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Biomedical subjects

P Holmes

Publications and source records attributed to P Holmes.

At least 37 records · Page 2Linked to original sources
PubMed1999

Improved cell line development by a high throughput affinity capture surface display technique to select for high secretors.

A novel process is described which permits rapid and objective selection of rare cells from a heterogeneous population based on quantity of secreted target protein. The process involves construction of an immobilised affinity surface display matrix that specifically binds secreted target product which is then detected using a fluorescent labelled ligand. Cells with the highest fluorescence can then be sorted using conventional flow cytometric technology. Overall, the whole process can be completed in less than 4 h during which time in the region of five million cells can be analysed. Cells are rapidly selected for in a quantitative manner compared to traditional methods which can take several months and have a reduced probability of finding low abundance high secretors due to practical limitations imposed on the number of cells which can be screened.

Affinity Labels↗
PubMed1999

A research strategy for investigating the ecological significance of endocrine disruption: report of a UK workshop.

In May 1997 the MRC Institute for Environment and Health hosted an expert, multidisciplinary workshop on the ecological effects of endocrine disruption, focusing on reproductive function, to identify research priorities. Particular objectives were to discuss the potential for effects at organisational levels higher than that of the individual (i.e. population, community and ecosystem levels), the range of taxa that may plausibly be susceptible, and our current knowledge of the environmental fate and behaviour of potential endocrine disrupters. The conclusions of this workshop are reported, with particular reference to a research strategy developed to ultimately address the significance of endocrine disruption at the level of the population. Specific research project areas considered to be of particular importance to the UK situation are also presented.

Animals↗
PubMed1998

Effects of Trypanosoma congolense and nutritional supplements on establishment and outcome of pregnancy in trypanotolerant Djallonké ewes.

Interactions between Trypanosoma congolense and nutritional statue were studied in 42 ewes, bred at the peak of parasitaemia after synchronisation of oestrus. As experimental design a randomised block design was used with four treatment combinations (2 x 2 factors), of which two were on restricted diet (L), the remainder on an unrestricted diet (H) and half of each nutritional group infected with T. congolense (LI, HI) remainder serving as controls (LC, HC). Severity of parasitaemia was not influenced by supplementation and mortality rates were higher in the HI and LC groups, but these differences were found not significant. Progesterone levels during the synchronised cycle were significantly lower in the infected groups. Levels of pregnant specific protein B (PSPB) in pregnant sheep at days 21 and 26 and were not significantly affected by nutrition or infection, despite the tendency of a decrease in infected groups. T. congolense clearly affected establishment of pregnancy, as shown by lower rates of pregnancy and extended intervals between breeding and confirmation of pregnancy, nor was there any benefit of nutritional supplementation. Mean progesterone concentration during pregnancy, in those ewes which lambed, was not different between groups. The effect of the T. congolense infection on the outcome of pregnancy was not clear with the LI and HC performing well and poor pregnancy outcomes on groups HI and LC, although differences in litter size might explain these anomalies. It is concluded that the most pronounced effect of T. congolense was a negative influence on establishment of pregnancy, with nutritional supplementation unable to overcome this effect but having a beneficial influence on maintenance and successful outcome of pregnancy. However, individual exceptions indicate that some ewes cope better with the negative effects of infection and poor nutrition.

Animals↗
PubMed1998

Simple models for excitable and oscillatory neural networks.

Chains of coupled oscillators of simple "rotator" type have been used to model the central pattern generator (CPG) for locomotion in lamprey, among numerous applications in biology and elsewhere. In this paper, motivated by experiments on lamprey CPG with brainstem attached, we investigate a simple oscillator model with internal structure which captures both excitable and bursting dynamics. This model, and that for the coupling functions, is inspired by the Hodgkin-Huxley equations and two-variable simplifications thereof. We analyse pairs of coupled oscillators with both excitatory and inhibitory coupling. We also study traveling wave patterns arising from chains of oscillators, including simulations of "body shapes" generated by a double chain of oscillators providing input to a kinematic musculature model of lamprey.

Animals↗
PubMed1998

Tailoring the management of nonparasitic liver cysts.

OBJECTIVE: To determine the optimal management of symptomatic non-parasitic liver cysts. SUMMARY BACKGROUND DATA: Management options for symptomatic nonparasitic liver cysts lack substantiation through comparative studies with respect to safety and long-term effectiveness. METHODS: A retrospective review of the surgical management of patients with hepatic cysts between October 1988 and August 1997 was undertaken to determine morbidity rates and to assess long-term recurrence. RESULTS: Thirty-eight patients (35 women, 3 men) underwent 48 operations for symptomatic hepatic cysts of mean diameter 12 cm, with a mean follow-up of 41 months. Twenty-three patients had simple cysts, and 15 patients had polycystic liver disease (PCLD). The symptomatic recurrence rates after laparoscopic or open deroofing for simple cysts were 8% and 29%, and for PCLD 71% and 20%, respectively. There were no symptomatic recurrences after 14 hepatic resections. There were no perisurgical deaths; however, morbidity rates were significant after laparoscopic deroofing, open deroofing, and hepatic resection (25%, 36%, and 50%, respectively). CONCLUSIONS: Selection of patients with truly symptomatic hepatic cysts is crucial before considering interventional techniques. For simple cysts, radical laparoscopic deroofing is usually curative; open deroofing should be reserved for cysts inaccessible by laparoscopy. The latter technique is well tolerated; however, long-term symptom control is unpredictable in patients with PCLD. Hepatic resection for PCLD provides satisfactory long-term symptom control but has an appreciable morbidity rate. Although laparoscopic and open deroofing procedures are less reliable in the long term for solitary cysts, they might be useful steps before embarking on this major procedure.

Adult↗
PubMed1998

Field evaluation of the prophylactic effect of an isometamidium sustained-release device against trypanosomiasis in cattle.

In order to compare the prophylactic effect provided by a poly(D,L-lactide) sustained-release device (SRD) containing isometamidium (ISMM) with that provided by the classical intramuscular injection of the drug, a field trial was carried out at the Madina Diassa Ranch in Mali. One- to 3-year-old N'Dama cattle were randomly divided into three groups. The first group (n = 42) was treated with ISMM at a dose of 1 mg/kg of body weight, the second group (n = 44) received the same dose of the drug via an SRD, which was subcutaneously implanted in the shoulder region, and the third group (n = 36) was kept as an untreated control group. All animals were treated with diminazene aceturate (7 mg/kg of body weight) 2 weeks before the start of the experiment and were tested monthly by the buffy coat technique for a period of 8 months. Glossina morsitans submorsitans was the most important tsetse species, with apparent densities (number of catches/trap/day) varying between 11.9 and 38.7 over the experimental period. Eight months after treatment the cumulative infection rates were 27.7, 58.5, and 77.4% in the group with the SRD implant, the group receiving the intramuscular injection, and the control group, respectively. Statistical analysis showed that the incidence of trypanosomiasis was significantly lower (P = 0.006) in the group which received ISMM via the SRD than in the one which was treated with ISMM intramuscularly.

Animals↗
PubMed1997

Reproductive health in humans and wildlife: are adverse trends associated with environmental chemical exposure?

In recent years, evidence from disparate observations has indicated adverse changes in the reproductive health and fecundity of animals and humans. In humans, there is strong evidence for such trends in the incidences of testicular and female breast cancer, and concern has also been expressed regarding semen quality, cryptorchidism, hypospadias and polycystic ovaries. Laboratory studies have indicated that some chemicals in the environment, both natural and synthetic, have the potential to disrupt the endocrine system and that these could, at least theoretically, be partly responsible for the observed changes. Chemicals thus identified include the naturally occurring steroid hormones, phyto- and myco-estrogens, and anthropogenic chemicals such as synthetic hormones, organotins, organochlorine pesticides, polychlorinated biphenyls, dioxins, alkylphenol polyethoxylates, phthalates and bisphenol-A. While there is no direct evidence from human studies to confirm a causal link between exposure and effect, concern exists and is strengthened by reports of adverse reproductive and developmental effects in wildlife, possibly mediated via endocrine disruptive pathways. The development of imposex in neogastropod molluscs exposed to tributyltin has been attributed to such a mechanism and in wild populations of fish, alligators and birds, instances of masculinisation or feminisation in polluted areas have been noted. Among mammals, disturbed fertility of Florida panthers and some marine species has also been reported. A concentrated research and monitoring programme is required to clarify the nature and extent of effects on reproductive health in humans and wildlife, and to assess human and wildlife exposure to relevant naturally occurring or anthropogenic endocrine disrupting substances. This will enable a more robust evaluation of the contribution that environmental chemical exposure may have on adverse trends in the reproductive health of humans and wildlife.

Animals↗
PubMed1992

Two consecutive thunderstorm associated epidemics of asthma in the city of Melbourne. The possible role of rye grass pollen.

OBJECTIVE: To document the clinical impact and identify the meteorological and environmental circumstances surrounding two epidemics of asthma exacerbations associated with thunderstorms in the city of Melbourne and to find a possible aetiology for these events. DESIGN: Collection of meteorological and environmental data from the Victorian Bureau of Meteorology and the Environment Protection Authority; collection of clinical data from metropolitan emergency departments and the Victorian Ambulance Service; and study of a cohort of affected patients with asthma and a control group of asthmatics who were not affected by the storms. SETTING: Tertiary institution. PATIENTS: Twelve storm-affected patients with asthma and 16 asthmatics not affected by the storms. INTERVENTION: Administration of a questionnaire, medical interview, pulmonary function tests and skin prick tests with common allergens. MAIN OUTCOME AND RESULTS: Both epidemics caused a major increase in the number of hospital attendances and admissions because of asthma exacerbation (five to ten fold rise). These events could not be related to atmospheric pollution or specific meteorological features of the storms. Patients affected by the second storm were significantly more likely to suffer from hay fever (P less than 0.05), rye grass pollen allergy (P less than 0.05) and allergy to rainfall released rye grass starch granules (P less than 0.025). CONCLUSIONS: Late spring thunderstorms in the city of Melbourne can trigger epidemics of asthma attacks. The seasonal nature of the phenomenon and the pattern of allergic responses found in affected patients suggest a possible aetiological role for rye grass pollen.

Air Pollution↗
PubMed1992

The rough (ro+) gene as a dominant P-element marker in germ line transformation of Drosophila melanogaster.

We describe a new vector for the P-element-mediated introduction of gene constructs into the germ line of Drosophila melanogaster. The P-element vector carries 6.8 kb of genomic DNA containing the rough gene (ro) from D. melanogaster and a polylinker (MCS) containing ten unique cloning sites. To demonstrate its utility, we have cloned into the MCS of this vector, the firefly luciferase (Luc)-encoding gene (luc) under the control of the D. melanogaster hsp70 promoter and have transformed flies with the resultant P-element. Single insertions of this element, whether in the hemizygous or homozygous condition, completely rescued the ro- mutation and directed heat-inducible synthesis of Luc mRNA and enzyme.

Animals↗
PubMed1992

Mechanism of grass-pollen-induced asthma.

Many asthmatics are sensitive to rye-grass pollen, but pollen grains are too large to penetrate the lower airways. Our aim was to investigate the mechanism by which rye-grass pollen causes asthma. A major allergen of rye-grass pollen, Lol pIX, is located in intracellular starch granules within pollen grains. In-vitro tests showed that pollen grains are ruptured in rainwater by osmotic shock, each grain releasing about 700 starch granules into the environment. These granules are small enough to enter the airways (less than 3 microns in diameter). The starch granules were present in atmospheric samples taken during the pollen season, and showed a 50-fold increase in atmospheric concentration on days following rainfall. Isolated granules elicited IgE-mediated responses in asthmatic patients, and 4 patients with rainfall-associated asthma who underwent an inhalation challenge test had striking bronchial constriction after exposure to starch granules. Starch granules released from rye-grass pollen seem to be capable of causing asthma.

Allergens↗
PubMed1992

Controllability and duration of stress alter central nervous system depressant-induced sleep time in rats.

Rats were exposed to either 80 escapable shocks or yoked inescapable shocks and then injected with several hypnotic doses of sodium pentobarbital, midazolam, or ethanol; their sleep-time duration was compared with that of naive controls. Inescapable shock exposure resulted in a significant increase in ethanol-induced sleep time compared with the escapable shock and naive control groups. Both escape and yoked groups showed an increase in barbiturate-induced sleep time compared with controls, although no difference was observed for midazolam. Acute stress (twenty 5-s inescapable shocks) did not alter the depressant-induced sleep time for any of the drugs tested. These results illustrate the importance of psychological aspects of stress and its influence on the potency of certain depressants.

Animals↗