A congenital form of myotonia with dystrophic changes in a quarterhorse.
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Biomedical subjects
Publications and source records attributed to J D Baird.
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Strict metabolic control has resulted in a striking fall in the rates for stillbirths, neonatal deaths and neonatal morbidity in diabetic pregnancy. However, clinical problems and challenges for research remain, particularly in relation to a high incidence of congenital malformation, low birth weight, and early growth delay; the detection and management of gestational diabetes; insulin delivery systems; the consequences of maternal hypoglycaemia on organogenesis and fetal well-being; the mechanisms underlying various categories of neonatal morbidity, and possible long-term morbidity in the children born to diabetic mothers. The nature of these problems determines that certain fundamental aspects of reproduction which are difficult to study in human pregnancy will have high priority for research. Progress in this field will be heavily dependent on animal models in the foreseeable future.
A cohort of BB/E rats derived from litters with a high and low incidence of IDDM was studied prospectively to examine the relationship between circulating autoantibodies, islet insulin secretion, pancreatic infiltration, and islet cell replication during the pre-diabetic period. Although a higher incidence of islet cell surface (ICSA) and insulin autoantibodies (IAA) was detected in the diabetes-prone than in the low diabetic-incidence BB/E rats there was no correlation between the two antibodies in individual animals. Moreover, ICSA, but not IAA, were associated with loss of first phase islet insulin release. Between 75 and 105 days of age the number of diabetes-prone rats with ICSA and impaired islet insulin secretory function increased. Over the same period, there was a concomitant increase in the proportion of diabetes-prone animals with pancreatic infiltration, and increased islet endocrine cell proliferation. All these interrelated phenomena were observed in diabetes-prone BB/E rats at a time when the animals were normoglycaemic.
The presence of insulin autoantibodies (IAA) and islet cell surface antibodies (ICSA) was sought in two longitudinal studies, involving BB/Edinburgh rats of high (BB/E/H, n = 157) and low (BB/E/L, n = 61) susceptibility to diabetes development. Both studies were designed to correlate pancreatic morphology with cellular and humoral immunity. In Study I, groups of eight male and eight female non-diabetic rats of the BB/E/H line were killed at 15 day intervals from 30-105 days and plasma samples were obtained by cardiac puncture. In study II, 61 BB/E/H and 41 BB/E/L rats underwent pancreatic biopsy 1-3 times from 30 days of age until onset of diabetes or 150 days, plasma samples being taken from the tail vein at biopsy. Both studies revealed a higher prevalence for ICSA than IAA in BB/E rats. Whereas a highly significant association of ICSA with diabetes development was observed in study II (chi 2 = 8.30, P less than 0.005), IAA were associated with diabetes development only weakly (P less than 0.03, Mann-Witney U-rank test). No correlation between the presence of ICSA and IAA in individual rats was observed and IAA were not significantly associated with BB/E/H in preference to BB/E/L rats, although positive IAA values were significantly elevated in the former compared with the latter (P less than 0.01). These observations support the concept that IAA form part of a background of heightened autoimmunity against which frank diabetes develops in some animals.
Several immunological responses of the spontaneously diabetic BB rat colony in Edinburgh designated (BB/E) have been studied. The proliferative responses to Con A and LPS, ability to make IL-2 and to show NK activity have been studied using diabetic and non-diabetic BB/E rats and normal Wistar rats. Our data suggest that the diabetic animals in the BB/E colony do not have marked deficiencies in any of these parameters. Lymphopenia and depressed T-cell responses do not appear to be a prerequisite for the development of diabetes in the BB/E colony.
The effect of resection of 75% (length measurement) of the large colon in ponies was studied. Ten ponies in good physical condition were divided into two groups: group I consisted of the six experimental ponies and group II of four control ponies. Preoperatively and postoperatively for five months, ten clinicopathological parameters were determined: body weight, venous blood pH, plasma bicarbonate, total plasma protein concentration, serum electrolyte values (sodium, potassium, chloride), and fecal osmolarity. Subjective assessment of attitude and appetite revealed no difference between the groups or within groups at any time. Resection of a major portion of the large colon did not significantly influence the clinicopathological parameters evaluated. The hematocrit of the ponies in group I did decrease during the first postoperative month and this was attributed to whole blood loss associated with the resection procedures. The results of this investigation indicated that resection of 75% of the large colon in ponies is compatible with life.
The nutritional implications and adaptive processes resulting from resection of 75% of the length of the large colon in ponies were investigated. Ten ponies in good physical condition were divided into two groups: six in the experimental group and four in the control group. During the sixth postoperative month, two digestibility studies were conducted, and phosphate fractional renal excretion and serum biochemical profiles were determined in both groups. The ponies (N = 10) were euthanized six months postoperatively, and gross and histopathological examinations were performed. Results of the serum biochemical profiles, phosphate fractional renal extraction and digestibility studies showed no statistically significant difference between groups except for the serum phosphate concentration. However, large colon resection was associated with hypophosphatemia in three of the six ponies and produced an overall significantly lower phosphate concentration in the experimental ponies. This hypophosphatemia suggests that some dietary modifications may be needed postoperatively in ponies or horses undergoing this surgical procedure. Postmortem examination and histopathological examination failed to demonstrate differences between groups. Adaptive mechanisms, specifically mucosal hypertrophy or hyperplasia, were not observed.
A preliminary investigation was made into the effect of fourth-stage Strongylus vulgaris larvae sequestered in the tunica media of ileocolic arteries of pony foals treated with ivermectin. The foals had been reared parasite-free, inoculated with infective larvae and given orally a placebo or ivermectin paste. Two foals received subsequently one or two further inoculations with larvae and treatment with ivermectin. Arteriography was used to identify the lesions in the ileocolic artery following inoculation and their regression following treatment. At necropsy, foals were examined for lesions and larvae grossly and histologically. Ivermectin was highly effective against fourth-stage larvae and those present in the media appeared not to unduly affect the integrity of the ileocolic artery. Increased numbers of larvae were not found in the media of foals receiving repeat inoculations and repeat treatments. Larvae were not found in the media of foals treated with a placebo. The major pathological changes in the arterial wall of all foals were attributed to infection with S. vulgaris and there was no strong tendency for the damaged arteries to return to normal after the S. vulgaris were removed.
The ability of recombinant Interferon-gamma to induce class II expression in vitro on pancreatic islet B cells has been investigated by exposing islets isolated from BB/E and normal Wistar rats to Interferon-gamma and then staining successively with monoclonal antibodies specific for rat class II MHC antigens and insulin. Induction of class II expression was never observed on islet cells obtained from either normal Wistar rats or rats from the BB/E low diabetes incidence (less than 2%) subline. In contrast, pancreatic B cells from rats from the BB/E high diabetes incidence (60-70%) subline expressed class II antigen following culture with Interferon-gamma.
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Metabolic adaptations to pregnancy are directed towards ensuring fetal growth and development, provision of a fetal store of energy, and the establishment of a maternal bank of energy. At any one time the demands of these objectives are competing for the available dietary energy, yet to ensure successful reproduction all three must be met. Current concepts suggest that the metabolic adaptation to pregnancy is designed primarily to safeguard against variable and restricted energy intake and that this is achieved by 1) a reduction in energy expenditure, resulting from decreased activity combined with increased metabolic efficiency, 2) phased metabolic activity affecting carbohydrate, fat and protein. Conservation of energy in maternal adipose tissue dominates the first half of pregnancy, while in late pregnancy the available energy is redirected to the fetus. This biphasic metabolism is programmed by the placental steroids whose secretion is independent of maternal diet. Internal redistribution of substrate under hormonal control is the main characteristic of the metabolic adaptation to pregnancy. The precise mechanisms underlying these adjustments have still to be defined.
Twenty pony foals (reared worm free), 6.5 to 10 weeks of age, were inoculated with Strongylus vulgaris and allocated to 5 groups, each with 4 foals. One week after inoculation, 1 group of 4 foals was given oxfendazole (OFZ) at a dosage rate of 10 mg/kg of body weight, another group was given 2 such treatments 48 hours apart, and a 3rd group was given a placebo. All treatments were administered by stomach tube. Three weeks later, foals were euthanatized and necropsied in a test for efficacy against early 4th-stage larvae. Oxfendazole was 80% and 94.9% effective against early 4th-stage S vulgaris with 1 and 2 doses, respectively. A 4th group of 4 foals was given 2 treatments of OFZ, 48 hours apart, about 8 weeks after inoculation, and a 5th group was given a placebo. These foals were euthanatized and necropsied 5 weeks after treatment in a test for efficacy against later 4th-stage larvae. Two doses of OFZ were 96.6% effective against later 4th-stage larvae.
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Use of monoclonal antibodies specific for rat lymphocyte subsets and an anti-insulin marker has allowed us to document the following sequence of events leading to the development of clinical diabetes in this animal model. The first change observed in the pancreas is increased expression of MHC class II molecules on vascular endothelium and this precedes lymphocytic infiltration. Next, T cells of the T helper phenotype infiltrate the pancreas around blood vessels. Many of the infiltrating T cells show class II expression indicating that they are activated. A few cytotoxic and suppressor cells and B lymphocytes are also present and their numbers increase proportionately with rat age. Some macrophages are also seen. Finally, at a late stage class II MHC molecules can be detected in partially destroyed islets on beta cells which are still actively synthesising insulin. We have never observed expression of class II molecules on glucagon or somatostatin secreting cells which are invariably well preserved.
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A generalized, chronic, progressive, exfoliative dermatitis in five horses is described. Histologically, the lesion is characterized by a superficial and deep perivascular dermatitis which is eosinophil-rich with a marked lymphocytic and plasmacytic component, accompanied by marked acanthosis and hyperkeratosis. More severe cases progress to a lichenoid pattern with the same cellular composition with focal eosinophilic spongiosis and eosinophilic subcorneal pustules. Clinically, the disease is associated with chronic, severe weight loss and is fulminating. The skin lesions are accompanied by lymphoplasmacytic and eosinophilic infiltrates and formation of eosinophilic granulomas in other epithelial organs, most noticeably the pancreas, in which a chronic, fibrosing pancreatitis develops. Other epithelial organs involved to various degrees are salivary glands, the gastrointestinal system, including the oral cavity and esophagus, biliary epithelium and bronchial epithelium. The etiology of this disease is unknown.
Valproate is an effective anticonvulsant which is rarely associated with hepatotoxicity. It has profound effects on the intermediary metabolism of isolated rat hepatocytes. In this paper the effect of valproate on blood metabolite concentrations in spontaneously diabetic BB/E rats has been studied. Valproate causes a marked fall in blood ketone body concentrations and a smaller fall in blood glucose concentrations following either oral or intraperitoneal administration. Valproate may have a role in the treatment of patients with "brittle" diabetes.
Sixty-two subjects not seeking health care, aged 18 to 80 yr, recorded diet intake, collected feces for 7 days, and gave fasting blood lipids. There was a great variation in stool weight passed (19 to 278 g/24 h). Fecal constituents (bile acids, sterols, fat, electrolytes) correlated strongly with fecal mass. Fecal mass correlated inversely with transit time. There was no relationship between age and fecal weight or transit time. Multiple regression analysis showed that only dietary fiber contributed to stool weight. No single component of fiber appeared to be responsible for this relationship with stool mass. Multiple regression analysis of serum cholesterol showed a relationship only with age and fecal neutral sterols.