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1.
Dis Aquat Organ ; 155: 165-174, 2023 Sep 14.
Article in English | MEDLINE | ID: mdl-37706647

ABSTRACT

Sea lice are a key limitation to sustainable salmon aquaculture, and effective monitoring strategies are critical for the management of these parasites. Sentinel cages are an established means of assessing infestation pressure at fixed locations, but as smolts move through systems they will be exposed to varying lice densities. As a means of assessing infestation pressure along trajectories, we describe the development and application of towed sentinel cages (TSCs) in a Scottish sea loch containing salmonid aquaculture. Trial deployments took place over 3 yr (2016-2018), and levels of sea lice infestation were compared between methodologies. Oceanographic data was collected alongside TSCs to put the results into the environmental context that smolts and sea lice experienced during the tows. The sea lice infestation rates found from TSCs were comparable to those on contemporaneously deployed fixed sentinel cages. Thus, due to their practicability and consistency with other surveillance methods, TSCs could be used to improve the assessment of exposure risk along wild salmonid smolt migration trajectories, where these are known.


Subject(s)
Copepoda , Lice Infestations , Salmo salar , Animals , Lice Infestations/veterinary , Aquaculture
2.
J Intellect Disabil Res ; 63(1): 49-63, 2019 01.
Article in English | MEDLINE | ID: mdl-30417575

ABSTRACT

BACKGROUND: Providing effective weight management to adults with intellectual disabilities is necessary to challenge the high rates of obesity. The aim of this process evaluation was to explore the feasibility of conducting a full-scale clinical trial of the TAKE 5 multi-component weight management programme. METHODS: The study was a 12-month pilot cluster-randomised controlled trial. Adults with intellectual disabilities and obesity were randomised to either TAKE 5, which included an energy deficit diet (EDD) or Waist Winners Too, based on health education principles. A mixed-methods process evaluation was conducted focussing on the reach, recruitment, fidelity, implementation, dose (delivered/received) and context. RESULTS: The study successfully recruited adults with intellectual disabilities. Both weight management programmes were delivered with high fidelity and implemented as intended. Only one weight management programme, TAKE 5, demonstrated potential efficacy in reducing body weight and body composition. The effectiveness was largely attributed to the EDD and social support from carers. CONCLUSIONS: The extensive process evaluation illustrated that a full-scale trial of a multi-component programme including an EDD is feasible and an acceptable approach to weight management for adults with intellectual disabilities and obesity.


Subject(s)
Intellectual Disability/rehabilitation , Obesity/therapy , Process Assessment, Health Care , Weight Reduction Programs/methods , Adult , Comorbidity , Feasibility Studies , Female , Humans , Intellectual Disability/epidemiology , Male , Obesity/epidemiology , Pilot Projects , Weight Reduction Programs/standards
3.
J Fish Dis ; 41(6): 901-919, 2018 Jun.
Article in English | MEDLINE | ID: mdl-28782801

ABSTRACT

Sea lice are a constraint on the sustainable growth of Scottish marine salmonid aquaculture. As part of an integrated pest management approach, farms coordinate procedures within spatial units. We present observations of copepodids being at relatively greater density than nauplii in upper waters, which informs the development of surface layer sea lice transmission modelling of Loch Linnhe, Scotland, for informing farm parasite management. A hydrodynamic model is coupled with a biological particle-tracking model, with characteristics of plankton sea lice. Simulations are undertaken for May and October 2011-2013, forced by local wind data collected for those periods. Particles are continually released from positions representing farm locations, weighted by relative farm counts, over a 2-week period and tracked for a further 5 days. A comparison is made between modelled relative concentrations against physical and biological surveys to provide confidence in model outputs. Connectivity between farm locations is determined in order to propose potential coordination areas. Generally, connectivity depends on flow patterns in the loch and decreases with increased farm separation. The connectivity indices are used to estimate the origins of the sea lice population composition at each site, which may influence medicinal regimens to avoid loss of efficacy.


Subject(s)
Animal Distribution , Copepoda/physiology , Ectoparasitic Infestations/veterinary , Fish Diseases/epidemiology , Age Factors , Animals , Aquaculture , Copepoda/growth & development , Ectoparasitic Infestations/epidemiology , Hydrodynamics , Models, Biological , Scotland/epidemiology
4.
J Fish Dis ; 40(3): 351-365, 2017 Mar.
Article in English | MEDLINE | ID: mdl-27524425

ABSTRACT

Amoebic gill disease (AGD) in farmed Atlantic salmon is caused by the amoeba Paramoeba perurans. The recent establishment of in vitro culture techniques for P. perurans has provided a valuable tool for studying the parasite in detail. In this study, flow cytometry was used to generate clonal cultures from single-sorted amoeba, and these were used to successfully establish AGD in experimental Atlantic salmon. The clonal cultures displayed differences in virulence, based on gill scores. The P. perurans load on gills, determined by qPCR analysis, showed a positive relationship with gill score, and with clonal virulence, indicating that the ability of amoebae to proliferate and/or remain attached on gills may play a role in virulence. Gill scores based on gross signs and histopathological analysis were in agreement. No association between level of gill score and specific gill arch was observed. It was found that for fish with lower gill scores based on histopathological examination, gross examination and qPCR analysis of gills from the same fish were less successful in detecting lesions and amoebae, respectively.


Subject(s)
Amebiasis/veterinary , Amoebozoa/physiology , Amoebozoa/pathogenicity , Salmo salar , Amebiasis/parasitology , Amoebozoa/genetics , Animals , DNA, Protozoan/genetics , Fish Diseases/parasitology , Flow Cytometry/veterinary , RNA, Ribosomal, 18S/genetics , Real-Time Polymerase Chain Reaction/veterinary , Sequence Analysis, DNA/veterinary , Virulence
5.
J Fish Dis ; 38(6): 515-21, 2015 Jun.
Article in English | MEDLINE | ID: mdl-25102953

ABSTRACT

Viral haemorrhagic septicaemia virus (VHSV) was isolated from five species of wrasse (Labridae) used as biological controls for parasitic sea lice predominantly, Lepeophtheirus salmonis (Krøyer, 1837), on marine Atlantic salmon, Salmo salar L., farms in Shetland. As part of the epidemiological investigation, 1400 wild marine fish were caught and screened in pools of 10 for VHSV using virus isolation. Eleven pools (8%) were confirmed VHSV positive from: grey gurnard, Eutrigla gurnardus L.; Atlantic herring, Clupea harengus L.; Norway pout, Trisopterus esmarkii (Nilsson); plaice, Pleuronectes platessa L.; sprat, Sprattus sprattus L. and whiting, Merlangius merlangus L. The isolation of VHSV from grey gurnard is the first documented report in this species. Nucleic acid sequencing of the partial nucleocapsid (N) and glycoprotein (G) genes was carried out for viral characterization. Sequence analysis confirmed that all wild isolates were genotype III the same as the wrasse and there was a close genetic similarity between the isolates from wild fish and wrasse on the farms. Infection from these local wild marine fish is the most likely source of VHSV isolated from wrasse on the fish farms.


Subject(s)
Disease Outbreaks/veterinary , Fish Diseases/epidemiology , Hemorrhagic Septicemia, Viral/epidemiology , Animals , Fish Diseases/transmission , Fish Diseases/virology , Fisheries , Fishes , Genotype , Glycoproteins/genetics , Hemorrhagic Septicemia, Viral/transmission , Hemorrhagic Septicemia, Viral/virology , Novirhabdovirus/genetics , Novirhabdovirus/isolation & purification , Nucleocapsid Proteins/genetics , Salmo salar , Scotland/epidemiology
6.
J Intellect Disabil Res ; 59(11): 1010-21, 2015 Nov.
Article in English | MEDLINE | ID: mdl-25496397

ABSTRACT

BACKGROUND: Important work has been carried out adapting cognitive behavioural therapy for people with intellectual disabilities. However, there is a lack of alternative psychological therapies available for people with intellectual disabilities and emotional difficulties. Behavioural activation for depression is less reliant on verbal communication and focuses on increasing purposeful activity and reducing avoidance. METHOD: This feasibility study involved the development and piloting of an adapted manual of behavioural activation for people with intellectual disabilities. The intervention consisted of 10-12 sessions and a key adaptation was that the therapist worked with the clients alongside a significant other in their life, either a paid carer or family member. Baseline, post-intervention (3 months after entering the study) and 6-month quantitative follow-up data were obtained. Primary outcome data were gathered, concerning depressive symptoms, participants' levels of activity and general well-being. RESULTS: Twenty-three adults with intellectual disabilities with symptoms of depression were recruited from specialist health services. In terms of acceptability, the behavioural activation intervention was well received and only two individuals dropped out, with a further two lost to follow-up. The main measures of depression appeared to be sensitive to change. Pre- to post-intervention data showed a significant reduction in self-report of depressive symptoms with a strong effect size (r = 0.78), that was maintained at follow-up (r = 0.86). Positive change was also obtained for informant reports of depressive symptoms from pre- to post-intervention, with a strong effect size (r = 0.7). Once again, this positive change was maintained at follow-up (r = 0.72). CONCLUSIONS: The study suggested that behavioural activation may be a feasible and worthwhile approach to tackling depression in people with intellectual disabilities. However, a randomised controlled trial would be required to establish its effectiveness, with more sensitive measurement of change in activity.


Subject(s)
Behavior Therapy/methods , Depression/therapy , Intellectual Disability/psychology , Adult , Feasibility Studies , Female , Follow-Up Studies , Humans , Male , Middle Aged , Pilot Projects , Treatment Outcome , Young Adult
7.
J Fish Dis ; 36(3): 323-37, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23305449

ABSTRACT

Salmon aquaculture in Scotland continues to increase; however, one of the potential limitations to its further sustainable growth is the ectoparasitic sea louse Lepeophtheirus salmonis. The industry in Scotland undertakes coordinated management procedures to control the levels of sea lice on farms in designated production areas. We developed a biophysical sea lice dispersal model for Loch Linnhe, one of the largest fjords on the west coast of Scotland, to provide further information to help establish more effective farm management areas. We successfully extend modelling principles previously applied to a small Scottish fjordic system. Modelling scenarios demonstrate heterogeneity in the distribution of sea lice within the system and simulations, suggesting that lice could be transmitted up to 30 km. The scenarios are assessed by comparing model predictions against lice sampled by both planktonic trawls and settlement on sentinel caged fish. The model predicts the ranked abundance of both planktonic and settled lice assuming that the lice input to the system is relative to host biomass. Data collection is ongoing for undertaking and assessing additional scenarios.


Subject(s)
Copepoda/physiology , Ectoparasitic Infestations/veterinary , Fish Diseases/epidemiology , Fisheries , Models, Biological , Animals , Computer Simulation , Ectoparasitic Infestations/epidemiology , Population Dynamics , Scotland/epidemiology
8.
J Intellect Disabil Res ; 57(4): 359-69, 2013 Apr.
Article in English | MEDLINE | ID: mdl-22533494

ABSTRACT

BACKGROUND: Clinicians working with clients who have mild intellectual disabilities (IDs) have shown growing enthusiasm for using a cognitive behavioural approach, amid increasing evidence of good treatment outcomes for this client group. However, very little is known about the views and experiences of clients with IDs who have undergone cognitive behavioural therapy. This study aims to explore the perspective of these clients. METHODS: Fifteen participants with borderline to mild IDs and problems of anxiety, depression and anger were interviewed regarding their experience of cognitive behavioural therapy (CBT). Two semi-structured interviews were carried out in the first phase of therapy between session four and session nine. An interpretive phenomenological approach was taken to seek out themes from participants' own personal accounts. RESULTS: Participants valued the opportunity to talk about problems with their therapist and benefitted from therapeutic relationships characterised by warmth, empathy and validation. Participants identified areas of positive change; however, many thought that this may be short lived or not maintained beyond discharge. CONCLUSIONS: The supportive aspects of therapeutic relationships were particularly important to participants undergoing CBT. The clinical implications are considered.


Subject(s)
Cognitive Behavioral Therapy/methods , Intellectual Disability/rehabilitation , Patient Satisfaction , Qualitative Research , Adult , Anger/physiology , Anxiety/rehabilitation , Cognitive Behavioral Therapy/standards , Depression/rehabilitation , Female , Humans , Interview, Psychological/standards , Male , Middle Aged , Professional-Patient Relations , Self Efficacy , Severity of Illness Index , Treatment Outcome
9.
J Intellect Disabil Res ; 57(1): 90-102, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22369631

ABSTRACT

BACKGROUND: To date, no studies have explored the role of carers in supporting adults with intellectual disabilities (ID) and obesity during a weight loss intervention. The present study explored perceptions of carers supporting adults with ID, as they participated in a 6-month multi-component weight loss intervention (TAKE 5). METHODS: Semi-structured interviews were used to explore the experiences of 24 carers. The transcripts were analysed qualitatively using thematic analysis. RESULTS: Three themes emerged from the analysis: carers' perceptions of participants' health; barriers and facilitators to weight loss; and carers' perceptions of the weight loss intervention. Data analysis showed similarities between the experiences reported by the carers who supported participants who lost weight and participants who did not. Lack of sufficient support from people from the internal and external environment of individuals with ID and poor communication among carers, were identified as being barriers to change. The need for accessible resources tailored to aid weight loss among adults with ID was also highlighted. CONCLUSION: This study identified specific facilitators and barriers experienced by carers during the process of supporting obese adults with ID to lose weight. Future research could utilise these findings to inform appropriate and effective weight management interventions for individuals with ID.


Subject(s)
Caregivers/psychology , Intellectual Disability/nursing , Obesity/therapy , Weight Loss , Attitude to Health , Female , Humans , Intellectual Disability/complications , Male , Obesity/complications , Obesity/nursing
10.
J Appl Res Intellect Disabil ; 25(1): 29-38, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22473946

ABSTRACT

BACKGROUND: Interpersonal conflict is a source of stress and contributes to poor mental health in people with mild to moderate intellectual disabilities. Understanding the contexts in which conflict typically occurs can better equip services to help people with such difficulties. However, existing studies into the contexts of conflict have included participants with wide-ranging ages and may not reflect the experiences of young adults in particular. MATERIALS AND METHODS: Twenty-six young adults (16-20 years) with intellectual disabilities and 20 non-disabled young adults completed a semi-structured interview about a recent experience of interpersonal conflict. Participants were asked to describe their beliefs and feelings about the event and their subsequent response. RESULTS: Participants with intellectual disabilities were more likely to encounter conflict with strangers or peers outside their friendship group and to describe incidents of aggression than non-disabled participants. They were also more likely to characterize the other person globally as 'bad' and to perceive the other's actions as being personally directed at them. Young women with intellectual disabilities were less likely to describe responding aggressively to incidents. CONCLUSIONS: Findings suggest that young adults with intellectual disabilities are often the target of overt aggression from those outside their inner social sphere, while their non-disabled peers are more likely to experience conflict with people close to them. Young adults with intellectual disabilities may also be more likely to feel victimized by interpersonal conflict. Implications of these findings and limitations of the study are discussed.


Subject(s)
Adolescent Development/physiology , Conflict, Psychological , Intellectual Disability/psychology , Interpersonal Relations , Persons with Mental Disabilities/psychology , Adolescent , Adult , Female , Humans , Interview, Psychological , Male , Young Adult
11.
J Intellect Disabil Res ; 53(9): 759-71, 2009 Sep.
Article in English | MEDLINE | ID: mdl-19627425

ABSTRACT

Cognitive behavioural therapy (CBT) is increasingly used to address the emotional and interpersonal problems of people with ID. There is a limited but promising evidence base supporting this activity. However, these individuals face real and continuing challenges in their lives that have implications for their self and interpersonal perceptions. These adversities have implications for the adaptation of CBT. First, it may mean that characteristically negative perceptions may be more common and may be the result of a complex interaction with a truly aversive environment and should not simply be considered as cognitive distortions. Secondly, clients may have limited control over their everyday lives, with limited opportunity to negotiate change with their informal and formal sources of support. This review suggests that it is important to consider the interpersonal context of therapy both to ensure effective work within sessions and to enable real change in clients' everyday lives. The review draws upon Vygotsky's theory of the zone of proximal development and ecological models of change to consider the challenges of establishing collaborative relationships and the potential to use CBT within a broad psychosocial model. The aim is to offer a helpful framework for practitioners and to identify directions for future research.


Subject(s)
Cognitive Behavioral Therapy/methods , Intellectual Disability/therapy , Interpersonal Relations , Humans , Self Concept , Social Environment
12.
Parasitology ; 136(8): 867-74, 2009 Jul.
Article in English | MEDLINE | ID: mdl-19493370

ABSTRACT

Harnessing the full utility of extensive gene sequences recently available for the economically important sea louse, Lepeophtheirus salmonis, requires the adaptation of modern molecular biology approaches to this non-model organism. Using a putative microsomal prostaglandin E synthase type-2 (PGES2) as a candidate gene, we investigated gene-knockdown by double-stranded RNA interference (dsRNAi) in the small free-living and the larger parasitic stages of L. salmonis. dsRNA was administered to nauplius and copepodid stages by immersion for 7 h. Pre-adult and adults received dsRNA by intra-haemocoelic injection. The extent, speed and persistence of the knockdown effects were determined by RT-PCR. LsPGES2 was abundantly expressed in all life stages, including the non-parasitic stages. Administration of dsRNA to nauplius and copepodids by immersion had no effect on mortality rates and moulting through to copepodids was observed. Dramatic knockdown of LsPGES2 was observed within 7 h and persisted for at least 48 h. Injection of dsRNA had no effect on mortality in pre-adults and adults, but knockdown of LsPGES2 was apparent within 24 h, reaching 95% over the 72 h and was persistent for at least 120 h. The methods developed resulted in rapid and persistent knockdown in L. salmonis suitable for studies in the different stadia.


Subject(s)
Copepoda/genetics , Gene Knockdown Techniques/methods , Intramolecular Oxidoreductases/genetics , RNA Interference , Animals , Female , Genes, Mitochondrial/genetics , Injections , Prostaglandin-E Synthases , RNA, Double-Stranded/genetics , Salmo salar/parasitology
13.
J Intellect Disabil Res ; 52(Pt 5): 393-403, 2008 May.
Article in English | MEDLINE | ID: mdl-18221332

ABSTRACT

BACKGROUND: A few recent studies have adopted a social cognitive perspective to explore how individuals with intellectual disabilities (IDs), who present problems of aggression, view their social world. The focus has mainly been on participants' perceptions of others' behaviour within conflict situations. The present exploratory study aims to compliment existing research by exploring social cognitive factors that may influence how individuals respond to conflict. METHODS: Study was carried out with 20 aggressive and 20 non-aggressive men and women who have a mild to moderate ID. The 'Social Goals and Strategies for Conflict' (SGASC) assessment was devised to explore whether group or gender differences could be found in participants' expected outcomes of aggressive strategies, their expected outcomes of submissive strategies and their emotional reaction to these outcomes. Participants' social goals within hypothetical situations of conflict were also explored. RESULTS: It was found that aggressive and non-aggressive participants have different social goals. There were no significant differences for expected outcomes of aggression or submissiveness. Nevertheless, a number of trends suggest that more aggressive participants expect negative outcomes for submissiveness compared with their non-aggressive peers. CONCLUSIONS: While the findings of this study are tentative, investigating the social outcomes that are valued by individuals with ID who present problems of aggression appears to be a promising area for further research, with possible implications for clinical assessment and treatment.


Subject(s)
Adaptation, Psychological , Aggression/psychology , Conflict, Psychological , Goals , Intellectual Disability/psychology , Social Behavior , Adult , Attitude , Emotions , Female , Hostility , Humans , Interpersonal Relations , Male , Middle Aged , Observer Variation , Predictive Value of Tests , Psychiatric Status Rating Scales , Reproducibility of Results , Severity of Illness Index , Sex Distribution
15.
Neuroscience ; 134(2): 671-6, 2005.
Article in English | MEDLINE | ID: mdl-15979806

ABSTRACT

Chronic neuroinflammation plays a prominent role in the progression of Alzheimer's disease. Reactive microglia and astrocytes are observed within the hippocampus during the early stages of the disease. Epidemiological findings suggest that anti-inflammatory therapies may slow the onset of Alzheimer's disease. Chemokine receptor 5 (CCR5) up-regulation may influence the recruitment and accumulation of glia near senile plaques; activated microglia express CCR5 and reactive astrocytes express chemokines. We have previously shown that neuroinflammation induced by chronic infusion of lipopolysaccharide into the 4th ventricle reproduces many of the behavioral, neurochemical, electrophysiological and neuropathological changes associated with Alzheimer's disease. The current study investigated the ability of D-Ala-peptide T-amide (DAPTA), a chemokine receptor 5 chemokine receptor antagonist of monocyte chemotaxis, to influence the consequences of chronic infusion of lipopolysaccharide. DAPTA (0.01 mg/kg, s.c., for 14 days) dramatically reduced the number of activated microglia and astrocytes, as compared with lipopolysaccharide-infused rats treated with vehicle. DAPTA treatment also reduced the number of immunoreactive cells expressing nuclear factor kappa binding protein, a prominent component of the proinflammatory cytokine signaling pathway. The present study suggests that DAPTA and other CCR5 antagonists may attenuate critical aspects of the neuroinflammation associated with Alzheimer's disease.


Subject(s)
Astrocytes/physiology , CCR5 Receptor Antagonists , Dipeptides/pharmacology , Hippocampus/physiopathology , Microglia/physiology , Animals , Astrocytes/drug effects , Astrocytes/pathology , Disease Models, Animal , Hippocampus/drug effects , Hippocampus/pathology , Inflammation , Lipopolysaccharides/toxicity , Microglia/drug effects , Microscopy, Confocal , Rats
16.
Br J Med Psychol ; 74(Pt 3): 305-21, 2001 Sep.
Article in English | MEDLINE | ID: mdl-11589324

ABSTRACT

This paper examines the changing approaches to working with people with a moderate to mild learning disability, who are frequently aggressive. Long-held assumptions about the lack of inter-personal understanding and impulsiveness continue to play a central role in clinical assessment and intervention for this group. Yet, there is a lack of controlled studies indicating the influence of such factors in frequent aggression. The dominant behavioural tradition has long encouraged such assumptions, but has focused on people with more severe disabilities where such assumptions are arguably more appropriate. The current review of the literature shows a clear evolution away from a strict behavioural approach towards cognitive-behavioural therapy (CBT) approaches that take account of the heterogeneous psychosocial causes of aggression. We find support for CBT in the child-development literature, which examines inter-personal difficulties from an information-processing perspective. Finally, we argue that much of the literature implicitly utilizes the concept of self, and we suggest that this should be made explicit in a reformulated theory of the 'person', incorporating the self concept and embedding individual cognitive processes and behaviour in a social context.


Subject(s)
Aggression/psychology , Learning Disabilities/psychology , Learning Disabilities/therapy , Models, Psychological , Reinforcement, Social , Self Concept , Behavior Therapy , Cognitive Behavioral Therapy , Humans , Impulsive Behavior/psychology
17.
Antiviral Res ; 52(1): 63-75, 2001 Oct.
Article in English | MEDLINE | ID: mdl-11530189

ABSTRACT

Peptide T, which is derived from the V2 region of HIV-1, inhibits replication of R5 and dual-tropic (R5/X4) HIV-1 strains in monocyte-derived macrophages (MDMs), microglia, and primary CD4(+)T cells. Little to no inhibition by peptide T was observed with lab adapted X4 viruses such as IIIB, MN, or NL4-3 propagated in CD4(+) T cells or in the MAGI entry assay. The more clinically relevant R5/X4 early passage patient isolates were inhibited via either the X4 or R5 chemokine receptors, although inhibition was greater with R5 compared to X4 receptors. Virus inhibition ranged from 60 to 99%, depending on the assay, receptor target, viral isolate and amount of added virus. Peak inhibitory effects were detected at concentrations from 10(-12) to 10(-9) M. Peptide T acted to block viral entry as it inhibited in the MAGI cell assay and blocked infection in the luciferase reporter assay using HIV virions pseudotyped with ADA envelope. These results using early passage virus grown in primary cells, together with two different entry reporter assays, show that peptide T selectively inhibits HIV replication using chemokine receptor CCR5 compared to CXC4, explaining past inconsistencies of in vitro antiviral effects.


Subject(s)
HIV-1/physiology , Peptide T/physiology , Receptors, CCR5/physiology , Virus Replication/drug effects , Antibodies, Monoclonal/immunology , Antiviral Agents/metabolism , Biological Assay , Cells, Cultured , Chemokines/antagonists & inhibitors , Chemokines/metabolism , Dose-Response Relationship, Drug , Enzyme-Linked Immunosorbent Assay , Fetus , Flow Cytometry , Genes, Reporter , HIV Core Protein p24/immunology , HIV-1/metabolism , HeLa Cells , Humans , Luciferases/analysis , Luciferases/genetics , Macrophages/drug effects , Macrophages/immunology , Macrophages/metabolism , Macrophages/virology , Microglia/cytology , Microglia/metabolism , Microglia/virology , Peptide T/immunology , Time Factors
18.
Am J Ment Retard ; 104(5): 399-409, 1999 Sep.
Article in English | MEDLINE | ID: mdl-10541411

ABSTRACT

An assessment task was devised to explore the attributional style and role-taking ability of 22 aggressive and 22 nonaggressive adults with moderate to mild mental retardation. Aggressive participants showed a hostile bias in their interpretation of others' intentions towards themselves within ambiguous interpersonal situations, although no difference was found across groups within clearly provocative situations. Furthermore, the role-taking ability of the aggressive participants was superior to the nonaggressive group, undermining the focus on global problems of interpersonal understanding as a causal factor of aggression for people with mental retardation.


Subject(s)
Aggression/psychology , Intellectual Disability/psychology , Internal-External Control , Role , Adolescent , Adult , Aged , Female , Humans , Intellectual Disability/rehabilitation , Interpersonal Relations , Male , Middle Aged , Projective Techniques , Social Perception
19.
Clin Immunol ; 93(2): 124-31, 1999 Nov.
Article in English | MEDLINE | ID: mdl-10527688

ABSTRACT

We previously reported that certain short gp120 V2 region peptides homologous to vasaoactive intestinal peptide (VIP), such as "peptide T," were potent inhibitors of gp120 binding, infectivity, and neurotoxicity. The present study shows that synthetic V2-region-derived peptides have potent intrinsic chemotaxis agonist activity for human monocytes and also act as antagonists of high-affinity (0.1 pM) gp120-mediated monocyte chemotaxis. Selectivity is shown in that peptide T is more potent at suppressing M-tropic than T-tropic gp120 chemotaxis. Peptide T was also able to suppress monocyte chemotaxis to MIP-1beta, a chemokine with selectivity for CCR5 chemokine receptors, while chemotaxis of the more promiscuous ligand RANTES was not inhibited, nor was chemotaxis mediated by SDF-1alpha. In order to determine if peptide T mediated its gp120 antagonistic effects via modulation of CCR5 receptors, RANTES chemotaxis was studied using a CCR5 receptor-transfected HOS cell line. In this case, RANTES chemotaxis was potently inhibited by V2-region-derived short peptides. Peptide T also partially suppressed (125)I-MIP1-beta binding to human monocytes, suggesting action at a subset of MIP1-beta receptors. The V2 region of gp120 thus contains a potent receptor binding domain and synthetic peptides derived from this region modulate CCR5 chemokine receptor chemotactic signaling caused by either gp120 or chemokine ligands. The results have therapeutic implications and may explain recent clinical improvements, in that HIV/gp120 actions at CCR5 receptors, such as occur in the brain or early infection, would be susceptible to peptide T inhibition.


Subject(s)
CCR5 Receptor Antagonists , Chemotactic Factors/antagonists & inhibitors , Chemotactic Factors/physiology , Chemotaxis/immunology , HIV Envelope Protein gp120/physiology , Peptide T/metabolism , Cells, Cultured , Chemokine CCL5/antagonists & inhibitors , Chemokine CCL5/immunology , Chemokines/antagonists & inhibitors , Chemokines/metabolism , Humans , Monocytes/immunology , Monocytes/metabolism , Peptide T/immunology , Peptides , Protein Isoforms/metabolism
20.
Brain Res ; 838(1-2): 27-36, 1999 Aug 14.
Article in English | MEDLINE | ID: mdl-10446313

ABSTRACT

Vasoactive intestinal peptide (VIP) and DAPTA (D-ala(1)-peptide T-amide, a gp120-derived octapeptide homologous to VIP) prevent neuronal cell death produced by five variants of HIV-1 (human immunodeficiency virus) envelope protein (gp120). VIP or DAPTA treatment of astrocyte cultures resulted in the release of macrophage inflammatory protein-1alpha (MIP-1alpha) and RANTES, beta chemokines known to block gp120 interactions with microglial chemokine receptors. In rat cerebral cortical cultures, gp120-induced neuronal killing was partially or completely prevented by chemokines that stimulate the CXCR4, CCR3 or CCR5 chemokine receptors. Chemokines exhibited marked differences in potency and efficacy in preventing toxicity associated with five gp120 variants (LAV/BRU, CM243, RF, SF2, and MN). RANTES had the broadest and most potent inhibition (IC(50)<3 pM for RF isolate). An octapeptide derived from RANTES also exhibited neuroprotection from gp120 (RF isolate) toxicity (IC(50)=0.3 microM). Treatment with chemokines alone had no detectable effect on neuronal cell number. However, antiserum to MIP-1alpha produced neuronal cell death that was prevented by co-treatment with MIP-1alpha, suggesting that this endogenous chemokine exerts a tonic regulation important to neuronal survival. The neuroprotective action of VIP on gp120 was attenuated by co-treatment with anti-MIP-1alpha. These studies suggest that the neuroprotective action of VIP is linked in part to its release of MIP-1alpha. Furthermore, neuroprotection produced by chemokines is dependent on both the type of chemokine and the variant structure of gp120 and may be relevant to drug strategies for the treatment of AIDS dementia.


Subject(s)
Chemokines/metabolism , HIV Envelope Protein gp120/genetics , HIV , Neurons/drug effects , Peptide T/pharmacology , Vasoactive Intestinal Peptide/pharmacology , Animals , Cell Death/drug effects , Cells, Cultured , Chemokine CCL5/analysis , Genetic Variation , Neurons/pathology , Neurotoxins/genetics , Rats
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