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P M Harris

Publications and source records attributed to P M Harris.

13 recordsLinked to original sources
PubMed1995

Metabolic response of sheep skin to a chronic infusion of a variant of insulin-like growth factor I.

The effects of a chronic (21-day) skin infusion of a variant of insulin-like growth factor I (IGF-I) (long-Arg3-IGF-I; LR3IGF-I) on short-term (48 h) responses of skin metabolism and 21-day plasma hormone concentration, wool-follicle characteristics and wool production were investigated in well-fed castrated Romney sheep. A bilateral arteriovenous preparation was used to infuse LR3IGF-I continuously into the skin on one abdominal flank and saline into the other abdominal flank of six sheep; a further six sheep had one flank infused with saline (controls). LR3IGF-I caused an initial (4-24 h) reduction in the plasma concentrations of amino acids, especially tyrosine, valine and lysine, and, after 24 h, significant (P < 0.05) reductions in blood oxygen and plasma glucose concentrations. After 4 h of LR3IGF-I infusion, there was a significant increase in blood flow (P < 0.05) and oxygen uptake (P < 0.05), and net uptake of amino acids [which was significant (P < 0.05) for valine and phenylalanine] by the LR3IGF-I-infused skin was increased. Total uptake of phenylalanine for skin protein synthesis, measured using [3H]phenylalanine uptake, was also significantly increased after 4 and 24 h of infusion. After 48 h of infusion all LR3IGF-I-dependent measurements of metabolic parameters had fallen to preinfusion values. By day 7 of the 21-day infusion there was a significant (P < 0.05) decrease in circulating endogenous IGF-I in plasma of treated sheep compared with that of control sheep, followed by a significant (P < 0.05) increase between day 7 and 21. Plasma insulin levels followed a similar pattern. There was no change at any stage of infusion in IGF-binding proteins in the plasma of the two LR3IGF-I-infused sheep tested, and it is concluded that LR3IGF-I caused a down-regulation of the type-I IGF-I receptors followed by a rise in endogenous IGF-I concentration consequent on lack of feedback regulation. After 21 days of infusion there was no effect of LR3IGF-I on wool-follicle-bulb-cell mitotic rate, bulb diameter or wool production.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acids↗
PubMed1994

Effect of food intake on energy and protein metabolism in the skin of Romney sheep.

Sheep fed on either a low (500 g lucern (Medicago sativa) chaff/d; L) or high (1100 g lucerne chaff/d; H) intake had measurements made, using arterio-venous techniques, of blood flow and energy metabolite and cysteine utilization in the skin. Sheep on the H intake had significantly increased skin blood flow (P = 0.014) and oxygen uptake (P = 0.05). Although the H sheep had higher skin blood flow they showed no difference in skin uptake of either glucose or acetate compared with the L sheep, but the H sheep had a significantly lower output of lactate (P = 0.014). Animals in each group had either [14C]glucose or [14C]acetate infused into the skin which showed that acetate was the predominant precursor of skin sterol and fatty acid synthesis in the H sheep while L sheep skin used both glucose and acetate. The H sheep showed an increase in the net uptake of cysteine by the skin (P = 0.053), and in the uptake of cysteine for protein synthesis (P = 0.078), relative to the L sheep and this increase was of a comparable magnitude to the increase in blood flow to the skin. Although blood flow, protein synthesis and energy supply increased in the skin of the H sheep by 200-300%, wool production would only have increased by 10-20%, suggesting that nutrient flux changes are not the sole level of regulation of wool production.

Acetates↗
PubMed1993

Direct infusion of a variant of insulin-like growth factor-I into the skin of sheep and effects on local blood flow, amino acid utilization and cell replication.

In vivo effects of local infusion of a variant of insulin-like growth factor-I (IGF-I), long-R3-IGF-I, into the skin were investigated using six conscious sheep with food available ad libitum. An artery and vein on the abdominal flank of each animal, as well as the saphenous artery, were catheterized so that infusion of isotopically labelled amino acids, with or without IGF-I, could be used to determine amino acid uptake by arteriovenous difference in combination with blood flow determined by dye dilution. Measurements were made on each animal prior to IGF-I infusion, at hourly intervals for the 4 h of IGF-I infusion into the skin artery, then 2 and 4 h after IGF-I infusion ceased. Numbers of cells replicating in the bulbs of wool follicles in the IGF-I-infused area and in the skin on the contralateral side of each animal were measured after labelling with 5-bromo-2'-deoxyuridine. IGF-I caused a significant increase in the skin blood flow (P < 0.05), utilization of oxygen (P < 0.05), uptake of cysteine (P < 0.05) and phenylalanine (P < 0.001), and the rate of utilization of cysteine (P < 0.05) for protein synthesis. IGF-I increased amino acid uptake regardless of whether the skin was in negative or positive amino acid balance prior to infusion. During the recovery period amino acid utilization by skin returned towards preinfusion levels. No effects of IGF-I were found on replicating cell numbers in the bulbs of wool follicles.

Amino Acids↗
PubMed1992

Responses in tissue protein synthesis to sub- and supra-maintenance intake in young growing sheep: comparison of large-dose and continuous-infusion techniques.

In ten lambs (average live weight 33 kg), five offered 300 g/d (approximately 0.6 x maintenance; L) and five 900 g/d (1.8 x maintenance; H), tissue protein synthesis was measured by three procedures simultaneously. The techniques involved continuous infusion of [U-14C]phenylalanine and [1-13C]leucine over 7-8 h followed by a terminal large dose of [15N]phenylalanine during the last 30 or 60 min. Rates of protein synthesis were then calculated based on the free amino acid or oxo-acid isotopic activity in either arterial, iliac venous blood or tissue homogenate for the continuous-infusion studies, or on plasma or tissue homogenate for the large-dose procedure. For muscle (> 99%), and to a lesser extent skin (85-93%), effective flood conditions were achieved with the [15N]phenylalanine but were either not established or maintained for liver and tissues of the gastrointestinal tract (< 50%). The large dose of phenylalanine also caused changes in the concentration and isotopic activity of blood leucine and 4-methyl-2-oxo-pentanoate. Based on the assumption that the large-dose procedure yields the closest value for the true rate of protein synthesis (L 1.97%/d, H 2.85%/d) then, for muscle, only values based on the homogenate as precursor gave comparable results for both leucine (L 1.83%/d, H 3.01%/d) and phenylalanine (L 1.67%/d, H 2.71%/d) continuous infusion. The values based on the arterial or venous amino or oxo-acid were significantly less, more so at the lower intake. In contrast, for skin, a tissue dominated by export protein synthesis, values from the large-dose procedure (L 6.37%/d, H 10.98%/d) were similar to those derived with arterial or venous metabolites as precursor (L 5.23 and 6.93%/d, H 9.98 and 11.71%/d for leucine), but much less than those based on homogenate data. Based on the large-dose technique, protein synthesis increased with intake in muscle (P < 0.001), skin (P = 0.009) and liver (26.7 v. 30.5%/d; P = 0.029). The contributions of muscle and skin to total protein synthesis were approximately equal. The incremental efficiency of conversion for muscle of synthesized protein into deposition appeared to be similar to values reported for rodents.

Animals↗
PubMed1992

Effect of food intake on hind-limb and whole-body protein metabolism in young growing sheep: chronic studies based on arterio-venous techniques.

Whole-body protein synthesis, estimated by the irreversible loss rate procedure, and hind-leg protein metabolism determined by arterio-venous techniques were monitored in response to three nutritional conditions (approximately 0.6, 1.2 and 1.8 x energy maintenance (M)) in ten wether lambs (33 kg average live weight). In all lambs and treatments measurements were based on radiolabelled phenylalanine, but the terminal procedures (five at 0.6 x M and five at 1.8 x M) also included infusion of [1-13C]leucine; this permitted comparison of amino acids catabolized (leucine) and non-metabolized (phenylalanine) by the hind-limb tissues. Whole-body protein synthesis increased with intake and the relationship with energy expenditure was slightly lower than that reported previously for pigs and cattle. The efficiency of protein retention:protein synthesis did not exceed 0.25 between the two intake extremes. Effects of intake on amino acid oxidation were similar to those observed for cattle. Hind-limb protein synthesis also increased significantly (P < 0.001) in response to intake. Estimates of protein gain, from net uptake values, indicated that the tissues made a greater proportional contribution to total protein retention above M and to protein loss below M, emphasizing the role played by muscle tissue in providing mobile protein stores. The rates of protein synthesis calculated depended on the selection of precursor (blood) metabolite, but rates based on leucine always exceeded those based on phenylalanine when precursor from the same pool was selected. The incremental efficiency of protein retained:protein synthesis was apparently unity between 0.6 and 1.2 x M but 0.3 from 1.2 to 1.8 x M. Blood flow through the iliac artery was also proportional to intake. Leucine and oxo-acid catabolism to carbon dioxide increased with intake such that the metabolic fate of the amino acid was distributed in the proportion 2:1 between protein gain and oxidation. The rates of oxidation were only 1-3% the reported capacity of the rate-limiting dehydrogenase enzyme in muscle, but sufficient enzyme activity resides in the hind-limb adipose tissue to account for such catabolism.

Amino Acids↗
PubMed1985

The generation of monoclonal antibodies against human pancreatic exocrine cancer: a study of six different immunisation regimes.

Six different immunisation regimes have been used to generate spleen cells with reactivity against human pancreatic exocrine cancer. Immunised spleen cells were fused with an NSO/1 myeloma line and supernatants from these hybridomas selectively screened for monoclonal antibodies which bound predominantly to a pancreatic cancer cell line (GER). The spleen cells from hairy litter mates immunised with pancreatic cancer xenograft homogenates and viable GER cells generated 13% of hybridoma supernatants which showed some selectivity for GER pancreatic cancer cells in a fixed cell ELISA assay. The other methods produced only 4% of hybrids with selectivity for GER cells. The antigen distribution on gluteraldehyde fixed cells was similar to that found for viable cell monolayers but many antigens were unstable on formalin fixation. Immunohistochemical staining of GER cells grown on glass slides showed a heterogeneity of antigen distribution with up to 70% of the cells exhibiting a vesicular pattern of staining. Fifty percent of the antibodies which bound to GER cells were also reactive against antigens in formalin-fixed paraffin-embedded tissue sections of the original GER tumour. Monoclonal antibody DD9E7 identified an antigen expressed on 12/14 pancreatic adenocarcinomas. The antibody showed strong staining of malignant luminal membranes and cytoplasm. The antigen was also present in normal salivary and sweat glands, and colon and breast carcinomas, but its tissue distribution was unlike that of CEA or EMA. The expression of this antigen in 12/14 of pancreatic carcinomas suggests that DD9E7 may be a useful reagent for pancreatic tumour detection.

Adenocarcinoma↗
PubMed1984

Response of male and female rats to undernutrition. 1. Changes in energy utilization, body composition and tissue turnover during undernutrition.

In two separate trials male and female Wistar rats, 12 weeks of age, were either killed as a preliminary control group, ad lib.-fed or undernourished for 4 weeks until one-third of their 12-week body-weight was lost. Food intakes, urinary and faecal collections and measurements of standard metabolic rate were made at one-weekly intervals on both the ad lib.-fed and undernourished animals of both sexes. The bodies of the preliminary controls, the ad lib.-fed and the undernourished animals of both sexes were analysed for protein and fat, and the weights of four fat depots, two muscles and the major organs of all groups were determined. Measurements of lipid synthesis rate (LSR) and lipoprotein lipase (EC 3.1.1.34) (LPL) activity in the four fat depots and measurements of whole-body protein synthesis rates were carried out on animals of both sexes in each group. Although both sexes lost the same proportion of body-weight the females required more food on a body-weight basis than the males during the undernutrition period. The females absorbed significantly more energy on a body-weight basis during undernutrition and so were less efficient than the males at withstanding nutritional stress. There were no significant differences between males and females, on a body-weight basis, in the excretion of nitrogenous waste products (urinary nitrogen, creatinine, hydroxyproline or NT-methylhistidine) suggesting that there were no differences between the sexes in protein sparing during undernutrition.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Response of male and female rats to undernutrition. 2. Influence of ovariectomy on partition of nutrients by female rats during undernutrition.

Female Wistar rats (5 and 11 weeks old) were either left intact or ovariectomized. Animals of each age- and treatment-group were either ad lib.-fed or undernourished for 4 weeks. The bodies of all animals were analysed for protein and fat and the weights, lipid synthesis rate and lipoprotein lipase (EC 3.1.1.34) activity of four fat depots were determined. The well-nourished ovariectomized animals of both age-groups gained weight more rapidly than the well-nourished intact animals of the same age, but there was no effect of ovariectomy on body composition, lipid synthesis rate or lipoprotein lipase activity in either the well-nourished or the undernourished animals of either age-group. There was a greater efficiency of energy utilization found in the ovariectomized animals than in the intact animals regardless of age or nutritional status.

Animals↗
PubMed1980

Changes in adipose tissue of the rat due to early undernutrition followed by rehabilitation. 1. Body composition and adipose tissue cellularity.

1. Male Black and White Hooded rats were allocated at birth to foster mothers in litters of three, nine or sixteen. At weaning animals from each of these litter sizes were ad lib.-fed on a stock diet forming three ad lib.-fed control groups. At weaning further animals from litters of nine and sixteen were fed on the stock diet in restricted amounts until 12 weeks of age. These undernourished animals were then rehabilitated by being allowed ad lib. access to the stock diet. 2. Five animals from each group were killed at various stages of the experiment, their bodies analysed for fat and nitrogen, and the size and number of cells determined in four specific fat depots. 3. The previously undernourished rats failed to make a complete recovery and were significantly smaller than ad lib.-fed animals from the same litter at 32 weeks of age when the experiment was terminated. 4. The previously undernourished rats from litters of nine deposited a significantly greater porportion of fat in their bodies during rehabilitation than ad lib.-fed animals from litters of nine over the same gain in body-weight. The previously undernourished rats from litters of sixteen deposited the same proportion of fat in their bodies during rehabilitation as ad lib -fed animals from litters of three, nine and sixteen over the same gain in body-weight. 5. There were no significant differences in apparent or total fat cell numbers between ad lib.-fed animals and undernourished-rehabilitated animals at any of the four sites studied at 32 weeks of age.

Adipose Tissue↗
PubMed1980

Changes in adipose tissue of the rat due to early undernutrition followed by rehabilitation. 2. Strain differences and adipose tissue cellularity.

1. Male Wistar rats were allocated at birth to foster mothers in litters of three, nine or sixteen. At weaning animals from each litter size were ad lib.-fed on a stock diet. Further animals from litters of nine and sixteen were fed on the stock diet in restricted amounts until 12 weeks of age and then rehabilitated by being allowed ad lib. access to the stock diet. 2. Five animals from each group were killed at 24 weeks of age and the size and number of cells determined in four specific fat depots. 3, Animals reared in litters of sixteen and further undernourished from 3 to 12 weeks (group L16/U) had significantly fewer fat cells at all sites studied than animals reared in litters of three and ad lib.-fed. Group L16/U animals also had significantly fewer observable fat cells at the epididymal site than ad lib.-fed animals reared in litters of nine. These results differ from those found in the Black and White Hooded rat where, after similar treatments, no significant differences in observable fat cell number were found.

Adipose Tissue↗
PubMed1980

Changes in adipose tissue of the rat due early undernutrition followed by rehabilitation. 3. Changes in cell replication studied with tritiated thymidine.

1. Well-nourished rats were injected with tritiated thymidine at 15, 22, 28 or 84 d of age. At 1, 6, 11 and 16 d after injection animals from each group were killed, samples of adipose tissue were removed from two subcutaneous sites (abdominal and scapular) and separated, using collagenase (EC 3.4.24.3), into 'fat cell' and 'stromal cell' fractions. The specific (radio)activity of DNA isolated from each fraction was measured. The specific activity of DNA isolated from two 'deep body' sites (perirenal and epididymal) was measured only in the animals injected at 84 d of age. 2. Animals undernourished from birth up to 84 d of age were injected with tritiated thymidine at 22, 28 or 84 d of age. Animals were killed 1 and 11 d after injection, adipose tissue removed, and the specific activity of DNA measured. Other undernourished animals were rehabilitated from 84 to 107 d and injected at 91 d of age with tritiated thymidine. The animals were killed 1, 6, 11 and 16 d after injection, adipose tissue was removed from the subcutaneous and deep body sites and the specific activity of DNA determined as before. 3. In well-nourished animals fat cell replication had largely ceased by 12 weeks of age in the subcutaneous depots. There were differences between the various sites of adipose tissue regarding the period of hyperplastic growth, its timing or rate of replication or both. 4. In undernourished animals replication was slow in the subcutaneous depots compared with well-nourished animals of the same age. Rehabilitation from undernutrition stimulated replication which resulted in higher rates in all four depots examined compared with those in well-nourished animals. 5. The findings are discussed in relation to the concept of a finite period of hyperplasia for adipose tissue.

Adipose Tissue↗