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M Gallagher

Publications and source records attributed to M Gallagher.

At least 73 records · Page 4Linked to original sources
PubMed1998

Polyreactive antigen-binding B cells are the predominant cell type in the newborn B cell repertoire.

Polyreactive antibodies bind to a variety of different self and non-self antigens. The B cells that make these antibodies express the polyreactive lg receptor on their surface. To determine the frequency of polyreactive antigen-binding B cells in peripheral blood, we incubated two different antigens, one (insulin) labeled with fluorescein isothiocyanate and the other (beta-galactosidase) with phycoerythrin, with peripheral B cells. The percentage of cells that bound these antigens was determined with the fluorescence-activated cells sorter. Approximately 21% of adult B cells bound insulin, 28% bound beta-galactosidase, and 11% bound both antigens. In contrast to B cells in the adult repertoire, 49% of B cells in cord blood bound insulin, 54% bound beta-galactosidase, and 33% bound both antigens. The properties of polyreactive antigen-binding B cells in adult and cord blood were similar, except for the fact that almost all the polyreactive antigen-binding B cells in cord blood were CD5 positive (93%), whereas only 40% of the polyreactive antigen-binding B cells in adult peripheral blood were CD5 positive, indicating that the CD5 marker is not directly linked to polyreactivity. The percentage of polyreactive antigen-binding B cells in patients with Sjögren's syndrome, systemic lupus erythematosus and rheumatoid arthritis was equal to or slightly below that found in the normal adult B cell repertoire. It is concluded that polyreactive antigen-binding B cells are a major constituent of the normal adult B cell repertoire and are the predominant cell type in the newborn B cell repertoire.

Adolescent↗
PubMed1998

Use of TCR ADV gene segments by the delta chain is independent of their position and of CD3 expression.

The CD3 signaling complex is required for cell surface expression and selection of both alphabeta and gammadelta TCR. In this study we analyzed TCRD transcripts in both wild-type and CD3-epsilon-deficient mice. We show that the repertoire of ADV segments used by the delta chain is unchanged in the latter. Not all ADV genes participate in making up the TCRD repertoire. However, their use does not depend on their distance from the other TCRD-forming segments. For example ADV12, situated at more than 870 kb from the DD region, is expressed as part of TCRD transcripts, whereas ADV8, members of which are proximal to the DD region, is not. These data suggest that the accessibility of ADV8 gene segments is differentially regulated during T cell development in the thymus. Taken together, our results suggest that TCRA and TCRD rearrangements are independently controlled, and that the absence of TCRA expression in CD3-epsilon-deficient mice is not due to a lack of accessibility of the ADV gene segments but rather to inaccessibility of the AJ gene region.

Animals↗
PubMed1998

Individual differences in spatial memory and striatal ChAT activity among young and aged rats.

Individual differences in spatial memory among young and aged rats were assessed using memory tasks related to integrity of the hippocampus and the neostriatum. Relationships were then examined between measures of spatial memory and regional choline acetyltransferase (ChAT) activity, a marker for cholinergic integrity. Twenty-four-month-old Long-Evans rats were impaired in comparisons with 6-month-old rats on measures of place learning, working memory, reference memory, and perseveration in water-maze tasks. Aged rats that were impaired on one measure of memory, however, were not necessarily impaired on other measures. ChAT activity in the ventromedial and dorsolateral neostriatum of aged rats was significantly reduced in comparisons with young rats whereas no difference was found in the hippocampus. Aged rats with the most ChAT activity in the anterior ventromedial neostriatum performed best on the place-learning and reference memory tasks but also made the most perseverative errors on the working memory task. In addition, young and aged rats with the most ChAT activity in the anterior dorsolateral neostriatum were those with the least accurate working memory. No relationships were found between ChAT activity in the hippocampus and spatial memory. Thus age-related memory impairment has components that can be segregated by measuring relationships between cholinergic integrity in subregions of the anterior neostriatum and memory tasks with different strategic requirements.

Aging↗
PubMed1998

Behavioural assessment of mice lacking D1A dopamine receptors.

Dopamine D1A receptor-deficient mice were assessed in a wide variety of tasks chosen to reflect the diverse roles of this receptor subtype in behavioural regulation. The protocol included examination of exploration and locomotor activity in an open field, a test of sensorimotor orienting, both place and cue learning in the Morris water maze, and assessment of simple associative learning in an olfactory discrimination task. Homozygous mice showed broad-based impairments that were characterized by deficiencies in initiating movement and/or reactivity to external stimuli. Data obtained from flash evoked potentials indicated that these deficits did not reflect gross visual impairments. The partial reduction in D1A receptors in the heterozygous mice did not affect performance in most tasks, although circumscribed deficits in some tasks were observed (e.g., failure to develop a reliable spatial bias in the water maze). These findings extend previous behavioural studies of null mutant mice lacking D1A receptors and provide additional support for the idea that the D1A receptor participates in a wide variety of behavioural functions. The selective impairments of heterozygous mice in a spatial learning task suggest that the hippocampal/cortical dopaminergic system may be uniquely vulnerable to the partial loss of the D1A receptor.

Animals↗
PubMed1998

Orbitofrontal cortex and basolateral amygdala encode expected outcomes during learning.

Reciprocal connections between the orbitofrontal cortex and the basolateral nucleus of the amygdala may provide a critical circuit for the learning that underlies goal-directed behavior. We examined neural activity in rat orbitofrontal cortex and basolateral amygdala during instrumental learning in an olfactory discrimination task. Neurons in both regions fired selectively during the anticipation of rewarding or aversive outcomes. This selective activity emerged early in training, before the rats had learned reliably to avoid the aversive outcome. The results support the concept that the basolateral amygdala and orbitofrontal cortex cooperate to encode information that may be used to guide goal-directed behavior.

Amygdala↗
PubMed1998

The influence of a breakfast meal on the assessment of body composition using bioelectrical impedance.

OBJECTIVE: To investigate the effect of a breakfast meal on bioelectrical impedance (BI). DESIGN: Three separate interventions. SETTING: A university based study. SUBJECTS: Young, healthy volunteers recruited from staff. Twenty-nine subjects (11 men, 18 women), ten subjects (two men and eight women) and 13 subjects (2 men and 11 women) completed the first, second and third protocol, respectively. INTERVENTIONS: Total body BI (protocol 1) or both total body BI and segmental BI (namely arm, leg or torso BI); (protocol 3) was measured in the fasting state and for up to 5 h after the consumption of a breakfast meal containing 28% energy from fat. In the second protocol, total body BI was measured in the same way on two occasions after subjects consumed isocaloric meals containing either 28% energy or 4% energy from fat. RESULTS: Consumption of a 2300 kJ meal was followed by a significant (P = 0.0002) decrease in BI (95% confidence intervals 12.5 and 35.3), a change which occurred 2 h after the meal and continued until 5 h, irrespective of meal fat content. The fall in total body BI was accounted for primarily by a fall in the BI of the limbs, with virtually no contribution from the torso. CONCLUSION: To ensure consistency in the interpretation of BI for body composition analysis, it is important that measurements are made in the fasting state.

Adult↗
PubMed1998

Telephone triage of acute illness by a practice nurse in general practice: outcomes of care.

BACKGROUND: Telephone working is an increasingly important way of managing general practice workload, particularly out of hours. The role of telephone triage, however, in managing acute consultations during the day has not been adequately researched. AIM: To determine the impact of telephone triage, conducted by a practice nurse, on the management of same day consultations in a general practice. METHOD: A general practice of 11,300 patients in South Tyneside collected prospective telephone and surgery consultation data over three months. Patient satisfaction, for those who had received only telephone advice, was measured using a postal questionnaire. Four outcomes were measured: changes in doctor and nurse workload; repeat consultations with the same problem; prescriptions issued; and patient satisfaction with the service. RESULTS: In three months, 1263 consultations were recorded. Doctor workload fell by 54%, from 1522 to 664 consultations, compared with the previous three months. A total of 325 (26%) telephone requests to see the doctor were managed by the nurse on the telephone without them visiting the surgery. Also, 273 (21%) patients saw the nurse in the surgery, 565 (45%) saw the doctor in the surgery, and 99 (8%) saw the doctor and the nurse in the surgery. The response rate to the postal questionnaire was 192/271 (71%); 154 (88%) were satisfied with nurse telephone advice. CONCLUSIONS: Telephone triage, by a practice nurse, of patients who wish to see the doctor on the same day, reduced doctor workload. This was a service that patients liked.

Family Practice↗
PubMed1998

Gender and age differences in the concerns of adolescents in Northern Ireland.

This study surveyed the self-expressed worries of 3,983 adolescents in Northern Ireland, with a specific focus on identifying age and gender differences. Students aged thirteen to eighteen years completed a 138-item scale in which they indicated frequency of worry across a range of social and personal issues. Analysis of their responses revealed that females reported worrying significantly more frequently than did males, particularly in regard to transition from school and personal and academic issues. Students over sixteen years old reported worrying significantly less frequently than did their younger counterparts. These results are discussed in the context of societal, gender-related, and developmental influences.

Adolescent↗
PubMed1997

Spatial memory is related to hippocampal subcellular concentrations of calcium-dependent protein kinase C isoforms in young and aged rats.

Relationships were examined between spatial learning and hippocampal concentrations of the alpha, beta2, and gamma isoforms of protein kinase C (PKC), an enzyme implicated in neuronal plasticity and memory formation. Concentrations of PKC were determined for individual 6-month-old (n = 13) and 24-month-old (n = 27) male Long-Evans rats trained in the water maze on a standard place-learning task and a transfer task designed for rapid acquisition. The results showed significant relationships between spatial learning and the amount of PKC among individual subjects, and those relationships differed according to age, isoform, and subcellular fraction. Among 6-month-old rats, those with the best spatial memory were those with the highest concentrations of PKCgamma in the particulate fraction and of PKCbeta2 in the soluble fraction. Aged rats had increased hippocampal PKCgamma concentrations in both subcellular fractions in comparison with young rats, and memory impairment was correlated with higher PKCgamma concentrations in the soluble fraction. No age difference or correlations with behavior were found for concentrations of PKCgamma in a comparison structure, the neostriatum, or for PKCalpha in the hippocampus. Relationships between spatial learning and hippocampal concentrations of calcium-dependent PKC are isoform-specific. Moreover, age-related spatial memory impairment is associated with altered subcellular concentrations of PKCgamma and may be indicative of deficient signal transduction and neuronal plasticity in the hippocampal formation.

Aging↗
PubMed1997

Animal models of memory impairment.

Memory impairment in the elderly resembles a mild temporal lobe dysfunction. Alterations in the hippocampal formation are also a probable basis for cognitive deficits in some animal models of ageing. For example, aged rats are impaired in hippocampal-dependent tests of spatial memory. Recent studies have revealed considerable structural integrity in the aged hippocampus, even in aged rats with the most impaired spatial memory. In contrast, atrophy/loss of cholinergic neurons in the basal forebrain and deficiency in cholinergic transduction in hippocampus correlate with the severity of spatial memory impairment in aged rats. This evidence supports the longstanding view that age-related loss of memory has a cholinergic basis. In this context, it is somewhat surprising that the use of a selective cholinergic immunotoxin in young rats to further test this hypothesis has revealed normal spatial memory after removing septo-hippocampal cholinergic neurons. Young rats with immunotoxic lesions, however, have other behavioural impairments in tests of attentional processing. These lines of research have implications for understanding the neurobiological basis of memory deficits in ageing and for selecting an optimal behavioural setting in which to examine therapies aimed at restoring neurobiological function.

Animals↗
PubMed1997

Brain aging: changes in the nature of information coding by the hippocampus.

Advanced age in rats is associated with a decline in spatial memory capacities dependent on hippocampal processing. As yet, however, little is known about the nature of age-related alterations in the information encoded by the hippocampus. Young rats and aged rats identified as intact or impaired in spatial learning capacity were trained on a radial arm maze task, and then multiple parameters of the environmental cues were manipulated to characterize the changes in firing patterns of hippocampal neurons corresponding to the presence of particular cues or the spatial relationships among them. The scope of information encoded by the hippocampus was reduced in memory-impaired aged subjects, even though the number of neurons responsive to salient environmental cues was not different from that in young rats. Furthermore, after repeated manipulations of the cues, memory-intact aged rats, like young rats, altered their spatial representations, whereas memory-impaired aged rats showed reduced plasticity of their representation throughout testing. Thus changes in hippocampal memory representation associated with aging and memory loss can be characterized as a rigid encoding of only part of the available information.

Aging↗
PubMed1997

Disruption of decrements in conditioned stimulus processing by selective removal of hippocampal cholinergic input.

The attention directed to environmental stimuli can be modified by experience. For example, preexposure of a conditioned stimulus (CS) in the absence of reinforcement can retard subsequent conditioning of that stimulus when it is paired directly with an unconditioned stimulus, a phenomenon referred to as latent inhibition. Similarly, consistent pairings of a CS with another event can slow the acquisition of new information about that CS. Such phenomena suggest that reductions in the processing of CSs occur when they are made behaviorally irrelevant or consistent predictors of other events. On the basis of the observation that hippocampal lesions prevented such reductions in CS processing, we hypothesized that damage to basal forebrain cholinergic neurons that project to the hippocampus, using microinjections of the selective immunotoxin 192 IgG-saporin into the medial septum/vertical limb of the diagonal band (MS/VDB), also would disrupt normal reductions in CS processing. Lesions of hippocampal cholinergic input disrupted decreases in CS processing, manifested in both an absence of latent inhibition and a lack of reduced processing of a CS that had been a consistent predictor of another CS. These results indicate that cholinergic neurons in the MS/VDB play a role in the regulation of CS processing. Furthermore, these findings (in conjunction with previous findings) implicate both rostral (hippocampal-projecting) and caudal (cortical-projecting) regions of the basal forebrain cholinergic system in the modulation of attention.

Animals↗
PubMed1997

The role of an amygdalo-nigrostriatal pathway in associative learning.

The present study examined the role of an amygdalo-nigrostriatal pathway in associative learning. An asymmetrical lesion model was used to test whether a circuit from the amygdala central nucleus to the dorsolateral striatum, via the substantia nigra, is critical for mediating conditioned orienting responses. Rats with an asymmetrical lesion, consisting of neurotoxic removal of central nucleus neurons in one hemisphere and depletion of the dopamine innervation of the dorsolateral striatum in the contralateral hemisphere, failed to acquire conditioned orienting responses. In contrast, the asymmetrical lesion had no effect on spontaneous orienting or learning another response directed to the source of the food unconditioned stimulus in the same task. A second experiment tested the effect of reversible inactivation of the dorsolateral striatum contralateral to a neurotoxic central nucleus lesion on acquisition of the conditioned orienting response. Although inactivation did not affect spontaneous orienting, rats failed to acquire the conditioned orienting response during sessions in which inactivation occurred. Immediately after the inactivation procedure was terminated, however, a significant increase in orienting to the conditioned stimulus was evident. These data support the interpretation that the dorsolateral striatum provides a route for the expression of the conditioned orienting response but is not essential for acquisition of this learned behavior.

Amygdala↗
PubMed1997

Acute non-A-E hepatitis in the United States and the role of hepatitis G virus infection. Sentinel Counties Viral Hepatitis Study Team.

BACKGROUND: Little is known about the relation of the newly discovered hepatitis G virus (HGV) to the cause and clinical course of acute and chronic viral hepatitis. METHODS: We selected patients from a surveillance study of acute viral hepatitis in four U.S. counties who had acute disease during 1985 to 1986 or 1991 to 1995. Serum samples were tested for HGV RNA by the polymerase chain reaction. RESULTS: HGV RNA was detected in 4 of 45 patients with a diagnosis of non-A-E hepatitis (9 percent), 23 of 116 patients with hepatitis C (20 percent), 25 of 100 patients with hepatitis A (25 percent), and 32 of 100 patients with hepatitis B (32 percent) (P<0.05 for the comparison of hepatitis B with hepatitis non-A-E or C). The clinical characteristics of the acute illness were similar for patients with HGV alone and those with hepatitis A, B, or C with or without HGV infection. During a follow-up period of one to nine years, chronic hepatitis did not develop in any of the patients with HGV alone, but 75 percent were persistently positive for HGV RNA, as were 87 percent of those with both hepatitis C and HGV infection. The rates of chronic hepatitis were similar in patients with hepatitis C alone (60 percent) and those with both hepatitis C and HGV infection (61 percent). CONCLUSIONS: The evidence from this surveillance study does not implicate HGV as an etiologic agent of non-A-E hepatitis. Persistent infection with HGV was common, but it did not lead to chronic disease and did not affect the clinical course in patients with hepatitis A, B, or C.

Acute Disease↗
PubMed1997

Hippocampal N-methyl-D-aspartate and kainate binding in response to entorhinal cortex aspiration or 192 IgG-saporin lesions of the basal forebrain.

Lesion models in the rat were used to examine the effects of removing innervation of the hippocampal formation on glutamate receptor binding in that system. Bilateral aspiration of the entorhinal cortex was used to remove the cortical innervation of the hippocampal formation and the dentate gyrus. The subcortical input to the hippocampus from cholinergic neurons of the basal forebrain was lesioned by microinjection of the immunotoxin 192 IgG-saporin into the medial septum and vertical limb of diagonal band. After a 30-day postlesion survival, the effects of these lesions on N-methyl-D-aspartate-displaceable [3H]glutamate and [3H]kainate binding in the hippocampus were quantified using in vitro autoradiography. The bilateral entorhinal lesion induced a sprouting response in the dentate gyrus, measured by an increase in the width of [3H]kainate binding. It also induced an increase in the density of [3H]kainate binding in CA3 stratum lucidum and an increase in N-methyl-D-aspartate binding throughout the hippocampus proper and the dentate gyrus. The selective lesion of cholinergic septal input did not have any effect on hippocampal [3H]kainate binding and induced only a moderate decrease in N-methyl-D-aspartate binding that was not statistically reliable. The entorhinal and cholinergic lesions were used as in vivo models of the degeneration of hippocampal input that occurs in normal aging and Alzheimer's disease. The results from the present lesion study suggest that some, but not all, of the effects on hippocampal [3H]kainate and N-methyl-D-aspartate binding induced by the lesions are consistent with the status of binding to these receptors in aging and Alzheimer's disease. Consistent with the effects of aging and Alzheimer's disease is an altered topography of [3H]kainate binding after entorhinal cortex lesion and a modest decline in N-methyl-D-aspartate binding after lesions of the cholinergic septal input to the hippocampus.

Acetylcholinesterase↗