced at all stimulus intensities. These intracellular responses never resembled control responses. Intracellur responss correlated precisely in morphology and duration with extracellular field potentials. (ABSTRACT TRUNCATED)

Animals↗
PubMed1993

An in vitro study of focal epileptogenesis in combined hippocampal-parahippocampal slices.

Brain slices from adult rats that included ventral hippocampus and adjacent parahippocampal areas were studied at various sites for the appearance of epileptiform discharges as extracellular potassium ([K+]o) was systematically varied over the range of 3 mM to 10 mM. The development of evoked epileptiform discharges (EEDs) and spontaneous epileptiform discharges (SEDs) was monitored in areas CA1, CA3, the hilus of the dentate gyrus (dentate hilus), the granule cell layer of the dentate gyrus (dentate gyrus), subiculum and entorhinal cortex. Increasing [K+]o elicited EEDs in a concentration-dependent manner. The entorhinal cortex and CA1 areas were most susceptible to this effect; the dentate gyrus was least susceptible. Increasing [K+]o also caused an increase in SEDs in all hippocampal areas. Separating entorhinal cortex from the rest of the slice by transections did not abolish discharges in any location. Lesions of the Schaeffer collaterals abolished discharges in CA1 but not in CA3. These findings demonstrate that changes in the extracellular milieu that are associated with epileptiform discharges in vivo are capable of eliciting paroxysmal discharges at multiple loci in the hippocampus and adjacent regions. Further, these findings demonstrate for the first time the intrinsic capacity of the entorhinal cortex to generate epileptiform discharges under in vitro ionic conditions known to occur in the intact brain during seizures.

Action Potentials↗
PubMed1989

Resistances and compliances of a compartmental model of the cerebrovascular system.

A lumped parameter compartmental model for the nonsteady flow of the cerebrovascular fluid is constructed. The model assumes constant resistances that relate fluid flux to pressure gradients, and compliances between compartments that relate fluid accumulation to rate of pressure changes. Resistances are evaluated by using mean values of artery and cerebrospinal fluid (CSF) fluxes and mean compartmental pressures. Compliances are then evaluated from clinical data of simultaneous pulse wave recordings in the different compartments. Estimate of the average CSF compartmental deformation, based on the compliance between the CSF and brain tissue compartments, proves to be of the order of magnitude of actual experimental measurements.

Blood-Brain Barrier↗
PubMed1988

A non-steady compartmental flow model of the cerebrovascular system.

A lumped parameter compartmental model for the cerebrovascular fluid system is constructed and solved for the general linear problem of a nonsteady flow with constant resistances and compliances. The model predicts the intracranial pressure waves in the various compartments of the brain in response to pressure changes in the vascular system.

Blood-Brain Barrier↗