Biomedical subjects

R M Leach

Publications and source records attributed to R M Leach.

At least 73 records · Page 4Linked to original sources

PubMed1991

Central hypoxaemia in rats provokes neurological defects similar to those seen in experimental diabetes mellitus: evidence for a partial role of endoneurial hypoxia in diabetic neuropathy.

Endoneurial hypoxia has been put forward as a factor contributing to diabetic neuropathy. The aim of this study was to determine whether alterations in motor nerve conduction velocity, Na+/K(+)-ATPase activity and substance P content of nerve and skin tissue, characteristic of the diabetic rat, could develop in non-diabetic animals subjected to a central hypoxaemia for five weeks. Compared to normoxic controls, five weeks of central hypoxaemia caused a fall in motor nerve conduction velocity of 30% (P less than 0.01), a decrease in sciatic nerve substance P content (68%; P less than 0.001) combined with elevated substance P content per unit area foot skin (44%; P less than 0.01). This pattern of change is qualitatively similar to that seen in diabetic rats. The Na+/K(+)-ATPase activity, however, was unaltered by the hypoxic environment. These findings support strongly a partial role for hypoxia in the pathogenesis of diabetic neuropathy.

Animals↗

PubMed1991

Kinetics of copper metabolism in rats: a compartmental model.

Model-based compartmental analysis was used to describe data on the whole body kinetics of copper metabolism in rats. Data were collected on recovery of radio-copper in plasma, liver, skin, skeletal muscle, bile, and feces for 3 days after the injection of 10 micrograms iv of copper labeled with 64Cu. Data on copper masses and on 64Cu kinetics were analyzed by the stimulation, analysis, and modeling computer programs. Observed data were fit to a 16-component "working hypothesis" model; fractional transfer coefficients were estimated, and steady-state compartment masses and copper transfer rates were calculated. The model postulates a rapid turnover of plasma nonceruloplasmin (NCp) copper (8.5 h-1), which exchanged a large amount of copper with extrahepatic tissues (16 micrograms/h) as well as liver (13 micrograms/h). In comparison, ceruloplasmin (Cp) transferred relatively little copper to tissues (less than 1 microgram/h). NCp copper is postulated to be the precursor for biliary copper. Regarding the intracellular metabolism of copper in hepatic and extrahepatic tissues, the data were compatible with a faster turning-over compartment that exchanged copper with NCp and a slower turning-over compartment with input from Cp. In the liver, the slower turning-over compartment was the copper present in peak II (mol mass 30,000-40,000 Da); this received much of its input from the faster turning-over compartment (peak III), which was hypothesized to represent, in large part, copper in metallothionein.

Animals↗

PubMed1991

Expression of the parathyroid hormone-related protein gene in the avian oviduct: potential role as a local modulator of vascular smooth muscle tension and shell gland motility during the egg-laying cycle.

The phylogenetic conservation of the primary structure of PTH-related protein (PTHrP) supports an important, yet undetermined, role(s) for this molecule in the biology of birds and mammals. As an initial step toward understanding the function of PTHrP in birds, we investigated the expression of PTHrP mRNA in tissues of the egg-laying hen. This analysis revealed that PTHrP mRNA is expressed at various levels in lung, brain, heart, and tissues of the digestive tract, including the proventriculus (secretory stomach), gizzard, and small intestine. In the oviduct tissues of adult birds, PTHrP mRNA was detected in the isthmus (membrane-secreting) and shell gland (calcium-secreting) portions, but not in magnum (albumin secreting) tissue. During oviduct development, high levels of PTHrP mRNA present in the oviducts of the 12-week-old bird suggest a role for PTHrP in oviduct development. Interestingly, as the oviduct matures, relatively high levels of PTHrP mRNA segregate with the distal tissues that ultimately differentiate into the isthmus and shell gland (uterus). To address a possible role for PTHrP in the differentiated function of the shell gland, we followed the expression of PTHrP in the shell gland at different times in the laying cycle and found levels of PTHrP to transiently increase as the egg moves through the oviduct, gradually returning to basal levels in the 15-h calcification period. We localized the cycle-associated fluctuations in PTHrP mRNA levels to the shell gland serosa and smooth muscle layer. Immunoreactive PTHrP was localized to the serosal membrane as well as the smooth muscle layer of serosal arterioles, suggesting that PTHrP may modulate vascular smooth muscle activity. In support of this hypothesis, synthetic chicken PTHrP (1-34)NH2 was found to relax the resting tension of isolated shell gland blood vessels in a dose-dependent manner. Together, these data indicate that the expression of the PTHrP gene in the avian oviduct is both temporally and spatially regulated during the egg-laying cycle and that PTHrP may function as an autocrine/paracrine modulator of shell gland smooth muscle activity of both ductal and vascular origins. The vasorelaxant property of N-terminal fragments of PTHrP supports a role for this molecule in the temporal increase in blood flow to the shell gland during egg calcification.

Animals↗

PubMed1991

Effects of dietary cadmium chloride throughout gestation on blood and tissue metabolites of primigravid and neonatal dairy cattle.

Thirty-six postpubertal Holstein heifers were allocated to three groups and fed the same diet, which differed only in the concentration of Cd: control group (.25 ppm of Cd), low-Cd group (1 ppm of Cd), and high-Cd group (5 ppm of Cd). Cadmium was supplemented to the low-Cd and high-Cd groups using CdCl2. Liver, kidney cortex, and abdominal muscle were biopsied for mineral analysis from one-half of the heifers of each group before Cd supplementation and again from the same animals within 5 d after parturition, 394 d later. Blood, liver, and muscle were collected from each calf within 5 h after birth. In the dam, 5 ppm of dietary Cd caused a 62-, 27-, and 4-fold increase in Cd of the kidney, liver, and muscle, respectively; kidney Zn and Fe increased (76%) and decreased (33%), respectively, whereas the serum Cu was reduced (31%). Liver Cu was reduced to 40 and 17% by dietary Cd of 1 and 5 ppm, respectively, in the dams. Calves from dams consuming 5 ppm of Cd had a 29 and 43% reduction in liver Cu and Zn, respectively. In these same calves, packed cell volume, hemoglobin concentration, and serum Cu were decreased by 17, 18, and 25%, respectively, whereas serum Zn was increased (55%). Serum sodium and potassium were reduced by 4 and 13%, respectively, and blood urea nitrogen was increased by 63% in calves from dams consuming 5 ppm of Cd. Feeding primigravid dairy cattle up to 5 ppm of Cd as CdCl2 throughout gestation did not influence the concentration of Cd in the neonate but caused reductions in liver Cu and Zn; teratogenesis was not apparent.

Animals↗

PubMed1991

Effects of long-term dietary cadmium chloride on tissue, milk, and urine mineral concentrations of lactating dairy cows.

The effects of long-term consumption of 1 and 5 ppm of Cd on Cd, Cu, Fe, and Zn concentrations in milk and a variety of tissues of first-lactation dairy cows was investigated. Thirty-six Holstein heifers were allocated to three groups and fed similar diets differing only in the concentration of Cd (.25, 1, and 5 ppm) for a 394-d period before calving. One- and 5-ppm Cd concentrations were achieved using CdCl2. Liver, kidney cortex, and muscle were biopsied from one-half of the heifers of each group before Cd supplementation and again from the same heifers within 5 d after parturition. Colostrum and milk were sampled throughout the 150 d of lactation. Urine was sampled after an average of 450 d of Cd exposure. At slaughter (after an average of 554 d), 11 tissues were sampled from 12 cows representing all treatment groups. During the first 394 d, Cd accumulated in kidney and liver with increasing dietary concentrations of Cd but did not further increase by 554 d. However, by 554 d Cd had also accumulated in the adrenal glands, ovaries, spleen, and uteri of cows consuming 5 ppm of Cd. Dietary Cd did not influence the concentration of Cd, Cu, Fe, or Zn in colostrum or milk. However, urine pH, Zn, and K were lower in cows consuming 5 ppm of Cd. Liver Cu was reduced by 1 and 5 ppm of Cd at both 394 and 554 d.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Non-invasive management of fever and breathlessness in HIV positive patients.

In a prospective study of 72 human immunodeficiency virus (HIV) positive patients presenting with fever and breathlessness, a non-invasive management protocol, incorporating a scanning technique using radioactively labelled diethylenetriamine penta acetate (DTPA) and sputum induction, was found to be highly sensitive and specific in the early detection of Pneumocystis carinii pneumonia (PCP). At presentation, the DTPA scan was abnormal in 34 of 36 cases of PCP, irrespective of smoking history, whilst the chest radiograph was diffusely abnormal in 21 cases. Sputum induction identified 7 of 14 patients with PCP in the first six months of its use and 7 of 10 patients over the last six months. The DTPA lung scan and induced sputum examination are non-invasive techniques which can be used to investigate out-patients. In combination they detected all cases of PCP at presentation, reduced the need for bronchoscopy, resulted in a low case fatality (5.4%) and reduced the need for admission.

Acquired Immunodeficiency Syndrome↗

PubMed1990

Brachioradial delay: a new clinical indicator of the severity of aortic stenosis.

During the assessment of patients with severe or symptomatic aortic stenosis, a clinically detectable delay between the brachial and radial pulses was observed. This delay was not present in normal subjects. The timed delay of 53.5 (SE 2.6) ms in severe aortic stenosis was significantly longer than that in normal volunteers 22.6 [1.3] ms) or in patients with low cardiac output. This increased delay was clinically detectable before the occurrence of left ventricular failure and often before the onset of symptoms.

Age Factors↗

PubMed1990

The mechanism of action of endothelin-1 on small pulmonary arterial vessels.

The effect of endothelin-1, a recently isolated vasoconstrictor peptide, was studied in preparations of pulmonary arterial vessels from the rat. Contraction was measured in large (1-2 mm diameter) and small (150-350 microns diameter) vessels on a Mulvany-Halpern myograph. Endothelin-1 was found to be one of the most potent vasoconstrictors yet described in these isolated pulmonary vessels. The contraction elicited was dose dependent, of slow onset, and prolonged. There was significant difference in sensitivity between the two vessel types, with an EC50 of 8.9 nM for the artery, and 33.1 nM for the smaller vessels. The endothelin-1 stimulated contraction was predominantly dependent on extracellular [Ca2+]. However 34.7% of the contraction in the pulmonary artery and 18.5% in the resistance vessel could be obtained in Ca2+ free (EGTA containing) solution. This extracellular Ca2+ independent fraction was sensitive to depletion of intracellular stores by pretreatment with caffeine or noradrenaline in the artery but not the arteriole. The extracellular Ca2+ dependent fraction was not affected by Ca2+ channel blockade with dihydropydridines or verapamil, but was inhibited by application of cadmium or lanthanum. The contraction was not altered by inhibition of Na+/H+ exchange.

Animals↗

PubMed1990

Effect of aluminum on performance and mineral metabolism in young chicks and laying hens.

This study was performed to determine the long-term effects of dietary aluminum on egg production and reproductive parameters in the mature laying hen and on growth rate and feed efficiency in young chicks. The diets used in these studies were adequate in phosphorus and other essential nutrients. Aluminum added to constitute 0.30% of the diet severely depressed growth and reduced feed efficiency, bone ash and plasma phosphorus in male Ross x Leghorn chicks. At the same time, 0.15% added aluminum mildly depressed growth, feed efficiency and bone ash but had no effect on plasma phosphorus levels. The reduction in bone ash was relatively mild, and no clinical signs of rickets were observed. In laying hens, diets containing 0.15% added aluminum did not affect egg production, but 0.30% added aluminum reduced production significantly. Long-term exposure to aluminum increased percent shell in both groups receiving aluminum, whereas egg weight remained similar to that in controls. There were no changes in hatchability or bone ash associated with dietary aluminum. Although dietary aluminum influenced bone aluminum content, egg aluminum content was not affected. These studies indicate that dietary aluminum interferes with systems in addition to phosphorus metabolism.

Aluminum↗

PubMed1990

Effect of the sex-linked dwarfing gene (dw) upon skeletal development of young broiler chicks.

The influence of the sex-linked dwarfing gene (dw) on growth and skeletal development in young male broiler chicks was investigated. Chickens that were homozygous (dw/dw) for the dwarfing gene had significantly lower BW and tibiotarsus lengths when compared with the heterozygous (Dw/dw) or normal (Dw/Dw) genotypes. All genotypes exhibited similar incidences of tibial dyschondroplasia. In contrast to several other types of dwarfism, there was no effect of the dw gene on the width of the epiphyseal growth plate or the proteoglycan content of this tissue.

Animals↗

PubMed1990

Broiler chicks fed low calcium diets. 1. Influence of zeolite on growth rate and parameters of bone metabolism.

An experiment with a factorial arrangement of treatments was conducted using five levels of dietary calcium and two levels of zeolite A. When dietary calcium was deficient or marginal, zeolite A improved calcium utilization, as evidenced by improved growth rate and a reduction in rachitic lesions. There was little benefit from adding zeolite A to diets adequate in calcium. The effect of zeolite A on the incidence of tibial dyschondroplasia was inconsistent.

Aluminum Silicates↗

PubMed1990

Broiler chicks fed low-calcium diets. 2. Increased sensitivity to copper toxicity.

Young broiler chicks were more sensitive to copper toxicity when they were fed diets deficient or marginal in calcium content. Growth rate was depressed and liver copper concentration was increased under these conditions. Chicks fed a casein-gelatin diet were more sensitive to copper toxicity than those fed a corn-soybean meal diet. Addition of phytic acid to the casein-gelatin basal diet enhanced copper toxicity as evidenced by effects on growth rate and liver copper content. Measurements of intestinal and biliary copper content suggested that the influence of calcium on copper toxicity was mediated via intestinal absorption rather than through influences on copper excretion.

Animal Feed↗

PubMed1989

A comparison of contractile function in large and small pulmonary arterial vessels of the rat.

The contractile function of rat pulmonary arterial vessels, ranging in internal diameter from 100 to 2000 microns, was studied in vitro using a small vessel myograph. It was found that vessels with a diameter of 200-400 microns produced considerably more force for a given intervention than those either smaller (less than 100-2000 microns) or larger (400-2000 microns). It is suggested that these vessels may play an important role in the generation of pulmonary vascular resistance.

Animals↗

PubMed1989

Neurological presentations of native valve endocarditis.

In a prospective study of 178 episodes of community-acquired native valve infective endocarditis seen at St Thomas' Hospital between 1969 and 1987, 59 patients (33 per cent) presented with neurological disorders that included meningitis, toxic confusion, major thromboembolic phenomena and headache. A neurological presentation occurred in 54 per cent of all cases of staphylococcal endocarditis, but in only 19 per cent of episodes of 'viridans' streptococcal and enterococcal endocarditis. Overall one-third of patients with staphylococcal endocarditis presented with clinical features of meningitis (40 per cent with no cardiac murmur). The mortality rate for community-acquired native valve endocarditis was higher for those with a neurological presentation than without.

Adolescent↗

PubMed1989

Type X collagen in avian tibial dyschondroplasia.

Tibial dyschondroplasia (TD) is an abnormality of the growth plate of growing chicks characterized by the presence of a mass of nonvascularized, nonmineralized cartilage. To determine if the morphologic changes observed in TD lesions are accompanied by biochemical abnormalities of the cartilage matrix, we performed quantitative and qualitative analyses of collagen in affected cartilage, placing special emphasis on the study of type X collagen, a recently described molecular species that may play a role in endochondral ossification. Collagen from TD lesions of 25-day-old chicks and from growth plate cartilage of normal age-matched chickens and from hypertrophic cones of 1-day-old chicks was sequentially extracted, purified and characterized. No differences were noted in total collagen content and extractibility between these tissues. Determination of the relative amounts of the various collagens extracted showed that type X collagen in the TD lesion was markedly reduced since it was less than half of that found in pure hypertrophic cartilage. These results are consistent with previous morphologic and biochemical studies which suggest a failure of the chondrocytes to fully achieve maturation and hypertrophy. No differences were demonstrated in the CNBr peptide patterns or amino acid composition of type X collagen from normal or TD and hypertrophic cartilages, suggesting that the low content of type X collagen in TD lesion was due to alterations in type X collagen metabolism rather than to structural abnormalities in these molecules.

Amino Acids↗

PubMed1987

Role of epiphyseal cartilage in endochondral bone formation.

The avian epiphyseal growth plate plays an important role in skeletal development. Compared with the mammalian species, the avian growth plate contains more cells, is less well organized and appears more susceptible to malformation. Abnormal cartilage development is associated with chondrodystrophy, tibial dyschondroplasia and rickets. Many nutrient deficiencies result in chondrodystrophy, which is characterized by shortened, thickened bones and a narrowing of the epiphyseal growth plate. Manganese, the most extensively studied of these deficiencies, is necessary for proteoglycan biosynthesis. Tibial dyschondroplasia is a condition in which the prehypertrophic cells fail to hypertrophy and vascularization is aborted. This abnormality is found in genetically predisposed animals and its occurrence is altered by subtle changes in calcium, phosphorus and electrolyte content of the diet. Calcium and vitamin D deficiencies cause rickets, which is characterized by an increase in the width of the prehypertrophic zone of the epiphyseal growth plate. Most of the biochemical and histological changes can be related to the need for calcium for chondrocyte hypertrophy and maturation, although there is some evidence that chondrocytes require specific vitamin D metabolites. Phosphorus deficiency increases the zones of hypertrophy and metaphyseal primary spongiosa.

Animal Nutritional Physiological Phenomena↗

PubMed1986

Episodic patterns of growth hormone secretion and growth hormone status of normal and tibial dyschondroplastic chickens.

Growth hormone status of normal and tibial dyschondroplastic (TD) birds was determined in 25 d old male chicks genetically selected for high and low incidence of TD. Birds were surgically prepared with indwelling venous catheters and blood samples remotely removed at 20 min intervals for 6 h to establish secretory patterns. Birds were maintained under a 16L:8D cycle, with free access to feed and water at all times. In a second experiment, secretory capacity was evaluated by administering a 10 micrograms/kg body weight dose of thyrotrophin releasing hormone (TRH). Blood samples were removed at 0, 5, 10, 20, 30, 60 and 120 min post-infusion of either TRH or saline (control). All birds displayed pulsatile patterns of GH secretion, with an average peak duration of 60 min and a 90 min inter-peak interval. Dyschondroplastic birds exhibited 50% higher mean peak amplitudes than normal birds (P less than .06), however, this difference was not translated into overall mean or total (curve area) differences. The magnitude of response to a TRH challenge was greater (P less than .10) for TD than for normal birds. In view of the relationships observed in other species between secretory pattern characteristics such as peak amplitude, and growth characteristics, it is suggested that differences in GH status of dyschondroplastic relative to normal birds may be related to initiation of the TD lesion.

Animals↗

PubMed1985

The influence of ascorbic acid on the occurrence of tibial dyschondroplasia in young broiler chickens.

Two distinctly different basal diets were used to test the influence of supplementary ascorbic acid on the occurrence of tibial dyschondroplasia. Addition of either .1 or .25% ascorbic acid to these diets did not alter the occurrence of tibial dyschondroplasia in 25-day-old broiler chickens. However, supplementary ascorbic acid did increase the amounts of ascorbic acid present in blood plasma. Also, individual differences in circulating ascorbic acid were not associated with this disease. Furthermore, two strains of chickens selected for high or low incidence of tibial dyschondroplasia had similar amounts of this vitamin in blood plasma. In contrast to the results reported for the Willow Ptarmigan, ascorbic acid does not appear to be involved in the development of tibial dyschondroplasia in the young broiler chicken.

Animals↗