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Biomedical subjects

S McKee

Publications and source records attributed to S McKee.

16 recordsLinked to original sources
PubMed2004

New measurement of the cosmic-ray positron fraction from 5 to 15 GeV.

We present a new measurement of the cosmic-ray positron fraction at energies between 5 and 15 GeV with the balloon-borne HEAT-pbar instrument in the spring of 2000. The data presented here are compatible with our previous measurements, obtained with a different instrument. The combined data from the three HEAT flights indicate a small positron flux of nonstandard origin above 5 GeV. We compare the new measurement with earlier data obtained with the HEAT-e(+/-) instrument, during the opposite epoch of the solar cycle, and conclude that our measurements do not support predictions of charge sign dependent solar modulation of the positron abundance at 5 GeV.

Journal Article↗
PubMed2002

Immunological and haematinic consequences of feeding a standardised Echinacea (Echinacea angustifolia) extract to healthy horses.

This study was undertaken to compile new data on the efficacy of Echinacea in stimulating the immune system of the horse. Use of Echinacea is becoming widespread in horses, despite an absence of controlled laboratory research into its effectiveness or safety. This paper documents results of a double-blind, placebo-controlled, cross-over trial investigating the effect of standardised Echinacea extract on 8 horses. Animals were supplemented with Echinacea or placebo for 42 days, and their response to supplements recorded. Treatment with Echinacea increased phagocytic ability of isolated neutrophils, boosted peripheral lymphocyte counts and appeared to stimulate neutrophil migration from peripheral circulation into the tissues. Echinacea supplement also increased the size and concentration of peripheral red blood cells, and the concentration of haemoglobin and packed cell volume. It was concluded that Echinacea effectively stimulates equine immunocompetence, and the plant extract behaves, in equine subjects, as a haematinic agent, i.e. one which improves the quality of blood by increasing haemoglobin levels and the number of erythrocytes and which, by virtue of their effects on oxygen transport cells, are considered to improve parameters of exercise physiology and performance.

Adjuvants, Immunologic↗
PubMed2001

Measurement of the cosmic-ray antiproton-to-proton abundance ratio between 4 and 50 GeV.

We present a new measurement of the antiproton-to-proton abundance ratio, pbar/p, in the cosmic radiation. The HEAT-pbar instrument, a balloon borne magnet spectrometer with precise rigidity and multiple energy loss measurement capability, was flown successfully in Spring 2000, at an average atmospheric depth of 7.2 g/cm(2). A total of 71 antiprotons were identified above the vertical geomagnetic cutoff rigidity of 4.2 GV. The highest measured proton energy was 81 GeV. We find that the pbar/p abundance ratio agrees with that expected from a purely secondary origin of antiprotons produced by primary protons with a standard soft energy spectrum.

Journal Article↗
PubMed2000

Evidence for digenic inheritance in some cases of Antley-Bixler syndrome?

The Antley-Bixler syndrome has been thought to be caused by an autosomal recessive gene. However, patients with this phenotype have been reported with a new dominant mutation at the FGFR2 locus as well as in the offspring of mothers taking the antifungal agent fluconazole during early pregnancy. In addition to the craniosynostosis and joint ankylosis which are the clinical hallmarks of the condition, many patients, especially females, have genital abnormalities. We now report abnormalities of steroid biogenesis in seven of 16 patients with an Antley-Bixler phenotype. Additionally, we identify FGFR2 mutations in seven of these 16 patients, including one patient with abnormal steroidogenesis. These findings, suggesting that some cases of Antley-Bixler syndrome are the outcome of two distinct genetic events, allow a hypothesis to be formulated under which we may explain all the differing and seemingly contradictory circumstances in which the Antley-Bixler phenotype has been recognised.

Abnormalities, Drug-Induced↗
PubMed2000

Cryptic von Hippel-Lindau disease: germline mutations in patients with haemangioblastoma only.

OBJECTIVES: Central nervous system haemangioblastoma (HAB) is a major feature of von Hippel-Lindau (VHL) disease, and it is estimated that about 30% of HAB patients have VHL disease. Consequently, it is widely recommended that sporadic HAB patients are screened for clinical and radiological features of VHL disease because of the risk of multiple tumours. We investigated the frequency of VHL germline mutations in patients with HAB only with no clinical or radiological evidence of VHL disease to define the role of molecular genetic analysis in the management of such patients. METHODS: Eighty four patients with a single HAB (23 Dutch, 61 UK) and four with multiple HAB (two Dutch, two UK) were studied by direct sequencing of the coding region and quantitative Southern blotting. RESULTS: A VHL germline mutation was found in three of 69 (4.3%) single HAB patients aged 50 years or less (three of 84 (3.6%) total single HAB patients). A germline VHL mutation was detected in a 44 year old woman with a solitary cerebellar HAB, as well as in four clinically unaffected close relatives, and in two single HAB cases presenting at the ages of 29 and 36 years. Germline VHL mutations were detected in two of four cases with multiple HAB. CONCLUSIONS: Early detection of VHL disease is important to reduce morbidity and mortality and therefore we recommend that, in addition to conventional clinical and radiological investigations, VHL gene mutation analysis should be offered to all HAB patients younger than 50 years. HAB patients aged >50 years will have a lower a priori risk of VHL disease and further data are required to evaluate the role of routine molecular genetic investigations in late onset HAB cases. The failure to detect germline VHL mutations in some patients with multiple HAB may indicate the presence of somatic mosaicism or additional HAB susceptibility genes.

Adolescent↗
PubMed1999

Cryptosporidium, enterocytozoon, and cyclospora infections in pediatric and adult patients with diarrhea in Tanzania.

Cryptosporidiosis, microsporidiosis, and cyclosporiasis were studied in four groups of Tanzanian inpatients: adults with AIDS-associated diarrhea, children with chronic diarrhea (of whom 23 of 59 were positive [+] for human immunodeficiency virus [HIV]), children with acute diarrhea (of whom 15 of 55 were HIV+), and HIV control children without diarrhea. Cryptosporidium was identified in specimens from 6/86 adults, 5/59 children with chronic diarrhea (3/5, HIV+), 7/55 children with acute diarrhea (0/7, HIV+), and 0/20 control children. Among children with acute diarrhea, 7/7 with cryptosporidiosis were malnourished, compared with 10/48 without cryptosporidiosis (P < .01). Enterocytozoon was identified in specimens from 3/86 adults, 2/59 children with chronic diarrhea (1 HIV+), 0/55 children with acute diarrhea, and 4/20 control children. All four controls were underweight (P < .01). Cyclospora was identified in specimens from one adult and one child with acute diarrhea (HIV-). Thus, Cryptosporidium was the most frequent and Cyclospora the least frequent pathogen identified. Cryptosporidium and Enterocytozoon were associated with malnutrition. Asymptomatic fecal shedding of Enterocytozoon in otherwise healthy, HIV children has not been described previously.

Acute Disease↗
PubMed1998

De novo direct duplication 2 (p12-->p21) with paternally inherited pericentric inversion 2p11.2 2q12.2.

We report a 4-year-old girl with a previously undescribed de novo duplication of 2p12->2p21 on the same homologue as a paternally inherited pericentric inversion of region 2p11.2-->2q12.2, resulting in dysmorphic features, cardiac abnormality, cleft palate, respiratory problems, severe growth retardation and developmental delay. This case raises an important question--did the paternal pericentric inversion influence the occurrence of the de novo duplication?

Abnormalities, Multiple↗
PubMed1997

Infectious agents in acute respiratory disease in horses in Ontario.

A study of acute respiratory disease in horses in Ontario was undertaken to determine the identity of current causative infectious agents. A nasopharyngeal swab was designed and utilized to maximize isolation of viruses, mycoplasma, and pathogenic bacteria. Serum samples were collected for parallel determination of antibody titers to equine influenza virus type A subtype 1 (H7N7) and subtype 2 (H3N8), equine rhinovirus types 1 and 2, equine herpesvirus type 1, Mycoplasma equirhinius, and Mycoplasma felis. Equine rhinovirus type 2 was recovered from 28/92 horses tested, and equine influenza virus type A, subtype 2, was recovered from 5. The mycoplasma and bacteria isolated were consistent with those commonly associated with nonspecific respiratory diseases in horses, except that Streptococcus pneumoniae capsular type 3 was isolated from 10 horses.

Acute Disease↗
PubMed1996

Control of formation and dissociation of the high-affinity complex between cytochrome c and cytochrome c peroxidase by ionic strength and the low-affinity binding site.

A new ruthenium photoreduction technique was used to measure the formation and dissociation rate constants kf and kd of the high-affinity complex between yeast iso-1-cytochrome c (yCc) and cytochrome c peroxidase compound I (CMPI) over a wide range of ionic strength. These studies utilized Ru-39-Cc, which contains trisbipyridylruthenium attached to the cysteine residue in the H39C, C102T variant of yCc, and has the same reactivity with CMPI as native yCc. kd and kf were measured by photoreducing a small concentration of Ru-39-Cc in the presence of the oxidized yCcIII: CMPI complex, which must dissociate before Ru-39-CcII can bind to CMPI and reduce the radical action. The value of kd for the 1:1 high-affinity complex is very small at low ionic strength, < 5 s-1 but is increased significantly by binding yCc to a second low-affinity site. However, the low-affinity yCc binding site is not active in direct electron transfer to either the radical cation or the oxyferryl heme in CMPI, and is too weak to play a role in the kinetics at ionic strengths above 70 mM. The value of kd increases to 4000 s-1 at 150 mM ionic strength, while kf decreases from > 3 x 10(9) M-1 s-1 at low ionic strength to 1.3 x 10(9) M-1 s-1 at 150 mM ionic strength. These studies indicate that the rate-limiting step in enzyme turnover is product dissociation below 150 mM ionic strength and intracomplex electron transfer to the oxyferryl heme at higher ionic strength. The interaction between yCc and CcP is optimized at physiological ionic strength to provide the largest possible complex formation rate constant kf without allowing product dissociation to be rate-limiting. The effects of surface mutations on the kinetics provided evidence that the high-affinity binding site used for the reaction in solution is similar to the one identified in the yCc:CcP crystal structure.

Binding Sites↗
PubMed1992

Modelling coccidial infection in chickens: emphasis on vaccination by in-feed delivery of oocysts.

Trickle immunization of poultry by incorporating wildtype strains of coccidia in the feed has been shown to be an effective and practical means of controlling coccidiosis. Here we develop a mathematical model of the life cycle of Eimeria tenella and estimate the model parameters from extant experimental studies. Numerical solutions of the model compare well with experiment. The model provides quantitative estimates of the required trickle immunization hitherto only available after extensive time-consuming trials.

Animal Feed↗
PubMed1992

The effects of equine rhinovirus, influenza virus and herpesvirus infection on tracheal clearance rate in horses.

The response of horses exposed to three common respiratory viruses was studied by measuring tracheal mucociliary clearance rates in the trachea. Tracheal clearance rates (TCR) were determined before, during illness and following recovery in horses exposed to equine rhinovirus (ERhV-2), equine influenza virus (EIV) and equine herpesvirus (EHV-4) by means of lateral scintigraphs made following an injection of technetium-99m sulphide colloid into the tracheal lumen. In six horses exposed to ERhV-2, TCR remained within normal limits. Exposure to EIV resulted in reduced TCR in six of seven horses, with TCR remaining below the 95% confidence limits of normal values for each horse for up to 32 days despite the resolution of clinical signs. Moderate changes were observed in six horses exposed to EHV-4, but significant reductions in TCR were evident in three animals. Measurement of TCR was a useful, minimally-invasive technique which demonstrated that respiratory viruses may cause persistent changes in TCR, even though clinical signs are not evident.

Animals↗
PubMed1988

GESA--a two-dimensional processing system using knowledge base techniques.

The successful analysis of two-dimensional (2-D) polyacrylamide electrophoresis gels demands considerable experience and understanding of the protein system under investigation as well as knowledge of the separation technique itself. The present work concerns the development of a computer system for analysing 2-D electrophoretic separations which incorporates concepts derived from artificial intelligence research such that non-experts can use the technique as a diagnostic or identification tool. Automatic analysis of 2-D gel separations has proved to be extremely difficult using statistical methods. Non-reproducibility of gel separations is also difficult to overcome using automatic systems. However, the human eye is extremely good at recognising patterns in images, and human intervention in semi-automatic computer systems can reduce the computational complexities of fully automatic systems. Moreover, the expertise and understanding of an "expert" is invaluable in reducing system complexity if it can be encapsulated satisfactorily in an expert system. The combination of user-intervention in the computer system together with the encapsulation of expert knowledge characterises the present system. The domain within which the system has been developed is that of wheat grain storage proteins (gliadins) which exhibit polymorphism to such an extent that cultivars can be uniquely identified by their gliadin patterns. The system can be adapted to other domains where a range of polymorpic protein sub-units exist. In its generalised form, the system can also be used for comparing more complex 2-D gel electrophoretic separations.

Algorithms↗