Search PubMed⌕ Search

Biomedical subjects

B Roberts

Publications and source records attributed to B Roberts.

At least 55 records · Page 3Linked to original sources
PubMed1998

Export controls and biological weapons: new roles, new challenges.

This article considers the value of export controls in reducing the threat of biological weapons. It concludes that export control through export licensing is an essential element in the overall strategy to limit the spread of biological weapons. Modifications to existing export control systems can maximize the usefulness of export controls for limiting the threat of biological warfare and bioterrorism. Export controls are useful only within a broader strategy that includes both an arms control dimension and military defensive preparedness.

Australia↗
PubMed1998

Patients' experiences of Parkinson's disease.

Patients' (n = 101) experiences of Parkinson's disease (PD) were studied through structured interviews. Oblique factor analysis produced three moderately intercorrelated clusters of items reflecting reported severity of motoric, cognitive, and psychological problems, respectively. Scales formed from the factors were correlated with demographic, disease-related, and psychosocial variables. The demographic variables were not significantly correlated with the scales or with any other variables in the set. Hoehn and Yahr staging was significantly related to scores only on the motoric severity scale. Measures of functional capacity, in contrast, were significantly associated with all three scales. Although the addition of the psychosocial variables as a set significantly increased multiple Rs for each of the three scales, the specific patterns of correlation varied from scale to scale. The findings indicate that from the viewpoint of the patient the problems created by PD were not restricted to the motoric domain. Too narrow a focus by clinicians and researchers on medical symptomatology may give insufficient recognition to the multidimensional nature of the patient's experience.

Activities of Daily Living↗
PubMed1998

Selective glial vulnerability following transient global ischemia in rat brain.

Global cerebral ischemia selectively damages neurons, but its contribution to glial cell death is uncertain. Accordingly, adult male rats were sacrificed by perfusion fixation at 1, 2, 3, 5, and 14 days following 10 minutes of global ischemia. This insult produces CA1 hippocampal neuronal death at post-ischemic (PI) day 3, but minor or no damage to neurons in other regions. In situ end labeling (ISEL) and immunohistochemistry identified fragmented DNA of dead or dying glia and distinguished glial subtypes. Rare ISEL-positive oligodendroglia, astrocytes, and microglia were present in control brain. Apoptotic bodies and ISEL-positive glia significantly increased at PI day 1 in cortex and thalamus (p < 0.05), but were similar to controls in other regions and at other PI intervals. Most were oligodendroglia, although ISEL-positive microglia and astrocytes were also observed. These results show that oligodendroglia die rapidly after brief global ischemia and are more sensitive than neurons in certain brain regions. Their selective vulnerability to ischemia may be responsible for the delayed white matter damage following anoxia or CO poisoning or that associated with white matter arteriopathies. Glial apoptosis could contribute to the DNA ladders of apoptotic oligonucleosomes that have been found in post-ischemic brain.

Animals↗
PubMed1998

Characterisation and molecular typing of Burkholderia pseudomallei: are disease presentations of melioidosis clonally related?

Eighteen cases of culture positive melioidosis caused by Burkholderia pseudomallei, were seen in four geographically separate communities in North Queensland, Australia. The genetic inter-relatedness of the clinical isolates were compared utilising random amplification of polymorphic DNA (RAPD) and multilocus enzyme electrophoresis (MEE). The isolates segregated into two groups that correlated with clinical presentation rather than geographical location. This is the first described association between the varied clinical presentations of this condition and specific molecular type. If proven on larger studies, this may further our understanding of the pathogenesis of this important condition.

Adolescent↗
PubMed1998

The central and renal hemodynamic effects of amino acid infusion in the study of renal reserve in the baboon.

Normal human renal function is characterized by a large renal reserve. Recruitment of this reserve is a compensatory and pathological response to renal injury. This study was designed to assess the renal reserve and central hemodynamics of young female baboons and, in doing so, the appropriateness of the use of these animals in a model of human renal disease. Eight female baboons completed the protocol. PAH and inulin clearances were measured before and after an amino acid infusion. Central hemodynamics were measured with arterial and pulmonary artery catheters. Effective renal plasma flow and glomerular filtration rate increased by 42% after amino acid infusion (P = .025). Expansion of renal function was not consistent among individual baboons; two of the eight animals did not demonstrate renal reserve. Central hemodynamics were unaffected by the protocol.

Amino Acids↗
PubMed1998

Effects of spectral pattern on the perceptual salience of partials in harmonic and frequency-shifted complex tones: a performance measure.

A single even harmonic added to an odd-harmonic complex is often judged to be more salient than its odd neighbors in a clarity rating task [Roberts and Bregman, J. Acoust. Soc. Am. 90, 3050-3060 (1991)]. This study used similar complexes in a two-interval forced-choice procedure. Each interval consisted of a complex tone followed by a pure tone, whose frequency matched that of a harmonic in one interval but was changed by +/- 0.5 x fundamental frequency in the other. Subjects were asked to identify the matching interval. Since the pure tone followed the complex tone, it could not cue listening to a particular frequency region. The possibility of cross-interval cuing was reduced by changing the fundamental frequency between intervals (100-150 Hz range). The procedure was designed to maximize the effects on performance of differences in immediate perceptual salience between the partials. The added even harmonic was typically judged with greater accuracy than its odd neighbors (experiment 1), though this effect was greatly reduced for harmonics above 8 (experiment 2). The even-odd difference persisted when the original stimuli were made inharmonic by applying a frequency shift of 15%, but was abolished for stimuli consisting of successive partials (experiment 3).

Auditory Perception↗
PubMed1998

Perceptual segregation and pitch shifts of mistuned components in harmonic complexes and in regular inharmonic complexes.

It is unclear whether the perceptual segregation of a mistuned harmonic from a periodic complex tone depends specifically on harmonic relations between the other components. A procedure used previously for harmonic complexes [W. M. Hartmann et al., J. Acoust. Soc. Am. 88, 1712-1724 (1990)] was adapted and extended to regular inharmonic complexes. On each trial, subjects heard a 12-component complex followed by a pure tone in a continuous loop. In experiment 1, a mistuning of +/- 4% was applied to one of the components 2-11. The complex was either harmonic, frequency shifted, or spectrally stretched. Subjects adjusted the pure tone to match the pitch of the mistuned component. Near matches were taken to indicate segregation, and were almost as frequent in the inharmonic conditions as in the harmonic case. Also, small but consistent mismatches, pitch shifts, were found in all conditions. These were similar in direction and size to earlier findings for harmonic complexes. Using a range of mistunings, experiment 2 showed that the segregation of components from regular inharmonic complexes could be sensitive to mistunings of 1.5% or less. These findings are consistent with the proposal that aspects of spectral regularity other than harmonic relations can also influence auditory grouping.

Acoustic Stimulation↗
PubMed1998

Profiling the perceptual suppression of partials in periodic complex tones: further evidence for a harmonic template.

The basis for the perceptual cohesion of periodic complex tones was investigated. In experiment 1, 2-4 consecutive components (harmonics 6 and above) were removed from a 14-harmonic complex and replaced with a sinusoidal "probe," located at one of a set of regularly spaced positions spanning the gap. On each trial, subjects heard a complex tone followed by an adjustable pure tone in a continuous loop. Subjects were better able to match the pure tone to the probe when the probe did not coincide with a harmonic position. Minima in "hit rate" were more pronounced when harmonic probes were in positions adjacent to other harmonics than when they were not. These findings suggest that the pitch of each in-tune partial was actively suppressed by a template whose influence attenuated with distance from regions of consecutive harmonics. In experiment 2, the partials on either side of the spectral gap were harmonics of different fundamental frequencies. Hit-rate minima corresponding to both fundamentals were found, indicating an upward and downward spread of suppression, and also demonstrating the concurrent operation of two templates. The results confirm recent findings in support of template models, and are consistent with the idea that partial-pitch suppression underpins harmonic fusion.

Audiometry, Pure-Tone↗
PubMed1998

Contamination of propofol infusions in the intensive care unit: incidence and clinical significance.

Epidemics of bacteraemia and wound infection have been associated with the infusion of bacterially contaminated propofol administered during anaesthesia. We conducted an observational study to determine the incidence and clinical significance of administration of potentially contaminated propofol to patients in an ICU setting. One hundred patients received a total of 302 infusions of propofol. Eighteen episodes of possible contamination of propofol syringes were identified, but in all cases contamination was by a low-grade virulence pathogen. There were no episodes of clinical infection or colonization which could be attributed to the administration of contaminated propofol. During the routine use of propofol to provide sedation in ICU patients the risk of nosocomial infection secondary to contamination of propofol is extremely low.

APACHE↗
PubMed1997

Recombinant soluble interleukin-11 (IL-11) receptor alpha-chain can act as an IL-11 antagonist.

We have expressed a soluble N-glycosylated form of the murine interleukin-11 (IL-11) receptor alpha-chain (sIL-11R) and examined signaling in cells expressing the gp130 molecule. In the presence of gp130 but not the transmembrane IL-11R, the sIL-11R mediated IL-11-dependent differentiation of M1 leukemic cells and proliferation in Ba/F3 cells. Early intracellular events stimulated by the sIL-11R including phosphorylation of gp130, STAT 3, and SHP-2 were similar to signaling through the transmembrane IL-11R. IL-11 bound to sIL-11R with low affinity (kd 10 to 50 nmol/L). Binding of sIL-11R to gp130 was IL-11 dependent with intermediate affinity (kd 1.5 to 3.0 nmol/L). However, the concentration of IL-11 required for signaling through the sIL-11R was 10- to 20-fold greater than that required for cells expressing the transmembrane IL-11R and gp130 in the absence of sIL-11R. Furthermore, the sIL-11R was capable of antagonizing the activity of IL-11 when tested on cells expressing the transmembrane IL-11R and gp130. We propose that the observed IL-11 antagonism by the sIL-11R may depend on limiting numbers of gp130 molecules on cells already expressing the transmembrane IL-11R.

Amino Acid Sequence↗
PubMed1997

A family of bicistronic vectors to enhance both local and systemic antitumor effects of HSVtk or cytokine expression in a murine melanoma model.

The herpes simplex virus-thymidine kinase/ganciclovir (HSVtk/GCV) system produces both direct and immune-mediated tumor cell killing. Here, we compare the efficacy of HSVtk/GCV with cytokines, alone and in combination, on the tumorigenicity and immunogenicity of B16 cells. With respect to single gene modifications, only HSVtk/GCV, or high-level interleukin-2 (IL-2) secretion, completely prevented tumor growth, whereas granulocyte-macrophage colony-stimulating factor (GM-CSF) generated the best levels of long-term systemic protection. To augment both local killing and immune activation, we constructed bicistronic constructs that express HSVtk and a cytokine within the same cell. Co-expression of HSVtk with IL-2 or GM-CSF enhanced the local antitumor activity of any gene alone. In a tumor-prevention model, HSVtk killing, in an environment preprimed with GM-CSF, generated the best long-term immune protection. However, in a short-term therapy model, continued IL-2 expression was most effective against 3-day established tumors. This probably reflects differences in the activities of IL-2 and GM-CSF in generating short-term, nonspecific immune stimulation compared to long-term immunological memory, respectively. As a prelude to in vivo delivery experiments, we also demonstrated that these bicistronic cassettes can be packaged normally into retroviral (5 x 10(5) virus/ml from pooled populations) and adenoviral vectors (5 x 10(9) virus/ml) and function as predicted within virally infected cells. This family of bicistronic vectors can be used to stimulate synergy between suicide and cytokine genes, overcomes the problems of delivering two genes on separate vectors, and should allow easier preparation of vectors for the delivery of multiple genes to patients' tumor cells.

Adenoviridae↗
PubMed1997

The unusual species cross-reactivity of the leukemia inhibitory factor receptor alpha-chain is determined primarily by the immunoglobulin-like domain.

Human leukemia inhibitory factor (hLIF) binds to both human and mouse LIF receptors (LIFRs), while mouse LIF (mLIF) binds only to mouse LIFRs. Furthermore, hLIF binds with much higher affinity to the mouse LIFR (mLIFR) alpha-chain than does mLIF itself. To define the structural elements of the mLIFR alpha-chain conferring high affinity binding of hLIF and the species-specific interaction with mLIF, we first constructed C-terminally truncated extracellular domains of both the mLIFR and the human LIFR (hLIFR) alpha-chains, which contained only the two hemopoietin domains separated by an immunoglobulin-like domain. These recombinant truncated LIFR alpha-chains had identical binding and biological characteristics to either their naturally occurring or transfected counterparts. On the basis of this, we have generated eight interspecies receptor chimeras by combining different regions of the mouse and human LIFR sequence. Surprisingly, the immunoglobulin-like domain of the mLIFR alpha-chain played the predominant role in receptor-ligand interactions. Moreover, both high affinity binding for hLIF and the species-specific binding for mLIF mapped to the same domain of mLIFR molecule. These findings should enable the development of a "humanized" mouse LIFR that could act as a potent antagonist of hLIF biological activities in vivo.

Animals↗
PubMed1997

The mechanism of retroviral recombination: the role of sequences proximal to the point of strand transfer.

Transfer of nascent DNA from an RNA template (donor) to the homologous region of a second RNA template (acceptor) was studied. The templates were designed to assess the roles of the sequences proximal (3' relative to the transferring DNA) to the point of transfer. The donor template was primed with a specific 18 nucleotide DNA such that extension by reverse transcriptase to the end of the template produced a 79 nucleotide product. Homologous strand transfer and subsequent extension on the acceptors produced longer products allowing distinction between strand transfer and donor-directed synthesis. The donor and one particular acceptor shared a region of homology which included 8 tandem 5'-CAGU-3' repeats followed at the 3' end by a 17 nucleotide region of random homologous sequence. Derivatives of the acceptor either completely lacked the 17 nucleotide region or were progressively truncated resulting in a shorter region. With the acceptor lacking this region, prominent transfer products differing in length by 4 nucleotides were observed. Presumably this occurs because the transferring DNA can base-pair with several copies of the repeat elements of the acceptor. Addition of 5 or more of the 17 random nucleotides to the 3' end of the acceptor resulted in transfer products of essentially one length, and consistent with the transferring DNA correctly base-pairing with the 3' nucleotides. Results suggest that the transferring DNA interacts with the acceptor over several bases to form the most energetically stable hybrid duplex prior to extension on the acceptor. Hybrids formed from shorter interactions between the 3' end of the DNA and acceptor are either realinged prior to extension or precluded due to the mechanism of transfer.

Base Composition↗
PubMed1997

Mouth-state dependent changes in the judged pleasantness of water at different temperatures.

Dehydration increases the pleasantness of cold (0 degrees C) water (Boulze et al., 1983, Physiol. Behav. 30:97-102, 1983). The hypothesis that the mouth dryness induced by dehydration mediates this hedonic shift was investigated. Hydrated assessors (n = 16) judged 3 degrees C water as more pleasant after artificial mouth drying than did controls (n = 16). Mouth drying failed to influence similar judgements of water 13 degrees C, 23 degrees C, and 33 degrees C. We propose that preference shifts depend on temperature because cold water offers more rewarding relief from the sensations resulting from mouth dryness. Measures on saliva production were consistent with this proposal. Assessors swilled with water (3 degrees C, 13 degrees C, 23 degrees C, and 33 degrees C) for 5 s and then emptied their mouths. Measures of subsequent saliva flow confirmed that cold (3 degrees C) water induces an elevated rate of saliva flow and consequently leaves the mouth in a wetter state.

Adult↗
PubMed1997

Development of safe and efficient retroviral vectors for Gaucher disease.

We have generated amphotropic and Gibbon ape leukemia (GaLV) viruses carrying either a full-length (IG-GC2) or a shortened glucocerebrosidase cDNA (IG-GC4). For all recombinant retroviruses, a single infection was sufficient to augment glucocerebrosidase activity in unselected Gaucher type I and type II fibroblasts to levels which can be considered therapeutic. Transfer efficiency of the glucocerebrosidase cDNA into normal human and Gaucher type I CD34+ cells, using supernatant transduction, ranged from 4 to 50% as established on vector-positive CFU-GM. In these experiments, GaLV and amphotropic virus were equally efficient in transducing early human progenitors. Importantly, mixing amphotropic and GaLV pseudotyped retroviruses resulted in significantly higher transduction efficiencies as compared with single infections, up to 70% vector-positive CFU-GM. Glucocerebrosidase activity, measured in the progeny of human CD34+ cells, increased up to 460% compared with mock-infected CD34+ cells. Upon transduction of Gaucher CD34+ bone marrow cells the glucocerebrosidase deficiency was reversed.

Antigens, CD34↗
PubMed1997

Cloning and characterization of the genes encoding the murine homologues of the human melanoma antigens MART1 and gp100.

The recent identification of genes encoding melanoma-associated antigens has opened new possibilities for the development of cancer vaccines designed to cause the rejection of established tumors. To develop a syngeneic animal model for evaluating antigen-specific vaccines in cancer therapy, the murine homologues of the human melanoma antigens MART1 and gp100, which were specifically recognized by tumor-infiltrating lymphocytes from patients with melanoma, were cloned and sequenced from a murine B16 melanoma cDNA library. The open reading frames of murine MART1 and gp100 encode proteins of 113- and 626-amino acids with 68.8 and 77% identity to the respective human proteins. Comparison of the DNA sequences of the murine MART1 genes, derived from normal melanocytes, the immortalized nontumorgenic melanocyte line Melan-a and the B16 melanoma, showed all to be identical. Northern and Western blot analyses confirmed that both genes encoded products that were melanocyte lineage proteins. Mice immunized with murine MART1 or gp100 using recombinant vaccinia virus failed to produce any detectable T-cell responses or protective immunity against B16 melanoma. In contrast, immunization of mice with human gp100 using recombinant adenoviruses elicited T cells specific for hgp100, but these T cells also cross reacted with B16 tumor in vitro and induced significant but weak protection against B16 challenge. Immunization with human and mouse gp100 together [adenovirus type 2 (Ad2)-hgp100 plus recombinant vaccinia virus (rVV)-mgp100], or immunization with human gp100 (Ad2-hgp100) and boosting with heterologous vector (rVV-hgp100 or rVV-mgp100) or homologous vector (Ad2-hgp100), did not significantly enhance the protective response against B16 melanoma. These results may suggest that immunization with heterologous tumor antigen, rather than self, may be more effective as an immunotherapeutic reagent in designing antigen-specific cancer vaccines.

Amino Acid Sequence↗