Biomedical subjects

J B Burns

Publications and source records attributed to J B Burns.

At least 19 recordsLinked to original sources

PubMed2001

Isolation of CD45RO+, memory T cells recognizing proteolipid protein from neurologically normal subjects.

Previous studies provide evidence for in vivo activation of MBP-reactive T cells in subjects with multiple sclerosis. In general, in vivo activation occurs less frequently in healthy control subjects. In the current study we examined the T cell response to proteolipid protein in PBMC isolated from 9 control subjects. We used CD45 isotypes as markers for memory and naïve T cells to assess in vivo activation of CD4+ T cells reactive with PLP. In contrast to the results obtained using MBP, we found that approximately 50% of PLP-reactive T cells were derived from the CD45RO+ memory subpopulation of T cells isolated from these control subjects. These results indicate that some myelin-reactive T cells have undergone activation in vivo in neurologically intact individuals. This suggests that immunoregulatory mechanisms may be present that prevent overt disease in spite of in vivo activation of PLP-reactive T cells.

Adult↗

PubMed2000

In vivo reduction of telomere length in human antigen-reactive memory T cells.

There is a reduction in the average telomere lengths of CD4+ "memory" T cells, defined by the CD45RO+ phenotype, compared to CD54RA+ "naive" T cells. However, other studies suggest that telomerase activity often is sufficient to maintain the telomere length of certain B and T cell populations following immune activation in vivo. Thus it is uncertain whether genuine memory CD4+ T cells, defined by an immune response to specific recall antigens, would display telomeres of reduced length, or whether telomere size would be maintained. Therefore, we examined the telomere lengths of T cells responding to two common recall antigens, tetanus toxoid and Candida albicans. Telomere terminal restriction fragment length was assessed by Southern blots or by flow cytometry following in situ hybridization with telomere-specific peptide nucleic acid probes. For the five subjects tested, the Candida- or tetanus-reactive memory T cell populations demonstrated a significant reduction of telomere length even when compared to the phenotypically defined memory CD45RO+ T cell populations isolated from peripheral blood mononuclear cells. This finding suggests that telomerase activity does not fully compensate for the effects of in vivo activation and proliferation of some antigen-specific CD4+ T cell populations. This may contribute to immune senescence.

Adult↗

PubMed2000

A dynamical-systems model for Parkinson's disease.

The juxtaposition of hypokinetic and hyperkinetic symptoms in Parkinson's disease (PD) presents a challenge in modeling the basal ganglia. We propose a model of the striatum that can account for the mixture of symptoms seen in PD. In the model, the problem of motor planning is cast in terms of a particle in a potential, where potentials are generated internally in striatal modules, subject to afferent control. Planned movement is governed by Hamilton's equations, where potential energy is supplied by potentials expressed in the striatum. To test the model in realistic situations, a dynamic simulation of a two-link robot arm was used. Normal movement is modeled and shown to exhibit observed experimental properties. Symptoms of PD are reproduced by modeling hypothetical consequences of PD pathology.

Antiparkinson Agents↗

PubMed2000

Radiowave propagation from a tissue-implanted source at 418 MHz and 916.5 MHz.

Tissue-implanted ultra-high frequency (UHF) radio devices are being employed in both humans and animals for telemetry and telecommand applications. This paper describes the experimental measurement and electromagnetic modeling of propagation from 418-MHz and 916.5-MHz sources placed in the human vagina. Whole-body homogeneous and semi-segmented software models were constructed using data from the Visible Human Project. Bodyworn radiation efficiencies for a vaginally placed 418-MHz source were calculated using finite-difference time-domain and ranged between 1.6% and 3.4% (corresponding to net body losses of between 14.7 and 18.0 dB). Greater losses were encountered at 916.5 MHz, with efficiencies between 0.36% and 0.46% (net body loss ranging between 23.4 and 24.4 dB). Practical measurements were in good agreement with simulations, to within 2 dB at 418 MHz and 3 dB at 916.5 MHz. The degree of tissue-segmentation for whole-body models was found to have a minimal effect on calculated azimuthal radiation patterns and bodyworn radiation efficiency, provided the region surrounding the implanted source was sufficiently detailed.

Algorithms↗

PubMed2000

The design and performance of a 2.5-GHz telecommand link for wireless biomedical monitoring.

This paper details the implementation and operational performance of a minimum-power 2.45-GHz pulse receiver and a companion on-off keyed transmitter for use in a semi-active, duplex RF biomedical transponder. A 50-ohm microstrip stub-matched zero-bias diode detector forms the heart of a body-worn receiver that has a (CMOS baseband amplifier consuming 20 microA from +3 V and achieves a tangential sensitivity of -53 dBm. The base transmitter generates 0.5 W of peak RF output power into 50 ohms. Both linear and right-hand circularly polarized Tx-Rx antenna sets were employed in system reliability trials carried out in a hospital Coronary Care Unit. For transmitting antenna heights between 0.3 and 2.2 m above floor level, transponder interrogations were 95% reliable within the 67-m2 area of the ward, falling to an average of 46% in the surrounding rooms and corridors. Overall, the circular antenna set gave the higher reliability and lower propagation power decay index.

Coronary Care Units↗

PubMed1999

FDTD analysis of close-coupled 418 MHz radiating devices for human biotelemetry.

This paper describes the finite-difference time-domain (FDTD) analysis of antenna-body interaction effects occurring when chest-mounted 418 MHz radio transmitters are used for medical telemetry applications. Whole-body software models (homogeneous, layered and tissue-segmented) were developed for an adult male subject. Using an electrically small (300 mm2) planar loop antenna, calculated radiation efficiencies ranged between 33.5% and 39.2% for a whole-body model, and between 60.7% and 66.1% for a torso; radiation patterns were found to be largely independent of model composition. The computed radiation efficiency for a 21.5 kg phantom representing a six-year-old female was within 1.1 dB of measured results (actual body mass 28 kg) and well-correlated azimuthal radiation patterns were noted.

Adult↗

PubMed1999

Enterogastric reflux mimicking gallbladder disease: detection, quantitation and potential significance.

OBJECTIVE: Visualization of enterogastric reflux (EGR) may be present during hepatobiliary imaging. Reflux of bile may damage the gastric mucosa, altering its function, and cause such symptoms as epigastric pain, heartburn, nausea, intermittent vomiting and abdominal fullness. These symptoms also are associated with gallbladder disease. The aim of this study was to quantitate the EGR index (EGRI) and to determine if a difference exists in normal and abnormal responses using standard cholecystokinin (CCK)-augmented hepatobiliary imaging. METHODS: This study used 129 patients. LAO dynamic data on a 128 x 128 matrix at a rate of 1 frame/min were obtained. After the gallbladder ejection fraction (GBEF) was determined, the EGRI (%) was calculated by relating the counts in the gastric ROI to the counts in the hepatobiliary ROI at a specified time. The results were compared with the patient's final clinical diagnosis. RESULTS: Normal responders (GBEF > or = 35%) had a higher EGRI than abnormal responders with a P = 0.001 EGR observed in 75 patients (58.1%). Significant reflux (EGRI > or = 14.2% at 15 min) was observed in 29 additional patients (22.5%). Patients with EGRI > or = 24.5% showed a strong association with the pathophysiologic syndrome of gastritis, alkaline reflux, gastric ulcer and gastro esophageal reflux disease. There was no EGR observed in the remaining 25 patients (19.4%). CONCLUSION: This simple addition to the CCK-augmented hepatobiliary imaging may both detect and quantitate abnormal EGR as the cause of the patient's symptoms in the presence of a normal GBEF result, and/or those patients with risk factors for gastritis.

Aniline Compounds↗

PubMed1998

Suppression of antigen-specific T cell proliferation by measles virus infection: role of a soluble factor in suppression.

Measles virus infection causes a profound immunosuppression. The basis for this immunosuppression is not known. This immunosuppression could be due to virus acting directly on lymphoid cells, the production of an immunosuppressive viral product, or a lymphoid product. We have developed an antigen-specific T cell system to study measles virus-T-cell interactions. We demonstrate that as few as five infectious viral particles added to 1000 T cells results in profound inhibition of antigen-specific T cell proliferation. Supernates taken from measles virus-infected T cells suppress the proliferation of uninfected T cells. Measles-virus-infected HeLa or Vero cells do not produce the factor. The antiproliferative effects of the supernates cannot be attributed to infectious virus, IL-10 or TGF-beta. The soluble factor appears to be larger than 100 kDa, yet retains antiproliferative activity following trypsin digestion with a size less than 10 kDa. Loss of activity is seen following heat treatment at 56 degrees C. The factor is lymphoid cell specific and exhibits cytokine-like behavior yet appears not to be a known cytokine. This soluble factor may be responsible for the overt clinical immunosuppression seen in man and a previously undescribed cytokine induced by measles virus infection of human lymphocytes.

Animals↗

PubMed1998

On the design and assessment of a 2.45 GHz radio telecommand system for remote patient monitoring.

This paper discusses the design and operational assessment of a minimum-power, 2.45 GHz portable pulse receiver and associated base transmitter comprising the interrogation link in a duplex, cross-band RF transponder designed for short-range, remote patient monitoring. A tangential receiver sensitivity of - 53 dBm was achieved using a 50 ohms microstrip stub-matched zero-bias diode detector and a CMOS baseband amplifier consuming 20 microA from + 3 V. The base transmitter generated an on-off keyed peak output of 0.5 W into 50 ohms. Both linear and right-hand circularly-polarised antennas were employed in system evaluations carried out within an operational Coronary Care Unit ward. For transmitting antenna heights of between 0.3 and 2.2 m above floor level. transponder interrogations were 95% reliable within the 82 m2 area of the ward, falling to an average of 46% in the surrounding rooms and corridors. Separating the polarisation modes, using the circular antenna set gave the higher overall reliability.

Equipment Design↗

PubMed1998

Modulation of immune system function by measles virus infection: role of soluble factor and direct infection.

Measles virus infection can result in a variety of immunologic defects. We have begun studies to determine the basis for the lack of immune responsiveness to antigen and mitogen following infection. Here we present data showing that Epstein-Barr virus-transformed B-cell lines infected with measles virus produce a soluble factor that can inhibit antigen-specific T-cell proliferation and inhibit the proliferation of uninfected B cells. The soluble factor was neither interleukin-10, transforming growth factor beta, nor alpha/beta interferon. B cells infected with measles virus or treated with the soluble factor were unable to present antigen to T cells in a manner that supported antigen-specific proliferation. This could represent one mechanism of how measles virus limits T-cell expansion. However, we found that once CD4(+) or CD8(+) T cells were activated, their cytolytic activity was intact whether infected with measles virus or treated with soluble factor. Thus, while slow to be generated these cytoxic cells could participate in viral clearance.

Antigen Presentation↗

PubMed1997

Measles virus infection of human T cells modulates cytokine generation and IL-2 receptor alpha chain expression.

Measles virus (MV) suppresses specific functions in cells of the immune system and causes a generalized immunosuppression by mechanisms which remain undefined. It has been previously established that mitogen-induced proliferation of peripheral blood mononuclear cells (PBMC) is suppressed by infection with MV. Our current study demonstrates that MV infection inhibits antigen-specific proliferation of T lymphocytes. The inhibition of proliferation was not due to a decrease in IL-2 production. IL-2 production in cultures of infected and uninfected antigen-specific T cells was similar. In contrast, we found that expression of the IL-2R alpha subunit was decreased in mitogen-stimulated, MV-infected PBMC and antigen-stimulated, MV-infected T lymphocytes compared to stimulated but noninfected T cells. However, the expression of the IL-2R beta subunit was not altered in MV-infected T cells. We also examined the influence of MV infection on the production of the cytokines IL-4, IL-6, IL-10, and IFN-gamma by T lymphocytes. By comparing infected versus uninfected antigen-specific T cell lines, we found that MV infection of antigen-specific activated T cells caused no substantial change in generation of IFN-gamma, IL-6, or IL-10. There was a 50% reduction in IL-4 generation following MV infection. These data indicate that the immunosuppression by acute MV infection is not associated with a generalized inhibition of cytokine production. One mechanism for the suppression of proliferation following acute MV infection may be a block in the expression of the IL-2R alpha subunit by activated T cells.

CD4-Positive T-Lymphocytes↗

PubMed1995

Retinal degeneration slow (rds) in mouse results from simple insertion of a t haplotype-specific element into protein-coding exon II.

Retinal degeneration slow (rds) is a semidominant mutation of mice that causes dysplasia and degeneration of rod and cone photoreceptors. Mutations in RDS, the human ortholog of the rds gene, are responsible for several inherited retinal dystrophies including a subset of retinitis pigmentosa. The normal rds locus encodes rds/peripherin, an integral membrane glycoprotein present in outer segment discs. Genomic libraries from wildtype and rds/rds mice were screened with an rds cDNA, and phage lambda clones that span the normal and mutant loci were mapped. We show that in mice, rds is caused by the insertion into exon II of a 9.2-kb repetitive genomic element that is very similar to the t haplotype-specific element in the H-2 complex. The entire element is included in the RNA products of the mutant locus. We present evidence that rds in mice represents a null allele.

Alleles↗

PubMed1995

Uptake of systemically administered human anticerebellar antibody by rat Purkinje cells following blood-brain barrier disruption.

Paraneoplastic cerebellar degeneration accompanying gynecological or breast malignancies is frequently associated with an autoantibody response, termed "type I" or "anti-Yo" directed against cytoplasmic antigens of cerebellar Purkinje cells. The role of this antibody response in the pathogenesis of paraneoplastic cerebellar degeneration is unknown; however, it is also not known whether anti-Purkinje cell antibodies from the systemic circulation bind to target Purkinje cell antigens under the conditions of brain inflammation and blood-brain barrier disruption, which are frequently present at the onset of cerebellar symptoms. Inbred Lewis rats received intraperitoneal injections of type I or normal IgG in the setting of blood-brain barrier disruption induced by adoptive transfer of experimental allergic encephalomyelitis (EAE) and were killed after 24, 48, and 96 h. Brains of these animals were studied histologically for evidence of EAE and immunohistochemically for binding of human or endogenous rat IgG to target neurons. Rat IgG was detected around vessels and in Purkinje cells of all animals studied. Human IgG was detected around vessels of all animals. In animals examined 96h after receiving type I human IgG, human IgG was identified within processes of Purkinje cells and within occasional Purkinje cell bodies. Uptake of type I IgG by other cell types was not observed, and neuronal uptake of IgG was not seen in brains of animals receiving normal human IgG. Our data demonstrate that circulating type I IgG is internalized by cerebellar Purkinje cells in the setting of blood-brain barrier disruption and suggest a mechanism by which an antibody response directed against cytoplasmic antigens of Purkinje cells may reach target antigens at the onset of paraneoplastic cerebellar degeneration.

Animals↗

PubMed1995

Fading characteristics of a 2.3 GHz radio telemetry channel in a hospital building.

This paper reports on radio path attenuation measurements made in a hospital complex at a spot frequency of 2.340 GHz. Power loss figures for fixed path propagation in a variety of building types have been determined for proposed telemetry use in operational ward situations. Throughout the hospital, the radio paths assessed all exhibited a loss in excess of that calculated for free-space communications. Modern buildings had external wall losses of 10-25 dB, with dividing walls in wards contributing an additional 5 dB. Received signal strength levels indicated a Rayleigh distribution for obstructed paths. Temporal testing was used to find the rate and depth of signal fades caused by the movement of personnel and equipment during normal ward usage; signal level reductions of greater than 35 dB were common during busy periods.

Biomedical Engineering↗

PubMed1995

Primary central nervous system lymphoma following transfer of human peripheral blood lymphocytes into SCID mice.

Severe combined immunodeficiency (SCID) mice are genetically deficient in both B and T cells. To study immune-mediated phenomena in the CNS, myelin basic protein-reactive T cell clones, admixed with peripheral blood lymphocytes as a source of antigen-presenting cells, derived from a healthy human donor, were injected intracerebrally (IC) into 10 SCID mice. One mouse developed quadriplegia 2 months after the last injection. Autopsy revealed marked meningeal and parenchymal infiltration by large cell lymphoma. There was no evidence of lymphoma outside of the CNS. The majority of the tumor cells were positive for L26 (a human pan B cell marker), with some cells positive for UCHL-1 (a human pan T cell marker). The majority of the tumor cells were also positive for Epstein-Barr virus (EBV) genome by in situ hybridization. Thus, primary CNS, EBV-positive B cell lymphoma can be produced in SCID mice by IC injection of nontransformed human peripheral blood lymphocytes. This phenomenon can be used as a model system for the study of primary CNS lymphomas under immunodeficiency conditions.

Adoptive Transfer↗

PubMed1993

A model for the functioning of the striatum.

A model is presented for the operation of the striatum. The model posits that the basal ganglia are responsible for driving smooth transitions of state for an organism. We propose that this is accomplished through the computation of a potential function within the striatum on which a gradient descent is performed toward the goal state. The model suggests that various somatotopic regions of the striatum correspond to state spaces, each of which pertains to a different aspect of the organism. This paper discusses this model only in the context of motor control, i.e., egomotion and limb movement. The model appears to account for a variety of experimental results, and for some unusual properties of the striatum.

Animals↗

PubMed1993

A new striatal model and its relationship to basal ganglia diseases.

A new model of the striatum has recently been proposed. This model suggests that the somatotopic regions of the striatum correspond to state spaces governing various aspects of organism behavior (e.g., reaching, egomotion, task planning). The model is reviewed, and shown to be applicable to sequencing tasks. The model is also discussed in the context of some basal ganglia diseases.

Basal Ganglia Diseases↗

PubMed1989

Human T lymphocytes reactive with whole myelin recognize predominantly myelin basic protein.

Human T-cell lines and clones reactive with whole human myelin were isolated from three normal subjects by in vitro sensitization techniques. The CD4+ T-cell lines were maintained in long-term culture by periodic antigen restimulation with myelin and use of interleukin-2. Although myelin basic protein (MBP) represents only about 10% of the dry weight of myelin and the myelin-reactive T-cell populations were never exposed to purified MBP, each of the three cell lines responded to in vitro stimulation with both MBP and whole myelin. Seventeen of 18 T-cell clones derived from the myelin-reactive cell lines also responded to MBP. One myelin-reactive T-cell clone did not recognize MBP or the major myelin lipids but responded to delipidated myelin proteins suggesting that this clone recognized another myelin protein antigen. These results indicate that MBP is the predominant antigen in whole myelin recognized by human T cells under the culture conditions described. However, there is at least one additional protein antigen in myelin that is also immunogenic.

Cell Line↗