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Biomedical subjects

G K Chambers

Publications and source records attributed to G K Chambers.

At least 19 recordsLinked to original sources

Maori origins, Y-chromosome haplotypes and implications for human history in the Pacific.

An assessment of 28 pertinent binary genetic markers on the non-recombining portion of the Y chromosome (NRY) in New Zealand Maori and other relevant populations has revealed a diverse genetic paternal heritage of extant Maori. A maximum parsimony phylogeny was constructed in which nine of the 25 possible binary haplotypes were observed. Although approximately 40% of the samples have haplotypes of unequivocal European origin, an equivalent number of samples have a single binary haplotype that is also observed in Indonesia and New Guinea, indicative of common indigenous Melanesian ancestry. The balance of the lineages has either typical East Asian signatures or alternative compositions consistent with their affinity to Melanesia or New Guinea. Molecular analysis of mtDNA variation confirms the presence of a single predominant characteristic Southeast Asian (9-bp deletion in the Region V) lineage. The Y-chromosome results support a pattern of complex interrelationships between Southeast Asia, Melanesia, and Polynesia, in contrast to mtDNA and linguistic data, which uphold a rapid and homogeneous Austronesian expansion. The Y-chromosome data highlight a distinctive gender-modulated pattern of differential gene flow in the history of Polynesia.

Chromatography, High Pressure Liquid↗

The expectations of patients undergoing revision hip arthroplasty.

Sixty patients were prospectively assessed using the Western Ontario and McMaster Osteoarthritis Index (WOMAC) scale for osteoarthritis of the hip and the Short Form 36 (SF-36) general health status scale as well as the expectation WOMAC, which asked patients to estimate how they expected to feel 6 months after revision hip arthroplasty. There was a wide range of expectations, but we were unable to find any significant correlation between the patients' preoperative pain and stiffness levels and their expectations for pain and stiffness after revision hip arthroplasty. There was no significant correlation between the SF-36 scores and the patients' expectations. Our findings suggest that the expectations of patients awaiting revision hip arthroplasties are high and are not related closely to the level of preoperative disability.

Adult↗

Evaluating hypotheses on the origin and evolution of the New Zealand alpine cicadas (Maoricicada) using multiple-comparison tests of tree topology.

The statistical testing of alternative phylogenetic trees is central to evaluating competing evolutionary hypotheses. Fleming proposed that the New Zealand cicada species Maoricicada iolanthe is the sister species to the major radiation of both low-altitude and montane Maoricicada species. However, using 1,520 bp of mitochondrial DNA sequence data from the cytochrome oxidase subunit I, tRNA aspartic acid, and the ATPase subunit 6 and 8 genes, we inferred that both M. iolanthe and another low-altitude species, Maoricicada campbelli, are nested within the montane Maoricicada radiation. Therefore, we examined the stability of the inferred phylogenetic placement of these two species using the newly developed Shimodaira-Hasegawa test (SH test) implemented in a maximum-likelihood framework. The SH test has two advantages over the more commonly used Kishino-Hasegawa (KH) and Templeton tests. First, the SH test simultaneously compares multiple topologies and corrects the corresponding P: values to accommodate the multiplicity of testing. Second, the SH test is correct when applied to a posteriori hypotheses, unlike the KH test, because it readjusts the expectation of the null hypothesis (that two trees are not different) accordingly. The comparison of P: values estimated under the assumptions of both the KH test and the SH test clearly demonstrate that the KH test has the potential to be misleading when the issue of comparing of a posteriori hypotheses is ignored and when multiple comparisons are not taken into account. The SH test, in combination with a variety of character-weighting schemes applied to our data, reveals a surprising amount of ambiguity in the phylogenetic placement of M. iolanthe and M. campbelli.

Animals↗

Phylogeography of the New Zealand cicada Maoricicada campbelli based on mitochondrial DNA sequences: ancient clades associated with cenozoic environmental change.

New Zealand's isolation, its well-studied rapidly changing landscape, and its many examples of rampant speciation make it an excellent location for studying the process of genetic differentiation. Using 1520 base pairs of mitochondrial DNA from the cytochrome oxidase subunit I, ATPase subunits 6 and 8 and tRNA(Asp) genes, we detected two well-differentiated, parapatrically distributed clades within the widespread New Zealand cicada species Maoricicada campbelli that may prove to represent two species. The situation that we uncovered is unusual in that an ancient lineage with low genetic diversity is surrounded on three sides by two recently diverged lineages. Using a relaxed molecular clock model coupled with Bayesian statistics, we dated the earliest divergence within M. campbelli at 2.3 +/- 0.55 million years. Our data suggest that geological and climatological events of the late Pliocene divided a once-widespread species into northern and southern components and that near the middle of the Pleistocene the northern lineage began moving south eventually reaching the southern clade. The southern clade seems to have moved northward to only a limited extent. We discovered five potential zones of secondary contact through mountain passes that will be examined in future work. We predict that, as in North American periodical cicadas, contact between these highly differentiated lineages will exist but will not involve gene flow.

Adenosine Triphosphatases↗

Exploring among-site rate variation models in a maximum likelihood framework using empirical data: effects of model assumptions on estimates of topology, branch lengths, and bootstrap support.

We have investigated the effects of different among-site rate variation models on the estimation of substitution model parameters, branch lengths, topology, and bootstrap proportions under minimum evolution (ME) and maximum likelihood (ML). Specifically, we examined equal rates, invariable sites, gamma-distributed rates, and site-specific rates (SSR) models, using mitochondrial DNA sequence data from three protein-coding genes and one tRNA gene from species of the New Zealand cicada genus Maoricicada. Estimates of topology were relatively insensitive to the substitution model used; however, estimates of bootstrap support, branch lengths, and R-matrices (underlying relative substitution rate matrix) were strongly influenced by the assumptions of the substitution model. We identified one situation where ME and ML tree building became inaccurate when implemented with an inappropriate among-site rate variation model. Despite the fact the SSR models often have a better fit to the data than do invariable sites and gamma rates models, SSR models have some serious weaknesses. First, SSR rate parameters are not comparable across data sets, unlike the proportion of invariable sites or the alpha shape parameter of the gamma distribution. Second, the extreme among-site rate variation within codon positions is problematic for SSR models, which explicitly assume rate homogeneity within each rate class. Third, the SSR models appear to give severe underestimates of R-matrices and branch lengths relative to invariable sites and gamma rates models in this example. We recommend performing phylogenetic analyses under a range of substitution models to test the effects of model assumptions not only on estimates of topology but also on estimates of branch length and nodal support.

Animals↗

Microsatellites: consensus and controversy.

Microsatellite DNA loci have recently been adopted for many biological applications. Comparative studies across a wide range of species has revealed many details of their mutational properties and evolutionary life cycles. Experience shows that a full understanding of these processes is essential to ensure the effective use of microsatellites as analytical tools. In this article, we review the controversies that have arisen as biologists have taken up this new technology and the emerging consensus that has resulted from their debates. We point to the need for comparative DNA sequencing studies to produce input data for a new generation of theoretical models of microsatellite behaviour. We conclude by presenting our own conceptual model, 'Snakes and Ladders', as an aid to theory development.

Animals↗

An assessment of the use of intravesical potassium in the diagnosis of interstitial cystitis.

PURPOSE: We evaluated the use of intravesical potassium in the diagnosis of interstitial cystitis. MATERIALS AND METHODS: A blinded test assessment on 39 consecutive subjects attending our urology clinic for the evaluation of symptoms consistent with interstitial cystitis was performed. The pain response to intravesical potassium and water as a control was measured. The response rate was compared to the results of cystoscopy using standard outcome measures associated with diagnostic test assessment. RESULTS: The probability of having interstitial cystitis given a positive intravesical potassium test was 66%. This finding added no new useful information and would not be helpful with clinical decisions as the probability of having interstitial cystitis in this population was already 56% before the test. Similarly, if the test was negative then 46% or nearly half of the subjects were still likely to have interstitial cystitis. Therefore, a negative test would have no ability to rule out disease nor would it be useful in making clinical decisions about how to proceed with evaluation or therapy. Test characteristics were considered poor with a sensitivity of 69.5% and a specificity of 50%. Likelihood ratios (positive 1.39, negative 0.61) also indicated poor inclusion and exclusion capabilities. CONCLUSIONS: The general use of intravesical potassium as a diagnostic test for interstitial cystitis is not validated. The diagnosis of interstitial cystitis must depend on the clinical presentation and endoscopic findings based on National Institutes of Health criteria.

Administration, Intravesical↗

The albumin of the brown trout (Salmo trutta) is a glycoprotein.

The albumin from an Atlantic salmonid, the brown trout (Salmo trutta), is 1730 Da higher in molecular mass than the albumin from a Pacific salmonid, the chinook salmon (Oncorhynchus tshawytscha), at 65230 Da. Digestion with neuraminidase revealed that purified brown trout albumin contained sialic acid while chinook salmon albumin did not. Concanavalin A-sepharose affinity chromatography was used to purify a glycopeptide from a total tryptic digest of brown trout albumin. The mass of this glycopeptide (3815 Da) was determined by mass spectrometry, and the sequence largely confirmed by N-terminal sequencing. The identified sequence of IAHCCNQSYSM-, contains an Asn-Gln-Ser glycosylation site and is identical to residues 475-485 derived from the cDNA of the albumin from the Atlantic salmon, the closest relative of the brown trout. Glycosylation of albumin is very unusual, and has not been identified in either reptilian or mammalian albumins. The finding of a glycoalbumin in salmonids, ancient members of the teleost fish subclass, coupled with evidence of albumin glycosylation in the oldest vertebrates, agnathans, as well as amphibians, suggests that albumin was originally a glycoprotein, but lost this modification sometime between the divergence of amphibians and reptiles.

Animals↗

Purification, partial characterization and peptide sequences of vitellogenin from a reptile, the tuatara (Sphenodon punctatus).

Vitellogenin (Vg), a major precursor to egg yolk proteins, was purified from plasma of an estradiol-treated female tuatara (Sphenodon punctatus) by MgCl2-EDTA precipitation and DEAE-cellulose chromatography. The amino acid composition of tuatara Vg is similar to that of other vertebtate Vgs and contains a large proportion of serine (13.7 mol/100 mol of total amino acid). The amino acid sequences of the N-terminus of mature Vg (33 residues) and of several trypsin- and CNBr-generated peptides were determined. Six peptide sequences obtained from tuatara Vg could be aligned with Vg sequences from other vertebrates. Reduced and non-reduced forms of tuatara Vg have the same apparent molecular mass (approximately 218 kDa) when resolved by SDS-PAGE, indicating that inter-chain disulfide bonds are not a feature of the molecule in this species. Western blot analysis with anti-tuatara Vg antiserum indicated that at least some epitopes are shared among Vgs of turtle, alligator and tuatara.

Amino Acid Sequence↗

Purification and partial amino acid sequences of two distinct albumins from turtle plasma.

Two putative albumins, denoted Alb-1 (apparent molecular mass of 67 kDa) and Alb-2 (68 kDa), were purified from plasma of the emydid turtle (Trachemys scripta). Concentrations in serum or plasma were determined by radioimmunoassay using 125I-labeled Alb-1. In juvenile turtles (less than 2 years of age), serum concentrations of Alb-1 and Alb-2 were 2.72 +/- 0.23 mg/ml and 1.68 +/- 0.22 mg/ml, respectively, while concentrations in plasma pooled from adult turtles were 4.2 mg/ml and 2.6 mg/ml, respectively. The two albumins are immunologically distinct from one another as determined by both radioimmunoassay with 125I-labeled Alb-1 and Western blot analysis with antichicken albumin antiserum. Determination of the amino acid compositions of Alb-1 and Alb-2, and of albumin purified from plasma of the common snapping turtle (Chelydra serpentina), suggested that Alb-1 is more similar to albumins of other animals than is Alb-2. This was also indicated by Western blot analysis and by determining the N-terminal amino acid sequences of Alb-1 (40 residues) and Alb-2 (15 residues). Thus, it appears that two distinct forms of albumin are synthesized by T. scripta, possibly as a result of gene duplication and divergence.

Amino Acid Sequence↗

Simulated dose reduction in conventional chest CT: validation study.

PURPOSE: To validate a technique of computer-simulated dose reduction for conventional chest computed tomography (CT). MATERIALS AND METHODS: In 27 patients, CT scans were obtained at 200, 100, and 40 mAs at two levels. The raw data from the 200-mAs scan were modified on a computer workstation to simulate the increased noise present on 100- and 40-mAs scans. Real and simulated 100- and 40-mAs images were independently assessed in random order for overall image quality and radiologic findings by four subspecialty-trained chest radiologists who were blinded to the technique. The four observers were given paired real and simulated images. They were asked to identify the real image and note any difference in diagnostic quality. RESULTS: No difference was seen in overall image quality or radiologic findings between real and simulated images (P > .05). In the paired comparison, 433 of 864 (50.1%) real images were correctly identified. CONCLUSION: Computer modification of 200-mAs raw scan data to simulate 100- and 40-mAs noise levels produces reconstructed images indistinguishable from real 100- and 40-mAs scans. This technique provides realistic reduced-dose images without patient radiation exposure and with identical image registration and motion artifact.

Adult↗

Identification and partial characterization of alpha 2-macroglobulin from the tuatara (Sphenodon punctatus).

alpha 2-Macroglobulin (alpha 2-M), a large molecular mass proteinase-binding protein, was identified in plasma from tuatara (Sphenodon), a rare reptile endemic to New Zealand. In this genus, alpha 2-M constitutes 11-13% of total plasma protein (approximately 2.2-3.9 mg/mL). Analysis of blood samples collected at approximately monthly intervals from individual tuatara indicated that the plasma level of alpha 2-M remains fairly constant. The subunits of tuatara alpha 2-M have an apparent molecular mass of approximately 160 kDa as determined by SDS-polyacrylamide gel electrophoresis and the intact protein is an oligomer that contains inter-chain disulfide bonds. N-terminal sequence analyses of tuatara alpha 2-M revealed a distinct similarity to alpha-macroglobulins of other vertebrates and that at least two types of alpha 2-M subunits are present in plasma of tuatara.

Amino Acid Sequence↗

Assessment of the appropriateness of services provided by a multidisciplinary meningomyelocele clinic.

Since 1969, the Meningomyelocele Clinic at British Columbia's Children's Hospital has been serving the needs of children with spina bifida. In 1994, the clinic provided urgent and routine multidisciplinary clinical assessments to 330 patients and families. The purpose of this study was to assess, from the patients' and families' perspective, the appropriateness of the frequency of routine clinic visits and the value of the health services provided. Sixty-five patients/families were interviewed and completed a questionnaire developed by the clinic. Current visit frequency and services provided appear to meet the patient/family needs. The medical and nursing contributions were seen as valuable resources for the patient/families resulting in most patient/families feeling well informed about spina bifida.

Child↗

Identification of a 130-kDa albumin in tuatara (Sphenodon) and detection of a novel albumin polymorphism.

Electrophoretic, immunochemical, and protein sequence analyses were performed on plasma albumin of the tuatara (Sphenodon), a rare reptile endemic to New Zealand. The analyses revealed that, unlike other terrestrial vertebrates, tuatara do not seem to possess a 60- to 75-kDa plasma albumin. The common form of plasma albumin in this genus has an apparent molecular mass of 130 kDa, making it by far the largest albumin reported for any terrestrial vertebrate. Starch gel electrophoresis of samples from tuatara on 24 of the 30 islands inhabited by this genus resolved two forms of the 130-kDa albumin (albumins A and C). A third albumin of approximately 170 kDa (albumin B), reflecting a novel alloalbuminemia, was found in tuatara in three geographically isolated populations. Albumin A appears to be restricted to populations at the southern extremity of the tuatara's distribution, while albumin C was found in all but four (southern) populations. Possible explanations for the origin and distribution of these albumins are discussed.

Alleles↗