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Susan White

Publications and source records attributed to Susan White.

15 recordsLinked to original sources
PubMed2007

Biological and molecular studies of a cypovirus from the black fly Simulium ubiquitum (Diptera: Simuliidae).

A cypovirus from the black fly Simulium ubiquitum (SuCPV) was isolated and examined using biological and molecular techniques. SuCPV produces small (typically 0.25mum), polyhedral shaped inclusion bodies (polyhedra), in which the virus particles become multiply embedded. SuCPV is the third cypovirus isolated from Diptera, but the first from Simuliidae that has been characterized using molecular analyses. SuCPV has a genome composed of 10 segments of dsRNA, with an electrophoretic migration pattern that is different from those of recent UsCPV-17 and CrCPV-17 isolates from the mosquitoes Uranotaenia sapphirina and Culex restuans, respectively. The SuCPV electropherotype appears to show significant differences from those of the previously characterized lepidopteran cypoviruses. Sequence analysis of SuCPV segment 10 shows that it is unrelated to either of the two CPV isolates from Diptera or to the CPV species for which Seg-10 has been previously characterized from Lepidoptera. A comparison of the terminal regions of SuCPV genome segments to those of CPV-1, 2, 4, 5 14, 15, 16, 17, 18, and 19 also revealed only low levels of conservation. We therefore, propose that SuCPV is classified within a new Cypovirus species, which we have tentatively identified as Cypovirus-20. We have therefore referred to this virus isolate as S. ubiquitum CPV-20 (SuCPV-20).

Amino Acid Sequence↗
PubMed2006

A single nucleotide polymorphism chip-based method for combined genetic and epigenetic profiling: validation in decitabine therapy and tumor/normal comparisons.

Progress on several unresolved issues in cancer epigenetics will benefit from rapid and standardized methods for profiling DNA methylation genome-wide. In the area of epigenetic therapy, the demethylating drug decitabine (5-aza-2'-deoxycytidine) is increasingly used to treat acute myelogenous leukemia and myelodysplastic syndrome, but the mechanisms of its anticancer activity have remained unclear. Given the clinical efficacy of decitabine and the uncertainties about its mode of action, it will be useful to optimize methods for following DNA methylation as a biochemical response in individual patients. Here, we describe a single nucleotide polymorphism (SNP) chip-based method (MSNP) for profiling DNA methylation. Using this procedure, the extent of demethylation in bone marrow aspirates from patients with leukemia receiving decitabine can be assessed genome-wide using commercially available (Affymetrix) SNP chips. We validated the accuracy of MSNP by comparing the results with combined bisulfite restriction analysis and by sequencing cloned PCR products from bisulfite-converted DNA. We further validated MSNP in a Wilms' tumor/normal kidney comparison, comparing the results with methylation-sensitive Southern blotting. MSNP simultaneously detects aberrations in DNA copy number and loss of heterozygosity, making it a generally useful approach for combined genetic and epigenetic profiling in tissue samples from cancer patients.

Antimetabolites, Antineoplastic↗
PubMed2005

Molecular and biological characterization of a Cypovirus from the mosquito Culex restuans.

A cypovirus from the mosquito Culex restuans (named CrCPV) was isolated and its biology, morphology, and molecular characteristics were investigated. CrCPV is characterized by small (0.1-1.0 microm), irregularly shaped inclusion bodies that are multiply embedded. Laboratory studies demonstrated that divalent cations influenced transmission of CrCPV to Culex quinquefasciatus larvae; magnesium enhanced CrCPV transmission by approximately 30% while calcium inhibited transmission. CrCPV is the second cypovirus from a mosquito that has been confirmed by using molecular analysis. CrCPV has a genome composed of 10 dsRNA segments with an electropherotype similar to the recently discovered UsCPV-17 from the mosquito Uranotaenia sapphirina, but distinct from the lepidopteran cypoviruses BmCPV-1 (Bombyx mori) and TnCPV-15 (Trichoplusia ni). Nucleotide and deduced amino acid sequence analysis of CrCPV segment 10 (polyhedrin) suggests that CrCPV is closely related (83% nucleotide sequence identity and 87% amino acid sequence identity) to the newly characterized UsCPV-17 but is unrelated to the 16 remaining CPV species from lepidopteran hosts. A comparison of the terminal segment regions of CrCPV and UsCPV-17, an additional method for differentiating various Cypovirus species, revealed a high level of conservation. Therefore, we propose that CrCPV is a member of the Cypovirus-17 group and designate this species as CrCPV-17.

Amino Acid Sequence↗
PubMed2005

Molecular analysis of an occlusion body protein from Culex nigripalpus nucleopolyhedrovirus (CuniNPV).

CUN085 is an occlusion body (OB) protein from the nucleopolyhedrovirus of Culex nigripalpus (CuniNPV). SDS-PAGE analysis indicated that the CuniNPV OB protein is about 3 times the size (approximately 90 kDa) of characterized nucleopolyhedrovirus (NPVs) and granulovirus OB proteins. Rapid amplification of cDNA ends (RACE), RNase protection assay, real-time PCR, and protein sequencing were used to characterize CUN085 from CuniNPV. RACE data revealed that the transcriptional start and termination sites for the CUN085 gene yielded a polypeptide comprised of 822 amino acids indicating that translation initiates within a larger 882 amino acid open reading frame that was originally predicted from the CuniNPV genome sequence. Transcription of CUN085 started at a consensus baculovirus late transcription start site TAAG at nucleotide position 75433 of the CuniNPV genome sequence. RNase protection assays and quantitative real-time PCR show that the CUN085 transcript is first detected in mosquito larvae at approximately 6 h after infection with CuniNPV and its prevalence increased progressively over the subsequent 18 h.

Amino Acid Sequence↗
PubMed2005

Cerebral blood flow during spontaneous and cholinergically induced behavioral states in the sheep fetus.

The sleep-wake cycle has been studied extensively in both adult and fetal mammalian species with emphasis in different areas. Fetal studies have focused on characterization of behavioral states and responses to challenges such as hypoxia, and there have been relatively fewer studies that have investigated the control of fetal behavioral state. The objective of this study was to determine whether cerebral blood flow during cholinergically induced fetal behavioral states was similar to that during spontaneous fetal behavioral states in chronically catheterized near-term sheep fetuses. Injection of carbachol (1.25 microg) into the cisterna magna increased the duration of the subsequent low-voltage electrocortical epoch. Scopolamine infusion (0.3 mg) increased the duration of the subsequent high-voltage electrocortical activity epoch. Cerebral blood flow and oxygen delivery were higher during both spontaneous and carbachol-induced low-voltage/rapid eye movement behavioral state than during spontaneous and scopolamine-induced high-voltage/non-rapid eye movement behavioral state. Thus, pharmacologic manipulation of fetal behavioral state induced a state that resembled spontaneous fetal behavioral state both electrophysiologically and metabolically. This study shows that inducing extended periods of a desired fetal behavioral state is possible and that this method may be used to study their function.

Analysis of Variance↗
PubMed2005

Enzymes of drug metabolism during delirium.

BACKGROUND: Delirium is common in ill medical patients. Several drugs and polypharmacy are recognised risk factors, yet little is known about drug metabolism in people with delirium. OBJECTIVE: The aim of this study was to investigate the activities of plasma esterases (drug metabolising enzymes) in delirium. DESIGN: This was a prospective study of delirium present at time of hospital admission (community acquired) or developing later (hospital acquired) in patients admitted as a medical emergency and aged 75 years or over. METHODS: Following informed consent or assent cognitive screening was completed on all patients on admission and every 48 hours subsequently. Delirium was diagnosed by Confusion Assessment Method and DSM IV criteria. Blood samples were taken on admission and at onset of delirium if this was later. Four plasma esterase assays were performed spectrophotometrically: acetylcholinesterase, aspirin esterase, benzoylcholinesterase, butyrylcholinesterase. RESULTS: 283 patients (71% of eligible) were recruited, with mean age 82.4 years and 59% female. 27% had community acquired delirium, 10% developed hospital acquired delirium, 63% never developed delirium. On admission the mean activities of all four esterase assays were statistically significantly lower in delirious than non delirious patients. There were no significant differences on admission in any plasma esterase activity between patients with hospital and community acquired delirium. In-hospital mortality was associated with low plasma esterase activities on admission. CONCLUSION: Plasma esterase activities are suppressed during delirium. These data reinforce the need for extreme caution with drugs in this vulnerable population.

Acetylcholinesterase↗
PubMed2005

Morphological and molecular characterization of a Cypovirus (Reoviridae) from the mosquito Uranotaenia sapphirina (Diptera: Culicidae).

A novel cypovirus has been isolated from the mosquito Uranotaenia sapphirina (UsCPV) and shown to cause a chronic infection confined to the cytoplasm of epithelial cells of the gastric ceca and posterior stomach. The production of large numbers of virions and inclusion bodies and their arrangement into paracrystalline arrays gives the gut of infected insects a distinctive blue iridescence. The virions, which were examined by electron microscopy, are icosahedral (55 to 65 nm in diameter) with a central core that is surrounded by a single capsid layer. They are usually packaged individually within cubic inclusion bodies (polyhedra, approximately 100 nm across), although two to eight virus particles were sometimes occluded together. The virus was experimentally transmitted per os to several mosquito species. The transmission rate was enhanced by the presence of magnesium ions but was inhibited by calcium ions. Most of the infected larvae survived to adulthood, and the adults retained the infection. Electrophoretic analysis of the UsCPV genome segments (using 1% agarose gels) generated a migration pattern (electropherotype) that is different from those of the 16 Cypovirus species already recognized. UsCPV genome segment 10 (Seg-10) showed no significant nucleotide sequence similarity to the corresponding segment of the other cypoviruses that have previously been analyzed, and it has different "conserved" termini. A BLAST search of the UsCPV deduced amino acid sequence also showed little similarity to Antheraea mylitta CPV-4 (67 of 290 [23%]) or Choristoneura fumiferana CPV-16 (33 of 111 [29%]). We conclude that UsCPV should be recognized as a member of a new Cypovirus species (Cypovirus 17, strain UsCPV-17).

Amino Acid Sequence↗
PubMed2004

GW433908/ritonavir once daily in antiretroviral therapy-naive HIV-infected patients: absence of protease resistance at 48 weeks.

OBJECTIVES: To investigate the emergence of resistance to GW433908 (908), a protease inhibitor (PI) with demonstrated antiviral efficacy, safety and tolerability, when administered once daily (q.d.) with low dose ritonavir (908/r). DESIGN: A 48-week Phase III open-label study (SOLO, APV30002) in which antiretroviral therapy-naive patients (n = 649) were treated with 908/r, (1400 mg/200 mg, q.d.) or nelfinavir [1250 mg, twice daily (b.i.d.)] with two nucleoside reverse transcriptase inhibitors (NRTI), abacavir (300 mg, b.i.d.) and lamivudine (150 mg, b.i.d.). METHODS: Viral genotype and phenotype were analysed at baseline and on treatment up to 48 weeks and beyond. RESULTS: Emergence of genotypic resistance was significantly different between the 908/r q.d. and the nelfinavir b.i.d. treatment arms for both PIs (0 versus 50%; P < 0.001) and the NRTI (13% versus 69%; P < 0.001) received. In the nelfinavir arm the key protease mutations D30N and/or L90M were frequently observed. The absence of protease resistance mutations and reduced incidence of NRTI resistance mutations in the 908/r q.d. arm was confirmed by phenotyping, which showed a lack of PI cross-resistance. CONCLUSIONS: The absence of resistance to 908 or cross-resistance to other PIs, and reduced NRTI resistance, following a 908/r q.d. regimen supports the use of this boosted PI early in therapy.

Antiretroviral Therapy, Highly Active↗
PubMed2004

Changes in brain size in hepatic encephalopathy: a coregistered MRI study.

Magnetic resonance imaging (MRI) coregistration techniques can be used to track changes in brain volume. We aimed to determine whether treatment in chronic liver disease altered brain size. The study group comprised nine patients with cirrhosis (7 Child's grade B and 2 Child's grade C). Six had minimal and three had overt hepatic encephalopathy on clinical, psychometric, and electrophysiological testing. Cerebral MRI was performed in seven patients before and 6 weeks after starting lactulose. A further two patients underwent transjugular intrahepatic portosystemic stent shunting with MRI performed before and 24 h afterwards. One patient had a further scan 3 months after TIPSS. Brain size was measured using a semiautomated contour/thresholding technique. Measurable changes were found after treatment intervention, but there was no correlation with severity of encephalopathy (West Haven criteria) or liver dysfunction (Child's score). Three patients improved on lactulose, the brain size decreased with an increase in ventricular volume. Two patients deteriorated; the brain size increased with a concomitant decrease in ventricular volume. Two stable patients had small changes, one with an increase in brain size and a decrease in ventricular volume and the other showing the converse. Following TIPSS, there was an increase in brain size in both patients, evident within 24 h in one patient and at 3 months in the other. Coregistered MRI demonstrates easily detectable changes in brain size following treatment intervention. Our results support the hypothesis that low-grade brain swelling is present, even in minimal hepatic encephalopathy.

Aged↗
PubMed2004

Screening of athletes: Australian experience.

OBJECTIVE: To present an overview of medical screening of athletes in Australia DATA SOURCES: Data was obtained from Australian sports physicians involved in elite national and professional programs. DATA SYNTHESIS/METHODS: The status in Australia of medical screening and in particular the Pre-participation Examination (PPE) was reviewed. RESULTS: The PPE as practised in North America is not performed in Australia. However medical screening of elite national level and professional athletes is widely practised. A variety of screening methods is used. The medical screening protocol recently developed on behalf of the Australasian College of Sports Physicians (ACSP) is presented. CONCLUSIONS: Medical screening of high performance athletes takes place regularly in Australia. Valuable information may be obtained from this process. The extent of the screening is limited by financial and time constraints. The proposed protocol is a basis for a comprehensive medical screening, but can be adapted depending on the individual and the sport played.

Australia↗
PubMed2003

Cerebral blood flow and metabolism in relation to electrocortical activity with severe umbilical cord occlusion in the near-term ovine fetus.

OBJECTIVE: The purpose of this study was to determine the change in cerebral blood flow and substrate metabolism in relation to electrocortical activity in the near-term ovine fetus with repeated umbilical cord occlusion of a severe degree. STUDY DESIGN: Eight near-term fetal sheep were studied through a 2-hour control period, a 6-hour experimental period with repeated cord occlusion of 4 minutes' duration every 90 minutes, and a 16-hour recovery period. Regional cerebral blood flow was measured with the microsphere technique before, during, and after the first cord occlusion; blood flow in the superior sagittal sinus, the cerebral perfusion pressure, and the electrocortical activity were monitored continuously. Brachiocephalic arterial and sagittal venous blood were sampled at selected time points for blood gas and pH, oxygen content, and glucose and lactate levels. RESULTS: Severe umbilical cord occlusion as studied resulted in profound hypoxemia with modest hypercapnia and acidemia, to a similar degree with each insult, but with a return to preocclusion values after occluder release. Glucose values also fell acutely with each cord occlusion by approximately 30% but showed an overall increase through the experimental period, from 0.80 to 1.44 mmol/L; lactate values showed an increase, from 1.21 to 6.10 mmol/L (both P 1 <.01). Fetal electrocortical activity was disrupted markedly, with an abrupt flattening of the electrocortical amplitude by 1.5 minutes of each cord occlusion on average and with an overall increase in indeterminate state activity during the experimental and through the recovery periods. Cerebral blood flow increased approximately 2.5- and 2.8-fold, as measured at 2 and 3.5 minutes during the first cord occlusion (both P <.01) and with the regional flow increase greater in the subcortex and brainstem. Cerebral extraction of oxygen fell toward zero, as measured at 2 minutes during the second and fourth occlusions (P <.05) with oxygen uptake no longer measurable; glucose extraction was now increased approximately 2-fold (P <.05), which indicates that anaerobic metabolism of glucose must be the predominant source of energy at this time. Superior sagittal sinus blood flow also increased in all animals, approximately 1.4- and 1.6-fold at 2 and 3.5 minutes of the first cord occlusion, but much less than the corresponding increase in arterial inflow; the increase was in response to subsequent occlusions was further reduced. CONCLUSION: Severe umbilical cord occlusion in the near-term ovine fetus results in a rapid decrease in the availability of oxygen to the brain. The low PO (2) gradient from blood to tissue rate limits for oxygen consumption by 2 minutes of insult (despite the marked increase in blood flow) and signals the shift to anaerobic metabolism, the suppression in electrocortical activity, and the probable shutdown of other energy-using processes.

Animals↗
PubMedDate not supplied

Screening for visual impairment in older people: validation of the Cardiff Acuity Test.

Poor visual acuity (VA) is a risk factor for falls, and a common impediment to rehabilitation, but conventional VA testing is difficult in dysphasic, deaf or confused patients. In the Cardiff acuity test (CAT) observation of the subject's eye movements (preferential looking) indicates if they can see a vanishing optotype on a card. The test is quick, and requires no speech or understanding on the part of the subject. We consider its usefulness in frail, elderly patients. Seventy-three patients aged 47-99 (mean 78) years, were tested in good lighting, wearing their usual spectacles. Cards ordered 'A' to 'K' with increasingly faint targets were sequentially presented at 1 m, until the subject's eye movements indicated the target to be invisible. We then performed conventional Snellen acuity chart testing. Twenty-three were retested by a second observer, and 24 subjects were retested by the same observer on another day. We used correlation coefficients to confirm inter-observer (r=0.95, P<0.01), and test-retest (r=0.97, P<0.01) reliability. Snellen chart measurements of VA were possible in all but six subjects. The results of CAT and Snellen acuity tests showed statistically significant correlation (r=0.35, P<0.01). The World Health Organisation (WHO) define significant impairment as a Snellen test acuity below 6/18, and using the 'G' card as a threshold were able to detect this degree of impairment with a sensitivity of 91.7%, and a specificity of 90.9%. The CAT is reliable, and highly acceptable to elderly patients, and may be useful as a screening tool in clinical practice, and for epidemiological purposes.

Age Factors↗
PubMedDate not supplied

Nosocomial pressure ulcer rates in critical care: performance improvement project.

Assessment, monitoring, and prevention of pressure ulcers in the hospitalized patient are required standards of care. The annual nosocomial pressure ulcer (NPU) rates for the adult intensive care units at our facility had trended up to 33% from 14% over a 13-month period. Our performance improvement team decided to track 5 variables that may have contributed to the increased incidence of NPU. Weekly skin care rounds were conducted to collect data, educate staff, and reinforce skin care policy and standards of care. Data analysis revealed 3 areas that required further emphasis with nursing staff: daily assessment with the Braden Scale, prevention of NPU beginning on the day of hospital admission, and the effect of sedation on patient mobility. Implementation of appropriate interventions targeted to specific Braden subscales needs to be included in the plan of care.

Academic Medical Centers↗