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Biomedical subjects

J A Barrett

Publications and source records attributed to J A Barrett.

At least 19 recordsLinked to original sources
PubMed2003

A hypothesis: self-propulsion in a wheelchair early after stroke might not be harmful.

BACKGROUND: There is often strong clinical resistance to patients self-propelling a wheelchair post stroke as this is believed to produce immediate increases in abnormal posture and movement. Research to support this viewpoint is limited. OBJECTIVE: To begin investigation of the immediate effects of self-propulsion on symmetrical sitting. DESIGN: Replicated single-case studies ABABA. SETTING: Movement analysis laboratory. SUBJECTS: Four patients, a maximum of eight weeks post stroke and six age-matched healthy volunteers. INTERVENTIONS: Subjects sat in the wheelchair during the A phases and self-propelled forwards during the B phases. The Manchester Active Position Seat (consists of 68 force transducers which transmit data at 10 Hz) measured the magnitude of peak force and the position of peak force on both sides of the seat. The mean symmetry index and standard deviation for each study phase were calculated and graphed for each subject. Interpretation was by visual inspection. RESULTS: Only one stroke patient and one volunteer increased asymmetry of magnitude of peak force following the two periods of self-propulsion. Only one of the stroke patients increased asymmetry of position of peak force following self-propulsion compared with three of the healthy volunteers. CONCLUSIONS: These results raise the hypothesis that self-propulsion early post stroke might not produce immediate detrimental effects on seated symmetry.

Aged↗
PubMed2002

Hordein variation and reaction to powdery mildew in composite cross XLII of barley.

A bulk hybrid population, CCXLII was investigated for hordein variation and reaction to powdery mildew. The results indicated that the population in F4 was genetically variable and contained an appreciable proportion of heterozygotes. Evidence was found for differential viability within families. This was possibly the result of a high segregation load. The pattern of genetic variation suggests that although the population could be a useful source of breeding material for the selection of new lines, it may be risky as a method of conservation of germplasm.

Crosses, Genetic↗
PubMed2002

Evidence of natural selection for disease resistance in Composite Cross Five (CCV) of barley.

Cambridge Composite Cross Five (CCV) of barley was studied utilising hordeins, restriction fragment length polymorphisms (RFLPs) and reaction to powdery mildew with a view to understanding the genetic changes occurring in the population. Changes in the frequency of individual hordein patterns as well as pattern combinations showed directional trends in successive generations in three parallel populations maintained as discrete populations since 1977 in Cambridge. Certain hordein pattern combinations were more common in the resistance classes and there was a strong association between hordein patterns and mildew reaction. RFLP analysis revealed that 80% of a random sample taken from generation F24 of Population I had the same restriction pattern as that of the cultivar Algerian, which was one of the original 30 parental lines of CCV. This cultivar is the source of the Mla1 allele in barley improvement programmes in Europe. We argue, based on supporting evidence from hordein analysis and tests of reaction to selected mildew isolates of known virulence isolates together with UK virulence surveys, that selection for Mla1 in Cambridge has been the predominant evolutionary force in CCV in Cambridge.

Biological Evolution↗
PubMed2002

Polyploidy, phylogeography and Pleistocene refugia of the rockfern Asplenium ceterach: evidence from chloroplast DNA.

Chloroplast DNA sequences were obtained from 331 Asplenium ceterach plants representing 143 populations from throughout the range of the complex in Europe, plus outlying sites in North Africa and the near East. We identified nine distinct haplotypes from a 900 bp fragment of trnL-trnF gene. Tetraploid populations were encountered throughout Europe and further afield, whereas diploid populations were scarcer and predominated in the Pannonian-Balkan region. Hexaploids were encountered only in southern Mediterranean populations. Four haplotypes were found among diploid populations of the Pannonian-Balkans indicating that this region formed a northern Pleistocene refugium. A separate polyploid complex centred on Greece, comprises diploid, tetraploid and hexaploid populations with two endemic haplotypes and suggests long-term persistence of populations in the southern Mediterranean. Three chloroplast DNA (cpDNA) haplotypes were common among tetraploids in Spain and Italy, with diversity reducing northwards suggesting expansion from the south after the Pleistocene. Our cpDNA and ploidy data indicate at least six independent origins of polyploids.

Base Sequence↗
PubMed2001

Increased frequency of HLA-DR2 in patients with paroxysmal nocturnal hemoglobinuria and the PNH/aplastic anemia syndrome.

Many autoimmune diseases are associated with HLA alleles, and such a relationship also has been reported for aplastic anemia (AA). AA and paroxysmal nocturnal hemoglobinuria (PNH) are related clinically, and glycophosphoinositol (GPI)-anchored protein (AP)-deficient cells can be found in many patients with AA. The hypothesis was considered that expansion of a PNH clone may be a marker of immune-mediated disease and its association with HLA alleles was examined. The study involved patients with a primary diagnosis of AA, patients with myelodysplastic syndrome (MDS), and patients with primary PNH. Tests of proportions were used to compare allelic frequencies. For patients with a PNH clone (defined by the presence of GPI-AP-deficient granulocytes), regardless of clinical manifestations, there was a higher than normal incidence of HLA-DR2 (58% versus 28%; z = 4.05). The increased presence of HLA-DR2 was found in all frankly hemolytic PNH and in PNH associated with bone marrow failure (AA/PNH and MDS/PNH). HLA-DR2 was more frequent in AA/PNH (56%) than in AA without a PNH clone (37%; z = 3.36). Analysis of a second cohort of patients with bone marrow failure treated with immunosuppression showed that HLA-DR2 was associated with a hematologic response (50% of responders versus 34% of nonresponders; z = 2.69). Both the presence of HLA-DR2 and the PNH clone were independent predictors of response but the size of PNH clone did not correlate with improvement in blood count. The results suggest that clonal expansion of GPI-AP-deficient cells is linked to HLA and likely related to an immune mechanism.

Alleles↗
PubMed2001

Acylation stimulating protein (ASP) acute effects on postprandial lipemia and food intake in rodents.

BACKGROUND: In vitro studies have shown that acylation stimulating protein (ASP) stimulates triglyceride (TG) synthesis and storage in adipocytes. We have previously demonstrated that intraperitoneal (i.p.) injection of ASP in C57BL/6J mice accelerated TG clearance following an orally-administered fat load as well as reducing postprandial glucose levels. RESULTS: In the present study, we first examined the effect of i.p. and intracerebroventricular (i.c.v.) injection of ASP on food intake in Sprague-Dawley rats. Intraperitoneal injection resulted in a short-term increase in food intake (maximum increase 29.3% within the first hour, P<0.025) decreasing thereafter as compared to vehicle alone. i.c.v. Administration of a comparable dose of ASP resulted in a similar but delayed increase in food intake with a maximum at 2-4 h, suggesting that the actions of ASP are peripherally mediated. However, there was no significant difference in 24 h food intake with either i.p. or i.c.v. injection. We also examined the effects of ASP on TG clearance in two obese mouse strains with different metabolic profiles: ob/ob (C57BL/6J-Lep(ob)) and db/db (C57BLKS/J-Lepr(db)). In a crossover design, the response to an oral fat load was determined with and without i.p. injection of exogenous ASP. In ob/ob mice, there was a 44% greater clearance of postprandial TG (area under the curve (AUC)=245+/-49 control vs 138+/-43 mg/dl h with ASP; P<0.05 by RM ANOVA). The db/db mice showed a greater response, with a 62% decrease in postprandial TG (AUC=4080+/-1489 control vs 1540+/-719 mg/dl h with ASP; P=0.004 by RM ANOVA). In addition there were decreases in postprandial glucose and non-esterified fatty acid (NEFA) levels in response to ASP. CONCLUSION: These results are the first to report that ASP can increase food intake in rats and also enhance postprandial TG clearance in obese animals. These data therefore support previous in vitro evidence pointing to ASP as a regulator of lipid metabolism.

Animals↗
PubMed2001

Coincident myelodysplastic syndrome and T-cell large granular lymphocytic disease: clinical and pathophysiological features.

Myelodysplastic syndrome (MDS) and T-cell large granular lymphocytic disease (T-LGL) are bone marrow failure disorders. Successful use of immunosuppressive agents to treat cytopenia in MDS and LGL suggests a common pathophysiology for the two conditions. Of 100 patients with initial diagnoses of either MDS or T-LGL referred to the National Institutes of Health for immunosuppressive treatment of cytopenia, nine had characteristics of both T-LGL and MDS (T-LGL/MDS). Fifteen patients with T-LGL received cyclosporin (CSA) (10 responses). Eight out of nine patients with T-LGL/MDS received CSA (two responses) and one patient received ATG (one response). Of 76 patients with MDS, eight received CSA (one response) and 68 received ATG (21 responses). The response to immunosuppression was significantly lower in patients with T-LGL/MDS and MDS than in patients with T-LGL disease alone (28% vs. 66%, P = 0.01). The proportion of T-helper cells and T-suppressor cells with an activated phenotype (HLA-DR(+)) was increased in patients with T-LGL, T-LGL/MDS and MDS, but the increase in activated T-suppressor cells in patients with T-LGL/MDS was not statistically significant. Autoreactive T cells may suppress haematopoiesis and contribute to the cytopenia in T-LGL and some patients with MDS, leading to T-LGL/MDS. The lower response rate of MDS or T-LGL/MDS to immunosuppression, compared with T-LGL alone, may reflect the older age and intrinsic stem cell abnormalities in MDS and T-LGL/MDS patients.

Adult↗
PubMed2001

The COSTAR wheelchair study: a two-centre pilot study of self-propulsion in a wheelchair in early stroke rehabilitation. Collaborative Stroke Audit and Research.

OBJECTIVE: It is uncertain whether self-propulsion in a wheelchair should be encouraged or discouraged in the early stages of stroke rehabilitation. DESIGN: A two-centre pilot study to assess the feasibility of performing a multicentre randomized controlled trial on this subject. SETTING: Clatterbridge and Aintree Stroke Rehabilitation Units, Merseyside, UK. SUBJECTS: Forty early stroke patients (mean age 67 years) in whom it was uncertain whether self-propulsion in a wheelchair should be encouraged were studied. INTERVENTION: A central randomization service at Newcastle University was used to determine the policy about wheelchair provision and use for each patient. They were allocated to either an 'encouraged to self-propel' or a 'discouraged from self-propulsion group'. OUTCOME MEASURES USED: Independent outcome assessment was performed by postal questionnaire and telephone interview using the Barthel ADL Scale, Nottingham Extended ADL Scales and the shortened General Health Questionnaire (GHQ-12) at 3 and 12 months. Patient's length of stay and their Ashworth tone score were also measured either at three months or when they were discharged from hospital. RESULTS: After considerable preparation time it was possible to conduct a trial on self-propulsion in early stroke rehabilitation in the two-pilot centres. No major differences were found between the pilot groups for any of the outcome measures. CONCLUSIONS: A multicentre randomized controlled trial to assess this question is feasible but further work is being conducted before proceeding, to satisfy the concerns expressed to our group regarding the appropriateness of the intervention and the outcome measures.

Aged↗
PubMed2000

Effects of threonine injections in the lateral hypothalamus on intake of amino acid imbalanced diets in rats.

Previous work from this laboratory suggests that animals decrease their intake of an amino acid imbalanced diet (IMB), due in part to a drop in the concentration of the dietary limiting amino (DLAA) in the anterior piriform cortex (APC). Administration of the DLAA, but not of a non-limiting amino acid into the APC, blocks the anorectic response to IMB. To our knowledge, the effects of DLAA injections on intake of a diet devoid of the DLAA (DEV), have not been examined in areas outside the APC. We hypothesized that the LH is a potential chemosensory area for DLAA. Our objectives were: (1) to determine whether injections of the DLAA threonine into the lateral hypothalamus (LH) alter intake of a threonine-devoid diet (DEV); and (2) to examine the dose-response effects of threonine injections into the LH on intake of threonine-corrected diet (COR). Administration of threonine into the LH stimulated DEV intake during the first 6 h at the 0.25 and 1-nmol doses by approximately 26 and 24%, respectively. Threonine (0.25, 2.5 nmol) did not alter COR intake at any time during the first 12 h. Our results suggest that: (1) the LH, along with the APC, likely acts as a chemosensory brain area for indispensable amino acids; and (2) both the APC and LH are part of a circuit that is involved in the short term anorectic response to amino acid imbalanced diets.

Amino Acids↗
PubMed2000

Scintigraphic detection of acute experimental endocarditis with the technetium-99m labelled glycoprotein IIb/IIIa receptor antagonist DMP444.

Bacterial endocarditis is an important clinical problem that may result in persistent bacteraemia and irreversible cardiac damage. Since endocarditis is characterized by aggregation of activated platelets, fibrin and bacteria, we studied DMP444, a technetium-99m labelled high-affinity antagonist of the GP IIb/IIIa receptor that is expressed on activated platelets. In seven Beagle dogs (11-15 kg), the left ventricle was catheterized via the right carotid artery. One hour later, 5x10(7) colony forming units of Staphylococcus aureus were injected intracardially. Half an hour later, the catheter was removed. Two extra dogs underwent a complete sham procedure. One day after the intervention, five infected and the two non-infected dogs were injected with 37 MBq/kg 99mTc-DMP444 and two infected dogs with 37 MBq/kg 99mTc-IgG (used as a non-specific control agent) and imaged up to 4 h after injection. Samples were obtained for tissue counting, microbiology and histology. From 1 to 2 h post injection onward, there was clear focal accumulation of DMP444 in the aortic valve region when endocarditis was present, and this accumulation increased with time. The non-infected and the 99mTc-IgG injected dogs showed only persisting blood pool activity without any focal abnormality. At 4 h post injection, the in vivo valve-to-blood pool ratios were 1.87+/-0.18 in endocarditis, 1.01+/-0.05 in non-infected controls and 1.09+/-0.02 in 99mTc-IgG injected dogs (P<0.05). It is concluded that targeting activated platelets with the 99mTc-labelled GP IIb/IIIa antagonist DMP444 allows a final diagnosis of experimental bacterial endocarditis within 4 h owing to high, specific and fast in vivo uptake.

Acute Disease↗
PubMed2000

Basolateral and central amygdaloid lesions leave aversion to dietary amino acid imbalance intact.

Expression of c-fos is increased in the central amygdaloid nucleus (CE) of rats ingesting a diet with a severely imbalanced essential amino acid profile (IMB), at a time associated with development of a conditioned taste aversion (CTA). The CE and the basolateral amygdaloid nucleus (BL) both are reported to be involved in the development of CTA. Large amygdaloid lesions involving CE and BL mitigate the normal decrease in intake of IMB; this treatment also impairs CTA to a flavor cue associated with gastrointestinal discomfort. To differentiate their potential roles in aversive responses to IMB, we electrolytically lesioned CE and BL separately. Neither lesion attenuated IMB-induced anorexia, or prevented the avoidance of flavored solutions previously paired with IMB. In contrast, after saccharin-LiCl pairing, CE-lesioned animals showed attenuated CTA to saccharin solution in a two-bottle test. We conclude that neither the CE nor the BL is essential for the reduction of IMB intake, or for CTA associated with IMB. Furthermore, these results suggest that the aversive consequences of IMB intake do not involve gastrointestinal malaise-evoked neurotransmission involving the CE.

Amino Acids↗
PubMed2000

A 99Tcm-labelled leukotriene B4 receptor antagonist for scintigraphic detection of infection in rabbits.

In a search for a rapid and accurate imaging agent for scintigraphic detection of infection and inflammation, an LTB4 receptor antagonist, 99Tcm-RP517, which contains the hydrazino nicotinamide moiety, has been developed recently. To study the in vivo behaviour of 99Tcm-RP517, rabbits with Escherichia coli infection were injected intravenously with 99Tcm-RP517. Gamma camera images were obtained and ex vivo bio-distribution was determined at several hours post-injection (p.i.). In a separate set of rabbits the choledochal duct was cannulated to quantitatively monitor the hepatobiliary clearance of the radiopharmaceutical. The receptor binding fraction of the radiolabelled RP517 exceeded 70%. Accumulation of 99Tcm-RP517 in the abscess was visualized as early as 1 h p.i. Due to rapid blood clearance (t1/2 alpha=18+/-0.6 min, t1/2 beta=6.5+/-0.4 h) and high abscess uptake, the abscess-to-muscle ratios increased with time from 7.0+/-2.3 at 1 h p.i. to 44.3+/-4.6 at 20 h p.i. The agent mainly cleared via the hepatobiliary route: 50% of the radiolabel was recovered in the small bowel at 1 h p.i., whereas 85% was found in cecum and sigmoid at 20 h p.i. In conclusion, 99Tcm-RP517 rapidly visualized E. coli abscesses in rabbits. The agent rapidly cleared from the blood, mainly via the hepatobiliary route. High abscess-to-background ratios were achieved. The accumulation in the intestines could limit the applicability of this agent for detecting infectious processes in the abdominal area. The development of a more hydrophilic analogue of 99Tcm-RP517 could improve the clinical applicability of this agent.

Acute Disease↗
PubMed1999

CCK(A) and 5-HT3 receptors interact in anorectic responses to amino acid deficiency.

Serotonin3 (5-HT3) receptors in the periphery mediate anorectic responses to the amino acid deficiency, which occurs after eating amino acid-imbalanced diets (IMB). However, other neurochemical systems, notably cholecystokinin (CCK), are known to affect food intake. We pretreated rats systemically with tropisetron, a 5-HT3 receptor antagonist, alone and combined with antagonists of CCK(A) and CCK(B) receptors, and measured intake of an IMB. Devazepide, a CCK(A) receptor antagonist, appeared to interact with tropisetron in the anorectic responses to IMB, blunting the usual remediation of IMB anorexia by tropisetron. The CCK(B) receptor antagonist, L-365, 260, increased intake of both IMB and an amino acid-balanced basal diet (BAS) and did not interact with tropisetron. Our data suggest that activation of CCK(A) receptors is interactive with 5-HT3 receptor activity in mediating IMB anorexia in the aminoprivic feeding model.

Amino Acids↗
PubMed1999

DA1 receptor activity opposes anorectic responses to amino acid-imbalanced diets.

The serotonin3 (5-HT3) receptor plays an important role in the aminoprivic feeding model. Other neurochemical systems, including cholecystokinin (CCK) and dopamine (DA), are known to affect food intake. We pretreated rats systemically with tropisetron, a 5-HT3 receptor antagonist, alone and combined with antagonists of DA1 and DA2 receptors, and measured intake of an amino acid-imbalanced diet (IMB). As expected, tropisetron significantly increased intake of IMB. SCH-23390, a DA1 antagonist, increased IMB anorexia. When combined with tropisetron, DA2 antagonism with eticlopride reduced short-term intake of both the basal diet (BAS) and IMB. In the IMB model, specificity of 5-HT3-DA2 interactions, and of 5-HT3-CCK(A) interactions from previous studies, prompted investigation of CCK(A)-DA2 interactions; there appeared to be none. SKF-38393, a DA1 agonist, combined with the CCK(A) receptor antagonist, devazepide, increased BAS and tended to increase IMB intake. Thus, CCK(A)-DA1 interactions were not specific for IMB. These data suggest that DA1 receptor activity opposes IMB anorexia, possibly via an interaction with the 5-HT3 receptor.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗