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Biomedical subjects

G A Harrison

Publications and source records attributed to G A Harrison.

At least 37 records · Page 2Linked to original sources

Isolation and sequence of a cDNA coding for the heavy chain constant region of IgG from the Australian brushtail possum, Trichosurus vulpecula.

A brushtail possum (Trichosurus vulpecula) mesenteric lymph node cDNA library was screened with a South American short-tailed opossum (Monodlelphis domestica) immunoglobulin gamma heavy chain constant region (Cgamma) probe, resulting in the isolation of a 1518 nucleotide cDNA clone. The sequence corresponds to exons 1-3 of Cgamma. The Australian marsupial (T. vulpeculla) sequence is 70% identical at the amino acid level with the American marsupial (M. domestica) sequence, but less similar to the eutherian mammals (45-50%). These data provide the opportunity to compare the evolution of IgG between orders of marsupials separated by at least 75 million years and confirm the appearance of IgG prior to the metatherian/eutherian divergence.

Amino Acid Sequence↗

Molecular cloning of the brushtail possum (Trichosurus vulpecula) immunglobulin E heavy chain constant region.

The immunobiology of marsupial IgE is poorly understood. As a first step towards the development of immunological reagents for marsupials and to obtain a further understanding of immunoglobulin evolution, a brushtail possum (Trichosurus vulpecula) mesenteric lymph node cDNA library was screened for the heavy chain constant region of IgE (Cepsilon), using a partial Cepsilon probe from the American marsupial, Monodelphis domestica. The cDNA sequence for T. vulpecula Cepsilon was determined and found to be most similar to the M. domestica Cepsilon sequence [(76%) at the amino acid level]. T. vulpecula Cepsilon has amino acid sequence similarities ranging from 43-52% with various eutherian Cepsilon sequences. The secondary structure of T. vulpecula Cepsilon, based on loops formed by internal disulfide bonds, more closely resembles rodent Cepsilon than the American marsupial sequence.

Amino Acid Sequence↗

Infective endocarditis: an epidemiological review of 128 episodes.

OBJECTIVES: The objective was to determine the current epidemiology of infective endocarditis. PATIENTS AND METHODS: All microbiologically positive episodes of infective endocarditis treated at The University Hospital of Wales over a 9-year period from March 1987 to March 1996 was reviewed. Patients originated from the catchment area of The University Hospital of Wales or were referred from other hospitals in Wales. Data extraction was from records held in the Microbiology Department and, whenever possible, from patients' casenotes. The epidemiological parameters were: (1) age and sex of patients; (2) distribution of affected sites; (3) frequency of predisposing risk factors (cardiac and extracardiac); (4) incidence of early prosthetic valve endocarditis; and (5) mortality rates. RESULTS: There were 128 microbiologically positive episodes of endocarditis in 125 patients. The mean age of the population was 53.1 years and the aortic valve was the most frequently involved site of infection (51.6%). A presumed source of infection was identified in 20% if episodes. The commonest predisposing cardiac risk factor in native valve episodes was bicuspid aortic valve (16.7%) but there was no identifiable cardiac risk factor in a much larger proportion (37.7%) of native valve episodes. There was a low incidence (0.6%) of culture positive early prosthetic valve episodes and low mortality rates for both native and prosthetic valve endocarditis (12.3% and 24.5%) in this study. Viridans streptococci were the predominant organisms. In prosthetic valve episodes with onset after the 60th postoperative day but within one postoperative year the identity of the isolate suggested, in most cases, perioperative valve contamination. CONCLUSIONS: The epidemiology of infective endocarditis has undergone significant change. Inability to detect clinically common predisposing lesions, and the frequent absence of any identifiable predisposing cardiac risk factor mean that initial diagnosis is often difficult and demands a high index of suspicion. There was a low incidence of culture positive early prosthetic valve episodes and there were low mortality rates for both native and prosthetic valve endocarditis; these figures suggest improvements in cardiac care. The microbiological evidence indicates that the duration of the postoperative time period used for classifying prosthetic valve endocarditis into 'early' and 'late' episodes should be extended from 60 days to 1 year.

Adolescent↗

cDNA sequence of the lymphotoxin beta chain from a marsupial, Macropus eugenii (Tammar wallaby).

In humans and mice, the lymphotoxin (LT) complex is a heterotrimer that consists of alpha (LT-alpha) and beta (LT-beta) chains, predominantly in the ratio 1:2 (LT-alpha:LT-beta). LT-beta is a type II membrane-bound protein that anchors the complex to the surface of activated lymphocytes and, in gene targeting experiments in mice, has been shown to be crucial for normal lymphoid organogenesis. However, a similar role for LT in noneutherian mammals has not yet been established. Indeed, there has been no previous evidence for the existence of LT in noneutherian species. We have isolated, by rapid amplification of cDNA ends on mammary lymph node cDNA, the transcript coding for LT-beta from the tammar wallaby, Macropus eugenii. This constitutes the first report of an LT component from a marsupial and hence from a noneutherian mammal. The predicted amino acid sequence encoded by this transcript shares 63% and 46% sequence identity with mouse and human LT-beta, respectively.

Amino Acid Sequence↗

The need for undergraduate education in critical care. (Results of a questionnaire to year 6 medical undergraduates, University of New South Wales and recommendations on a curriculum in critical care)

One hundred and fifteen final year medical students of the University of New South Wales (UNSW) who were gathered together for mid-year lectures were asked to respond to a questionnaire which sought their perceptions of their knowledge of and competence in those skills required to prevent loss of life of patients with acute reversible life-threatening illnesses. There were 101 responders (88% response rate). A high proportion of students lacked practical experience of many of the skills or had not witnessed some procedures. They lacked confidence in their ability to manage acute emergencies. The results were similar to those in a separate study of the perceptions of New South Wales interns and resident medical officers of their competencies at the beginning of their intern year. The authors concluded that undergraduate education in critical care had not kept pace with the rapid evolution of critical care practice and describe the development and implementation of an explicit vertical and horizontal curriculum of critical care in the undergraduate curriculum of the UNSW.

Attitude of Health Personnel↗

Variation in epinephrine and cortisol excretion rates associated with behavior in an Australian Aboriginal community.

Urinary epinephrine and cortisol hormone output in a remote Australian Aboriginal community was on average about twice as high in those individuals measured on a Thursday or Friday as those measured at the beginning of the next week (Monday or Tuesday). Diastolic blood pressure was about 6 mm Hg higher in the Thursday-Friday group, but the difference in mean systolic blood pressure between the day groups does not reach statistical significance. These physiological differences are associated with a marked dichotomy in behavior in the two time periods: on the first 2 days, virtually all adults were involved in intense gambling activity for large stakes, but this was not a feature of the latter period. This behavior pattern occurs on a regular weekly basis. If substantiated by longitudinal studies, this phenomenon may provide an additional link between human behavior and a poor health profile mediated via the physiological consequences of high stress hormone output.

Adult↗

Cloning and sequence analysis of a pituitary prolactin cDNA from the brushtail possum (Trichosurus vulpecula).

Overlapping cDNA partial clones of pituitary prolactin from the marsupial brushtail possum (Trichosurus vulpecula) were isolated and sequenced. The nucleotide and deduced amino acid sequences showed high sequence identity with pig prolactin (84.3 and 92.5%, respectively) and all of the expected structural features of a quadruped prolactin. A prolactin gene tree was constructed and rates of evolution calculated for possum along with several mammalian and nonmammalian prolactins. Possum prolactin was most closely linked to the prolactins of eutherian mammals but branched from the main mammalian line well before the eutherian prolactins. The prolactin/GH family shows variable rates of evolution ranging from 0.3 substitutions/amino acid site/year x 10(9) for pig prolactin to 7.0 substitutions/ amino acid site/year x 10(9) for the mouse. Since divergence from the eutherian mammals, possum prolactin has shown a slow rate of evolution (0.2 substitutions/ amino acid site/year x 10(9)). As expected, the prolactin gene was expressed in the possum pituitary gland but not in the liver, lung, kidney, heart, or mammary gland.

Amino Acid Sequence↗

cDNA cloning of growth hormone from the brushtail possum (Trichosurus vulpecula).

The full-length nucleotide sequence for the cDNA of growth hormone (GH) from the marsupial brushtail possum (Trichosurus vulpecula) was determined using reverse transcription followed by polymerase chain reaction (RT-PCR) and the 5'/3' rapid amplification of cDNA ends (RACE) technique. Sequence information showed that the possum GH cDNA was 831 base pairs (bp) in length, including the 5'untranslated region (60 bp), the signal peptide (75 bp), the mature protein (573 bp, including stop codon), and the 3' untranslated region (123 bp). At both the nucleotide and the amino acid level (deduced from nucleotide sequence), there was a high degree of sequence identity with pig and horse. These species were similar at 82.8 and 83.0% of bases at the nucleotide level and 91.6 and 91.1% at the amino acid level, respectively. Northern analysis showed that GH mRNA is present in the pituitary gland and was similar in size to that seen in other mammals (approximately equal to 0.9 kb). Analysis of molecular evolution of GH in the possum indicated that the rate of evolution is relatively slow (0.4 substitutions/ amino acid site/year x 10(9) and typical of that seen for nonprimate mammals, which exhibit rates ranging between 0.2 and 1.3 substitutions/amino acid site/year x 10(9).

Amino Acid Sequence↗

cDNA cloning of luteinizing hormone subunits from brushtail possum and red kangaroo.

Luteinizing hormone (LH) plays an important role in the reproductive cycles of all mammals. There is a large amount of both nucleotide and amino acid sequence data available for LH from eutherian mammals, but little is known about the primary structure of LH in marsupials. We have used consensus PCR primers to generate specific probes for screening pituitary cDNA libraries and report the cloning of the cDNAs encoding the alpha-subunit of LH (also shared by a number of other glycoprotein hormones) and the LH-specific beta-subunit, from the common brushtail possum, Trichosurus vulpecula, and the red kangaroo, Macropus rufus. Southern blotting experiments indicated that both genes are probably present as single copies. Comparison of the deduced marsupial protein sequences with homologous sequences from other vertebrates revealed a high degree of conservation, especially for the alpha-subunit. These sequences represent the first complete primary structures for a marsupial glycoprotein hormone to have been elucidated.

Amino Acid Sequence↗

Molecular cloning of the cDNA encoding the constant region of the immunoglobulin A heavy chain (C alpha) from a marsupial: Trichosurus vulpecula (common brushtail possum)

A cDNA encoding the brushtail possum immunoglobulin A heavy chain constant region (C alpha) was isolated by screening a mesenteric lymph node cDNA library with a porcine C alpha exon 3 probe. The larger of the two positive clones isolated (Tv4a) consisted of 1325 bp of possum cDNA that included an open reading frame of 1191 bp. Its deduced amino acid sequence had a high degree of sequence identity with known eutherian C alpha sequences. This clone appears to encode the entire possum IgA heavy chain constant region. The possum C alpha sequence had a nucleotide sequence identity of 57.7% with porcine C alpha, 51% with mouse C alpha, 46.7% with dog C alpha and 45.9% with human C alpha2. The corresponding amino acid identities were 46.7, 45.6, 49.4 and 49%, respectively.

Amino Acid Sequence↗

The small child: anthropometric and physical performance characteristics of short-for-age children growing in good and in poor socio-economic conditions.

OBJECTIVE: To ascertain whether individuals whose short stature is caused by poor living conditions differ in their other biological characteristics from those individuals who grow short, supposedly due to their genetic endowment, under favourable environmental conditions. DESIGN: From the growth survey of nearly 4000 children of the 'Cape Coloured' community aged 6-18 y half of whom lived in the middle-class suburbs of Cape Town [high socio-economic status (SES)], the other half who lived in poor rural settlements (low SES), boys and girls of similarly short stature were selected. Average body height by sex and age in each selected sample was close to the 5th percentile of height distribution among all high SES individuals surveyed. SETTING: Cape Town and neighbouring rural settlements in South Africa. SUBJECTS: Four thousand children of the Cape Coloured community aged 6-18 y. Among these were 109 high SES boys, 123 high SES girls, 302 low SES boys and 344 low SES girls selected for short stature study. INTERVENTIONS: Anthropometric measurements in public schools with appropriate permissions. RESULTS: Both short stature males and females from the low SES group tended to be significantly (P < 0.05) different from the high SES group of comparable stature in having lower body weights, shorter limbs, longer trunks, narrower shoulders, hips and chests, thinner skinfolds, smaller arm circumferences, and were very notably weaker and had poorer neuromuscular reaction times. Biepicondylar widths and pulse rates were little different between groups. Genetically short children do differ in various anthropometric and functional traits from those who are small from environmental causes.

Adolescent↗

Cloning of the red kangaroo (Macropus rufus) follicle stimulating hormone beta subunit.

The cDNA encoding the follicle stimulating hormone beta subunit (FSH-beta) was isolated from a red kangaroo pituitary cDNA library by using a porcine probe and the nucleotide sequence for the coding region was determined. The highest degree of deduced amino acid sequence identity (91%) was observed between the red kangaroo and another marsupial, the brushtail possum (Trichosurus vulpecula), followed by eutherian species (76%, 75% and 74%, respectively, for pig, mouse and sheep). Based on the deduced red kangaroo FSH-beta amino acid sequence, putative antigenic sites have been identified that may prove useful for studying the hormonal control of reproduction in marsupials.

Amino Acid Sequence↗

The third five-year survey of fellows (by examination) of the Faculty of Intensive Care, Australian and New Zealand College of Anaesthetists.

A questionnaire was sent to 126 Fellows who had passed the Fellowship Examination in Intensive Care up to and including the examination of October, 1995. The major objectives were to assess the continuing involvement of Fellows in Intensive Care and obtain feedback on training and the examinations. Only six Fellows failed to respond. Ninety-six per cent of responders had some involvement in Intensive Care and 89% had a current formal Intensive Care appointment. The median percentage of the week spent in the Intensive Care was high. Forty-seven per cent were practising some anaesthesia. Although there was considerable individual variation, the Fellows had not changed their median amount of Intensive Care practice over time. The responders provided feedback on their work patterns in the public and private systems, and their training and examinations. Overall, the training/examination system appears to satisfy Fellows although some fine tuning is required.

Anesthesiology↗

A genomewide linkage study of preeclampsia/eclampsia reveals evidence for a candidate region on 4q.

Preeclampsia (PE) and eclampsia (E) are potentially life-threatening conditions that can occur during human pregnancy. Generally considered to be different degrees of severity of the same disease process, the PE/E syndrome is thought to be predominantly genetic in origin, although its exact etiology and genetics are not fully understood. Here we report results of a genomewide linkage search for the gene(s) responsible for susceptibility to PE/E, using 15 informative pedigrees and 90 polymorphic DNA markers from all autosomes. Because of uncertainties concerning inheritance and diagnosis, four different models that assume maternal gene expression have been used to carry out LOD-score analysis. The region between D4S450 and D4S610 (2.8 cM) on the long arm of chromosome 4 was identified as a strong candidate region for a PE/E-susceptibility locus. The maximum multipoint LOD score within this interval was 2.9. Analysis of markers in the region around D4S450 and D4S610 by the affected-pedigree-member method also supported the possibility of a susceptibility locus in this region. However, to verify or exclude definitively linkage to this region, other groups of PE/E pedigrees will be required.

Australia↗

A comparison of the endobronchial segment of modern left-sided double-lumen tubes in anesthesia for bilateral sequential lung transplantation.

OBJECTIVE: To compare a range of currently available left-sided double-lumen endotracheal tubes (DLTs) in order to demonstrate differences among them with respect to the length of the endobronchial segment. It is proposed that a tube with a short endobronchial segment is better suited to anesthesia under the conditions imposed by double sequential lung transplantation. SETTING: A university hospital with a large heart and lung transplant unit. PARTICIPANTS: The DLTs included in the study were Sher-I-Bronch (Sheridan of Kendall Australia, North Ryde, Sydney, Australia); BronchoCath and BronchoCath II (Mallinckrodt Medical, St Louis, MO); Rüsch single use (Rüsch, Wailbilngen, Germany); Portex single use (Portex, Keen, NH); and Phoenix single-use Robertshaw (Promedica, Preston, Lancashire, UK). MEASUREMENTS AND MAIN RESULTS: The endobronchial segment was measured as the distance from the point of inflation of the bronchial cuff to the tip of the tube. This distance was measured for each manufactured brand in a range of tubes and the mean obtained. The DLTs were compared to assess variability within the brand, and the influence of size on the endobronchial segment. All brands were then compared. Variability within brands is consistent with manufacturer's specified range of +/- 1 to 3 mm. The endobronchial segment increases with size for Rusch and Phoenix DLTs as a design feature. The average lengths of the endobronchial segments are Rusch 23 +/- 2 mm (sizes 35/37) and 25 +/- 2 mm (sizes 39/41); Mallinckrodt 30 +/- 3 mm (BronchoCath) and 31 +/- 3 mm (BronchoCath II); Portex 35 +/- 2 mm; Sheridan 35 +/- 2 mm; Phoenix 47 mm (small), 52 mm (medium), and 56 mm (large). CONCLUSIONS: There exists marked variability in the length of the endobronchial segment of left-sided double-lumen tubes currently available. These differences may be significant in anesthesia for bilateral sequential lung transplantation.

Anesthesia↗

Impact of migration, environment and socioeconomic conditions on the physique of Sikhs.

This study is based on a cross-sectional sample of 459 Sikh adults, male and female, from three castes representing three levels of socioeconomic affluence. The sedentes group stayed all their lives in the native state of Punjab, India; the migrant group completed their active physical growth in the Punjab and left for the UK at around 20 years of age. The pattern of stature, weight, BMI and skinfolds in both groups reflects their level of socioeconomic affluence in their native Punjab. In the migrants, the caste differences in the mass measures largely disappear, but the differences in the skeletal dimensions remain. Both male and female migrants are heavier than their sedente counterparts and the male migrants have substantially higher amounts of subcutaneous fat. The change in weight, BMI and skinfolds in the migrants is inversely proportional to the original values of these variables in the native settings. Male sedentes and migrants are not statistically significantly different in stature, but the female migrants are taller than their sedente peers in all three castes. In a multivariate analysis, caste remains the most significant factor in the skeletal variables; in the mass characters, both caste and migration are statistically significant factors; age explains very little of the variation.

Adult↗

Patterns of cortisol and adrenaline variation in Australian aboriginal communities of the Kimberley region.

Urinary cortisol and adrenaline excretion rates were measured in three Australian Aboriginal communities in the Kimberley region in the north-west of the country. The three communities, Derby, Kalumburu and Kupungarri, differ in size and remoteness and some lifestyle parameters. Cortisol excretion rate is associated with age and urine flow rate, but there is no association with smoking or the consumption of alcohol. All three communities show very high cortisol excretion rates compared to a sample of UK (Oxford) residents and there are also differences between the three communities. Adrenaline excretion rate also shows associations with age and urine flow rate, but not with smoking. Aboriginal people in the Kimberley region excrete adrenaline at a slightly higher rate than that found in Oxford, which itself is high by world standards. There are no marked differences between communities in their adrenaline excretion rates. Alcohol drinkers in Derby, where alcohol is freely available, have higher adrenaline output than non-drinkers.

Adolescent↗