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Biomedical subjects

J D Baird

Publications and source records attributed to J D Baird.

At least 19 recordsLinked to original sources
PubMed2005

Basal ganglia calcification in BB/E rats with diabetes.

Human diabetes is associated with cognitive impairment and structural abnormalities in the brain such as cerebral atrophy. The aetiology of these abnormalities is not known. The BB/E rat is a well-established model of type 1 (insulin dependent) diabetes. A cohort of 34 BB/E rats with diabetes was divided into three sub-groups according to age (and duration of diabetes). Basal ganglia calcification (BGC) was present in the brains of more than 50% of diabetic animals, but not in any of 37 non-diabetic BB/E rats. BGC occurred more commonly in those animals which had the longest duration of diabetes (p=0.001), such that BGC was present in only 8% of animals with diabetes for 20 weeks, but in 100% of animals with diabetes for 60 weeks. There were no other significant light microscopic neuropathologic changes in diabetic animals. It will be important to investigate the mechanism of brain calcification, whether a similar process occurs in humans with diabetes, and its possible relationship to cognitive decline.

Actins↗
PubMed2001

Emergence of Salmonella typhimurium definitive type 104 (DT104) as an important cause of salmonellosis in horses in Ontario.

Salmonella Typhimurium definitive type 104 (DT104) has emerged as a common cause of salmonellosis in humans and cattle, yet previous reports involving horses are sparse. This study reports the emergence of DT104 as an important pathogen in horses in Ontario. The first clinical case of DT104 infection at the Ontario Veterinary College was identified in 1997. Seventeen cases of DT104-associated salmonellosis were identified between 1997 and 2000. In 2000, 12 of 13 cases of salmonellosis were due to DT104. Salmonellosis in horses due to DT104 is of concern, since the organism is multiresistant to antibiotics and poses increased zoonotic risk. Phage type distribution of Salmonella isolates should be monitored to determine whether DT104 will remain a prevalent equine pathogen.

Animals↗
PubMed1998

Tissue ascorbic acid and polyol pathway metabolism in experimental diabetes.

Previous studies demonstrating reduced plasma concentrations of ascorbic acid (AA) in diabetes and interactions between this vitamin and biochemical mechanisms such as synthesis of structural proteins, oxidative stress, polyol pathway and nonenzymatic glycation of proteins suggest that disturbed AA metabolism may be important in the pathogenesis of diabetic microangiopathy. However, limited information is available on the concentration of AA in tissues which develop diabetic complications. This study demonstrates reduced renal but not sciatic nerve or plasma AA concentration in two animal models of insulin-dependent diabetes mellitus, namely the STZ-diabetic rat and the spontaneously diabetic BB rat. Decreased lens AA concentration was also observed in STZ-diabetic rats. Improvement of glycaemic control by insulin treatment (albeit insufficient to achieve normoglycaemia) partially corrected lens and renal AA concentration in STZ-diabetic rats. AA treatment increased kidney and lens AA concentrations of STZ-diabetic and non-diabetic rats and corrected the abnormalities observed for untreated diabetic rats. Sciatic nerve AA concentration was not increased by AA treatment in any group. Tissue ratios of dehydroascorbic acid (DHAA)/AA, one index of oxidative stress, were not different between the diabetic and non-diabetic groups and were unaltered by AA supplementation. AA treatment of STZ-diabetic rats had no effect on elevated tissue concentrations of glucose, sorbitol and fructose or reduced myo-inositol concentration. The effect of reduced tissue AA levels in diabetes on either collagen synthesis or ability to combat increased free radical production is not known. However, correction of abnormal kidney and lens AA concentrations in experimental diabetes by AA supplementation suggests that if AA does have a role in the development or progression of the renal and ocular complications of diabetes, this treatment could be beneficial.

Animals↗
PubMed1998

Tumor necrosis factor-alpha mRNA-positive cells in spontaneous resorption in rodents.

PROBLEM: It has been proposed that high rates of resorption/spontaneous abortion may result from interaction in the decidua of gamma-interferon-producing natural killer (NK) cells and tumor necrosis factor (TNF)-alpha-producing macrophages. An increased release of TNF-alpha from placental tissue of resorptions has been reported, but macrophages producing TNF-alpha have so far not been demonstrated at the feto-maternal interface. Therefore, we have sought to identify TNF-alpha-producing cells by in situ hybridization at the feto-maternal interface in two inbred, well-characterized, and stable strains of laboratory rodents with high and low resorption rates. METHOD OF STUDY: Pregnant DBA/2-mated CBA/J mice with a resorption rate of 20% to 30% (dependent on NK cells and macrophages) and diabetes-resistant Bio-Breeding/Edinburgh (DR-BB/E) rats with low resorption rates (presumed to result from chromosomal abnormalities) were studied. AsialoGM1+ cells were detected by immunohistochemistry, and TNF-alpha mRNA+ cells were detected by in situ hybridization. RESULTS: TNF-alpha mRNA+ cells were detected in DBA/2-mated CBA/J mice at the time of resorption but only at the trophoblast-decidual junction. AsialoGM1+ cells were present in decidua, as assessed by immunohistochemistry, but few if any gave a positive signal for TNF-alpha. In rat resorptions, TNF-alpha mRNA-positive cells were present within the yolk sac and in contact with the trophoblast, but not at the trophoblast-decidual junction. In neither species did a significant accumulation of detectable TNF-alpha mRNA+ cells occur before the usual time of onset of resorption. CONCLUSIONS: In the DBA/2-mated CBA/J mouse, the removal of the placenta is associated with removal of a thin rim of adherent decidua similar to the location of the TNF-alpha mRNA+ cells detected in this study. Our data suggest that increased TNF-alpha in tissues associated with failing feto-placental units may arise from infiltration/activation of scavenger cells from decidua that are likely to be macrophages. Local TNF-alpha production in decidua, which occurs as a prelude to resorption in the CBA x DBA/2 model, could not be detected due to the insensitivity of the TNF-alpha probe we used; the release of TNF-alpha from decidual tissue left after the removal of the placenta does not differ between resorbing and healthy implant sites. AsialoGM1+ cells did not seem to be major producers of TNF-alpha. TNF-alpha mRNA+ cells in a low rate of resorption (rat) model were only found on the fetal side of the trophoblast, and they may also represent a macrophage response (to dying embryo tissue) derived from a nondecidual source. The location of TNF-alpha mRNA+ cells may identify distinct and different mechanisms of resorption in rodents.

Abortion, Veterinary↗
PubMed1998

Retrospective study of toxic metal analyses requested at a veterinary diagnostic toxicology laboratory in Ontario (1990-1995).

During the 5-year period from January 1, 1990, to December 31, 1995, 887 diagnoses of metal toxicosis in domestic animals and wild birds were documented at the Veterinary Laboratory Services Branch of the Ontario Ministry of Agriculture, Food and Rural Affairs. Most of these cases involved cattle, sheep, and birds. Lead toxicosis was diagnosed in 399 cases, copper toxicosis in 387, zinc toxicosis in 49, mercury toxicosis in 44, iron toxicosis in 4, and selenium in 4 cases. Trends in species affected and sources of metals are discussed.

Animals↗
PubMed1997

The effect of delta-gluconolactone, an oxidised analogue of glucose, on the nonenzymatic glycation of human and rat haemoglobin.

Nonenzymatic glycation of proteins and oxidative stress are considered independent factors important in the development of the complications of diabetes but may be interrelated by the process of autoxidative glycation. This pathway involves monosaccharide autoxidation to a reactive ketoaldehyde analogue and subsequent reaction with protein to form a ketoimine adduct. This study demonstrates that delta-gluconolactone (delta-GL), an oxidised analogue of glucose, is a potent glycating agent in vitro of haemoglobin present in blood samples from insulin-dependent diabetic and non-diabetic human subjects and from spontaneously diabetic, insulin-dependent BB/Edinburgh (BB/E) rats. The percentage glycated haemoglobin after incubation (37 degrees C, 5 h) with delta-GL (25 mmol/l) was significantly (P < 0.002) higher than that observed using an equimolar concentration of glucose. Intravenous administration of delta-GL (1 g/kg) to non-diabetic BB/E rats also significantly increased glycation of haemoglobin (6.0 +/- 0.1% vs 4.9 +/- 0.1%, P < 0.01) whereas intravenous injection of an identical dose of glucose had no significant effect (5.1 +/- 0.1% vs 5.0 +/- 0.2%). These results support the hypothesis that nonenzymatic glycation of proteins involves attachment by both native and oxidised monosaccharides. Further investigation of the interactions between diabetes-associated increases in oxidative stress and glycation on the development and progression of the vascular complications of diabetes is necessary.

Animals↗
PubMed1997

In vivo and in vitro evidence of altered nitric oxide metabolism in the spontaneously diabetic, insulin-dependent BB/Edinburgh rat.

1. Altered vasoreactivity may contribute significantly to the pathogenesis of diabetic vascular complications. This study investigated the effect of (a) insulin-related diabetes, and (b) chronic in vivo administration of N(omega)-nitro-L-arginine ester (L-NAME), a nitric oxide (NO) synthase inhibitor, on mean arterial pressure and in vitro vascular reactivity to noradrenaline in mesenteric arterial bed preparations from spontaneously diabetic, insulin-dependent and treated BB rats, the best animal model of insulin-dependent mellitus (IDDM) currently available. Four groups of animals from the Edinburgh colony (BB/E) of spontaneous diabetic BB rats were studied: age-matched (mean +/- s.e. mean = 156 +/- 2d) non-diabetic (glycated haemoglobin = 3.8 +/- 0.1%) and insulin-treated diabetic (glycated haemoglobin = 6.2 +/- 0.5%; duration of diabetes = 56 +/- 4 d) groups were either L-NAME treated (oral dose = 27 +/- 1 mg kg-1 d-1; duration of treatment from 30 until 153 days of age) or untreated. Although our diabetic BB/E rats do not achieve overall normoglycaemia, individual adjustment of the daily insulin dose administered to every diabetic rat achieves better glycaemic control than previous groups studying altered vascular reactivity and endothelial dysfunction in this animal model of diabetes. 2. Mean arterial pressure (measured directly via indwelling carotid arterial cannulae) was not significantly different between non-diabetic (116 +/- 3 mmHg; n = 10) and diabetic (122 +/- 2 mmHg; n = 12) BB/E rats. L-NAME treatment significantly (P < 0.001) increased mean arterial pressure in both groups (165 +/- 6 mmHg; n = 9 and 142 +/- 4 mmHg; n = 6 respectively) but the degree of hypertension observed in L-NAME-treated diabetic rats was significantly (P < 0.01) attenuated compared to non-diabetic rats treated with L-NAME. 3. Mesenteric arterial bed preparations were cannulated under anesthesia, excised and intralumenally perfused ex vivo with noradrenaline (0.2-20 microM). Basal perfusion pressures were not significantly different in mesentery preparations from non-diabetic (27.0 +/- 2.6 mmHg) and diabetic (27.1 +/- 3.2 mmHg) BB/E rats. There was no significant difference in maximal response above basal perfusion pressure (MAX) or pEC50, defined as the negative log of the agonist concentration required to give 50% of the maximal response above basal perfusion pressure, to noradrenaline in untreated non-diabetic (166 +/- 7 mmHg and 5.74 +/- 0.05 respectively) and diabetic (170 +/- 11 mmHg and 5.59 +/- 0.05) BB/E rats. 4. In vivo treatment of non-diabetic and diabetic BB/E rats with L-NAME had no significant effect on basal perfusion pressure (25.9 +/- 4.3 mmHg and 28.5 +/- 3.9 mmHg respectively). L-NAME treatment in vivo increased (P < 0.001) MAX to noradrenaline of non-diabetic rats (224 +/- 8 mmHg) but did not affect the value for diabetic rats (178 +/- 14 mmHg). L-NAME treatment did not alter after the pEC50 values in either group (5.71 +/- 0.05 and 5.65 +/- 0.05). 5. Consistent with previous studies using vascular preparations from spontaneously diabetic BB rats, mesentery preparations from diabetic BB/E rats (n = 12) exhibited a significantly reduced vasodilator response to acetylcholine (F value = 4.4, P < 0.05) across the concentration range studied compared to non-diabetic BB/E rats (n = 12) although there was no significant difference in maximal relaxation (diabetic 53.1 +/- 4.3% vs non-diabetic 55.7 +/- 5.5%) or pEC50, (diabetic 6.92 +/- 0.25 vs non-diabetic 7.49 +/- 0.22). There was no significant (F value = 0.8, P > 0.1) difference in the response to GTN between preparations from non-diabetic and diabetic rats (maximal relaxation: 49.6 +/- 3.7% vs 48.5 +/- 4.3%; pEC50: 7.84 +/- 0.12 vs 7.89 +/- 0.22 respectively). 6. In conclusion, vascular responsiveness to noradrenaline is not impaired in spontaneously diabetic BB/E rats with significantly better glycaemic control than those used in previous studies. However, following chronic L-NAME treatment, diabetic BB/E rats exhibit attenuated hypertension and an absence of enhanced vascular responsiveness to noradrenaline in vitro compared to similarly treated non-diabetic rats. These results, together with the significantly impaired endothelium-dependent vasodilatation and unchanged endothelium-independent vasodilatation in vitro of preparations from diabetic BB/E rats, are consistent with the hypothesis that functional changes in the synthesis and metabolism of NO (rather than altered vascular responsiveness to NO) occur in diabetes. Our results indicate that good glycaemic control alone is insufficient to prevent these abnormalities in NO availability and further studies to characterize the origin of these changes are necessary.

Animals↗
PubMed1997

Mutations in the hepatocyte nuclear factor-1alpha gene are a common cause of maturity-onset diabetes of the young in the U.K.

Mutations in the hepatocyte nuclear factor-1alpha (HNF1alpha) gene have recently been shown to cause maturity-onset diabetes of the young (MODY). We have examined 15 U.K. MODY families for mutations in the coding region of the HNF-1alpha gene. Eight different mutations, three frameshift (P291fsinsC, P379fsdelCT, and A443fsdelCA) and five missense mutations (P129T, R131W, R159W, P519L, and T620I), were identified in eleven families (73%). The previously reported mutation P291fsinsC was found in four pedigrees. A screen of a further 32 probands with early onset (<40 years of age) NIDDM showed the mutation in two additional families. This common mutation was present on at least three different haplotypes, suggesting that its high frequency is due to recurrent mutation rather than a founder effect. We have demonstrated that mutations in the HNF-1alpha gene are a common cause of MODY in U.K. families and result in early onset NIDDM with a progressive clinical course. Mutation-based genetic counseling can now be considered for the majority of patients with MODY.

Adolescent↗
PubMed1996

Disturbed development of the preimplantation embryo in the insulin-dependent diabetic BB/E rat.

Although improved regulation of maternal IDDM during pregnancy has resulted in a major fall in the stillbirth rate, the rates for other problems, such as spontaneous preterm labor, fetuses small for gestational age, congenital malformation, and the incidence of large placentas, remain raised. This has suggested the possibility that the damaging effect of conventionally treated but poorly regulated IDDM may operate primarily at the earliest stages of gestation, even before the diagnosis of pregnancy has been made. This study shows that spontaneous autoimmune IDDM in the Bio Breeding/Edinburgh (BB/E) rat is associated with severe disturbance in the development of the preimplantation embryo in a majority of pregnancies, as indicated by a fivefold increase in the incidence of degenerate fragmented embryos and a 33% reduction in the number of expanded blastocysts and in those blastocysts that reach the expanded stage a 20% cellular deficit in the inner-cell mass without any change in trophectoderm cell number. In addition, we find that blastocysts removed from diabetic rats and cultured in vitro for 24 h show no sign of "catch-up" growth of the inner-cell mass, although under these conditions, the trophectoderm exhibits a 25% cellular accretion. It is tempting to speculate that these phenomena are a presage of the characteristic combination of fetal growth retardation and large placentas, which are a feature of both BB/E rat and human IDDM pregnancy.

Animals↗
PubMed1995

Candidate gene studies in pedigrees with maturity-onset diabetes of the young not linked with glucokinase.

Maturity-onset diabetes of the young (MODY) is a form of non-insulin-dependent diabetes mellitus characterised by an early age of onset and an autosomal dominant mode of inheritance. Only a proportion of cases are due to mutations in the glucokinase gene. We have studied five Caucasian MODY families, including the first MODY family to be described, with five candidate genes implicated in regulation of insulin secretion. The affected subjects showed more marked hyperglycaemia than that found in subjects with glucokinase mutations. We assessed polymorphic markers close to the genes for glucokinase, hexokinase II, adenosine deaminase, pituitary adenylate cyclase-activating polypeptide receptor, and glucagon-like peptide-1 receptor. Linkage analysis with diabetes gave cumulative log of the odds (LOD) scores of less than -3, implying that mutations in these genes are unlikely to provide a major genetic contribution to this form of MODY.

Adolescent↗
PubMed1995

N omega-nitro-L-arginine methyl ester reduces the incidence of IDDM in BB/E rats.

Evidence that nitric oxide (NO) is involved in cytokine-mediated islet beta-cell dysfunction and destruction in vitro has led to the hypothesis that increased production of NO may contribute to the pathogenesis of insulin-dependent diabetes mellitus (IDDM). This study demonstrates that oral administration of N omega-nitro-L-arginine methyl ester (an inhibitor of NO synthase) from 30 to 150 days of age significantly reduced (P < 0.05) the incidence of IDDM in diabetes-prone BB/E rats. This supports the idea that NO plays a significant role in the pathogenesis of IDDM in this animal model.

Administration, Oral↗
PubMed1995

Reduced diurnal variation of blood pressure in non-insulin-dependent diabetic patients with microalbuminuria.

In essential hypertension reduced diurnal blood pressure (BP) variation is associated with an increased prevalence of target organ damage. We have examined diurnal BP variation in 25 microalbuminuric (MA) and 19 normoalbuminuric (NMA) patients with non-insulin-dependent diabetes and related albumin excretion rate (AER) to diurnal BP variation in the microalbuminuric group. There were no significant differences in age, body mass index (BMI), renal function, diabetic control, clinic or daytime ambulatory BP between the groups. Night-time SBP was higher (MA 145 mm Hg (137-153), NMA 132 mm Hg (125-139); P = 0.019) in the microalbuminuric group while the diurnal variation as assessed by the day-night dip in BP was significantly reduced in the microalbuminuric group (systolic: (mean (95% confidence intervals) MA 4.7% (1.7-7.7), NMA 12.8% (9.5-16.0), p = 0.001; diastolic: MA 6.5% (3.0-10.0), NMA 14.5% (10.2-18.8), P = 0.007). Within the microalbuminuric group, the systolic dip in BP was inversely related to the AER (r = -0.48, P = 0.015). Reduced diurnal BP variation and high night-time BP may contribute to target organ damage in diabetes.

Aged↗
PubMed1994

Idiopathic megacolon in the BB rat.

It has been assumed that idiopathic megacolon occurring in the spontaneously diabetic BB rat results from metabolic decompensation associated with diabetes. In a large prospective necropsy study we have documented the incidence of idiopathic megacolon and its distribution between diabetic and non-diabetic animals in the BB rat colony in Edinburgh. A significantly increased incidence of megacolon was found in non-diabetic rats in the diabetes-prone subline compared with diabetic rats in the diabetes-prone subline and with non-diabetic rats in the diabetes-resistant subline. Affected animals were found to have an inflammatory infiltrate in the wall of the large bowel with destruction of both autonomic ganglia and muscularis propria. These necropsy observations indicate that megacolon cannot be a result of the metabolic disturbance due to the hyperglycaemia associated with diabetes.

Age Factors↗
PubMed1993

The in vivo glycation of diabetic tendon collagen studied by neutron diffraction.

Glycation (non-enzymatic glycosylation) sites in the axial unit cell of diabetic tendon collagen were investigated by neutron diffraction. Samples of diabetic and control tendon were reacted with sodium borodeuteride and sodium cyanoborodeuteride. This facilitated deuteration at aldimine, aldol or ketoimine groups in the molecule. These are natural collagen cross-links and sites where non-enzymatic glycation had occurred. The introduction of a deuteron at specific locations allowed the diabetic glycation collagen to be treated as multiple isomorphous derivatives for neutron fibre diffraction. Neutron diffraction was conducted at the Institut Laue Langevin, Grenoble. Standard crystallographic refinement techniques (modified for axial projections) were used to determine the structure of the control (non-diabetic) and diabetic samples. The results are shown as difference maps, these indicate that glycation takes place at different rates within the collagen axial unit cell. The position of glycation correlates well with the position of hydroxylysine residues. The reactions of periodate with enzymatically attached sugars, proteoglycan, natural cross-links and glycation products lead to complications in map interpretation.

Animals↗
PubMed1993

Lymphoma in the BB/E rat: c-myc translocation identified.

In a prospective necropsy study involving 257 animals in the BB rat colony in Edinburgh, there was an increased incidence of lymphoma (average 10.9 per cent in all three subgroups: 8 per cent in diabetic, 20 per cent in non-diabetic diabetes-prone, and 3.2 per cent in diabetes-resistant rats). The incidence was significantly increased (P < 0.05) in the non-diabetic diabetes-prone subgroup. These results differ markedly from previous results and indicate that the relationship between lymphoma and diabetes is more complex than previously suggested. All the lymphomas bar one involved the ileocaecal nodes and were classified as immunoblastic lymphomas of B-cell origin. There was a striking resemblance both in tissue distribution and in histological classification to the lymphoma seen in the established B-cell lymphoma model, the LOUVAIN rat. Southern blot analysis carried out on the BB rat lymphomas revealed a translocation of variable length involving the c-myc oncogene. Such a translocation has not been demonstrated in the BB rat before.

Animals↗