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Biomedical subjects

A R Peters

Publications and source records attributed to A R Peters.

At least 37 records · Page 2Linked to original sources

Follicular and luteal expression of insulin-like growth factors I and II and the type 1 IGF receptor in the bovine ovary.

The localization of mRNAs for insulin-like growth factors I (IGF-I) and II (IGF-II) and the type 1 IGF receptor (IGF-1R) in bovine follicles and corpora lutea was determined using in situ hybridization on sectioned ovaries collected from nonpregnant, cyclic Holstein cows in either the follicular (n = 3) or luteal (n = 5) phases of the cycle. Concentrations were measured as absorbance units of individual regions or follicles from autoradiographs. There was intense follicular expression of mRNAs encoding IGF-II and IGF-1R. For mRNA encoding IGF-II, expression was significantly higher in smaller follicles (< 5 mm diameter, P < 0.01) and, in this size range, expression was significantly greater in healthy compared with atretic follicles (P < 0.01). For mRNA encoding IGF-1R, there was no effect of size but concentrations were again significantly greater in healthy compared with atretic follicles of < 5 mm. In medium (5-10 mm) and large (> 10 mm) follicles, there was no effect of health for expression of either IGF-II or IGF-1R. mRNA encoding IGF-II was found exclusively in the theca, whereas mRNA encoding IGF-1R was confined to the granulosa layer. IGF-I expression was not detectable in 83% of the 53 follicles examined. In the remaining 17% of follicles, expression was very low and was unrelated to size or state of atresia. mRNAs encoding IGF-I, -II and IGF-1R were all present in the corpus luteum, whereas only those for IGF-II and IGF-1R were found in ovarian stroma. These data indicate that the insulin-like growth factors play a significant role in follicular and luteal development in the bovine ovary. Locally produced IGF-II is probably an important regulator of follicular growth, whereas most of the IGF-I present in follicular fluid is likely to be derived from the circulation.

Animals↗

Treatment of bovine retained placenta and its effects.

The literature on the treatment of retained placenta and its effects is reviewed. Manual removal, the oldest and commonest method of treatment, benefits parlour hygiene but may adversely affect the cow. The use of collagenase may allow manual removal without such side effects. Ecbolic drugs are often ineffective, both as prophylaxis and treatment for the condition. They are most effective within one hour of parturition, particularly after a caesarean section in which tocolytic drugs have been used. Endometritis is a very common sequel to retained placenta. Antibiotics and oestrogens have been used to treat, control or prevent the condition, but they are not routinely effective and may have deleterious side effects. Gonadotrophin releasing hormone and/or prostaglandins have been used to reduce the deleterious effect of retained placenta on fertility, but the results obtained have been inconsistent.

Animals↗

Bovine retained placenta: aetiology, pathogenesis and economic loss.

The literature on the effects and causes of retained placenta in the cow is reviewed. On a herd basis the condition can adversely affect milk yield and fertility, but on an individual cow basis the effects are unpredictable. The aetiology of retained placenta has been extensively studied and many causal factors have been implicated, but little is known of how many of them cause the condition. As a result its prevention and prediction is uncertain, primarily because of the lack of knowledge of the normal process of placental release. Vascular changes and uterine contractions play a role in placental release, but current opinion suggests that the primary cause of retained placenta is the retention of the feto-maternal union. Release only occurs after a process of maturation, which involves hormonal and structural changes. The factors which are thought to influence these changes, and thus cause the condition, are discussed.

Animals↗

Suppression in the secretion of follicle-stimulating hormone and luteinizing hormone, and ovarian follicle development in heifers continuously infused with a gonadotropin-releasing hormone agonist.

A novel experimental model was developed in cattle to investigate the requirement for FSH and LH during ovarian follicle growth and development. On Day 5 of the estrous cycle, 7 heifers were each implanted with an osmotic minipump containing a GnRH agonist (GnRHa), Buserelin (release rate, 2.5 micrograms/h). Another 7 heifers served as controls. Each minipump was replaced 28 days later with a second pump, which was left in place for a further 20 days. Blood samples were collected daily throughout the experimental period, and frequent samples were also collected on both days of minipump insertion and at 10 days after insertion of the second pump. The ovaries of all heifers were scanned daily by real-time ultrasonography to monitor follicular dynamics. All controls displayed 2 or 3 waves of FSH and follicular development per estrous cycle during the experiment. Insertion of the first minipump produced a large LH and FSH surge and induced ovulation in all 7 animals. Within 8 days of the start of treatment, serum LH concentrations fell to basal levels; they then remained constant at this level throughout the infusion period, only beginning to recover 4-5 days after the termination of infusion. After the initial increase, FSH returned to basal levels before showing a normal wave that was coincident with the emergence, growth, and regression of a dominant follicle. However, despite the peak levels of FSH, dominant follicles from the next wave failed to grow beyond 7-9 mm; they remained at this size for 3 wk until 3-4 days after insertion of the second minipump, when FSH fell precipitously to reach low levels that were maintained throughout the remainder of the infusion. After this fall in FSH concentrations, these follicles regressed rapidly, and no antral follicles > 4 mm were detected until after the termination of treatment. Thereafter, FSH concentrations increased significantly; the increase was accompanied by the emergence of a follicular wave and development of a dominant follicle, with estrus observed 8-11 days later. In conclusion, this study has demonstrated clearly that in cattle the early stages of follicle development (< or = 4 mm) are not dependent on acute support by gonadotropins. However, FSH is required for further growth of follicles up to 9 mm, while LH pulses are indispensable for follicle development beyond 9 mm in diameter. The model developed in this study should be valuable for studying the control of ovarian follicle development and atresia in vivo.

Animals↗

A study of multiple sclerosis patients with magnetic resonance spectroscopic imaging.

Eleven patients with clinically definite MS and three healthy controls were investigated by magnetic resonance spectroscopic imaging. The data sets were analysed for all voxels containing white matter only. We classify these voxels in healthy controls as normal white matter (NWM), and in MS patients as normal-appearing white matter unaffected by MS lesions (NAWM) or white matter affected by MS lesions. The spectra belonging to the voxels were analysed for content of cholines, creatines and N-acetylaspartate (NAA), and compared as a group. It was found that lesions differ from white matter in chemical composition and, moreover, that normal-appearing white matter differs from healthy white matter. Specifically, levels of NAA are lower in patients. There seems to be a linear relation between the composition of white matter and the expanded disability status scale value for the patient. The presence of lactate could not be established, and no unambiguous differences were found between patients with relapsing-remitting and relapsing-progressive disease.

Adult↗

Effects of chronic treatment with a gonadotrophin-releasing hormone agonist on peripheral concentrations of FSH and LH, and ovarian function in heifers.

The effect of chronic treatment with a gonadotrophin-releasing hormone agonist (GnRHa) on ovarian function in cattle was investigated by injecting heifers i.m. twice a day with saline, 5 micrograms GnRHa (Buserelin) or 10 micrograms GnRHa (n = 7) for 21 days. Blood samples were taken twice a day during the treatment period, and then three times a day for 7 days and once daily for a further 4 days. Frequent samples were also collected on day 1, day 10 and day 21 of treatment. The ovaries of all heifers were examined daily using real-time ultrasonography throughout the experimental period. No significant differences in the response were observed between two doses of GnRHa. The first GnRHa injection produced a large LH and FSH surge and this acute response was still present by day 21 of treatment, but both the magnitude and duration of response were significantly attenuated (P < 0.01). After an initial increase, LH returned to the basal concentration, which was maintained until the termination of treatment, when concentrations increased significantly, with a preovulatory surge occurring approximately 6 days later. Peripheral FSH concentrations during the oestrous cycle in control animals displayed a pattern of three waves, each of which closely preceded a wave of follicular development. Concentrations of FSH in GnRHa-treated heifers showed a normal pattern for the first wave after the start of treatment. During the next wave, concentrations increased and remained at the peak values until about 4 days after the end of treatment. An additional ovulation was induced in 11 of 14 GnRHa-treated heifers within 2-3 days of the start of treatment, and a significant (P < 0.05) increase in serum progesterone concentrations was detected 2 days later. All GnRHa-treated heifers then showed a normal follicular wave, with the development and regression of a dominant follicle. The dominant follicles from the next wave grew to only 7-9 mm in diameter and remained at this size until the end of treatment, when they resumed growth, ovulated approximately 7 days later and formed corpora lutea. We conclude that chronic treatment of heifers with GnRHa for 3 weeks suppresses pulsatile secretion of LH and blocks the development of dominant follicles beyond 9 mm in diameter, preventing the preovulatory LH surge and ovulation. However, GnRHa did not suppress the secretion of FSH within the 3 week treatment period. The maintenance of the dominant follicles for an extended period should provide an ideal model to study the control of follicular atresia in cattle in vivo.

Animals↗

Effect of buserelin on pregnancy rates in dairy cows.

Three field trials were carried out to assess the effect of buserelin on the fertility of dairy cows. In the first, 10 micrograms of buserelin was injected on the day of insemination; there were no significant effects on fertility in comparison with untreated control cows. In the second study the cows were injected 12 days after insemination; the mean pregnancy rates to first insemination were 53.4 and 65.4 per cent for the control and treated cows, respectively (P < 0.01) and the mean pregnancy rates to repeat inseminations were 52.9 and 59.4 per cent for the control and treated cows. The mean calving to conception intervals were 91.4 and 85.3 days (P < 0.01) and the incidences of barren cows were 10.2 and 5.2 per cent. In the third study the cows were injected with buserelin either eight days or 10 days after insemination; there were no significant effects on fertility in comparison with untreated control cows.

Animals↗

Associations between viral infections and respiratory disease in artificially reared calves.

Market-purchased, week-old, dairy bred calves entering a commercial calf-rearing unit were blood sampled at six-week intervals until three months old. Viral infections were monitored by ELISA for antibodies to bovine herpesvirus 1, bovine respiratory syncytial virus, parainfluenzavirus-3, bovine adenovirus subgroup 1 and bovine viral diarrhoea virus (BVDV). The immunoperoxidase test was used to detect BVDV in serum. The total immunoglobulin concentration in the initial blood sample was measured by the zinc sulphate turbidity test. The relationship between clinical respiratory disease, viral seroconversion and the initial concentration of serum immunoglobulin was investigated by the use of the relative risk statistic, Fisher's exact test, chi 2 techniques and the correlation coefficient. Treatment rates for respiratory disease of 45 per cent were observed during the first period of the study and 19 per cent during the second period. During the first period there was a significant positive association between clinical respiratory disease and seroconversion for all the viruses except parainfluenzavirus-3 and BVDV but in the second period there was no such relationship. Similarly, in the first period, but not in the second, there was a significant negative association between clinical respiratory disease and both antiviral immunoglobulin as measured by ELISA and total immunoglobulin as measured by the zinc sulphate turbidity test. Two of the 536 calves that survived to three months of age were found to be persistently infected with BVDV.

Animals↗

Conformational changes in phospholipase A2 upon binding to micellar interfaces in the absence and presence of competitive inhibitors. A 1H and 15N NMR study.

An NMR study has been made of porcine pancreatic phospholipase A2 (PLA) in three environments: free in solution, in a binary complex with dodecylphosphocholine micelles, and in a ternary complex with a micelle and the substrate-like inhibitor (R)-1-octyl-2-(N-dodecanoylamino)-2-deoxyglycero-3-phosph oglycol. 1H and 15N chemical shifts, amide exchange rates, and NOE intensities are compared for the enzyme in different environments. From these data, structural differences are found for the N-terminal part, the end of the surface loop at residues Tyr69 and Thr70, and the active site residue His48, and also for the Ca-binding loop (residues 28-32). Specifically, when binding to a micelle, the side chains of residues Ala1, Trp3, and Tyr69, as well as all protons of Thr70, are found to be closer together. After subsequent introduction of the competitive inhibitor, further changes are found for these residues. The N-terminus is flexible in PLA free in solution, in contrast with the crystal structures where it adopts an alpha-helical conformation. According to the NMR data, this helix is rigidly formed only in the ternary complex. Furthermore, in the ternary complex, the N-terminal amino group and the exchangeable hydrogen at N3 of the ring of His48 are observed. We propose that PLA is activated in two steps. An initial conformational change occurs upon binding to a micellar interface. The catalytically active conformation of the enzyme, which has an extensive network of hydrogen bonds, is formed only when binding a substrate or competitive inhibitor at a lipid-water interface.

Animals↗

Endocrine manipulation--toxicological frontiers.

A variety of hormonal products has been developed for use in food animal production. Applications include therapy, particularly for fertility problems, zootechnical purposes comprising mainly the management of reproduction, for example the synchronization of oestrus, and the improvement of performance such as increased growth rate or increased milk yield. Although there is well established legislation both domestically and internationally for the registration of veterinary pharmaceutical products, hormones have become a special case at least to the public. This is particularly true when hormones are used to improve animal performance. The two notable issues to date have been the use of anabolic steroids as growth promoters and of bovine somatotrophin (BST) to increase milk yield in dairy cows. The high public profiles of these two issues have separately forced the introduction of new legislation in the EC, which will continue to have far-reaching implications for research and development in animal health and production for many years. This paper interprets recent developments in legislation concerning veterinary products and hormonal products in particular, giving examples of the toxicological assessment of four specific molecules and speculating upon the likely implications for the future practical exploitation of endocrine mechanisms in food animal production.

Animals↗

Experimental and practical approaches to the establishment and maintenance of pregnancy.

A series of three large field trials was carried out to assess the effect of buserelin on fertility in dairy cows. In the first, 10 micrograms buserelin was injected on the day of insemination. There were no significant effects on fertility parameters compared to untreated controls. In the second trial cows were injected on day 12 after insemination. Mean pregnancy rates to first insemination were 53.4 and 65.4% for control and treated cows respectively (P < 0.01). Mean pregnancy rates to repeat inseminations were 52.9 and 59.4% for control and treated cows (NS). Mean calving to conception intervals were 91.4 and 85.3 days (P < 0.01) and the incidence of barren cows was 10.2 and 5.3% (NS). Overall the economic benefit of buserelin injection on day 12 was calculated to be 27.43 pounds per cow treated excluding the cost of the treatment. In trial 3 cows were injected with buserelin either on day 8 or 10 after insemination. There were no significant effects on fertility parameters compared to untreated control cows. In a fourth trial ewes were injected with 4 micrograms buserelin on day 12 after service. There were indications that both pregnancy rate and lambing percentage could be increased by buserelin treatment. Daily blood samples were collected from 5 dairy cows during a control cycle and a cycle in which 10 microgram buserelin was injected on days 11 and 13. Cycle length was unaffected by treatment and the concentration and pattern of progesterone secretion did not differ between control and treated cycles. Plasma oestradiol concentrations were similar in the control and treated cycles before day 11. However from day 12 to 16, equivalent to the time of maternal recognition of pregnancy, the mean concentration of oestradiol was significantly reduced in the treated cycle. As oestradiol stimulates both the development of uterine oxytocin receptors and the secretion of PGF2 alpha we suggest that any improvement in pregnancy rate after buserelin is due to a weakened luteolytic mechanism, resulting from a lower plasma oestradiol concentration.

Animals↗

Two-dimensional 1H-NMR studies of phospholipase-A2-inhibitor complexes bound to a micellar lipid-water interface.

One- and two-dimensional NMR studies were performed on the complexes of porcine pancreatic phospholipase A2 with substrate analogs bound to a micellar lipid-water interface of fully deuterated dodecylphosphocholine. The interactions between the inhibitor and the enzyme were localized by comparison of the two-dimensional NOE spectra recorded for the enzyme-inhibitor complex using both protonated and selectively deuterated inhibitors. These experiments led us to the following conclusions for the phospholipase-A2-micelle complex: (i) the 38-kDa phospholipase A2 complex gives NMR spectra with relatively narrow lines, which is indicative of high mobility of the enzyme; (ii) the residues Ala1, Trp3, Phe63 and Tyr69 located in the interface recognition site, as well as Phe22, Tyr75, Phe106 and Tyr111 are involved in the micelle-binding process; (iii) when present on the micelle, phospholipase A2 is stereospecific for the inhibitor binding; (iv) the inhibitor, (R)-dodecyl-2-aminohexanol-1-phosphoglycol, binds stoichiometrically to phospholipase A2 with high affinity (Kd less than or equal to 10 microM); (v) the inhibitor binds in the active site of the enzyme, which is evidenced by large chemical-shift differences for Phe5, Ile9, Phe22, His48, Tyr52 and Phe106; (vi) the acyl chain of the inhibitor makes hydrophobic contacts (less than 0.4 nm) near Phe5, Ile9, Phe22 and Phe106. Comparison of our results on the enzyme-inhibitor-micelle ternary complex with the crystal structure of the enzyme-inhibitor complex [Thunnissen, M. M. G. M., AB, E., Kalk, K. H., Drenth, J., Dijkstra, B. W., Kuipers, O. P., Dijkman, R., de Haas, G. H. & Verheij, H. M. (1990) Nature 347, 689-691] shows that the mode of inhibitor binding is similar.

Animals↗

Porcine pancreatic phospholipase A2: sequence-specific 1H and 15N NMR assignments and secondary structure.

The solution structure of porcine pancreatic phospholipase A2 (124 residues, 14 kDa) has been studied by two-dimensional homonuclear 1H and two- and three-dimensional heteronuclear 15N-1H nuclear magnetic resonance spectroscopy. Backbone assignments were made for 117 of the 124 amino acids. Short-range nuclear Overhauser effect (NOE) data show three alpha-helices from residues 1-13, 40-58, and 90-109, an antiparallel beta-sheet for residues 74-85, and a small antiparallel beta-sheet between residues 25-26 and 115-116. A 15N-1H heteronuclear multiple-quantum correlation experiment was used to monitor amide proton exchange over a period of 22 h. In total, 61 amide protons showed slow or intermediate exchange, 46 of which are located in the three large helices. Helix 90-109 was found to be considerably more stable than the other helices. For the beta-sheets, four hydrogen bonds could be identified. The secondary structure of porcine PLA in solution, as deduced from NMR, is basically the same as the structure of porcine PLA in the crystalline state. Differences were found in the following regions, however. Residues 1-6 in the first alpha-helix are less structured in solution than in the crystal structure. Whereas in the crystal structure residues 24-29 are involved both in a beta-sheet with residues 115-117 and in a hairpin turn, the expected hydrogen bonds between residues 24-117 and 25-29 do not show slow exchange behavior. This and the absence of several expected NOEs imply that this region has a less well defined structure in solution. Finally, the hydrogen bond between residues 78-81, which is part of a beta-sheet, does not show slow exchange behavior.

Amino Acid Sequence↗

Improving food quality through new technology.

New technological developments make it possible to improve the quality of animal disease therapy, prophylaxis and diagnosis, and to improve animals' growth and fertility. The term 'quality' includes not only objective measurements, such as the fatness or leanness of meat, but also organoleptic factors such as flavour and others which are of increasing importance to consumers, such as animal welfare. Is new technology consistent with the improvement of quality? For example, beta-agonists and porcine somatotrophin reduce the fatness and increase the protein content of carcases, but there are also subtle positive relationships between fatness and eating quality. In contrast, bovine somatotrophin appears to have no effect on milk composition but there are indications that it may affect the perception of milk quality by some consumers. Improved vaccines can increase food quality by improving animal health and welfare and increasing the uniformity of the product; immunological techniques may also be used to improve meat quality. A gulf has developed between the benefits from new technology and consumer perceptions; indeed there is evidence of political resistance to some technological advances. Despite the stringent regulation of veterinary medicinal products in the United Kingdom and other countries, there is continued pressure for greater political control over their approval. The exchange of information between scientists, industry, the legal regulators and consumers must be improved so that advances in technology are acceptable to the majority and used to the advantage of all.

Animal Feed↗

Changes in electrical resistance of the vaginal mucosa in prostaglandin-treated cows.

Ten Hereford x Friesian cows each received 1 mg fenprostalene by a single subcutaneous injection between days 5 and 16 of their ovarian cycles and the treatment was repeated 17 days later. The cows' ovarian cycles were monitored by daily plasma progesterone measurements, and the electrical resistance of their vaginal mucosae was also measured daily, with a Wallsmeta. Luteolysis occurred after 13 of the 20 injections of fenprostalene, and vaginal resistance measurements corresponded to changes in progesterone concentrations in 14 of the 20 potential luteolytic periods. Vaginal resistance measurements decreased in three cases where progesterone concentrations did not decrease (false positive results) and failed to decrease in three cases where progesterone concentrations did decrease (false negative results).

Animals↗

Beta-agonists as repartitioning agents: a review.

Several beta-adrenergic agonist compounds are undergoing commercial development as carcase repartitioning agents. Significant increases in feed conversion efficiency, carcase lean content and decreases in carcase fatness have been reported consistently in all the major meat animal species. The use of these compounds is consistent with consumer demand for leaner meat but could prove controversial in the current political climate in the EC.

Adipose Tissue↗