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Biomedical subjects

D Gordon

Publications and source records attributed to D Gordon.

At least 19 recordsLinked to original sources
PubMed2007

Current-year and subsequent-year effects of crop-load manipulation and epicormic-shoot removal on distribution of long, short and epicormic shoot growth in Prunus persica.

BACKGROUND AND AIMS: The distribution of canopy growth among different shoot types such as epicormic, long and short shoots is not well understood in the peach tree. In this experiment, the effects of crop load and early epicormic sprout removal on current and subsequent-year distribution of vegetative growth among epicormic, long and short shoots was investigated in Prunus persica. METHODS: Field trials were conducted in Winters, California, in 2003-2004. Crop load was manipulated with fruit thinning in 2003 to produce trees that were de-fruited, commercially thinned or full crop, and half of the trees in each cropping treatment had all current year epicormic sprouts removed at the time of fruit thinning. Yield was recorded and trunk and root carbohydrates were sampled to confirm the effect of 2003 crop load differences on tissue carbohydrate concentration. All current-season vegetative-shoot extension growth was harvested from half of the trees in each treatment in the autumn of 2003 and from the other half in the autumn of 2004. Epicormic, long and short shoots were separately evaluated for dry weight, node number and leaf-stem parameters. KEY RESULTS: In 2003, long-shoot dry weight and node number were significantly affected by crop load; however, short-shoot dry weight and node number were not significantly affected. The 2003 crop-load treatments did not affect 2004 vegetative growth of any shoot type. Some re-growth of epicormic shoots followed early epicormic sprout removal: by the end of the 2003 season, trees in the early shoot-removal treatment had approximately one-third of the epicormic-shoot dry weight as unpruned trees. CONCLUSIONS: Fruit thinning promoted distribution of growth similar to that of de-fruited trees. While thinning was effective in increasing fruit size, it exacerbated the problem of epicormic sprouting. Early epicormic sprout removal did not stimulate the excessive epicormic re-growth in the same or subsequent year relative to previously studied summer pruning methods.

Carbohydrate Metabolism↗
PubMed2006

Preformation in vegetative buds of Prunus persica: factors influencing number of leaf primordia in overwintering buds.

We investigated the influence of bud position, cultivar, tree age, tree carbohydrate status, sampling date, drought and light exposure on the number of leaf primordia formed in dormant vegetative peach buds (Prunus persica (L.) Batsch) relative to the number of primordia formed after bud break (neoformed). During winter dormancy, vegetative peach buds from California and Italy were dissected and the number of leaf primordia recorded. Between leaf drop and bud break, the number of leaf primordia doubled from about five to about 10. Parent shoot length, number of nodes on the parent shoot, cross-sectional area of the parent shoot, bud position along the parent shoot and bud cross-sectional area were correlated with the number of leaf primordia. Previous season light exposure, drought and tree carbohydrate status did not affect the number of leaf primordia present. The number of leaf primordia differed significantly among peach varieties and tree ages at leaf drop, but not at bud break. Our results indicate that neoformation accounted for all shoot growth beyond about 10 nodes. The predominance of neoformed shoot growth in peach allows this species great plasticity in its response to current-season conditions.

California↗
PubMed2005

Something not quite right: Gardner syndrome diagnosed by multiple cutaneous lesions and genetic testing.

Gardner syndrome is a variant of familial adenomatous polyposis characterized by intestinal adenomatous polyps, which can progress to adenocarcinoma, and a variety of extraintestinal manifestations, including skin cysts, osteomas, soft tissue fibrous tumours and a characteristic ocular lesion. The extraintestinal manifestations are often the presenting feature but are usually not sufficiently characteristic on their own to trigger recognition of the syndrome. We report a case of a 17-year-old female who had been treated by a number of specialists over a 13-year period for a variety of cutaneous lesions without a hereditary condition being suspected. Gardner syndrome was considered only after excision of subcutaneous fibrous tumours from the mastoid region and paraspinal area and was confirmed by genetic testing in spite of the patient's refusal to undergo colonic endoscopic examination. Subsequent resection revealed approximately 70 adenomatous colonic polyps in the colon and rectum but no invasive tumour, highlighting the benefits of genetic testing in treatment planning.

Adolescent↗
PubMed2005

Ascertaining the prevalence of childhood disability.

OBJECTIVES: To reapply 1985 Office of Population Census and Surveys (OPCS) disability survey methods, modified as necessary, to a sample of children to ascertain presence of disability. To compare OPCS-based prevalence with prevalence based on carer's views and medical records. DESIGN: Analytical study. Setting Community Child Health Department in UK. PARTICIPANTS: Principal carers of 100 children aged 5-15, selected from a district special needs register. Main outcome measures Comparable information about disability from three sources and diagnosis from carers and medical records. RESULTS: Medical records of 46% contained a diagnosis. Carers were always aware of this, although a single question did not always elicit their knowledge. OPCS-derived threshold disability criteria in categories of Hand function, Personal care, Consciousness and Continence gave prevalence results similar to medical records and carers. OPCS criteria yielded higher prevalence of disability in the areas of Locomotion (8%), Communication (14%) and Hearing (18%). Carers, OPCS and medical records disagreed markedly about prevalence of disabilities of Vision, probably because of the use of differing definitions. OPCS learning criteria were judged unsuitable and standard attainment targets (SATs) were substituted. These provided similar prevalence figures to carers and medical records. OPCS behaviour criteria were also unsuitable and were replaced by the General Health and Behaviour Questionnaire (GHBQ). This found an increased prevalence of problems compared with carers and doctors. CONCLUSIONS: Diagnostic labels have limited use when collecting data about disabled children. Doubt is cast on the validity of some of the 1985 OPCS threshold criteria, and reassessment is suggested before their future use. Further work is needed on the use of SATs and GHBQ in the benchmarking of disability. To collect population data it would be easier and at least equally effective (with caution in the case of Vision) to ask carers directly rather than applying descriptive thresholds and external judgements. Similar information could be obtained from medical records, however, they are likely to be out of date.

Adolescent↗
PubMed2005

"Hello, hello--it's English I speak!": a qualitative exploration of patients' understanding of the science of clinical trials.

Informed consent may be seriously compromised if patients fail to understand the experimental nature of the trial in which they are participating. Using focus groups, the authors explored how prospective trial participants interpret and understand the science of clinical trials by using patient information sheets relative to their medical condition. An opportunity was provided to hear in the patients' own words how they interpret the information and why there is variable understanding. Respondents struggled to comprehend the meaning and purpose of concepts such as randomisation and double blinding, and found them threatening to their ideas of medical care. Suggestions are made about how to improve the national guidelines on written information for trial participants and pretesting of the information sheets is advocated.

Adult↗
PubMed2004

Increased revascularization efficacy after administration of an adenovirus encoding VEGF(121).

Adenovirus-mediated VEGF gene delivery is being evaluated in clinical trials as a treatment for patients with vascular diseases that stem from ischemia, such as diffuse coronary artery disease and peripheral vascular disease. Although adenoviral vectors are one of the most widely utilized vectors to deliver therapeutic genes to cells, they also have a major limitation in that their inherent immunogenicity leads to the production of neutralizing antibodies that block effective repeat administration. Although this may be true of intravenous, intranasal, and other routes of administration, recent studies have indicated that it may be possible to effectively readminister adenovirus to skeletal muscle. The present study found improved efficacy after administration of AdVEGF(121.10), an E1/E3-deleted adenovirus encoding human VEGF(121) under the control of a CMV promoter in a rat hindlimb ischemia model. As expected, repeat administration of adenovirus resulted in a marked increase of circulating neutralizing antibody, yet nanogram quantities of VEGF protein were still detectable within the hindlimb skeletal muscle after a second administration of vector. The amount of VEGF protein produced after repeat administration translated into improved efficacy as evidenced by increased blood flow as measured by laser Doppler, increased vessel number upon post-mortem angiography, and an increased number of CD31-positive vessels. These findings have important implications for increasing the efficacy of adenovirus-mediated gene therapy in the treatment of peripheral vascular disease and coronary artery disease.

Adenoviridae↗
PubMed2004

Tradeoff between no-call reduction in genotyping error rate and loss of sample size for genetic case/control association studies.

Single nucleotide polymorphisms (SNP) may be genotyped for use in case-control designs to test for association between a SNP marker and a disease using a 2 x 3 chi-squared test of independence. Genotyping is often based on underlying continuous measurements, which are classified into genotypes. A "no-call" procedure is sometimes used in which borderline observations are not classified. This procedure has the simultaneous effect of reducing the genotype error rate and the expected number of genotypes observed. Both quantities affect the power of the statistic. We develop methods for calculating the genotype error rate, the expected number of genotypes observed, and the expected power of the resulting test as a function of the no-call procedure. We examine the statistical properties of the chi-squared test using a no-call procedure when the underlying continuous measure of genotype classification is a three-component mixture of univariate normal distributions under a range of parameter specifications. The genotype error rate decreases as the no-call region is increased. The expected number of observations genotyped also decreases. Our key finding is that the expected power of the chi-squared test is not sensitive to the no-call procedure. That is, the benefits of reduced genotype error rate are almost exactly balanced by the losses due to reduced genotype observations. For an underlying univariate normal mixture of genotype classification to be analyzed with a 2 x 3 chi-squared test, there is little, if any, increase in power using a no-call procedure.

Case-Control Studies↗
PubMed2003

Comparison of metabolic abnormalities 48 weeks after switching from highly active antiretroviral therapy containing a non-nucleoside reverse transcriptase inhibitor to Trizivir versus continued highly active antiretroviral therapy.

Forty patients participating in the TRIZAL study were treated with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-containing regimen before being randomly assigned either to continue their baseline therapy or to switch to a triple nucleoside regimen. No difference was observed in treatment efficacy between the two groups, and total cholesterol was observed to improve significantly in the switch group. Switch maintenance may be an appropriate strategy in patients treated with an NNRTI.

Antiretroviral Therapy, Highly Active↗
PubMed2003

Insulinoma presenting with hyperandrogenism: a case report and a literature review.

An 18-year-old woman presented with a 6-month history of amenorrhoea and hyperandrogenism. Three months later she developed several episodes of fasting hypoglycaemia and was subsequently diagnosed with an insulinoma. Hyperinsulinaemia was observed in association with an elevated serum testosterone level. Surgical removal of the insulinoma resulted in resolution of the clinical and biochemical features of the polycystic ovarian syndrome (PCOS). Polycystic ovarian syndrome is unusual in a patient having an insulinoma. The rarity of this association may be the result of the late age of onset of this type of tumour, intermittent secretion of excessive insulin by the tumour, the degree of hyperinsulinism or other factors extrinsic to the insulin receptor that may facilitate insulin activity. However, we could not discover how our patient differs in having had PCOS from the majority of women with insulinoma who do not. If other patients with insulinoma are subsequently found to have hyperandrogenism, then this tumour might be added to the differential diagnosis of causes of anovulatory cycles and hyperandrogenaemia, although rare the association would be uncommon.

Adolescent↗
PubMed2003

A phylogenetic approach to assessing the targets of microbial warfare.

Bacteriocins are the most abundant and diverse defense systems in bacteria. As a result of the specific mechanisms of bacteriocin recognition and translocation into the target cell it is assumed that these toxins mediate intra-specific or population-level interactions. However, no published studies specifically address this question. We present here a survey of bacteriocin production in a collection of enteric bacteria isolated from wild mammals in Australia. A subset of the bacteriocin-producing strains was assayed for the ability to kill a broad range of enteric bacteria from the same bacterial collection. A novel method of estimating killing breadth was developed and used to compare the surveyed bacteriocins in terms of the phylogenetic range over which they kill. The most striking result is that although bacteriocin-producers kill members of their own species most frequently, some kill phylogenetically distant taxa more frequently than they kill closer relatives. This study calls into question the role these toxins play in natural populations. A significant number of bacteriocins are highly effective in killing inter-specific strains and thus bacteriocins may serve to mediate bacterial community interactions.

Bacteriocins↗
PubMed2003

Identification of a locus for type I punctate palmoplantar keratoderma on chromosome 15q22-q24.

BACKGROUND: The identification of the molecular basis of disorders of keratinisation has significantly advanced our understanding of skin biology, revealing new information on key structures in the skin, such as the intermediate filaments, desmosomes, and gap junctions. Among these disorders, there is an extraordinarily heterogeneous group known as palmoplantar keratodermas (PPK), for which only a few molecular defects have been described. A particular form of PPK, known as punctate PPK, has been described in a few large autosomal dominant pedigrees, but its genetic basis has yet to be identified. AIM: Identification of the gene for punctate PPK. METHODS: Clinical examination and linkage analysis in three families with punctate PPK. RESULTS: A genomewide scan was performed on an extended autosomal dominant pedigree, and linkage to chromosome 15q22-q24 was identified. With the addition of two new families with the same phenotype, we confirmed the mapping of the locus for punctate PPK to a 9.98 cM interval, flanked by markers D15S534 and D15S818 (maximum two point lod score of 4.93 at theta = 0 for marker D15S988). CONCLUSIONS: We report the clinical and genetic findings in three pedigrees with the punctate form of PPK. We have mapped a genetic locus for this phenotype to chromosome 15q22-q24, which indicates the identification of a new gene involved in skin integrity.

Chromosome Mapping↗
PubMed2003

Errors and linkage disequilibrium interact multiplicatively when computing sample sizes for genetic case-control association studies.

Single nucleotide polymorphisms (SNP) may be used in case-control designs to test for association between a SNP marker and a disease. Such designs may assume that the genotype data are reported without error. Our goal is quantifying the effects that errors have on sample size for case-control studies with haplotypes formed by a disease locus and a SNP marker locus in the presence of linkage disequilibrium (LD). We consider the effects of a recently published error model on 2x3 chi-square analysis. We study the joint relation of LD and errors with sample size for three specific genetic disease models and two settings each of marker allele frequencies (total of 6 studies). Minimal sample size necessary for fixed asymptotic power is estimated as a 4th degree polynomial in the variables S (error) and D' (LD measure) via a backward step-wise regression. We find that increased error rates lower power. In all studies, we observe that LD and errors interact in a non-linear fashion. In particular, regression analyses shows that several higher order interaction terms have coefficients significantly different from 0 in each study, with fraction of variance explained greater than 0.9999. Finally, the increase in sample size necessary to maintain constant asymptotic power and level of significance as a function of S is smallest when D' = 1 (perfect LD). The increase grows monotonically as D' decreases to 0.5 for all studies.

Case-Control Studies↗
PubMed2002

The causal links between stress and burnout in a longitudinal study of UK doctors.

Burnout and stress are common, linked problems in health-care workers. We aimed to clarify their causal associations. We assessed stress and the three components of burnout (emotional exhaustion, depersonalisation, and low personal accomplishment) using structural equation modelling in a 3-year longitudinal study of a representative sample of 331 UK doctors. Emotional exhaustion and stress showed reciprocal causation: high levels of emotional exhaustion caused stress (beta=0 189), and high levels of stress caused emotional exhaustion (beta=0 175). High levels of personal accomplishment increased stress levels (beta=0 080), whereas depersonalisation lowered stress levels (beta=-0 105).

Adult↗
PubMed2001

The genome of the natural genetic engineer Agrobacterium tumefaciens C58.

The 5.67-megabase genome of the plant pathogen Agrobacterium tumefaciens C58 consists of a circular chromosome, a linear chromosome, and two plasmids. Extensive orthology and nucleotide colinearity between the genomes of A. tumefaciens and the plant symbiont Sinorhizobium meliloti suggest a recent evolutionary divergence. Their similarities include metabolic, transport, and regulatory systems that promote survival in the highly competitive rhizosphere; differences are apparent in their genome structure and virulence gene complement. Availability of the A. tumefaciens sequence will facilitate investigations into the molecular basis of pathogenesis and the evolutionary divergence of pathogenic and symbiotic lifestyles.

Agrobacterium tumefaciens↗
PubMed2001

Effect of depolarization on binding kinetics of scorpion alpha-toxin highlights conformational changes of rat brain sodium channels.

Binding of scorpion alpha-toxins to receptor site 3 on voltage-gated sodium channels inhibits sodium current inactivation and is voltage-dependent. To reveal the direct effect of depolarization, we analyzed binding kinetics of the alpha-toxin Lqh-II (from Leiurus quinquestriatus hebraeus) to rat brain synaptosomes and effects on rat brain II (rBII) channels expressed in mammalian cells. Our results indicated that the 33-fold decrease in toxin affinity for depolarized (0 mV, 90 mM [K(+)](out), K(d) = 5.85 +/- 0.5 nM) versus polarized (-55 mV, 5 mM [K(+)](out), K(d) = 0.18 +/- 0.04 nM) synaptosomes at steady state results from a 48-fold reduction in the association rate (k(on) at 5 mM [K(+)] = (12.0 +/- 4) x 10(6) M(-1) s(-1) and (0.25 +/- 0.03) x 10(6) M(-1) s(-1) at 90 mM [K(+)](out)) with nearly no change in the dissociation rate. Electrophysiological analyses of rBII channels expressed in mammalian cells revealed that approximately 75% and 40% of rBII occupied fast- and slow-inactivated states, respectively, at resting membrane potential of synaptosomes (-55 mV), and Lqh-II markedly increased the steady-state fast and slow inactivation. To mimic electrophysiological conditions we induced fast depolarization of toxin-bound synaptosomes, which generated a biphasic unbinding of Lqh-II from toxin-receptor complexes. The first fast off rate closely resembled values determined electrophysiologically for rBII in mammalian cells. The second off rate was similar to the voltage-independent steady-state value, attributed to binding to the slow-inactivated channel states. Thus, the Lqh-II voltage-dependent affinity highlights two independent mechanisms representing conformational changes of sodium channels associated with transitions among electrically visible and invisible inactivated states.

Animals↗
PubMed2001

A transmission/disequilibrium test that allows for genotyping errors in the analysis of single-nucleotide polymorphism data.

The present study assesses the effects of genotyping errors on the type I error rate of a particular transmission/disequilibrium test (TDT(std)), which assumes that data are errorless, and introduces a new transmission/disequilibrium test (TDT(ae)) that allows for random genotyping errors. We evaluate the type I error rate and power of the TDT(ae) under a variety of simulations and perform a power comparison between the TDT(std) and the TDT(ae), for errorless data. Both the TDT(std) and the TDT(ae) statistics are computed as two times a log-likelihood difference, and both are asymptotically distributed as chi(2) with 1 df. Genotype data for trios are simulated under a null hypothesis and under an alternative (power) hypothesis. For each simulation, errors are introduced randomly via a computer algorithm with different probabilities (called "allelic error rates"). The TDT(std) statistic is computed on all trios that show Mendelian consistency, whereas the TDT(ae) statistic is computed on all trios. The results indicate that TDT(std) shows a significant increase in type I error when applied to data in which inconsistent trios are removed. This type I error increases both with an increase in sample size and with an increase in the allelic error rates. TDT(ae) always maintains correct type I error rates for the simulations considered. Factors affecting the power of the TDT(ae) are discussed. Finally, the power of TDT(std) is at least that of TDT(ae) for simulations with errorless data. Because data are rarely error free, we recommend that researchers use methods, such as the TDT(ae), that allow for errors in genotype data.

Alleles↗
PubMed2001

A novel series of highly potent benzimidazole-based microsomal triglyceride transfer protein inhibitors.

A series of benzimidazole-based analogues of the potent MTP inhibitor BMS-201038 were discovered. Incorporation of an unsubstituted benzimidazole moiety in place of a piperidine group afforded potent inhibitors of MTP in vitro which were weakly active in vivo. Appropriate substitution on the benzimidazole ring, especially with small alkyl groups, led to dramatic increases in potency, both in a cellular assay of apoB secretion and especially in animal models of cholesterol lowering. The most potent in this series, 3g (BMS-212122), was significantly more potent than BMS-201038 in reducing plasma lipids (cholesterol, VLDL/LDL, TG) in both hamsters and cynomolgus monkeys.

Administration, Oral↗