Search PubMed⌕ Search

Biomedical subjects

A Nelson

Publications and source records attributed to A Nelson.

At least 73 records · Page 4Linked to original sources

Differential effects of global ischemia on delayed matching- and non-matching-to-position tasks in the water maze and Skinner box.

In order to assess effects of global ischemia in tasks of spatial learning and working memory, male Wistar rats were subjected to four vessel occlusion (4 VO) for periods of 5, 10, and 20 min and compared with sham-operated controls over four test phases, from 6 to 54 weeks after surgery. Rats were assessed on acquisition in the water maze, a task that is sensitive to ischemic impairments, before testing in Skinner box and water maze working memory tasks, which both require the short-term storage of information, but make different demands on spatial information processing. Phases 1 and 3 assessed spatial learning in a standard water maze procedure (12 and 10 training days, 2 trials/day with a 10-min intertrial interval: ITI). Phase 2 involved training and testing in delayed non-matching-to-position task in the Skinner box, with delays of 2-10 s between the information and choice stages. Phase 4 examined working memory in a water maze delayed matching-to-position task with 4 trials/day, an ITI of 30 s, and a novel platform position on each day. Ischemic rats showed duration-related impairments in water maze acquisition and working memory, but not in the less spatially demanding Skinner box task. Since water maze acquisition deficits were seen both before and after testing in the Skinner box the lack of effect cannot be attributed to time or to prior training. Ischemic deficits were more marked in Phase 3 than in Phase 1 of acquisition, suggesting that impairment may be progressive. Histological assessment showed that cell loss was largely confined to the hippocampal CA1 field and was linearly related to duration of occlusion. At the maximal level of loss (5.7 mm before the interaural line) the 20-min group showed 90% loss, the 10-min group 60% loss, and the 5-min group, which did not differ from controls, less than 10% loss. Only the 20-min group showed significant damage beyond the CA1 field, ranging from 30-40% loss in the CA3 field to 5% loss in one striatal area. No cortical damage was seen. The extent of CA1 cell loss correlated modestly with water maze acquisition (Phase 3) and working memory scores, but not with trials to criterion in the Skinner box task. There were significant correlations between different measures both within and between water maze tasks, but not Skinner box tasks, suggesting that the two types of procedure engaged different cognitive processes. The results indicate that the intrahippocampal damage induced by 4 VO impaired tasks which required processing of allocentric spatial information, but did not impair the storage of limited spatial information in working memory.

Animals↗

Cognitive deficits induced by global cerebral ischaemia: prospects for transplant therapy.

Global ischaemia induced by interruption of cerebral blood flow results in damage to vulnerable cells, notably in the CA1 and hilar hippocampal fields, and is frequently associated with memory deficits. This review examines cognitive deficits that occur in animal models of global ischaemia in rats and monkeys, the extent to which these deficits are associated with CA1 cell loss, and the evidence for functional recovery following transplants of foetal CA1 cells and grafts of conditionally immortalised precursor cells. In rats, impairments are seen most consistently in tasks of spatial learning and spatial working memory dependent on use of allocentric environmental cues. In monkeys, ischaemic deficits have been shown to a moderate extent in delayed object recognition tasks, but animals with a selective excitotoxic CA1 lesion show a profound impairment in conditional discrimination tasks, suggesting that these may be a more sensitive measure of ischaemic impairments. Several studies have reported correlational links between the extent of CA1 cell loss following two or four vessel occlusion (2 VO, 4 VO) in rats and behavioural impairments, but recent findings indicate that at intermediate levels of damage these relationships are weak and variable, and emerge clearly only when animals with maximal CA1 cell loss are included, suggesting that the deficits involve more than damage to the CA1 field. Nevertheless, ischaemic rats and CA1-lesioned marmosets with grafts of foetal CA1 cells show substantial improvements; in rats these are not found with grafts from other hippocampal fields. Conditionally immortalised cell lines and trophic grafts are currently being assessed for their functional potential in animal models, because clinical use of foetal cells will not be practicable. Recent findings suggest that an expanded population of neuroepithelial cells derived from the conditionally immortalised H-2Kb-tsA58 transgenic mouse improve spatial learning as effectively as CA1 foetal grafts in rats subjected to 4 VO, and clonal lines from the same source show similar promise. Lines derived from precursor cells have the potential to develop into different types of cell (neuronal or glial) depending on signals from the host brain. These cell lines may therefore have the capacity to repair damaged host circuits more precisely than is possible with foetal grafts, and offer a promising, approach both to functional recovery and to elucidating graft-host interactions.

Animals↗

Comparison of effects of global cerebral ischaemia on spatial learning in the standard and radial water maze: relationship of hippocampal damage to performance.

Groups of rats which had undergone global ischaemia for 10, 15 or 20 min using the four-vessel occlusion technique were compared with sham-operated controls on learning to locate a submerged platform in both acquisition and working memory tasks in a standard Morris water maze, and in a working memory task in an eight-channel water radial maze. Ischaemic rats showed duration-related impairments in all three tasks. The water radial maze task was learned more slowly than standard water maze tasks, but deficits were long-lasting. In the first phase of training in the radial water maze controls were more reluctant than ischaemic rats to visit all arms of the maze, and were subsequently found to spend less time on the open arms of an elevated plus-maze. However, differences in anxiety are not likely to account for differences in working memory performance in the radial water maze, as groups showed similar error rates before and after habituation to the maze. Histological examination showed that cell loss occurred chiefly in the CA1 field of the hippocampus and was linearly related to duration of occlusion. Cell loss was significantly correlated with the extent of impairment, but the pattern of relationships varied across the different tasks. For water maze acquisition, deficits in latency, heading angle and time spent in the training quadrant related more strongly to CA1 than CA3 cell loss, but radial water maze impairments showed the reverse tendency. In all cases correlations were substantially reduced following exclusion of rats with maximal CA1 cell loss, although a modest relationship with CA1 damage remained for latency in acquisition and working memory tasks, and heading angle on the probe trial. These results suggested that relationships between water maze impairments and cell loss are robust only after near total destruction of the dorsal CA1 field.

Animals↗

Recovery of spatial learning by grafts of a conditionally immortalized hippocampal neuroepithelial cell line into the ischaemia-lesioned hippocampus.

Transient global cerebral ischaemia in rats causes relatively circumscribed and specific damage to the CA1 pyramidal cells of the dorsal hippocampus, along with a cognitive deficit manifest as difficulties in the performance of a range of spatial learning and memory tasks. Our previous studies have shown that restoration of behavioural performance in ischaemic rats by neural grafts taken relatively late in fetal development occurs only after local replacement of cells homotypic to those lost through the ischaemic insult. This lesion-plus-behaviour model therefore offers a powerful means for establishing whether multipotent embryonic neuroepithelial cells will engraft the damaged CA1, develop into appropriate neuronal phenotypes and produce behavioural recovery. Here we report that, in rats subjected to 15 min of global cerebral ischaemia, intrahippocampal implants of a conditionally immortal, multipotent cell line, directly derived from the embryonic day 14 hippocampal neuroepithelium of the H-2Kb-tsA58 transgenic mouse, selectively repopulated the lesioned CA1 pyramidal layer and restored ischaemia-induced deficits in acquisition of a hidden platform location in the Morris water maze.

Animals↗

Pityriasis lichenoides et varioliformis acuta in HIV-1+ patients: a marker of early stage disease. The Military Medical Consortium for the Advancement of Retroviral Research (MMCARR).

BACKGROUND: The high incidence of cutaneous disease in HIV-1+ patients may be a marker of the chronic state of immune activation. In addition, specific cutaneous diseases may be related to the pattern and degree of immune dysregulation present in the patients at the time of the eruption. We have observed that HIV-1+ patients with pityriasis lichenoides et varioliformis acuta (PLEVA) were in the early to midstage of HIV-1 disease. MATERIALS AND METHODS: To determine if there was a correlation between the phenotype of the lymphoid infiltrate and surface markers of the epidermis and the known changes in early or late-stage HIV-1 disease, we studied five HIV-1+ patients with PLEVA. Cutaneous biopsy specimens were obtained and immunohistochemical stains were used to determine the expression of ELAM-1, ICAM-1, and HLA-DR and the phenotype of the lymphoid infiltrate. RESULTS: The HIV-1+ patients showed increased expression of HLA-DR on keratinocytes as well as on the mononuclear and dendritic cell populations in the epidermis and dermis. The majority of T cells were activated CD8+ cells. CONCLUSIONS: Immunophenotyping of the inflammatory infiltrate in these patients is consistent with a pattern of immune dysregulation seen only in earlier stages of HIV-1 disease. Thus, PLEVA may be useful as a marker of early to midstages of HIV-1 disease.

Adult↗

Preservation of allergic contact dermatitis to poison ivy (urushiol) in late HIV disease. The implications and relevance to immunotherapy with contact allergens.

BACKGROUND: Delayed hypersensitivity reactions (DTH) are lost with progression of HIV disease. This loss of DTH commonly occurs before the onset of opportunistic infections and is an independent predictor of disease progression. OBJECTIVE: We wanted to determine whether patients in late HIV disease with a history of allergic contact dermatitis (ACD) to poison ivy continue to react to poison ivy. METHODS: Twelve HIV+ patients with a past history of ACD to poison ivy were tested with an extract prepared from poison ivy leaves. All but 1 patient had CD4+ T cell counts < 200/microliters, and 5 patients had had an opportunistic infection. RESULTS: All 12 patients showed positive reactions ranging from mild erythema and infiltration to marked erythema with bulla formation. CONCLUSIONS: ACD is considered a variant of DTH, and as DTH results in a T helper 1 cytokine pattern. However, the antigen-specific effector cells in ACD may be more diverse than in DTH. This diversity could explain the continued reaction to some contact allergens in late disease and may be important in the use of contact allergens for immunotherapy.

Catechols↗

Barbiturate anticonvulsants: a neuropsychological and quantitative electroencephalographic study.

We studied 11 epileptic children aged 7 to 14 years with quantitative electroencephalographic (EEG) and neuropsychological tests, both on and off the barbiturate anticonvulsants phenobarbital and mephobarbital, comparing them to 13 controls matched for age and IQ who received testing at similar intervals. Neuropsychological tests employed were the Wechsler Intelligence Scale for Children-Revised (WISC-R), Bender-Gestalt, controlled oral word association test (COWAT), selected subtests of the Wechsler Memory Scale-Revised, Purdue Peg Board, Stroop Test, Trail Making Test, Wide Range Achievement Test-Revised, and Achenbach Behavior Rating Scale. There was no difference between on- and off-drug quantitative EEG in percentage power of any frequency band between 0.6 and 32 Hz. Neuropsychological data from all 11 subjects were analyzed with a two-factor analysis of variance with repeated measures on the time factor. The only difference from controls was on the Stroop Test. Parents reported clear behavioral changes in 6 of 11 subjects, but in 4 of these children the behavioral changes were sufficiently mild that parents chose to continue the barbiturate anticonvulsants: irritability, oppositional attitude, and overactivity were described. Mephobarbital was reported by parents to cause less severe problems than phenobarbital in subjects who had taken both barbiturate anticonvulsants. Barbiturate anticonvulsants have no effect on quantitative EEG and limited effects on neuropsychological tests in school-aged children.

Adolescent↗

A breastfeeding drop-in center survey evaluation.

A survey evaluated a Breastfeeding Drop-In Center's (BDC) provision of "hands-on" professional breastfeeding help and support in a community setting. Results from telephone interviews using a pretested 29-item open- and closed-ended questionnaire with a sample of 57 BDC clients showed: (1) 81% were breastfeeding at 4 months, (2) 51% were exclusively or primarily breastfeeding at 4 months, (3) 50% breastfed to or beyond their intended duration, (4) return to work/school was the main factor in weaning, (5) wanting reassurance, crying/fussy baby and poor latch were the most common reasons for attending the BDC, and (6) 95% said their problems were completely or partially resolved after visiting the BDC, with crying/fussy baby and difficulties latching as problems sometimes not resolved. These results suggest the BDC is an effective community breastfeeding support strategy.

Adult↗

Electrochemical modeling of electron and proton transfer to ubiquinone-10 in a self-assembled phospholipid monolayer.

Ubiquinone-10 (UQ) was incorporated at concentrations ranging from 0.5 to 2 mol% in a self-assembled monolayer of dioleoylphosphatidylcholine (DOPC) deposited on a mercury drop electrode, and its electroreduction to ubiquinol (UQH2) was investigated in phosphate and borate buffers over the pH range from 7 to 9.5 by a computerized chronocoulometric technique. The dependence of the applied potential for a constant value of the faradaic charge due to UQ reduction upon the electrolysis time t at constant pH and upon pH at constant t was examined on the basis of a general kinetion approach. This permitted us to conclude that the reduction of UQ to UQH2 in DOPC monolayers takes place via the reversible uptake of one electron with the formation of the semiubiquinone radical anion UQ.-, followed by the rate-determining protonation of this anion with UQH. formation; this neutral radical is more easily reduced than UQ, yielding the ubiquinol UQH2. In spite of the very low concentration of hydrogen ions as compared with that of the acidic component of the buffer, the only effective proton donor is the proton itself; this strongly suggests that the protonation step takes place inside the polar head region of the DOPC monolayer, which is only accessible to protons.

Biophysical Phenomena↗

Patient evaluation of prone carts used in spinal cord injury.

Prone carts are used for mobility by individuals with spinal cord injury who cannot use a wheelchair due to the risk of aggravating existing pressure ulcers. A prone cart is a flat/horizontal cart with a fixed height, propelled by the user while laying in a prone position. Patients reported that prolonged use of a prone cart resulted in chronic neck, shoulder and back pain. Additionally the existing prone carts lack user accessible angle adjustability, chest support area, as well as a storage, eating or working area. An interdisciplinary research team collaborated to address these concerns. Three prone carts were evaluated: E&J, Gendron, and a newly developed prototype, MIAD/PVA. Questionnaires were administered to caregivers and patients regarding usage and effectiveness of the prone carts as well as the features of an ideal cart. This data led to the design and refinement of a prototype prone cart which was tested on 20 patients and 19 caregivers at the SCI Centers of the Milwaukee and Tampa VAMC's from 1994-1995. The new prone cart enables the user to lie at an angle rather than laying flat. This position has been found to relieve back and neck pressure. With an hydraulic system, the the user can adjust both the front and rear angles of the cart to achieve desired comfort. In addition, a front deck provides an eating and working area. This study resulted in research-based information and criteria for the design of new prone carts. Findings of this pilot study will be incorporated in a development merit review proposal to the VA Rehabilitation Research & Development service for the design of a new manual and motorized prone cart. The researchers are collaborating with Ortho-Kinetics Inc. to promote ease in manufacturing.

Activities of Daily Living↗

An in-gel assay for protein tyrosine phosphatase activity: detection of widespread distribution in cells and tissues.

A method is described for the detection of protein tyrosine phosphatase activity in sodium dodecyl sulfate-polyacrylamide gels. A radiolabeled substrate, 32P-labeled poly(glutamic acid-tyrosine) (random copolymer) is incorporated into gels prior to polymerization. Following electrophoresis, the sodium dodecyl sulfate is removed; the proteins are fully denatured by soaking gels in 6 M guanidine hydrochloride and then renatured by incubation in buffers containing 0.04% Tween 40 and high concentrations of reducing agents. Protein tyrosine phosphatase activity is detected in autoradiographs of dried gels as regions from which the 32P has been selectively removed. Electrophoresis of known cytoplasmic protein tyrosine phosphatases indicates activity as the predicted molecular weights. As little as 10 pg of some cytoplasmic phosphatases is detectable. However, transmembrane tyrosine phosphatases, such as CD45, are detected only at very high protein loadings in this assay. Electrophoresis of whole cell lysates indicates multiple bands of tyrosine phosphatase activity, some of which comigrate with known cytoplasmic protein tyrosine phosphatases. The activity is inhibited by sodium orthovanadate or the omission of reducing agents during the renaturation process. The assay has been used to analyze embryonic and adult tissues, as well as whole cell lysates. A similar profile of bands of tyrosine phosphatase activity is seen with many different cells and tissues. However, some that are highly differentiated, such as adult skeletal muscle, erythrocytes, or sperm, reveal either a reduced level of tyrosine phosphatase activity or a simplified profile of bands.

Adult↗

Cloning of the murine counterpart of the tumor-associated antigen H-L6: epitope mapping of the human and murine L6 antigens.

The murine monoclonal antibody (mAb) L6 was raised against human lung carcinoma cells and found to recognize an antigen which is highly expressed on lung, breast, colon, and ovarian carcinomas. Promising results in phase 1 clinical studies with this antibody or its chimerized counterpart suggest the antigen recognized by mAb L6 (H-L6) is an attractive target for monoclonal antibody-based cancer therapy. Further development of L6 as an anti-tumor-targeting agent would benefit from the development of a murine model. However, initial attempts to develop such a model were hampered by our inability to generate antibodies against the murine homologue of the L6 antigen, M-L6. Here we describe the preparation of the mAb 12A8, which was raised against murine thymic epithelial cells, the tissue distribution of the murine antigen recognized by 12A8, the cloning of a cDNA encoding the 12A8 target antigen, and the demonstration that this antigen is M-L6. Using H-L6/M-L6 chimeric proteins, we show that the region of the M-L6 protein recognized by mAb 12A8 corresponds to the region of H-L6 recognized by mAb L6. There are five amino acid differences in the regions of the H-L6 and M-L6 proteins recognized by L6 and 12A8, respectively. We further mapped the protein epitope recognized by L6 by individually exchanging each of these residues in H-L6 with the corresponding residue found in M-L6. Substitution of the single H-L6 residue Leu122 with Ser resulted in the H-L6 mutant HL6-L122S which failed to bind L6. The HL6-L122S mutant also failed to bind 12A8.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗