PubMed Health⌕ Search

Biomedical subjects

A Gunn

Publications and source records attributed to A Gunn.

At least 19 recordsLinked to original sources
PubMed2003

Evaluation of a commercial ELISA for detecting Norwalk-like virus antigen in faeces.

A commercially available enzyme immunoassay, the IDEIA Norwalk-like virus (NLV) enzyme linked immunosorbent assay (ELISA; Dako Cytomation, Ely, UK) for detecting NLV antigen in faecal samples and determining the NLV genogroup was evaluated. The performance of the ELISA was compared with that of electron microscopy and the reverse transcription polymerase chain reaction by testing a panel of faecal samples collected from patients involved in outbreaks of gastroenteritis. When compared with reverse transcription-polymerase chain reaction (RT-PCR), the ELISA had a sensitivity and specificity of 55.5 and 98.3%, respectively. This compares with a sensitivity and specificity for EM of 23.9 and 99.2%, respectively. The sensitivity and specificity of the ELISA for determining the aetiology of a Norwalk virus-like outbreak, based on two or more positive samples within an outbreak, were 52.2 and 100% when two samples were collected from an outbreak and 71.4 and 100% when six or more samples were collected. The ELISA correctly identified the NLV genogroups of viruses previously characterised by partial DNA sequencing. The ELISA is a suitable alternative to the preliminary screening by EM for investigating outbreaks of gastroenteritis. Outbreaks, negative by ELISA should be examined by RT-PCR in order to detect strains non-reactive in the assay and virus strains from representative ELISA positive outbreaks should be characterised fully to allow the genetic diversity of NLVs co-circulating in the population to be described.

Antigens, Viral↗
PubMed2001

Colonic crypt cell proliferation state assessed by whole crypt microdissection in sporadic neoplasia and familial adenomatous polyposis.

BACKGROUND: It has yet to be established whether proliferative activity in the macroscopically normal colonic mucosa is causally correlated with neoplastic risk. Measurement of proliferative activity in human subjects is of necessity usually undertaken using indirect methods with inherent limitations, and relatively little has been published on the effect of normal biological variables on such indices. AIMS: To establish the validity of mitosis counts following whole crypt microdissection as an index of the crypt cell proliferative state (CCPS) and to examine the effect of normal biological variables (age, sex, and colonic site) and colonic neoplasia on the mitotic index in macroscopically normal human colon. SUBJECTS: Mucosal samples were obtained at colectomy or colonoscopy from 107 individuals (24 controls, 23 sporadic adenoma patients, 31 sporadic carcinoma patients, and 29 patients with familial adenomatous polyposis (FAP)). METHODS: Mucosal specimens were hydrated, hydrolysed, and small groups of crypts separated from the main specimen under a dissecting microscope. The total number of mitoses/crypt were counted by one observer for each of 10 complete crypts. RESULTS: Validation work established that whole crypt mitoses counts were reliable and reproducible. There was no relation between age and mean mitoses/crypt (Pearson correlation coefficient -0.1). The CCPS count was higher for males than for females (difference in means 2.8 (95% confidence interval 0.80-4.66)) among controls but there was no gender difference in the three disease groups. For all disease groups and controls, the crypt mitotic count showed a significant linear increase (p=0.004) from the rectum to the caecum. Biopsies from within 5 cm of the macroscopic margin of a carcinoma (near) gave a mean mitosis count of 12.6 while those from more than 10 cm (far) were lower but not significantly so (p=0.12) with a count of 9.0. The mean mitoses/crypt were similar for the controls and adenomas (5.6 and 4.7, respectively) but greater for the cancers and especially for FAP (8.3 and 14.2, respectively). Statistical analysis confirmed that there were significant differences (p<0.05) between controls and all disease groups together, between sporadic disease and FAP, and between adenoma and carcinoma subjects at each of the four colonic sites. Post hoc comparison by t test showed significantly greater CCPS for FAP compared with controls (p<0.001) and for sporadic cancer versus controls (p=0.04). CONCLUSIONS: Whole crypt microdissection and mitosis counting is a reliable, reproducible, and robust technique for assessing CCPS in the human colon. CCPS is unaffected by age but increases from the distal to the proximal colon. CCPS is increased if a sporadic cancer is present and markedly increased in FAP. However, the precise relation of an increased CCPS to the neoplastic process remains uncertain.

Adenoma↗
PubMed2000

Evidence for a two-electron transfer using the all-ferrous Fe protein during nitrogenase catalysis.

The nitrogenase-catalyzed H(2) evolution and acetylene-reduction reactions using Ti(III) and dithionite (DT) as reductants were examined and compared under a variety of conditions. Ti(III) is known to make the all-ferrous Fe protein ([Fe(4)S(4)](0)) and lowers the amount of ATP hydrolyzed during nitrogenase catalysis by approximately 2-fold. Here we further investigate this behavior and present results consistent with the Fe protein in the [Fe(4)S(4)](0) redox state transferring two electrons ([Fe(4)S(4)](2+)/[Fe(4)S(4)](0)) per MoFe protein interaction using Ti(III) but transferring only one electron ([Fe(4)S(4)](2+)/[Fe(4)S(4)](1+)) using DT. MoFe protein specific activity was measured as a function of Fe:MoFe protein ratio for both a one- and a two-electron transfer reaction, and nearly identical curves were obtained. However, Fe protein specific activity curves as a function of MoFe:Fe protein ratio showed two distinct reactivity patterns. With DT as reductant, typical MoFe inhibition curves were obtained for operation of the [Fe(4)S(4)](2+)/[Fe(4)S(4)](1+) redox couple, but with Ti(III) as reductant the [Fe(4)S(4)](2+)/[Fe(4)S(4)](0) redox couple was functional and MoFe inhibition was not observed at high MoFe:Fe protein ratios. With Ti(III) as reductant, nitrogenase catalysis produced hyperbolic curves, yielding a V(max) for the Fe protein specific activity of about 3200 nmol of H(2) min(-1) mg(-1) Fe protein, significantly higher than for reactions conducted with DT as reductant. Lag phase experiments (Hageman, R. V., and Burris, R. H. (1978) Proc. Natl. Acad. Sci. U. S. A. 75, 2699-2702) were carried out at MoFe:Fe protein ratios of 100 and 300 using both DT and Ti(III). A lag phase was observed for DT but, with Ti(III) product formation, began immediately and remained linear for over 30 min. Activity measurements using Av-Cp heterologous crosses were examined using both DT and Ti(III) as reductants to compare the reactivity of the [Fe(4)S(4)](2+)/[Fe(4)S(4)](1+) and [Fe(4)S(4)](2+)/[Fe(4)S(4)](0) redox couples and both were inactive. The results are discussed in terms of the Fe protein transferring two electrons per MoFe protein encounter using the [Fe(4)S(4)](2+)/[Fe(4)S(4)](0) redox couple with Ti(III) as reductant.

Azotobacter↗
PubMed2000

Reactions of Azotobacter vinelandii nitrogenase using Ti(III) as reductant.

Nitrogenase-catalyzed reactions using Ti(III) were examined under a wide variety of conditions to determine the suitability of Ti(III) to serve as a general nitrogenase reductant. Solutions prepared from H2-reduced TiCl3, aluminum-reduced TiCl3, TiCl2, evaporated TiCl3 from an HCl, solution, and TiF3 were evaluated as reductants. Three general types of reactivity were observed. The first showed that, below Ti(III) concentrations of about 0.50 mM, nitrogenase catalysis utilized Ti(III) in a first-order reaction. The second showed that, above 0.50 mM, the rate of nitrogenase catalysis was zero order in Ti(III), indicating the enzyme was saturated with this reductant. Above 2.0-5.0 mM, nitrogenase catalysis was inhibited by Ti(III) depending on the titanium source used for solution preparation. This inhibition was investigated and found to be independent of the buffer type and pH, while high salt and citrate concentrations caused moderate inhibition. [Ti(IV)] above 2.0-3.0 mM and [Ti(III)] above about 5.0 mM were inhibitory. ATP/2e values were 4-5 for [Ti(III)] at or below 1.0-2.0 mM, 2.0 from 5.0 to 7.0 mM Ti(III) where nitrogenase is not inhibited, and 2.0 above 7.0 mM Ti(III) where severe inhibition occurs. For nitrogenase-catalyzed reactions using Ti(III) as reductant, the potential of the solution changes with time as the Ti(III)/Ti(IV) ratio changes. From the change in the rate of product formation (Ti(III) disappearance) with change in solution potential, the rate of nitrogenase catalysis was determined as a function of solution potential. From such experiments, a midpoint turnover potential of -480 mV was determined for nitrogenase catalysis with an associated n = 2 value.

Adenosine Triphosphate↗
PubMed2000

International Guidelines for Neonatal Resuscitation: An excerpt from the Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: International Consensus on Science. Contributors and Reviewers for the Neonatal Resuscitation Guidelines.

The International Guidelines 2000 Conference on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiac Care (ECC) formulated new evidenced-based recommendations for neonatal resuscitation. These guidelines comprehensively update the last recommendations, published in 1992 after the Fifth National Conference on CPR and ECC. As a result of the evidence evaluation process, significant changes occurred in the recommended management routines for: * Meconium-stained amniotic fluid: If the newly born infant has absent or depressed respirations, heart rate <100 beats per minute (bpm), or poor muscle tone, direct tracheal suctioning should be performed to remove meconium from the airway. * Preventing heat loss: Hyperthermia should be avoided. * Oxygenation and ventilation: 100% oxygen is recommended for assisted ventilation; however, if supplemental oxygen is unavailable, positive-pressure ventilation should be initiated with room air. The laryngeal mask airway may serve as an effective alternative for establishing an airway if bag-mask ventilation is ineffective or attempts at intubation have failed. Exhaled CO(2) detection can be useful in the secondary confirmation of endotracheal intubation. * Chest compressions: Compressions should be administered if the heart rate is absent or remains <60 bpm despite adequate assisted ventilation for 30 seconds. The 2-thumb, encircling-hands method of chest compression is preferred, with a depth of compression one third the anterior-posterior diameter of the chest and sufficient to generate a palpable pulse. * Medications, volume expansion, and vascular access: Epinephrine in a dose of 0.01-0.03 mg/kg (0.1-0.3 mL/kg of 1:10,000 solution) should be administered if the heart rate remains <60 bpm after a minimum of 30 seconds of adequate ventilation and chest compressions. Emergency volume expansion may be accomplished with an isotonic crystalloid solution or O-negative red blood cells; albumin-containing solutions are no longer the fluid of choice for initial volume expansion. Intraosseous access can serve as an alternative route for medications/volume expansion if umbilical or other direct venous access is not readily available. * Noninitiation and discontinuation of resuscitation: There are circumstances (relating to gestational age, birth weight, known underlying condition, lack of response to interventions) in which noninitiation or discontinuation of resuscitation in the delivery room may be appropriate.

Blood Volume↗
PubMed2000

Prevalence of Toxoplasma gondii antibodies in muskox (Ovibos moschatus) sera from northern Canada.

Prevalence of antibodies to Toxoplasma gondii was determined in 203 muskoxen (Ovibos moschatus) from 3 geographically distinct areas of northern Canada (near the hamlets of Kugluktuk and Cambridge Bay, Nunavut and Holman, Northwest Territories) by the modified agglutination test (MAT). Antibodies were found in 13 (6.4%) of 203 animals with MAT titers of 1:25 in 2, 1:50 in 7, 1:200 in 2, 1:400 in 1, and 1:800 in 1. The 4 muskoxen with MAT titers > or =1:200 were adult females and were among 10 animals examined from a mainland population near Kugluktuk. The seroprevalence was lower in Victoria Island muskoxen collected near Cambridge Bay (4.6% of 151) and Holman (4.8% of 42). This is the first serologic survey for T. gondii infection in muskoxen.

Agglutination Tests↗
PubMed1999

Enhanced efficiency of ATP hydrolysis during nitrogenase catalysis utilizing reductants that form the all-ferrous redox state of the Fe protein.

The amount of MgATP hydrolyzed per pair of electrons transferred (ATP/2e) during nitrogenase catalysis (1.0 atm N(2), 30 degrees C) using titanium(III) citrate (Ti(III)) as reductant was measured and compared to the same reaction using dithionite (DT). ATP/2e values near 2.0 for Ti(III) and 5.0 for DT indicate that nitrogenase has a much lower ATP requirement using Ti(III) as reductant. Using reduced Azotobacter vinelandii flavoprotein (AvFlpH(2)), a possible in vivo nitrogenase reductant, ATP/2e values near 2.0 were also observed. When the reaction was conducted using Ti(III) under N(2), 5% CO in N(2), Ar, 5% CO in Ar, or acetylene, ATP/2e values near 2.0 were also observed. With Ti(III) as reductant, ATP/2e values near 2.0 were measured as a function of temperature, Fe:MoFe protein ratio, and MoFe:Fe protein ratio, in contrast to measured values of 4.0-25 when DT is used under the same conditions. Both Ti(III) and AvFlpH(2) are capable of forming the [Fe(4)S(4)](0) cluster state of the Fe protein whereas DT is not, suggesting that ATP/2e values near 2.0 arise from operation of the [Fe(4)S(4)](2+)/[Fe(4)S(4)](0) redox couple with hydrolysis of only 2 ATPs per pair of electrons transferred. Additional experiments showed that ATP/2e values near 2. 0 correlated with slower rates of product formation and that faster rates of product formation produced ATP/2e values near 5.0. ATP/2e values of 5.0 are consistent with the operation of the [Fe(4)S(4)](2+)/[Fe(4)S(4)](1+) redox couple while ATP/2e values of 2.0 could arise from operation of the [Fe(4)S(4)](2+)/[Fe(4)S(4)](0) redox couple. These results suggest that two distinct Fe protein redox couples may be functional during nitrogenase catalysis and that the efficiency of ATP utilization depends on which of these redox couples is dominant.

Adenosine Triphosphate↗
PubMed1999

The transmission of deformed wing virus between honeybees (Apis mellifera L.) by the ectoparasitic mite varroa jacobsoni Oud

Under field conditions, Varroa jacobsoni were shown to be highly effective vectors of deformed wing virus (DWV) between bees. Adult female mites obtained from honeybee pupae naturally infected with DWV contained virus titers many times in excess of those found in their hosts and, beyond that, which might be expected from a concentration effect. It is therefore possible that DWV may be capable of replicating within V. jacobsoni. Bees which tested positive for DWV exhibited characteristic morphological deformity and/or they died during pupation. Asymptomatic bees had much lower virus titers than those which were deformed or had died during pupation. It is therefore suggested that for DWV to cause pathology it must be present in pupae above a certain concentration. The amount of DWV vectored by V. jacobsoni will depend on the mites' level of infection, which will in turn depend on whether they had fed previously on dead or deformed bees and also on the rate of replication of the virus within the mites. Consequently, developing bees infested with large numbers of mites could suffer a high incidence of deformity if the mites are heavily infected or harbor an especially virulent strain of virus. A positive relationship was found between increasing numbers of mites on individual bees and the incidence of morphological deformity and death. This probably reflected the large number of viral particles transmitted by the mites, which resulted in many multiply infested bees dying before emergence. These results demonstrate the importance of the role of viruses when considering the pathology of V. jacobsoni and that much of the pathology previously associated with the effects of mite feeding could be attributed directly to secondary pathogens vectored by V. jacobsoni. Copyright 1999 Academic Press.

Journal Article↗
PubMed1998

Asphyxial brain injury--the role of the IGF system.

Transient neural injuries, such as asphyxia, can trigger considerable delayed neuronal death. Inappropriate induction of apoptosis is thought to play an important role in this process. Our studies have shown marked changes in the IGF system in the brain in response to these injuries with an induction of insulin growth factor (IGF)-1 and insulin growth factor binding protein (IGFBP)-2 and IGFBP-3 in glial cells in the region of injury. This suggests that the IGF-1 system may be an endogenous neuroprotective system. Earlier administration of IGF-1 - 2 h after injury reduced the phase of secondary neuronal loss suggesting that IGF-1 may well have therapeutic potential as a neuronal rescue agent. The action of IGF-1 appears to involve binding proteins, transport to the site of injury and the IGF-1 receptor and inhibition of apoptosis, but might also involve generation of GPE which itself appears to be neuroprotective. Together these results indicate considerable potential of these agents to treat stroke, perinatal asphyxia and other forms of acute brain injury.

Animals↗
PubMed1998

The influence of fatness on the likelihood of early-winter pregnancy in muskoxen (Ovibos moschatus).

Among wild ruminants, muskoxen have an exceptional ability to fatten, but their pregnancy rates are variable and often low. To test whether the likelihood of pregnancy in muskoxen is associated with exceptionally good body condition, we used logistic regression analysis with data from 32 pregnant and 18 nonpregnant muskoxen > or = 1.5 yr of age shot in November (1989 to 1992) on Victoria Island in Arctic Canada. We assayed their serum for insulin-like growth factor-1 (IGF-1). All fatness and mass measures were positively related to the likelihood of pregnancy (P < 0.001), with the strongest associations for estimated total fat mass (80% of outcomes predicted correctly) and kidney fat mass (77%), and weaker models for body mass. Pregnancy was less likely to occur in lactating females than in nonlactating ones (P = 0.03). Although IGF-1 concentrations were higher (P = 0.001) in nonlactating females than in lactating ones (28.7 +/- 1.7 vs. 22.5 ng/ml), no association with pregnancy was detected (P = 0.57). Fatness associated with a 50% probability of pregnancy in muskoxen (22% of ingesta-free body mass or 32 kg fat in females > 3.5 yr old) is much higher than in caribou and somewhat higher than in cattle, and this may partly account for the low calving rates often observed in this species.

Adipose Tissue↗
PubMed1998

Maturational change in the cortical response to hypoperfusion injury in the fetal sheep.

A characteristic of perinatal encephalopathies are the distinct patterns of neuronal and glial cell loss. Cerebral hypoperfusion is thought to be a major cause of these lesions. Gestational age is likely to influence outcome. This study compares the cortical electrophysiologic and histopathologic responses to hypoperfusion injury between preterm and near term fetuses. Chronically instrumented 0.65 (93-99-d, n = 9) and 0.9 (119-133-d, n = 6) gestation fetal sheep underwent 30 min of cerebral hypoperfusion injury. The parasagittal cortical EEG and impedance (measure of cytotoxic edema) responses plus histologic outcome (3 d) were compared. The acute rise in impedance was similar in amplitude, but the onset was delayed (5.0 +/- 0.7 versus 9.1 +/- 1.1 min, p < 0.05) in the preterm fetuses relative to those near term. In contrast the extent of the secondary rise was reduced (p < 0.01) and peaked earlier in the preterm fetuses (19.8 +/- 1.0 versus 40.5 +/- 3.5 h, p < 0.01). Both groups had a similar fall in EEG spectral edge frequency. The preterm fetuses had a milder loss of EEG intensity at 72 h (-7.7 +/- 1.5 versus -12.8 +/- 0.9 dB, p < 0.05). At both ages there was a predominantly parasagittal cortical distribution of damage with a similar pattern of neuronal loss in the thalamus and striatum. There was extensive selective neuronal loss within the upper layers of the cortex in those near term. In contrast the preterm fetuses developed subcortical infarcts (p < 0.05). The cortical response to injury altered during the last trimester. The results suggest the severity of the delayed phase of cortical neuronal injury and selective neuronal loss increased near term. In contrast, the preterm fetuses had a more rapidly evolving injury leading to necrosis of the subcortical white matter.

Animals↗
PubMed1997

Endoscopic screening and surgery for familial adenomatous polyposis: dangerous delays.

BACKGROUND: Registries for patients with familial adenomatous polyposis (FAP) can improve patient management. However, in relation to colorectal cancer, a critical review has not previously been undertaken of the effectiveness of screening and surgical protocols within a registry. METHODS: A review was undertaken of 63 gene carriers who received primary treatment for FAP between 1987, when the Northern Region Polyposis Registry was formed, and 1995. RESULTS: In some gene carriers with colorectal cancer, surgery was delayed because of social factors or unpleasant surgical experiences in the family. Colonoscopy failed to detect five colorectal cancers. CONCLUSIONS: Delays in treatment still occur in patients with FAP and colorectal cancer, often because of complex social problems and patients' fear of surgery. If multiple colorectal polyps are present, colonoscopy is not a reliable screening test for malignancy and prophylactic surgery is indicated, preferably before the patient is 20 years old.

Adenomatous Polyposis Coli↗
PubMed1997

Bizarre ECG in head injury mimicking ventricular tachycardia.

Bizarre electrocardiographic (ECG) changes were found in an 18-year-old girl who had a subdural haematoma following head trauma. The initial diagnosis was of ventricular tachycardia (VT) and she was treated with intravenous anti-arrhythmic drugs and electrical cardioversion, but to no effect. It was later concluded that the ECG appearances were not of a ventricular arrhythmia but were the result of the intracranial pathology. ECG abnormalities related to head injuries have been reported on many occasions, and our case report illustrates how this can create difficulties for the attending clinicians.

Adolescent↗