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Biomedical subjects

A M Campbell

Publications and source records attributed to A M Campbell.

At least 19 recordsLinked to original sources
PubMed2005

MAGIC Tool: integrated microarray data analysis.

SUMMARY: Several programs are now available for analyzing the large datasets arising from cDNA microarray experiments. Most programs are expensive commercial packages or require expensive third party software. Some are freely available to academic researchers, but are limited to one operating system. MicroArray Genome Imaging and Clustering Tool (MAGIC Tool) is an open source program that works on all major platforms, and takes users 'from tiff to gif'. Several unique features of MAGIC Tool are particularly useful for research and teaching. AVAILABILITY: http://www.bio.davidson.edu/MAGIC

Algorithms↗
PubMed2004

Cattle and environmental sample-level factors associated with the presence of Salmonella in a multi-state study of conventional and organic dairy farms.

The objective of this study was to evaluate associations between cattle-level factors and environmental samples with the isolation of Salmonella from dairy farms in Minnesota, Wisconsin, Michigan, and New York. The study farms included 129 conventional and organic farms enrolled without regard to previous history of Salmonella infection. Herds were sampled at two-month intervals over a one-year period. Cattle groups more likely to be associated with Salmonella shedding (compared to preweaned calves) were cows designated as sick by farm personnel (OR=2.5, 95% CI: 1.7, 3.7), cows within 14 days of calving (OR=1.8, 95% CI: 1.1, 2.8), and cows due for culling within 14 days (OR=1.9, 95% CI: 1.0, 3.4). State of origin was also associated with the presence of Salmonella in samples from cattle and the farm environment; Midwestern states were more likely to have Salmonella-positive samples compared to New York. Cattle treated with antimicrobials within 14 days of sampling were more likely to be Salmonella-negative compared with nontreated cattle (OR=2.0, 95% CI: 1.1, 3.4). Farms with at least 100 cows were more likely to have Salmonella-positive cattle compared with smaller farms (OR=2.6, 95% CI: 1.4, 4.6). Season was associated with Salmonella shedding in cattle, and compared to the winter period, summer had the highest odds for shedding (OR=2.4, 95% CI: 1.5, 3.7), followed by fall (OR=1.9, 95% CI: 1.2, 3.1) and spring (OR=1.8, 95% CI: 1.2, 2.6). Environmental samples significantly more likely to be Salmonella-positive (compared to bulk tank milk) included, in descending order, samples from sick pens (OR=7.4, 95% CI: 3.4, 15.8), manure storage areas (OR=6.4, 95% CI: 3.5, 11.7), maternity pens (OR=4.2, 95% CI: 2.2, 8.1), haircoats of cows due to be culled (OR=3.9, 95% CI: 2.2, 7.7), milk filters (OR=3.3, 95% CI: 1.8, 6.0), cow waterers (OR=2.8, 95% CI: 1.4, 5.7), calf pens (OR=2.7, 95% CI: 1.3, 5.3), and bird droppings from cow housing (OR=2.4, 95% CI: 1.3, 4.4). Parity, stage of lactation, and calf age were not associated with Salmonella shedding.

Animals↗
PubMed2003

Crystallization and preliminary crystallographic analysis of a new class of glutathione transferase from nematodes.

Mouse and Heligmosomoides polygyrus constitute a readily manipulated small-animal laboratory model for investigating host-nematode interactions. Two major forms of glutathione transferase (GST) are expressed in H. polygyrus adult worms following primary infection. One of these forms belongs to a new class of GST which has only been found in the nematode phylum and therefore presents a possible target for nematode control. In this study, crystals were obtained of a recombinant representative of this new GST class from H. polygyrus. These crystals belong to the triclinic space group P1, with unit-cell parameters a = 72.7, b = 74.0, c = 88.6 A, alpha = 79.1, beta = 80.1, gamma = 81.5 degrees, and are likely to contain four homodimers in the asymmetric unit. X-ray diffraction data were collected to 1.8 A resolution on station A1 at the Cornell High-Energy Synchrotron Source (CHESS).

Animals↗
PubMed2001

Chronic psychosocial stress impairs learning and memory and increases sensitivity to yohimbine in adult rats.

BACKGROUND: It is well known that intense and prolonged stress can produce cognitive impairments and hippocampal damage and increase noradrenergic activity in humans. This study investigated the hypothesis that chronic psychosocial stress would affect behavior, drug sensitivity, and hippocampal-dependent learning and memory in rats. The work provides a novel connection between animal and human studies by evaluating the effects of stress on a rat's response to yohimbine, an alpha(2) adrenergic receptor antagonist. METHODS: Rats were exposed to a cat for 5 weeks and randomly housed with a different group of cohorts each day (psychosocial stress). The effects of the stress manipulations were then assessed on open field behavior, spatial learning and memory in the radial arm water maze and the behavioral response to a low dose of yohimbine (1.5 mg/kg). RESULTS: Stressed rats displayed impaired habituation to a novel environment, heightened anxiety, and increased sensitivity to yohimbine. In addition, the stressed rats exhibited impaired learning and memory. CONCLUSIONS: There are commonalities between the current findings on stressed rats and from studies on traumatized people. Thus, psychosocial stress manipulations in rats may yield insight into the basis of cognitive and neuroendocrine disturbances that commonly occur in people with anxiety disorders.

Adrenergic alpha-2 Receptor Antagonists↗
PubMed2001

Proteomic analysis of Fasciola hepatica excretory-secretory products.

This paper describes a global investigation of the components of Fasciola hepatica excretory-secretory (ES) products by a proteomic approach. Despite the absence of a F. hepatica genome sequencing project we have shown that it was possible to identify 29 of the 60 prominent proteins found using two-dimensional gel electrophoresis. As well as cathepsin L proteases, a number of enzymes implicated in parasite protection from the host immune system were also found to be present in relatively large abundance. These included superoxide dismutase, thioredoxin peroxidase, glutathione S-transferases and fatty acid binding proteins, all of which may play a part in the detoxification of reactive oxygen intermediates. Interestingly, ovine superoxide dismutase was the only protein from the host identified on the gel. We suggest that the relative abundance and protective nature of the components of the ES products of this organism play an important role in its survival within the host. The precise identification, to individual NCBI database entries, of a number of glutathione S-transferases and cathepsin Ls from F. hepatica, by peptide mass fingerprinting, was hampered by multi-database submissions of the two protein superfamilies from this organism.

Amino Acid Sequence↗
PubMed2001

A common class of nematode glutathione S-transferase (GST) revealed by the theoretical proteome of the model organism Caenorhabditis elegans.

The genome verified C. elegans free-living nematode model is a new tool for investigating gene expression in human and animal nematode parasites. There is limited information on designating glutathione S-transferase (GST) to specific classes in lower invertebrates such as nematodes. Following cloning, amino acid sequence alignment, recombinant expression and Western blotting we provide evidence of a new GST class in nematodes or lower invertebrates.

Amino Acid Sequence↗
PubMed2001

Tumour dosimetry in human liver following hepatic yttrium-90 microsphere therapy.

Radiation dose distributions arising from intrahepatic arterial infusion of 90Y microspheres have been investigated. Tissue samples from normal liver, the tumour periphery and tumour centre were taken from a patient following infusion of 3 GBq of 32 microm diameter resin microspheres labelled with 90Y as treatment for an 80 mm diameter metastatic liver tumour. The measured microsphere distributions in three dimensions were used to calculate radiation dose patterns. Although microspheres concentrated in the tumour periphery, heterogeneous doses were delivered to all tissues. Within the tumour periphery average doses ranged from 200 Gy to 600 Gy with minimum doses between 70 Gy and 190 Gy. The average and minimum doses for the tumour centre sample were 6.8 Gy and 3.7 Gy respectively. In the normal liver sample the average dose was 8.9 Gy with a minimum dose of 5 Gy. Less than 1% of the normal liver tissue volume received more than 30 Gy, the level above which complications have resulted for whole liver exposure using external beam radiotherapy. These calculations suggest that preferential deposition of microspheres in the well-vascularized periphery of large tumours will lead to a high proportion of the tumour volume receiving a therapeutic dose, with most of the normal liver tissue being spared substantial damage.

Biophysical Phenomena↗
PubMed2001

Haemostasis in ischaemic stroke and vascular dementia.

Abnormalities of coagulation and fibrinolysis may play an important role in the pathogenesis of ischaemic stroke and vascular dementia. We aimed to determine whether haemostatic function is altered in acute recent-onset or chronic ischaemic cerebrovascular disease. We studied consecutive patients with ischaemic stroke (n = 74) and vascular dementia (n = 42) compared with healthy controls (n = 40) in a case-control study. The ischaemic stroke group was assessed twice, 3-10 days after the acute stroke and at 1-3 months. Fibrinogen, fibrin D-dimer (marker of fibrin turnover) and von Willebrand factor (vWF) (marker of endothelial disturbance) were elevated acutely (P < 0.0001) and in the convalescent phase after ischaemic stroke (P < 0.0001, P < 0.0001, and P < 0.01 respectively, compared with controls). Similar results were seen in the vascular dementia group. Stepwise multivariate regression analyses showed that cerebrovascular disease correlated independently with fibrinogen (P < 0.001) and fibrin D-dimer levels (P < 0.001), while vWF correlated independently with electrocardiograph evidence of ischaemic heart disease (P = 0.004). Changes between acute and convalescent phases in ischaemic stroke were slightly inconsistent. However, in the acute stage there were tendencies for fibrinogen, D-dimer and vWF to be increased, and factor VIII was significantly higher. Abnormalities of haemostasis, including increased fibrin turnover and endothelial disturbance, are found in both acute and chronic cerebral ischaemia. Many of these patients have co-existent ischaemic heart disease and this may contribute to some of these changes. Acute ischaemic stroke is associated with transient changes in haemostatic factors; however, most abnormalities persist into the convalescent phase, and are also demonstrable in subjects with vascular dementia.

Acute-Phase Reaction↗
PubMed2000

Effects of interlayer coupling on the irreversibility lines of NbN/AlN superconducting multilayers.

We have studied the temperature dependence of the in-plane resistivity of NbN/AlN multilayer samples with varying insulating layer thickness in magnetic fields up to 7 T parallel and perpendicular to the films. The upper critical field shows a crossover from 2D to 3D behavior in parallel fields. The irreversibility lines have the form (1-T/T(c))(alpha), where alpha varies from 4 / 3 to 2 with increasing anisotropy. The results are consistent with simultaneous melting and decoupling transitions for the low anisotropy sample, and with melting of decoupled pancakes in the superconducting layers for higher anisotropy samples.

Journal Article↗
PubMed2000

Beta-carbonyl substituted glutathione conjugates as inhibitors Of O. volvulus GST2.

A series of beta-carbonyl substituted glutathione conjugates were prepared and evaluated as inhibitors of OvGST2. Their specificity for the parasite derived protein was assessed through comparison with their inhibition of human piGST. Inhibition of OvGST2 has been demonstrated at low micromolar concentrations for these conjugates and selectivity for OvGST2 over human pi-GST of greater than 10-fold has been achieved.

Animals↗
PubMed2000

Inhibition of glutathione S-transferases (GSTs) from parasitic nematodes by extracts from traditional Nigerian medicinal plants.

Piliostigma thonningii, Ocimum gratissimum, Nauclea latifolia and Alstonia boonei are used in Nigerian traditional medicines against gastrointestinal helminths of animals and man. Proanthocyanidins were detected in Piliostigma and Nauclea, but not Alstonia or Ocimum. Extracts of these plants killed 50% of brine shrimp nauplii at <10 ppm (Nauclea), 100 ppm (Piliostigma) and <1000 ppm (Ocimum and Alstonia), the Nauclea LD50 being similar to the anthelmintic drug piperazine. Extracts were also toxic to the parasitic nematode Haemonchus infective L3 stage. Nematode glutathione-S-transferases (GSTs) are potential drug targets. Apart from Alstonia all the medicinal plants contained heat-stable inhibitory activities against recombinant Ascaris and Onchocerca GSTs in vitro. Piliostigma, Ocimum and Nauclea had IC50s of 2, 10 and 15 microg/mL respectively for Ascaris GST and 4, 8, 28 microg/mL respectively for Onchocerca GST. We suggest that the inhibitory properties of some of these Nigerian plant extracts against GST may contribute to the pharmacological basis of their efficacy against helminths in traditional herbal use.

Animals↗
PubMed2000

Xenognosin sensing in virulence: is there a phenol receptor in Agrobacterium tumefaciens?

BACKGROUND: The mechanisms of signal perception and transmission in the 'two-component' autokinase transmitters/response regulators are poorly understood, especially considering the vast number of such systems now known. Virulence induction from the tumor-inducing (Ti) plasmid of Agrobacterium tumefaciens represents one of the best understood systems with regard to the chemistry of the activating signal, and yet the existing data does not support a receptor-mediated perception event for the xenognostic phenols. RESULTS: Here we provide the first conclusive evidence that a specific receptor must be involved in xenognostic phenol perception, detail structural requirements of the xenognosins necessary for perception by this receptor, and develop a genetic strategy that demonstrates critical components of the phenol recognition system are not encoded on the Ti plasmid. CONCLUSIONS: Although the basic elements of the two-component system required for phenol-mediated induction of virulence gene expression are encoded on the Ti plasmid, they are dependent on the chromosomal background for even the very first stage of signal perception. This discovery suggests a curious evolutionary history, and also provides functional insight into the mechanisms of two-component signal detection and transmission in general.

Agrobacterium tumefaciens↗
PubMed2000

Analysis of the distribution of intra-arterial microspheres in human liver following hepatic yttrium-90 microsphere therapy.

The microscopic distribution of microspheres in human liver following hepatic infusion of 32 microm diameter resin microspheres labelled with 90Y as treatment for an 80 millimetre diameter liver cancer has been investigated. Microspheres were found to deposit inhomogeneously in tissues, preferentially lodging in a region approximately 6 mm wide around the periphery of the tumour. A relative concentration of microspheres of 50 to 70 times that of normal hepatic parenchyma and 65 to 94 times that in the tumour centre was measured in this region. The deposition of spheres in the tumour periphery was not uniform, and cluster analysis showed that the spheres could be classified into clusters. The number of microspheres in a cluster was skewed towards low numbers and cluster sizes varied from 20 to 1500 microm. The observed deposition patterns indicate that the vascular tumour periphery will receive much greater radiation doses from radioactive microspheres than both normal tissue and the avascular tumour centre.

Arteries↗
PubMed1999

A chimeric prokaryotic ancestry of mitochondria and primitive eukaryotes.

We provide data and analysis to support the hypothesis that the ancestor of animal mitochondria (Mt) and many primitive amitochondrial (a-Mt) eukaryotes was a fusion microbe composed of a Clostridium-like eubacterium and a Sulfolobus-like archaebacterium. The analysis is based on several observations: (i) The genome signatures (dinucleotide relative abundance values) of Clostridium and Sulfolobus are compatible (sufficiently similar) and each has significantly more similarity in genome signatures with animal Mt sequences than do all other available prokaryotes. That stable fusions may require compatibility in genome signatures is suggested by the compatibility of plasmids and hosts. (ii) The expanded energy metabolism of the fusion organism was strongly selective for cementing such a fusion. (iii) The molecular apparatus of endospore formation in Clostridium serves as raw material for the development of the nucleus and cytoplasm of the eukaryotic cell.

Amino Acid Sequence↗
PubMed1999

Swallowing abnormalities after acute stroke: A case control study.

Dysphagia is a common and potentially fatal complication of acute stroke. However, the underlying pathophysiology, especially the relative importance of motor and sensory dysfunction, remains controversial. We conducted a case control study of 23 acute stroke patients (mean age = 72 yr) at a median of 6 days post-stroke and 15 healthy controls (mean age = 76 yr). We used novel methods to assess swallowing in detail, including a timed videoendoscopic swallow study and oral sensory threshold testing using electrical stimulation. Vocal cord mobility and voluntary pharyngeal motor activity were impaired in the stroke group compared with the controls (p = 0.01 and 0.03). There was a delay during swallowing in the time to onset of epliglottic tilt in the stroke group, particularly for semisolids (p = 0.02) and solids (p = 0.01), consistent with a delay in initiation of the swallow. Sensory thresholds were not increased in the stroke group compared with controls. We conclude that pharyngeal motor dysfunction and a delay in swallow initiation are common after acute stroke. Vocal cord mobility is reduced, and this may result in reduced airway protection. We found no evidence to support the hypothesis that oropharyngeal sensory dysfunction is common after acute stroke.

Acute Disease↗
PubMed1999

Effect of loratadine on nitrogen dioxide-induced changes in electrical resistance and release of inflammatory mediators from cultured human bronchial epithelial cells.

BACKGROUND: Recent studies have demonstrated that some antihistamines can attenuate histamine-induced release of inflammatory mediators from bronchial epithelial cells. OBJECTIVE: The purpose of study was to test the hypothesis that loratadine may influence pollution-induced inflammation of the airways by modulating epithelial membrane integrity and the synthesis and/or release of inflammatory mediators from airway epithelial cells. METHODS: We have cultured human bronchial epithelial cell (HBEC) cultures from surgical explants and investigated the effect of loratadine on NO2-induced changes in both electrical resistance of HBEC cultures and release of IL-8, RANTES, and soluble intercellular adhesion molecule-1 (sICAM-1) from these cells after exposure for 6 hours to either air or 400 ppb NO2. RESULTS: Exposure for 6 hours to NO2 significantly decreased the electrical resistance of HBEC cultures by 18.1% from baseline (P <.05). Incubation with 0.25 to 25 micromol/L loratadine did not alter the NO2-induced decrease in the electrical resistance of HBEC cultures. NO2 also significantly increased the release of IL-8 from a control value of 52.5 pg/microgram cellular protein to 81.9 pg/microgram cellular protein (P <.05), RANTES from a control value of 0.023 pg/microgram cellular protein to 0.062 pg/microgram cellular protein (P <.05), and sICAM-1 from a control value of 7.7 pg/microgram cellular protein to 16.3 pg/microgram cellular protein (P <.05). The NO2-induced release of all 3 mediators was significantly attenuated by incubation of HBECs with 25 micromol/L loratadine. Incubation with 2.5 micromol/L loratadine also significantly attenuated the NO2-induced release of RANTES and sICAM-1, but not IL-8. CONCLUSIONS: These results suggest that loratadine has the potential to reduce airway inflammation by modulating the release of inflammatory cytokines from airway epithelial cells.

Adult↗