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Biomedical subjects

J Hamilton

Publications and source records attributed to J Hamilton.

At least 19 recordsLinked to original sources
PubMed2006

Synapsin I Cre transgene expression in male mice produces germline recombination in progeny.

The cre/LoxP system can produce conditional loss of gene function in specific cell types such as neurons. A transgenic mouse line, utilized by multiple studies, used the Synapsin I promoter to drive expression of cre (SynCre) to achieve neuronal-specific cre expression. Herein we describe that cre expression can also be observed in SynCre mice within the testes after being bred into a floxed transgenic mouse line. Cre transcript was expressed in testes resulting in recombination of the floxed substrate in testes. In the majority of cases, progeny of male SynCre mice inherited a germline recombined floxed allele, while this was never observed in progeny from female mice carrying the SynCre allele. This observation should alert investigators to a potential confound using these mice and enables male germ cell "deletor" strategies.

Animals↗
PubMed2005

Dietary strategies and uptake of reduced fat foods.

AIM: This research has sought to identify factors determining consumer uptake and rejection of reduced fat foods. Initial qualitative research implied that use of reduced fat products could be dependent upon which dietary health strategies people adopt. This analysis therefore explores the degree to which various dietary strategies predict uptake of reduced fat products. METHOD: Items were derived from prior qualitative findings and responses to relevant issues surveyed by interview (n = 1004) within selected retail outlets throughout Northern Ireland and England. RESULTS: Logistic regression analysis indicated that concern over health, drive to reduce calorie consumption, to increase intake of fish and poultry and fruit and vegetables consistently predicted consumption across a range of reduced fat products. These dietary strategies appeared to predict uptake of reduced fat foods to a greater degree than perceived taste or price. CONCLUSION: The findings imply that for reduced fat foods to achieve universal acceptance promotional messages need to be translated into commonly adopted dietary health strategies.

Adult↗
PubMed2004

Presentation and course of Type 2 diabetes in youth in a large multi-ethnic city.

AIM: To review the clinical experience of children and teens diagnosed with Type 2 diabetes (T2DM) at a paediatric hospital serving a large urban multi-ethnic population. METHODS: Retrospective chart review of patients with T2DM followed in the diabetes clinic at the Hospital for Sick Children (HSC) over an 8-year period. Patients who were included were younger than 18, referred at the onset of diabetes, and where presentation and/or clinical course was 'typical' of T2DM. RESULTS: Of 1020 children with diabetes followed at HSC, 4% were identified as having T2DM in 2002. There was a sixfold increase in new cases from 1994 to 2002. The mean age at diagnosis was 13.5 +/- 2.2 years (range 8.8-17.5) with a female-to-male ratio of 1.7. Most had a first- or second-degree relative with T2DM. There was an overrepresentation of children with T2DM from Asian and African Canadian ethnic groups relative to the regional population. The majority of teens were asymptomatic at presentation, with a smaller number in diabetic ketoacidosis (DKA) at diagnosis. Mean HbA1c at diagnosis was 10 +/- 3.4%. Approximately one half of patients were initially treated by diet and exercise with many requiring intensification of therapy over a short period of time. CONCLUSIONS: We report a similar increase in T2DM incidence and clinical presentation at HSC to other clinic reports in large North American urban centres. Of note is the high prevalence of children of South/South-East Asian descent.

Adolescent↗
PubMed2003

Adult midgut expressed sequence tags from the tsetse fly Glossina morsitans morsitans and expression analysis of putative immune response genes.

BACKGROUND: Tsetse flies transmit African trypanosomiasis leading to half a million cases annually. Trypanosomiasis in animals (nagana) remains a massive brake on African agricultural development. While trypanosome biology is widely studied, knowledge of tsetse flies is very limited, particularly at the molecular level. This is a serious impediment to investigations of tsetse-trypanosome interactions. We have undertaken an expressed sequence tag (EST) project on the adult tsetse midgut, the major organ system for establishment and early development of trypanosomes. RESULTS: A total of 21,427 ESTs were produced from the midgut of adult Glossina morsitans morsitans and grouped into 8,876 clusters or singletons potentially representing unique genes. Putative functions were ascribed to 4,035 of these by homology. Of these, a remarkable 3,884 had their most significant matches in the Drosophila protein database. We selected 68 genes with putative immune-related functions, macroarrayed them and determined their expression profiles following bacterial or trypanosome challenge. In both infections many genes are downregulated, suggesting a malaise response in the midgut. Trypanosome and bacterial challenge result in upregulation of different genes, suggesting that different recognition pathways are involved in the two responses. The most notable block of genes upregulated in response to trypanosome challenge are a series of Toll and Imd genes and a series of genes involved in oxidative stress responses. CONCLUSIONS: The project increases the number of known Glossina genes by two orders of magnitude. Identification of putative immunity genes and their preliminary characterization provides a resource for the experimental dissection of tsetse-trypanosome interactions.

Aging↗
PubMed2003

Analysis of the 5' flanking region of the interleukin 10 gene in patients with systemic sclerosis.

OBJECTIVES: Fibrosis, a feature of systemic sclerosis (SSc), is more severe in the diffuse compared with the limited disease variant. Interleukin 10 (IL-10) is an anti-inflammatory cytokine which reduces type 1 collagen mRNA levels in human fibroblasts. The 5' flanking region of the IL-10 gene is highly polymorphic, with three single base pair substitutions at position -1082(G/A), -819(C/T) and -592(C/A), which results in differential IL-10 production. The GCC/GCC genotype is associated with high IL-10 production while the ATA/ATA genotype with low production. We postulated that there would be a difference in IL-10 polymorphisms in patients with limited (lSSc) and diffuse (dSSc) disease. METHODS: Patients with limited (lSSc, n = 89) or diffuse (dSSc, n = 51) disease plus controls (n = 94) were recruited. DNA was isolated from peripheral blood and polymorphisms analysed using amplification refractory mutation system (ARMS) polymerase chain reaction (PCR). RESULTS: dSSc patients were less likely to carry the genotype indicative of high IL-10 production when compared with controls (controls vs dSSc; 29 vs 4%, chi2 = 15.7, 5 df, P = 0.005) and lSSc patients (lSSc vs dSSc; 21 vs 4%, chi2 = 17.5, 5 df, P = 0.002). There was no difference between control and lSSc patients. While there was no difference between controls and lSSc haplotypes, the GCC haplotype distribution did differ significantly between controls and dSSc patients (controls vs dSSc; 54 vs 36%, chi2 = 11.2, 2 df, P = 0.001). A significant difference was also observed between lSSc and dSSc haplotype distribution (lSSc vs dSSc; 48 vs 36%, chi2 = 13.5, 2 df, P < 0.001). CONCLUSION: We demonstrate that IL-10 genotypes associated with high IL-10 production are under-represented in dSSc. This may have implications in the disease pathology.

DNA↗
PubMed2003

Uncoupling proteins-2 and 3 influence obesity and inflammation in transgenic mice.

OBJECTIVE: To test the hypothesis that either uncoupling protein-2 UCP2 or UCP3 or both together influence obesity and inflammation in transgenic mice. DESIGN: We generated 12 lines of transgenic mice for both human UCP2 and 3 using native promoters from a human bacterial artificial chromosome (BAC) clone. The BAC expresses no genes other than UCP2 and 3. Mice used for experiments are N4 or higher of backcross to C57BL/6J (B6). Each experiment used transgenic mice and their nontransgenic littermates. RESULTS: Northern blots confirmed expression on human UCP2 in adipose and spleen, while human UCP3 expression was detectable in gastrocnemius muscle. Western blots demonstrated a four-fold increase of UCP2 protein in spleens of Line 32 transgenic animals. Heterozygous mice of four lines showing expression of human UCP2 in spleen were examined for obesity phenotypes. There were no significant differences between Lines 1 and 32, but female transgenics of both lines had significantly smaller femoral fat depots than the control (littermate) mice (P=0.015 and 0.005, respectively). In addition, total fat of transgenic females was significantly less in Line 1 (P=0.05) and almost significantly different in Line 32 (P=0.06). Male Line 1 mice were leaner (P=0.04) while male Line 32 mice were almost significantly leaner (P=0.06). Heterozygous mice of Lines 35 and 44 showed no significant differences from the nontransgenic littermate controls. Effects of the UCP2/UCP3 transgene on obesity in Line 32 mice were confirmed by crossing transgenic mice with the B6.Cg-Ay agouti obese mice. B6.Cg-Ay carrying the UCP2/UCP3 transgene from Line 32 were significantly leaner than nontransgenic B6.Cg-Ay mice. Line 32 UCP2/UCP3 transgenics showed increased hypothalamic Neuropeptide (NPY) levels and food intake, with reduced spontaneous physical activity. Transgenic baseline interleukin4 (IL-4) and interleukin6 (IL-6) levels were low with lower or later increases after endotoxin injection compared to wild-type littermates. Endotoxin-induced fever was also diminished in transgenic male animals. Low-density lipoprotein (LDL) cholesterol levels were significantly higher in both Line 1 and 32 transgenics (P=0.05 and 0.001, respectively) after they had been placed on a moderate fat-defined diet containing 32% of calories from fat for 5 weeks. CONCLUSION: Moderate overexpression of UCP2 and 3 reduced fat mass and increased LDL cholesterol in two independent lines of transgenic mice. Thus, the reduced fat mass cannot be due to insertional mutagenesis since virtually identical fat pad weights and masses were observed with the two independent lines. Line 32 mice also have altered inflammation and mitochondrial function. We conclude that UCP2 and/or 3 have small but significant effects on obesity in mice, and that their mechanism of action may include alterations of metabolic rate.

Adipose Tissue↗
PubMed2003

Fat distribution is altered in HIV-infected men without clinical evidence of the HIV lipodystrophy syndrome.

OBJECTIVE: To determine if fat distribution is altered in HIV-infected men without clinical evidence of lipodystrophy. METHODS: In a cross-sectional design, 14 protease inhibitor (PI)-treated men with lipodystrophy and 12 PI-treated and five PI-naive men without clinical evidence of lipodystrophy underwent body composition and fat distribution analysis by dual-energy X-ray absorptiometry and computed tomography. Their fat distribution was compared to 43 uninfected male controls matched for age and BMI. RESULTS: The percent of body fat in the trunk of men with HIV lipodystrophy was significantly greater compared to both HIV-infected and healthy controls. The percentage of body fat in the extremities was significantly lower in men with HIV lipodystrophy compared to both HIV-infected and healthy controls. HIV-infected men without clinical evidence of lipodystrophy also had a significantly greater percentage of total body fat in the trunk and a significantly lower percent of body fat in the extremities compared to healthy controls. Among the HIV-infected men, age was an independent predictor of truncal and extremity adiposity. CONCLUSION: This study suggests that a continuum of change is present in the adipose organ of HIV-infected men on antiretroviral therapy. Physical examination alone can miss significant changes in body fat distribution in HIV-infected patients.

Abdomen↗
PubMed2002

Peripheral bone density in patients with rheumatoid arthritis and factors which influence it.

INTRODUCTION: Patients with rheumatoid arthritis (RA) frequently possess a number of risk factors for osteoporosis. Additionally, oral steroids are often used to control active rheumatoid disease and may further potentiate bone loss. We wished to establish the degree of peripheral bone loss in RA and to assess the influence of oral steroids and other risk factors. METHODS: We measured bone mineral density (BMD) in the non-dominant forearm using a DTX 200 osteometer in 191 RA patients who were receiving oral prednisone in a dose of at least 5 mg daily for over 3 months. We compared the results with those of two other groups: 165 RA patients who had never received oral prednisone and 242 normal controls without RA or any history of steroid therapy. Forward stepwise multiple regression analysis was used to determine the effects of age, disease variables and steroids on BMD. RESULTS: Age (P<0.001), RA (P<0.02) and steroid therapy (P<0.05) were all associated with reduced BMD using multiple regression analysis. Duration of RA was also associated with reduced BMD (P<0.05), but activity of disease was not. By WHO criteria (BMD T score<-2.5 S.D.), 95 (50%) of the RA steroid-treated patients (RAS) had osteoporosis, while 48 (25%) of the RA patients not exposed to steroids (RAN) were osteoporotic. Among the normal controls (NC), 48 (20%) had osteoporosis. The mean (S.D.) BMD Z scores for the three groups were -0.8 (1.3) for RAS, -0.4 (1.3) for RAN and 0.0 (1.0) for NC (P<0.01 for all differences). The percentages of patients with a Z score of -1 or less were 51% for RAS, 29% for RAN and 14% for NC. These differences were also significant (P<0.01). Male sex was associated with reduced BMD when compared to female sex (Z<-1) in the RAS (57 vs. 49%; P<0.05) but not in the RAN (25 vs. 31%) groups. For men with RA, the mean (S.D.) BMD Z scores were -1.3 (1.3) for RAS compared to -0.5 (1.3) for RAN (P<0.005), while for women the differences were less marked at -0.7 (1.3) for RAS compared to -0.4 (1.3) for RAN (P<0.05). CONCLUSIONS: In general, patients with RA have a significantly reduced forearm BMD, which correlates with increasing disease duration. Exposure to oral steroids increases bone loss, notably in male patients. Patients with RA on oral steroids need BMD measurements with a view to prophylactic therapy in those with a low result. Previous fractures and a daily dose of 15 mg or more of prednisone are also important factors in determining when prophylaxis is indicated.

Journal Article↗
PubMed2002

Analysis of transforming growth factor beta1 gene polymorphisms in patients with systemic sclerosis.

OBJECTIVES: To determine the distribution of transforming growth factor beta1 (TGFbeta1) genotypes at codon 10 (+869 polymorphism) and codon 25 (+915 polymorphism) in patients with scleroderma (SSc). Differences between diffuse and limited SSc (dSSc and lSSc) were also investigated. METHODS: Patients with lSSc (n=89) and dSSc (n=63) were compared with 147 controls. DNA was isolated from peripheral blood and polymorphisms at codons 10 (C/T) and 25 (G/C) of the TGFbeta1 gene analysed by polymerase chain reaction and sequence specific oligonucleotide probing. RESULTS: Significantly more patients with SSc than controls carried allele C at codon 10 (controls v SSc, 38% v 48%, chi(2)=8.2, 1df, p=0.004), OR=1.95 (95% CI 1.16 to 3.27). The difference remained when patients with SSc were split into those with limited or diffuse disease, (controls v dSSc, chi(2)=5, 1df, p=0.02 and controls v lSSc, chi(2)=6, 1df, p=0.013). The patients with SSc had significantly more subjects heterozygous at codon 10 (controls v SSc, chi(2)=45, 1df, p<0.0001). Possession of allele C at codon 10 gave an OR=4.8 (95% CI 2.8 to 8.4). No difference in allele frequency was seen between patients with SSc and controls at codon 25. More patients with SSc than controls carried the GG genotype (controls v SSc, 80% v 88%, chi(2)=7, 2df, p=0.027). Possession of allele G gave an OR=1.7 (95% CI 0.5 to 5.9). There was no difference between diffuse and limited disease at either codon. CONCLUSIONS: These results suggest that patients with SSc are genetically predisposed to high TGFbeta1 production. These polymorphisms do not, however, explain the difference in the clinical phenotypes of limited and diffuse SSc.

Codon↗
PubMed2001

Icodextrin as salvage therapy in peritoneal dialysis patients with refractory fluid overload.

BACKGROUND: Icodextrin is a high molecular weight, starch-derived glucose polymer, which is capable of inducing sustained ultrafiltration over prolonged (12-16 hour) peritoneal dialysis (PD) dwells. The aim of this study was to evaluate the ability of icodextrin to alleviate refractory, symptomatic fluid overload and prolong technique survival in PD patients. METHODS: A prospective, open-label, pre-test/post-test study was conducted in 17 PD patients (8 females/9 males, mean age 56.8 +/- 2.9 years) who were on the verge of being transferred to haemodialysis because of symptomatic fluid retention that was refractory to fluid restriction, loop diuretic therapy, hypertonic glucose exchanges and dwell time optimisation. One icodextrin exchange (2.5 L 7.5%, 12-hour dwell) was substituted for a long-dwell glucose exchange each day. RESULTS: Icodextrin significantly increased peritoneal ultrafiltration (885 +/- 210 ml to 1454 +/- 215 ml, p < 0.05) and reduced mean arterial pressure (106 +/- 4 to 96 +/- 4 mmHg, p < 0.05), but did not affect weight, plasma albumin concentration, haemoglobin levels or dialysate:plasma creatinine ratio. Diabetic patients (n = 12) also experienced improved glycaemic control (haemoglobin Alc decreased from 8.9 +/- 0.7% to 7.9 +/- 0.7%, p < 0.05). Overall PD technique survival was prolonged by a mean of 11.6 months (95% CI 6.0-17.3 months). On multivariate Cox proportional hazards analysis, extension of technique survival by icodextrin was only significantly predicted by baseline net daily peritoneal ultrafiltration (adjusted HR 2.52, 95% CI 1.13-5.62, p < 0.05). CONCLUSIONS: Icodextrin significantly improved peritoneal ultrafiltration and extended technique survival in PD patients with symptomatic fluid overload, especially those who had substantially impaired peritoneal ultrafiltration.

Dialysis Solutions↗
PubMed2001

Cyathostome fecal egg count trends in horses treated with moxidectin, ivermectin or fenbendazole.

Commercial preparations of fenbendazole (Safe-Guard, Intervet), ivermectin (Eqvalan, Merial) or moxidectin (Quest, Fort Dodge) were administered once to horses scheduled for routine parasiticide treatment. In total, 93 horses from six cooperating farms were used in the study. Computer generated, random allocation of horses to treatment group was conducted at each farm. Fecal egg counts were determined for all horses on trial days 0, 56, 84 and 112, with corresponding calendar dates that were unique to each farm. Only strongyle egg counts from animals which were positive at day 0 were used for analysis of variance and comparisons. Counts for the three treatment groups were similar at day 0, moxidectin<ivermectin<fenbendazole for days 56 and 84, and moxidectin<ivermectin=fenbendazole on day 112 (P<0.05). Reductions of geometric mean egg counts from day 0 levels were 99.1, 97.6 and 94.9% for moxidectin, 16.4, -27.0 and -32.0% for fenbendazole and 85.9, 24.2 and -8.1% for ivermectin on trial days 56, 84 and 112, respectively. Adverse reactions to treatment were not observed for any of the parasiticides.

Animals↗
PubMed2001

NMDA receptor antagonist AP5 and nitric oxide synthase inhibitor 7-NI affect different phases of learning and memory in goldfish.

The present study investigated the amnestic effects of N-methyl-D-aspartate (NMDA) receptor antagonist AP5 and nitric oxide (NO) synthase inhibitor 7-NI in avoidance conditioning in goldfish. The results showed that both AP5 and 7-NI, without impairing performance processes, produced anterograde amnesia when given before training. Furthermore, 7-NI produced retrograde amnesia when given immediately following training while AP5 did not. Thus, AP5 and 7-NI affected different phases of learning and memory.

2-Amino-5-phosphonovalerate↗