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Biomedical subjects

B Harris

Publications and source records attributed to B Harris.

At least 19 recordsLinked to original sources
PubMed2006

Impact of trisomy on fertility and meiosis in male mice.

BACKGROUND: Chromosomal abnormalities frequently are associated with impairment or arrest of spermatogenesis in mammals but are compatible with fertility in female carriers of the same anomaly. In the case of trisomy, mice have extra genomic DNA as well as the chromosomal abnormality, usually present as an extra, unpaired chromosome. Thus, impairment of spermatogenesis in trisomic males could be due to the presence of extra genomic material (i.e. triplicated genes) or due to the chromosomal abnormality and presence of an unpaired chromosome in meiosis. METHODS: In this study, fertility and chromosomal pairing configurations during meiotic prophase were analysed in male mice trisomic for different segments of the genome. Four have an extra segmental or tertiary trisomic chromosome--Ts(17(16))65Dn, Ts(10(16))232Dn, Ts(12(17))4Rk and Ts(4(17))2Lws--and one has the triplicated segment attached to another chromosome--Ts(16C-tel)1Cje. Ts(17(16))65Dn and Ts(16C-tel)1Cje have similar gene content triplication and differ primarily in whether the extra DNA is in an extra chromosome or not. RESULTS: The presence of an intact extra chromosome, rather than trisomy per se, is associated with male sterility. Additionally, sterility is correlated with a high frequency of association of the unpaired chromosome with the XY body, which contains the largely unpaired X and Y chromosomes. CONCLUSIONS: Intact extra chromosomes disrupt spermatogenesis, and unpaired chromosomes establish a unique chromatin territory within meiotic nuclei.

Animals↗
PubMed2004

Randomized controlled trial of effects of the airflow through the upper respiratory tract of intubated brain-injured patients on brain temperature and selective brain cooling.

BACKGROUND: Pyrexia is common after brain injury; it is generally believed to affect outcome adversely and the usual clinical methods of reducing temperature are not effective. The normal physiological mechanisms of brain cooling are heat loss from the upper airways and through the skull, and these can produce selective brain cooling. METHODS: Air at room temperature and humidity was continuously administered to 15 brain-injured, intubated and mechanically ventilated patients via a sponge-tipped oxygen catheter in each nostril at a combined rate of 115 ml kg(-1) min(-1). Brain temperature was measured using a pressure-temperature Camino catheter which is designed to site the thermistor 1 cm into the parenchyma in the frontal lobe. Oesophageal temperature was measured using an oesophageal stethoscope with a thermistor. After establishing baseline for 30 min, patients were randomized to receive airflow or no airflow for 6 h and then crossed over for a further 6 h. RESULTS: Airflow replicating normal resting minute volume did not produce clinically relevant or statistically significant reductions in brain temperature [0.13 (SD 0.55) degrees C; 95% CI, 0.43-0.17 degrees C]. However, we serendipitously found some evidence of selective brain cooling via the skull, but this needs further substantiation. CONCLUSIONS: A flow of humidified air at room temperature through the upper respiratory tracts of intubated brain-injured patients did not produce clinically relevant or statistically significant reductions in brain temperature measured in the frontal lobe.

Adolescent↗
PubMed2004

Thyroid peroxidase antibodies in early pregnancy: utility for prediction of postpartum thyroid dysfunction and implications for screening.

Thyroid peroxidase antibodies (TPOAb) in pregnancy are a marker for postpartum (PPTD) and long-term thyroid dysfunction, with variable sensitivity and specificity in PPTD prediction. To test its utility in prediction, we recruited 308 TPOAb-positive (147 developed PPTD (PPTD group) and 161 remained euthyroid [PPTE group]) and 102 TPOAb-negative women (none developed PPTD), in early pregnancy (median, 18; range, 9-19 weeks' gestation). TPOAb levels were higher in the PPTD group (median) (125.2 kIU/L; p < 0.001), and in its hypothyroid (162.4 kIU.; p < 0.0001), hyperthyroid (114.2 kIU/L; p < 0.007), and biphasic (105.1 kIU/L; p < 0.02) variants, compared to the PPTE group (66.7 kIU/L) The incidence of PPTD was significantly higher with TPOAb levels above 58.2 kIU/L (early pregnancy versus postpartum; relative risk, 1.37 [95% confidence interval [CI] 1.17-1.61] versus 0.78 [95% CI 0.5-1.2]) compared to levels below. The integrated postpartum TPOAb response was higher in the PPTD group (median) (159 kIU/L per week) and its variants (hypothyroid; 199 kIU/L per week; biphasic, 180 kIU/L per week; hyperthyroid, 120 kIU/L per week), compared to the PPTE group (86 kIU/L per week p < 0.004). Median early pregnancy TPOAb levels in the PPTD and PPTE groups correlated well with the postpartum antibody response (r = 0.58, p < 0.001). The sensitivity of TPOAb in PPTD prediction was 100% (early pregnancy and postpartum), specificity 62% (early pregnancy) versus 41% (postpartum) and positive predictive value 48% (early pregnancy and postpartum). The timing of TPOAb testing, the sensitive assay used and the absence of PPTD in TPOAb-negative subjects contributed to this high sensitivity. We recommend TPOAb in early pregnancy as a useful predictor of PPTD, particularly in populations where PPTD does not occur in TPOAb-negative women.

Adolescent↗
PubMed2002

Sequence of Plasmodium falciparum chromosomes 1, 3-9 and 13.

Since the sequencing of the first two chromosomes of the malaria parasite, Plasmodium falciparum, there has been a concerted effort to sequence and assemble the entire genome of this organism. Here we report the sequence of chromosomes 1, 3-9 and 13 of P. falciparum clone 3D7--these chromosomes account for approximately 55% of the total genome. We describe the methods used to map, sequence and annotate these chromosomes. By comparing our assemblies with the optical map, we indicate the completeness of the resulting sequence. During annotation, we assign Gene Ontology terms to the predicted gene products, and observe clustering of some malaria-specific terms to specific chromosomes. We identify a highly conserved sequence element found in the intergenic region of internal var genes that is not associated with their telomeric counterparts.

Animals↗
PubMed2002

Glucose, insulin and potassium for heart protection during cardiac surgery.

BACKGROUND: Coronary artery bypass grafting with hypothermic cardiac arrest and cardiopulmonary bypass (CPB) is associated with myocardial injury. Our study investigated whether an infusion of glucose, insulin and potassium (GIK) during elective coronary artery bypass surgery decreases myocardial cell death. METHODS: We measured cardiac troponin I (cTnI), a myofibrillar structural protein, which is a sensitive and specific indicator of myocytic injury. With ethics committee approval, 42 patients were enrolled into a randomized, prospective, double-blinded study. In the GIK group, 500 ml of 50% dextrose solution containing 100 IU insulin and potassium 80 mmol was infused at the rate of 0.75 ml kg(-1) h(-1). Patients in the non-GIK group received 5% dextrose solution at the same rate. Arterial blood samples were taken before induction of anaesthesia, after removal of the aortic clamp and 6 and 12 h after CPB. RESULTS: In both groups there was an increase in cTnI concentration (P<0.05), which was greatest about 6 h after CPB. At no time did the cTnI concentration differ between the two groups. CONCLUSION: The results suggest that GIK does not decrease the irreversible myocardial damage associated with routine coronary artery bypass surgery.

Aged↗
PubMed2001

Mitochondrial cytochrome oxidase immunolabeling in aged human temporal bones.

Presbycusis, an age-related hearing loss, is accompanied by histopathological cochlear changes including variable amounts of degeneration of the auditory receptors, neurons and the stria vascularis. The causes of degeneration are unknown, although acoustic trauma and exposure to ototoxic agents are certainly contributors to the cellular degeneration. Acquired mitochondrial DNA defects are postulated as important determinants of aging in neuromuscular tissues. The cochlear neurons are highly metabolic and are, therefore, likely to be affected by mitochondrial DNA defects. Sequence analysis has demonstrated a significant number of acquired mutations in the cytochrome oxidase gene in the neurons from aged human cochleas. The current study used immunohistochemical labeling of cytochrome oxidase in the neuronal cell bodies in archival celloidin sections to evaluate relationships among label density, hearing loss, number of neurons and mitochondrial DNA changes within individual cochleas. Label density was less in many aged temporal bones, but not all. There was no relationship among any other variables. It is concluded that while there may be a decrease in the amount of cytochrome oxidase expression in aged spiral ganglion cell bodies, there are many other factors that contribute to hearing loss and cellular degeneration.

Aged↗
PubMed2001

Acamprosate is neuroprotective against glutamate-induced excitotoxicity when enhanced by ethanol withdrawal in neocortical cultures of fetal rat brain.

BACKGROUND: Acamprosate reduces relapse, and the drug may interact with glutamate transmission and with glutamate/NMDA receptors. Because these systems are implicated in excess calcium entry leading to alcohol withdrawal-induced neurotoxicity, we evaluated the effects of acamprosate on these parameters in neuronal cultures. METHODS: Primary cultures of neocortical neurons from fetal Sprague-Dawley rats were maintained either in normal medium or in medium containing 100 mM ethanol for 4 days. After this time, cultures were challenged with glutamate for 10 min and then returned to medium (all in the absence of ethanol). 45Ca2+ uptake was measured during the challenge, and glutamate-induced toxicity was assessed after 20 hr. The effects of acamprosate present during the glutamate challenge were measured on both parameters. RESULTS: In controls, acamprosate did not significantly affect glutamate-induced neurotoxicity but produced a significant inhibition of calcium entry. The NMDA receptor antagonists dizocilpine and d-amino-phosphonovalerate (D-APV) inhibited both glutamate neurotoxicity and calcium entry. In cultures previously exposed to ethanol, glutamate-induced neurotoxicity and calcium entry were both significantly enhanced. Dizocilpine reduced both these parameters to unstimulated control values, and D-APV reduced both calcium entry and neurotoxicity with the same relation that we obtained in control cultures. In the ethanol-withdrawn cultures, acamprosate reduced both the enhanced glutamate-induced calcium entry and the enhanced neurotoxicity in a concentration-dependent manner. Acamprosate also significantly reduced calcium entry caused by 80 mM K+ in control and ethanol-exposed cultures. CONCLUSIONS: Acamprosate had protective effects against glutamate-induced neurotoxicity only in ethanol-withdrawn cultures. The neuroprotective effects of the drug did not correlate with its effects on calcium entry, making it unlikely that acamprosate directly affects NMDA receptors via the glutamate binding site or the receptor-operated calcium channel. The results are, however, compatible with other inhibitory effects on NMDA receptor function.

Acamprosate↗
PubMed2001

Formulations of single or multiple H. pylori antigens with DC Chol adjuvant induce protection by the systemic route in mice. Optimal prophylactic combinations are different from therapeutic ones.

The ability to induce a protective response against Helicobacter pylori infection has been investigated by systemic immunization of mice with urease formulated with the cationic lipid DC Chol. This compound acts both as a formulating agent and as an adjuvant and induces a balanced Th1/Th2 response shown to be more effective for protection in our previous studies. Urease-DC Chol induced a significant protection in prophylaxis but not in therapeutic immunization. The protection level was between 1.5 and 2 log reduction of bacterial density measured by quantitative culture compared to unimmunized-infected mice. In parallel, the protective efficacy of other H. pylori antigens formulated in a similar way and administered with DC Chol was tested. These antigens were tested alone or in combination in prophylactic and therapeutic regimens. Some combinations of antigens induced a better prophylactic or therapeutic activity than urease alone (0.5-1.5 log further reduction in prophylaxis and therapy respectively, P<0.05). The combinations that induced the best protection were different in prophylaxis and therapy. In conclusion, DC Chol provides a convenient and efficient method to formulate different antigens even when they are present in non-compatible buffers initially. Moreover, the results obtained in protection against H. pylori with such formulations should lead the way to future clinical trials.

Adjuvants, Immunologic↗
PubMed2000

Progress in Arabidopsis genome sequencing and functional genomics.

Arabidopsis thaliana has a relatively small genome of approximately 130 Mb containing about 10% repetitive DNA. Genome sequencing studies reveal a gene-rich genome, predicted to contain approximately 25000 genes spaced on average every 4.5 kb. Between 10 to 20% of the predicted genes occur as clusters of related genes, indicating that local sequence duplication and subsequent divergence generates a significant proportion of gene families. In addition to gene families, repetitive sequences comprise individual and small clusters of two to three retroelements and other classes of smaller repeats. The clustering of highly repetitive elements is a striking feature of the A. thaliana genome emerging from sequence and other analyses.

Agriculture↗
PubMed2000

Unequal representation of the temporal and nasal retina in an anomalous projection to the lateral thalamus.

Study of an anomalously regenerated, nontopographically organized retinal projection in the frog olfactory cortex revealed that the temporal retina is the main source of this projection, suggesting the existence of specific temporal fiber-directed attractant or trophic influences. In the present study, we examined the organization of an anomalous retinal projection that forms in the frog thalamus after ablation of the optic tectum. The projections from different sectors of the retina were studied by means of the anterograde transport of biotinylated dextran-amine (BDA) delivered to incisions made across the nerve fiber layer in frogs surviving ablation of the contralateral tectal hemisphere for 13-46 weeks. The projections from nasal retinal sectors were always lightly constructed in the aberrant terminal field, whereas their projections to the lateral geniculate complex remained reasonably strong. In contrast, the projections from temporal retinal sectors, though also weak initially, in time became robust and filled the aberrant field over most of its extent. The specific amplification of the temporal fiber projection now observed in two foreign targets provides further evidence for the existence of target-based, attractant/trophic molecules with functional specificity for temporal retinal fibers. That such agents can exist or be inducible in a foreign area would suggest that they belong to a family of molecules having natural biological activity in normal development or regeneration. However, the possibility that the augmented role of the temporal retina in these projections is a result of experience-based plasticity is also discussed.

Animals↗
PubMed2000

'Infront outback' goes national.

The National Rural Health Alliance, the Toowoomba Hospital Foundation and the Cunningham Centre have agreed to merge the two biennial conferences for rural and remote health that have been running in alternate years since 1991. This means that in March 2001, the National Rural Health Conference will, for the first time, incorporate 'Infront Outback', the Australian Rural and Remote Health Scientific Conference. There will, therefore, be one major biennial rural heath conference, dealing coherently with health scientific research and policy development. The recommendations to governments and national bodies that result should be even stronger and more highly regarded than has been the case to date.

Australia↗
PubMed2000

Conventional physiotherapy and treadmill re-training for higher-level gait disorders in cerebrovascular disease.

OBJECTIVES: to compare the therapeutic effects of two approaches to gait re-training--a schedule of conventional physiotherapy and treadmill re-training--in patients with higher-level gait disorders associated with cerebral multiinfarct states. DESIGN: single-blind crossover study involving a 4-week baseline period, 4 weeks of treadmill re-training and 4 weeks of conventional physiotherapy. SETTING: a large teaching hospital. SUBJECTS: patients with cerebral multi-infarct states who met the criteria for higher-level gait disorders. Computed tomographic brain scans showed at least one large vessel infarct, basal ganglia and white matter lacunes or extensive leukoaraiosis. INTERVENTIONS: a schedule of treadmill re-training and a specific schedule of physiotherapy containing 31 interventions in three treatment modules: (i) for gait ignition failure and turning; (ii) to improve postural alignment and enhance balance reactions; and (iii) for other components of cerebral multi-infarct state disordered gait. MAIN OUTCOME MEASURES: spatial and temporal gait measures and activity of daily living assessments. RESULTS: we recruited 18 patients, mean (SD) age 79.1 (6.8) years. Patients walked an average of 7.9 (5.5) km on the treadmill and had an average of 6.7 (3.2) h of physiotherapy. There were clinically moderate but highly statistically significant (P < 0.001) improvements in the following indices: time taken to complete the sit-to-stand test; time taken to walk 10 m; number of steps over 10 m; walking velocity; right and left step lengths; and time taken to complete the 'S' test. There were no differences in the results obtained in each limb of the study. CONCLUSION: there is no difference between the effects of conventional physiotherapy and treadmill re-training on the gait of patients with higher-level gait disorders associated with cerebral multi-infarct states. However, the improvements seen during the treatment period suggest that there is scope to improve the gait of this group of frail, elderly patients.

Aged↗