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Biomedical subjects

A D Roberts

Publications and source records attributed to A D Roberts.

At least 37 records · Page 2Linked to original sources
PubMed2000

The influence of passive preexposure on escape from a Morris pool.

In 3 experiments rats were preexposed to the landmarks that surround a Morris pool by being placed on a submerged platform within the pool. They were then required to escape from the pool by swimming to the platform, which was in a location that had not been used during preexposure. Preexposure facilitated subsequent escape from the pool, provided that the platform was not moved during preexposure and the relative position of the landmarks to each other remained constant throughout preexposure. In contrast, if during preexposure the platform was moved from session to session (Experiment 1), or the array of landmarks was altered unsystematically from trial to trial (Experiments 2 and 3), then subsequent learning to escape from the pool was disrupted. These findings suggest that the effects of preexposure to the landmarks in a Morris pool is determined by whether or not they are of relevance for identifying the location of the platform. When they are relevant, then subsequent learning is facilitated, but when they are irrelevant, then subsequent learning is disrupted.

Animals↗
PubMed2000

Phagocytosis of mycobacteria by U937 cells: a rapid method for monitoring uptake and separating phagocytosed and free bacteria by magnetic beads.

A human-derived monocytic cell line (U937) was induced to phagocytose Mycobacterium phlei by the addition of phorbol myristate acetate (PMA) to the culture medium for 50-60 h. Cells not treated with PMA were unable to phagocytose M. phlei. Magnetic beads enabled a rapid and highly efficient separation of phagocytosed and free bacteria to be achieved, an approach which is particularly useful if colony plating is used to enumerate bacterial survival within phagocytic cells. Fluorescence-activated cell sorting (FACS) analysis showed that 98% of U937 cells contained viable bacteria after 3 h.

Cell Separation↗
PubMed2000

Lack of protection in mice and necrotizing bronchointerstitial pneumonia with bronchiolitis in guinea pigs immunized with vaccines directed against the hsp60 molecule of Mycobacterium tuberculosis.

In this study, the hsp60 and hsp70 heat shock protein antigens of Mycobacterium tuberculosis were tested as potential vaccine candidates, using purified recombinant protein antigens or antigens encoded in the form of a DNA plasmid vaccine. Guinea pigs vaccinated with a mixture of the two proteins showed no evidence of resistance to low-dose aerosol challenge infection and quickly developed severe lung damage characterized by necrotizing bronchointerstitial pneumonia and bronchiolitis. As a result, we turned instead to a DNA vaccination approach using a plasmid encoding the hsp60 antigen of M. tuberculosis. Although immunogenic in mice, vaccination with plasmid DNA encoding hsp60 was not protective in that model or in the guinea pig model and again gave rise to similar severe lung damage. This study seriously questions the safety of vaccines against tuberculosis that target highly conserved heat shock proteins.

Animals↗
PubMed2000

Efficacy of a contact lens cleaning device and its enhancement of the performance of contact lens care products.

BACKGROUND: Corneal infections due to contact lens contamination are risks associated with contact lens wear. Care systems which reduce these risks are desirable. METHODS: This study evaluated a contact lens cleaning device using normal saline initially and then four contact lens solutions. RESULTS: Using saline, six out of 10 tests resulted in complete removal of challenge organisms or showed reductions to 10 cfu/ml or <10 cfu/ml. Tests upon organism using multipurpose solutions showed >6 log reductions in 2-3 minutes. With laboratory made biofilms, similar results were obtained. CONCLUSIONS: This device improves lens cleaning and enhances lens care solutions. When used correctly it should lead to significant reductions in microbial keratitis associated with inadequate contact lens hygiene.

Bacteria↗
PubMed1999

FluoroDOPA PET shows the nondopaminergic as well as dopaminergic destinations of levodopa.

OBJECTIVE: To evaluate the visible and quantitative anatomic distribution of fluorine-18-labeled L-DOPA in the healthy human brain, to thereby expand the understanding of extrastriatal sites of levodopa function, and to provide a broader foundation for clinical and research studies of fluoroDOPA accumulation in patients. METHODS: The authors performed dynamic three-dimensional fluoroDOPA PET imaging in 10 healthy volunteers and analyzed the images visually and quantitatively. Twenty-eight regions of interest were applied to parametric images of the uptake rate constant (using the multiple-time graphic plot method with cortical input function) and also were used to quantitate regional radioactivity at 80 to 90 minutes. The authors correlated the uptake constants with published human regional neurotransmitter and decarboxylation data. RESULTS: PET imaging with fluoroDOPA demonstrates trapping of labeled dopamine or its metabolites in substantial quantities in many areas of the brain other than the mesostriatal pathways, including considerable uptake in the serotonergic and noradrenergic areas of the hypothalamus and brainstem as well as in extrastriatal cerebral sites. Total fluoroDOPA uptake correlates best with the sum of catecholamine and indolamine concentrations in the brain and moderately well with regional activity of aromatic L-amino acid decarboxylase, but correlates poorly with extrastriatal dopamine concentration. CONCLUSION: Neither L-DOPA nor its radiolabeled analog fluoroDOPA is metabolized or accumulates specifically in dopaminergic or even catecholaminergic neurons. Substantial dopamine production within serotonin and norepinephrine neurons may play a role in either therapeutic effects or adverse effects of therapy with L-DOPA.

Aged↗
PubMed1999

Identification of novel immunogenic Mycobacterium tuberculosis peptides that stimulate mononuclear cells from immune donors.

Proteins which are secreted or associated with the cell envelope of Mycobacterium tuberculosis may contain protective T-cell epitopes. Prior to this study, a recombinant clone bank of enzymatically active M. tuberculosis-alkaline phosphatase fusions, were screened for immunogenicity in a murine T-cell model. Five of these were selected for further study, and the IFN-gamma secretion and proliferation of human PBMC from purified protein derivative- (PPD)-positive and PPD-negative donors were measured in response to oligopeptides, Mtb-PhoA fusions and one full-length protein. Epitopes from four of the five selected antigens were immunoreactive in the human model and corresponded to cytochrome d ubiquinol oxidase, cytochrome c oxidase subunit II, MTV005.02 and MTV033.08. Thus, this strategy identified novel human immunogenic peptides as possible candidates for a subunit vaccine.

Alkaline Phosphatase↗
PubMed1999

Localization of trapping of 6-[(18)F]fluoro-L-m-tyrosine, an aromatic L-amino acid decarboxylase tracer for PET.

The purpose of this study was to address four major questions regarding 6-FMT, a noncatecholic PET tracer for AAAD: 1) Where is the specific uptake of 6-FMT? 2) Why does it accumulate where and to the degree that it does? 3) How does its uptake differ from that of fluoroDOPA globally? and 4) Does its regional uptake differ significantly from that of fluoroDOPA? High-resolution PET scans were obtained in three rhesus monkeys using 6-FMT and in two of them using fluoroDOPA. Anatomic distribution was analyzed visually and quantitative uptake of 6-FMT was compared with published regional decarboxylase activity and monoamine neurotransmitter concentrations. In addition to high uptake in the dopamine-rich striatal nuclei, there was specific uptake of 6-FMT in brain regions which have little dopaminergic innervation but which have other amines in significant concentration. 6-FMT uptake correlated best with regional AAAD activity (r = 0.97). It correlated slightly less well with the sum of catecholamine and indolamine neurotransmitter concentrations, but does not correlate with dopamine concentration. The uptake of 6-FMT is greater than that of fluoroDOPA, with only slight differences in their regional distributions. Radiolabeled analogs of DOPA are often implicitly or explicitly regarded as tracers for presynaptic dopaminergic function. However, localization of these tracers more broadly includes many regions with relatively high concentrations of norepinephrine and serotonin. This may be especially important in diseases or experimental states in which dopaminergic neurons are selectively reduced, and may allow for the study of nondopaminergic neuronal systems in vivo with this tracer.

Animals↗
PubMed1999

Blocking in the Morris swimming pool.

Four experiments demonstrate that spatial blocking is governed by the same principles that govern blocking in Pavlovian conditioning. In the 2nd stage of each experiment, rats escaped from a Morris swimming pool by swimming to a submerged platform with a beacon attached to it. Test trials were then conducted in the absence of the platform and the beacon to assess the extent to which subjects had learned about the position of the platform with reference to the room cues. For the 1st stage of their training, rats either swam to the platform and beacon in the presence of curtains that prevented the room cues from being seen (Experiments 1 & 2), or they swam to the platform and beacon that were moved from trial to trial (Experiments 3 & 4). In each experiment, learning about the room cues in the 2nd stage of the experiment was blocked by the presence of the beacon. This blocking effect was disrupted by changing the appearance of the beacon for the 2nd stage of training or by restricting the amount of exposure to the beacon during the 1st phase of training.

Animals↗
PubMed1999

Alterations in serum levels of lipids and lipoproteins with indinavir therapy for human immunodeficiency virus-infected patients.

Alterations in lipid metabolism have been associated with the use of protease inhibitors. Sequential lipid analyses were performed on serum samples from human immunodeficiency virus-infected antiretroviral-naive patients who received indinavir in combination with two nucleoside reverse transcriptase inhibitors. Serum levels of cholesterol, triglycerides, high-density lipoproteins (HDLs), and low-density lipoproteins (LDLs) were measured at baseline and at periodic intervals. After 48 weeks of indinavir therapy, mean serum levels +/- SD rose as follows: cholesterol, from 167.2 +/- 36.0 to 206.3 +/- 32.4 mg/dL (P < .0005); triglycerides, from 110.4 +/- 47.5 to 158.4 +/- 72.5 mg/dL (P < .0101); and LDLs, from 106.6 +/- 35.1 to 136.1 +/- 31.6 mg/dL (P = .0029). There was no significant change in the serum HDL fraction. Mean serum lipoprotein (a) levels +/- SD rose from 6.5 +/- 1.4 to 9.6 +/- 2.0 mg/dL after 30 weeks (P = .0695). Potential mechanisms for the noted increases include alterations in serum lipoprotein lipase activity or changes in hepatic lipid metabolism. The clinical significance of these changes remains to be determined.

Cholesterol↗
PubMed1999

Localized damage in vertebral bone is most detrimental in regions of high strain energy density.

It was hypothesized that damage to bone tissue would be most detrimental to the structural integrity of the vertebral body if it occurred in regions with high strain energy density, and not necessarily in regions of high or low trabecular bone apparent density, or in a particular anatomic location. The reduction in stiffness due to localized damage was computed in 16 finite element models of 10-mm-thick human vertebral sections. Statistical analyses were performed to determine which characteristic at the damage location--strain energy density, apparent density, or anatomic location--best predicted the corresponding stiffness reduction. There was a strong positive correlation between regional strain energy density and structural stiffness reduction in all 16 vertebral sections for damage in the trabecular centrum (p < 0.05, r2 = 0.43-0.93). By contrast, regional apparent density showed a significant negative correlation to stiffness reduction in only four of the sixteen bones (p < 0.05, r2 = 0.47-0.58). While damage in different anatomic locations did lead to different reductions in stiffness (p < 0.0001, ANOVA), no single location was consistently the most critical location for damage. Thus, knowledge of the characteristics of bone that determine strain energy density distributions can provide an understanding of how damage reduces whole bone mechanical properties. A patient-specific finite element model displaying a map of strain energy density can help optimize surgical planning and reinforcement of bone in individuals with high fracture risk.

Adult↗
PubMed1998

Hippocampal lesions disrupt navigation based on cognitive maps but not heading vectors.

Animals can find a hidden goal in several ways. They might use a cognitive map that encodes information about the geometric relationship between the goal and two or more landmarks. Alternatively, they might use a heading vector that specifies the direction and distance of the goal from a single landmark. Rats with damage to the hippocampus have difficulty in finding a hidden goal. Here we determine which of the above strategies is affected by such damage. Rats were required to swim in a water maze to a submerged platform, which was always at the same distance and direction from a landmark. The platform and landmark remained in the same place for the four trials of each session, but they were moved to a new position at the start of a session. Rats with damage to the hippocampus found the platform more efficiently than did normal rats in the first trial of a session but, in contrast to normal rats, their performance did not improve during a session. Our results indicate that hippocampally damaged rats are able to navigate by means of heading vectors but not cognitive maps.

Animals↗
PubMed1998

Changes in integrin/adhesion molecule expression, but not in the T-cell receptor repertoire, in old mice infected with tuberculosis.

The results of this study present data in support of the hypothesis that T lymphocytes in both young and old mice infected with virulent Mycobacterium tuberculosis undergo changes in expression of cell surface integrin/adhesion molecules as determined by flow cytometric analysis. These data thus further support the hypothesis that a reduced ability of T-cells in old mice to adequately and promptly accumulate at sites of inflammation induced by bacterial implantation is a central parameter underlying the increased susceptibility of these mice to this intracellular bacterial infection. In addition, however, no changes were observed in terms of the T-cell receptor expression (repertoire) of these animals, indicating that this facet of immunity is preserved in aging.

Aging↗
PubMed1998

CD95 expression in aged mice infected with tuberculosis.

The interaction between CD95 and its ligand is an important homeostatic mechanism that leads to the induction of apoptosis in activated T cells. In view of recent evidence that this pathway might be defective in aged mice, this study investigated CD95 expression on T cells in old mice activated by infection with Mycobacterium tuberculosis. The results of the study do not support the hypothesis that CD95 is poorly expressed on CD4 T cells from old mice; instead, it was found that similar numbers of T cells from young and old mice expressed CD95, with the intensity of expression if anything higher on the cells from the old mice. In addition, the study demonstrated that changes in CD44 and CD45RB expression previously observed in young infected mice proceeded in a similar fashion in old animals and, as would be predicted, that CD95(hi) expression was primarily associated with CD4 T cells expressing the activated CD44(hi) CD45RBhi phenotype.

Age Factors↗
PubMed1998

Disruption of the cellular inflammatory response to Listeria monocytogenes infection in mice with disruptions in targeted genes.

The results of this study to dissect the nature of the acquired immune response to infection with Listeria monocytogenes in mice with targetted gene disruptions show that successful resolution of disease requires the essential presence of alphabeta T cells and the capacity to elaborate gamma interferon. In the absence of either of these entities, mice experience increasingly severe hepatitis and tissue necrosis and die within a few days. The data from this study support the hypothesis that the protective process is the efficient replacement of neutrophils in lesions by longer-lived mononuclear phagocytes; alphabeta-T-cell-knockout mice died from progressive infection before neutrophil replacement could occur, whereas in gammadelta-T-cell-knockout mice this replacement process in the liver has previously been shown to be much slower. In the present study we attribute this delay to reduced production of the macrophage-attracting chemokine MCP-1 in the gammadelta-T-cell-knockout animals. These data further support the hypothesis that gammadelta T cells are important in controlling the inflammatory process rather than being essential to the expression of protection.

Animals↗
PubMed1998

Evaluation of new vaccines in the mouse and guinea pig model of tuberculosis.

The results of this study provide the first evidence that two completely separate vaccine approaches, one based on a subunit vaccine consisting of a mild adjuvant admixed with purified culture filtrate proteins and enhanced by the cytokine interleukin-2 and the second based on immunization with DNA encoding the Ag85A protein secreted by Mycobacterium tuberculosis, could both prevent the onset of caseating disease, which is the hallmark of the guinea pig aerogenic infection model. In both cases, however, the survival of vaccinated guinea pigs was shorter than that conferred by Mycobacterium bovis BCG, with observed mortality of these animals probably due to consolidation of lung tissues by lymphocytic granulomas. An additional characteristic of these approaches was that neither induced skin test reactivity to commercial tuberculin. These data thus provide optimism that development of nonliving vaccines which can generate long-lived immunity approaching that conferred by the BCG vaccine is a feasible goal.

Acyltransferases↗
PubMed1998

Fluorine-18-fluoro-L-DOPA dosimetry with carbidopa pretreatment.

UNLABELLED: This article presents dosimetry based on the measurement of fluoro-DOPA activity in major tissues and in the bladder contents in humans after oral pretreatment with 100 mg carbidopa. METHODS: Bladder activity was measured continuously by external probe and calibrated using complete urine collections. Quantitative dynamic PET scans provided time-activity curves for the major organs. Bladder wall dosimetry was calculated using the methods of MIRD Pamphlet No. 14. Effective dose was calculated as described in ICRP Publication 60. RESULTS: Mean absorbed dose to the bladder wall surface per unit administered activity was 0.150 mGy/MBq (0.556 rad/mCi) with the realistic void schedule used in our studies. The dose was 0.027 mGy/MBq (0.101 rad/mCi) to the kidneys, 0.0197 mGy/MBq (0.0728 rad/mCi) to the pancreas, and 0.0186 mGy/MBq (0.0688 rad/mCi) to the uterus. Absorbed doses to other organs were an order of magnitude or more lower than the bladder, 0.009-0.015 mGy/MBq. The effective dose per unit administered activity was 0.0199 mSv/MBq (0.0735 rem/mCi.) CONCLUSION: Urinary excretion of fluoro-DOPA was altered significantly by pretreatment with carbidopa. In general, any manipulation of tracer metabolism in the body should be expected to produce changes in biodistribution and dosimetry. The largest radiation dose was to the bladder wall, for which our estimate was one-fifth of that from the original report. The methods used reflect realistic urinary physiology and typical use of this tracer. The principles of MIRD Pamphlet No. 14 should be used in planning studies using tracers excreted in the urine to minimize the absorbed dose.

Aromatic Amino Acid Decarboxylase Inhibitors↗
PubMed1996

Comfort and frictional properties of dental gloves.

OBJECTIVES: A survey of general dental practitioners and dental surgery assistants was carried out to ascertain their preferences and opinions on powder-free hydrogel-coated gloves compared with starch-powdered gloves. The aim was to relate the survey findings to laboratory measurements of the frictional characteristics of glove inner surfaces and their water absorptive capability. METHODS: The survey was carried out using a questionnaire given to local dental practitioners. Glove friction and water absorption measurements were made using specially designed equipment. RESULTS: The survey showed that a selected group of dentist and dental surgery assistants preferred hydrogel-coated gloves, particularly for damp donning, durability and long-term wear comfort. Laboratory measurements showed that the hydrogel coating gave a low friction coefficient against damp skin. The coating was durable, and absorbed water more readily than other treatments. CONCLUSION: A survey of dental practitioners and dental surgery assistants and laboratory measurements indicates that hydrogel-coated gloves have superior properties, and are preferred to other non-sterile glove types.

Absorption↗