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Biomedical subjects

G Ward

Publications and source records attributed to G Ward.

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

Insulin secretion in growth hormone-deficient adults: effects of 24 months' therapy and five days' acute withdrawal of recombinant human growth hormone.

Beta-cell function in growth hormone (GH)-deficient (GHD) adults is poorly documented. Beta-cell function was therefore studied in 10 GHD adults (age, 40+/-3 years; weight, 79.3+/-4.8 kg; body mass index [BMI], 27.5+/-1.3 kg x m(-2)) before and after 6- and 24-month recombinant human GH (rhGH) therapy (0.24 IU x kg(-1) x wk(-1)) compared with 10 age-, sex-, weight-, and BMI-matched control subjects. With rhGH therapy, fat-free mass (FFM) increased (48.2+/-4.9, 52.5+/-4.8, and 59+/-6.8 kg, respectively) and fat mass (FM) decreased (33.8%+/-2.8%, 28.0%+/-3.0%, and 29.4%+/-2.5%, respectively), as did serum cholesterol. Oral glucose tolerance initially deteriorated at 6 months, but improved toward the control value by 24 months. Fasting insulin (FI) increased significantly, as did the acute insulin response to oral glucose (deltaAIR(OGTT)/deltaG) at 30 minutes (FI: pretreatment 9.8+/-0.8, 6 months, 14.0+/-1.8, 24 months 12.5+/-1.6 v control 11.4+/-1.9 mU x L(-1); deltaAIR(OGTT)/deltaG: pretreatment 201+/-24, 6 months 356+/-41, 24 months 382+/-86 v control 280+/-47 mU x mmol(-1)). However, the acute insulin response to intravenous (IV) glucose (AIR(G)) and IV glucagon at euglycemia and hyperglycemia did not change with rhGH therapy and were similar to the control group values. Importantly, the expected reciprocal relationships (as observed for the control group) between the various insulin secretory parameters and insulin sensitivity (SI) either were not present or were statistically weak in GHD subjects, despite the 35% decrease in SI by 24 months of rhGH therapy. In particular, over time, there was an attenuation of insulin secretion with respect to the ongoing insulin resistance with rhGH therapy, particularly for AIR(G) at 24 months. After 5 days of rhGH withdrawal, insulin secretion decreased and SI improved in GHD subjects. It is concluded that the current long-term rhGH treatment regimens appear to impact on insulin secretion such that the normal relationships between insulin secretion and SI are altered despite the favorable impact on body composition and serum lipid profiles.

Adult↗
PubMed1998

Two tests of instance-based and abstract rule-based accounts of invariant learning.

Two manipulations are argued to distinguish between instance-based and abstract rule-based accounts of invariant learning. Three experiments examined the effects of manipulating the type of invariant feature in the learning set, and the type of training schedules prior to test. In line with traditional research, selection bias at test was present when the invariant was the consistent inclusion of a stimulus item in the learning set. However, the degree of bias was identical when the invariant was the consistent exclusion of the stimulus item. In addition, negative transfer of training was observed when subjects were trained on one learning set and then shifted training to the opposite learning set, but no positive transfer of training was observed when subjects were trained on one learning set and then continued training using the same learning set. These results are argued to be evidence for instance-based accounts of invariant learning.

Adult↗
PubMed1998

Construction and evaluation of an attenuated vaccine for foot-and-mouth disease: difficulty adapting the leader proteinase-deleted strategy to the serotype O1 virus.

Over the last few years we have utilized a system to genetically engineer foot-and-mouth disease virus (FMDV) to produce live-attenuated vaccine candidates. These candidates have been generated in the genetic background of a tissue culture-adapted strain of serotype A12 virus. Based on this A12 system, we created a virus lacking the sequence encoding the leader (L) proteinase (Piccone et al., 1995), and demonstrated that this leaderless virus, A12-LLV2 was avirulent in bovine and swine, and could be used as an attenuated vaccine (Mason et al., 1997; Chinsangaram et al., 1998). The current study shows that a similar leader-deleted chimeric virus containing the genome of the type A12 virus with a substituted type O1 capsid coding region from a bovine-virulent virus can be constructed, and that the virus has low, but detectable virulence in swine. A second chimera specifying a tissue culture-adapted type O1 capsid lacking the RGD cell binding site, was avirulent in swine, but was not sufficiently immunogenic to provide protection from challenge. These results are described with respect to mechanisms of attenuation and antigen formation in live-attenuated virus-inoculated animals.

Amino Acid Substitution↗
PubMed1998

Response bias in visual serial order memory.

The recency-to-primacy shift represents a major challenge for all theories that attempt to explain the effects of serial order on memory. At short retention intervals, strong recency and no primacy effects occur, but as the retention interval increases, recency is attenuated and primacy increases. In 2 experiments, 24 participants were presented with sets of 4 unfamiliar faces and were asked to state the serial position of a probe face after 0 or 10 s. The predicted recency-to-primacy shift was obtained with accuracy responses. However, the distribution of responses also showed that there was a change in response bias with retention interval. When this was corrected for, the recency-to-primacy shift was eliminated. Response bias is suggested as the underlying cause of the recency-to-primacy shift in this task.

Adult↗
PubMed1998

Effect of docosahexaenoic acid on the synthesis of phosphatidylserine in rat brain in microsomes and C6 glioma cells.

Docosahexaenoic acid (22:6n-3) is the major polyunsaturated fatty acid (PUFA) in the CNS and accumulates particularly in phosphatidylserine (PS). We have investigated the effect of the 22:6n-3 compositional status on the synthesis of PS. The fatty acid composition of brain microsomes from offspring of rats artificially reared on an n-3-deficient diet showed a dramatic reduction of 22:6n-3 content (1.7 +/- 0.1%) when compared with control animals (15.0 +/- 0.2%). The decrease was accompanied by an increase in docosapentaenoic acid (22:5n-6) content, which replaced the 22:6n-3 phospholipids with 22:5n-6 molecular species, as demonstrated using HPLC/electrospray mass spectrometry. The n-3 deficiency did not affect the total amount of polyunsaturated phospholipids in brain microsomes; however, it was associated with a decrease in the total polyunsaturated PS content and with increased levels of 1-stearoyl-2-docosapentanoyl (18:0/22:5n-6) species, particularly in phosphatidylcholine. Incorporation of [3H]serine into PS in rat brain microsomes from n-3-deficient animals was slightly but significantly less than that of the control animals. Similarly, C6 glioma cells cultured for 24 h in 22:6n-3-supplemented media (10-40 microM) showed a significant increase in the synthesis of [3H]PS when compared with unsupplemented cells. Our data show that neuronal and glial PS synthesis is sensitive to changes in the docosahexaenoate levels of phospholipids and suggest that 22:6n-3 may be a modulator of PS synthesis.

Animals↗
PubMed1998

Antibody response in mice inoculated with DNA expressing foot-and-mouth disease virus capsid proteins.

Candidate foot-and-mouth disease (FMD) DNA vaccines designed to produce viral capsids lacking infectious viral nucleic acid were evaluated. Plasmid DNAs containing a portion of the FMDV genome coding for the capsid precursor protein (P1-2A) and wild-type or mutant viral proteinase 3C (plasmids P12X3C or P12X3C-mut, respectively) were constructed. Cell-free translation reactions programmed with pP12X3C (wild-type 3C) and pP12X3C-mut produced a capsid precursor, but only the reactions programmed with the plasmid encoding the functional proteinase resulted in P1-2A processing and capsid formation. Baby hamster kidney (BHK) cells also produced viral capsid proteins when transfected with these plasmids. Plasmid P12X3C was administered to mice by intramuscular, intradermal, and epithelial (gene gun) inoculations. Anti-FMD virus (FMDV) antibodies were detected by radioimmunoprecipitation (RIP) and plaque reduction neutralization assays only in sera of mice inoculated by using a gene gun. When pP12X3C and pP12X3C-mut were inoculated into mice by using a gene gun, both plasmids elicited an antibody response detectable by RIP but only pP12X3C elicited a neutralizing antibody response. These results suggest that capsid formation in situ is required for effective immunization. Expression and stimulation of an immune response was enhanced by addition of an intron sequence upstream of the coding region, while addition of the FMDV internal ribosome entry site or leader proteinase (L) coding region either had no effect or reduced the immune response.

3C Viral Proteases↗
PubMed1998

Longitudinal study of bone turnover after acute spinal cord injury.

Increased bone turnover is a sequel of spinal cord injury (SCI) and predisposes to a number of clinically relevant complications, including osteoporosis and fractures. There are limited data available regarding the changes in modern markers of bone metabolism after SCI. We report a 6-month longitudinal follow-up of biochemical markers of bone metabolism (free and total deoxypyridinoline, total pyridinoline, N-telopeptide, osteocalcin, and total alkaline phosphatase) and bone mineral densitometry in 30 subjects with acute SCI. Markers of bone formation showed only a minor rise, remaining within the reference range. In contrast, markers of bone resorption showed a significant rise after acute SCI, peaking around weeks 10-16, with values up to 10 times the upper limit of normal. Paired bone mineral densities (n = 11; on the average, determined 14 weeks apart) showed no change at the hip, lumbar spine, or radius, but demonstrated a decrement in the entire lower limbs. changes in biochemical markers of bone formation and resorption were comparable in patients with quadriplegia and paraplegia, except for a greater increase in quadriplegics in pyridinoline, expressed as a percentage of baseline. In conclusion, a marked increase in bone resorption and modest changes in bone formation occur after SCI, and possibly increased bone resorption occurs in quadriplegia.

Adolescent↗
PubMed1997

An investigation of cued recall of multiattribute stimuli.

Memory performance for sequences of letters positioned in particular spatial locations in a 3 x 3 grid was examined by requiring participants to recall attributes of the target stimuli given 1 or 2 features of the stimuli as cues. Cuing asymmetry was observed between the serial-position curves of object and sequential-order information, and location and sequential-order information, when the stimuli were presented in both the same and different locations. After correcting for response bias, this asymmetry was attenuated for the stimuli presented in different locations and was eliminated for the stimuli presented in the same location. Contrary to the predictions of the fragmentation hypothesis (G. V. Jones, 1976), asymmetry was also observed between object and location information. The roles of spatial location and response bias are offered as explanations for previous contradictory claims for cuing symmetry between item and order information.

Adult↗
PubMed1997

Metyrapone pre-treated inferior petrosal sinus sampling in the differential diagnosis of ACTH-dependent Cushing's syndrome.

BACKGROUND: Inferior petrosal sinus sampling (IPSS) is a useful investigative technique in the differential diagnosis of ACTH-dependent Cushing's syndrome. Diagnostic accuracy is improved by the administration of corticotrophin releasing-factor (CRF) during the procedure to stimulate ACTH secretion. We hypothesized that, given the unavailability of CRF in Australia, stimulation of ACTH secretion from tumorous corticotrophs with metyrapone treatment before IPSS may be useful. AIMS: To describe our clinical experience with a novel diagnostic test, and to compare results between IPSS with and without metyrapone pre-treatment. SETTING: Metropolitan, Australian university teaching hospital. PATIENTS: 18 patients were studied on 21 occasions: three with Cushing's disease without metyrapone treatment prior to IPSS (M-), 11 with Cushing's disease with metyrapone pretreatment (M+), three with ectopic ACTH syndrome, and one with pseudo-Cushing's syndrome. TREATMENT: Patients received oral metyrapone, median dose 750 mg 6 hourly, for 24 h before IPSS. RESULTS: No major side effects were noted. Metyrapone increased serum 11-deoxycortisol concentration to a median of 400 nmol/l (range 36-1310) on the morning of the test. Radiological confirmation of correct catheter placement was shown in 36/42 inferior petrosal sinuses (86%). Median peak central: peripheral ACTH ratios were 9.8 for M- pituitary adenomas (range 5.7-13.6), 12.9 for the technically successful M+ pituitary adenomas (range 8-54.1), and 1.6 for M+ ectopic ACTH syndrome cases (range 1.2-3.4). Repeat studies in unoperated patients with ectopic ACTH syndrome showed ratios < 1.6. IPSS showed median peak ACTH concentrations of 190 ng/l for M- pituitary adenomas (range 83-205), 595 ng/l for the technically successful M+ pituitary adenomas (range 80-7630; P = 0.035 compared to M-), and 62 ng/l for M+ ectopic ACTH syndrome cases (range 47-220). IPSS correctly identified the pituitary source of ACTH production in all cases of Cushing's disease (except one technical failure where MRI revealed a lesion). MRI scanning correctly identified a lesion in 3/14 operated Cushing's disease cases. IPSS correctly lateralized 1/3 M- and 7/8 M+ Cushing's disease cases where the procedure was technically successful and surgical descriptions adequate. Pituitary exploration revealed a visible lesion in 75% of cases corresponding to the side predicted by IPSS; 'blind' hemi-hypophysectomy was performed on the side predicted from IPSS in the remainder. All cases of Cushing's disease were cured or improved following surgery, with a median follow-up of 2.8 years (range 0.7-5.9). CONCLUSIONS: Metyrapone pre-treated inferior petrosal sinus sampling is safe, and appears to induce high ACTH output from pituitary corticotroph adenomas. The technique has allowed accurate localization and treatment of pituitary corticotroph microadenomas.

ACTH Syndrome, Ectopic↗
PubMed1997

Retinal and brain accretion of long-chain polyunsaturated fatty acids in developing felines: the effects of corn oil-based maternal diets.

A study was carried out in domestic felines to determine whether corn oil-based maternal diets are an adequate source of essential fatty acids to support normal accumulation of long-chain polyunsaturated fatty acids in the brains and retinas of offspring and whether these diets have any subsequent effect on visual function. Female domestic felines were acclimated to one of six different defined diets 1 mo before mating and maintained on the diets throughout pregnancy and lactation. Four diets contained only corn and hydrogenated coconut oils as their source of fat in ratios of 1:9, 3:7, 6:4, and 9:1, respectively. Two reference diets also contained the long-chain polyunsaturated fatty acids arachidonate (20:4n-6) and docosahexaenoate (22:6n-3). When the offspring were 8 wk old, electroretinograms were obtained and the a- and b-wave implicit times were determined. The results showed that animals raised in litters in which the maternal diets were devoid of 20:4n-6 and 22:6n-3 had an increase in a- and b-wave implicit times compared with the controls. In the rod outer segments and brains of these animals, there were lower amounts of 22:6n-3 and higher amounts of long-chain n-6 polyunsaturated fatty acids compared with control animals. These findings showed that although corn oil-based diets were capable of maintaining 20:4n-6 concentrations in the developing brain and retina, only those diets containing 22:6n-3 could support a high accumulation of docosahexaenoic acid in these tissues. Moreover, low amounts of 22:5n-6 in the brains of animals in all of the corn oil-diet groups suggested that young felines have a low biosynthetic capacity to produce this fatty acid or 22:6n-3. These findings suggest that in juvenile felines, maintenance of 22:6n-3 status in the nervous system is important for optimal retinal function.

Animals↗
PubMed1997

Heterophilic antibodies remain a problem for the immunoassay laboratory.

The prevalence of heterophilic antibody interference in a modern immunochemiluminometric assay containing blocking agents was determined using thyrotropin as an illustrative example. Serum samples were obtained from 295 consecutive patients who underwent routine thyroid function testing. The following versions of the thyrotropin assay were used: protocol A (zero blocker), protocol B (routine blocker concentration), and protocol C (extra blocker). Ten patients (prevalence 3.4%) had significant levels of heterophilic antibodies (protocol A value greater than 9 SD from the protocol B value). The observed thyrotropin levels for protocols B and C were the same for all patients, consistent with the reagent blockers in routine assays adequately eliminating heterophilic antibody interference. However, seven more patients (0.03%) in series of 21,000 assessed by routine thyroid function testing had discordant results because of a concentration of heterophilic antibodies so high as to overwhelm the added blocking agents.

Analysis of Variance↗
PubMed1997

Plasmid DNA encoding replicating foot-and-mouth disease virus genomes induces antiviral immune responses in swine.

DNA vaccine candidates for foot-and-mouth disease (FMD) were engineered to produce FMD virus (FMDV) particles that were noninfectious in cell culture or animals. The prototype plasmid, pWRM, contains a cytomegalovirus immediate-early promoter-driven genome-length type A12 cDNA followed by the bovine growth hormone polyadenylation site. BHK cells transfected with this plasmid produced virus, but the specific infectivity of pWRM was much lower than that achieved with in vitro-generated RNA genomes. To improve the infectivity of the plasmid, a cDNA encoding the hepatitis delta virus ribozyme was added to the 3' end of the FMDV cDNA. The resulting plasmid, pWRMH, exhibited slightly increased infectivity in cell culture and produced virus when inoculated into suckling mice. A third plasmid, pWRMHX, was created by removal of the sequences encoding the cell binding site found in capsid protein VP1 of pWRMH. Although cells transfected with pWRMHX produced viral capsids, this plasmid was not lethal in suckling mice, indicating that particles lacking the cell binding site were not able to initiate secondary infectious cycles. Swine inoculated with pWRMHX did not show any signs of disease and produced neutralizing antibodies to FMDV, and 20% of the vaccinated animals were protected from challenge. A derivative of pWRMHX, pWRMHX-pol-, harboring a mutation designed to inactivate the viral polymerase was much less immunogenic, indicating that immunogenicity of pWRMHX resulted, in part, from amplification of the viral genome in the animal.

Animals↗
PubMed1997

Characterization of synthetic foot-and-mouth disease virus provirions separates acid-mediated disassembly from infectivity.

One of the final steps in the maturation of foot-and-mouth disease virus (FMDV) is cleavage of the VP0 protein to produce VP4 and VP2. The mechanism of this cleavage is unknown, but it is thought to function in stabilizing the virus particle and priming it for infecting cells. To investigate the cleavage process and to understand its role in virion maturation, we engineered synthetic FMDV RNAs with mutations at Ala-85 (A85) and Asp-86 (D86) of VP0, which border the cleavage site. BHK cells transfected with synthetic RNAs containing substitutions at position 85 (A85N or A85H) or at position 86 (D86N) yielded particles indistinguishable from wild-type (WT) virus in sedimentation and electrophoretic profiles. Viruses derived from these transfected cells were infectious and maintained their mutant sequences upon passage. However, BHK cells transfected with synthetic RNAs encoding Phe and Lys at these positions (A85F/D86K) or a Cys at position 86 (D86C) produced noninfectious provirions with uncleaved VP0 molecules. Despite their lack of infectivity, the A85F/D86K provirions displayed cell binding and acid sensitivity similar to those of WT virus. However, acid breakdown products of the A85F/D86K provirions differed in hydrophobicity from the comparable WT virion products, which lack VP4. Taken together, these studies are consistent with a role for soluble VP4 molecules in release of the viral genome from the endosomal compartment of susceptible cells.

Animals↗
PubMed1997

Population change between 1986 and 1996 in Australia: population numbers, components of change and age profiles.

"This paper represents a preliminary analysis of the release of 1996 Census-based ERP [estimates of resident population] by examining regional population shifts and components of population change in Australia between 1986 and 1996.... With particular reference to Queensland, this paper also examines changes in the age profiles of regional populations over the decade to June 1996. Changes in the population structure of Queensland's growth regions are compared with those of regions experiencing population decline."

Age Distribution↗
PubMed1997

A study of two stretching techniques for improving hip flexion range of motion.

OBJECTIVES: To compare the effectiveness of a spinal (suboccipital) stretching technique and a peripheral stretching technique. DESIGN: Clinical cohort study. SETTING: Macquarie University Centre for Chiropractic Outpatient Clinic. METHOD: A reliable hand-held dynamometer was used to determine the end point of range of motion (ROM) before and after the application of a treatment. Three groups of subjects were treated: cervical stretch, hip stretch and sham/placebo. ROM of the hip in flexion (straight leg raise) was used as the independent variable. SAMPLE: Sixty randomly allocated university students aged between 18 and 35 yr. RESULTS: The two stretching treatments resulted in increased flexion ROM at the hip. Statistical analysis revealed that only the sub-occipital stretching procedure increased hip flexion ROM significantly. CONCLUSION: Manual therapy of the neck may have a role to play in the treatment of extraspinal, lower-limb musculoskeletal conditions.

Adolescent↗
PubMed1997

A prostate-specific antigen-like protein associated with renal cell carcinoma in women.

Renal cell carcinoma (RCC) is the most common form of cancer affecting the kidney. There is currently no biochemical marker for this disease. We have shown that serum-immunoreactive prostate-specific antigen (PSA) levels, as measured by the two-site Ciba-Corning ACS:180 immunochemiluminometric assay, are elevated in women with RCC. Although the levels were low (0.13-0.89 microgram/l), serum PSA was clearly measurable prior to surgery in 13 of 17 women (76%) with RCC. Significantly, the PSA levels fell to undetectable after nephrectomy. Seventeen normal women also had undetectable (<0. 1 microgram/l) PSA levels. Two women, who had several serum PSA measurements performed postoperatively, showed a t(1/2) of 2-3 days equivalent to that observed for PSA in men following radical prostatectomy for prostate cancer. The 17 RCCs evaluated in this study consisted of 10 stage A, 4 stage B, and 3 stage C tumors. There was no relationship between tumor size, stage, or serum-immunoreactive PSA level, although the majority of these tumors are low grade. We have shown by reverse transcription-PCR, using PCR primers directed to the NH2 terminal coding region of the KLK3 (PSA) gene and the closely related KLK1 and KLK2 genes, that these genes are not expressed in these tumors. Our findings show, however, that elevated levels of a circulating PSA-like protein are present in women with RCC.

Adult↗