PubMed Health⌕ Search

Biomedical subjects

C A Hart

Publications and source records attributed to C A Hart.

At least 19 recordsLinked to original sources
PubMed2006

Promotion of prostatic metastatic migration towards human bone marrow stoma by Omega 6 and its inhibition by Omega 3 PUFAs.

Epidemiological studies have shown not only a relationship between the intake of dietary lipids and an increased risk of developing metastatic prostate cancer, but also the type of lipid intake that influences the risk of metastatic prostate cancer. The Omega-6 poly-unsaturated fatty acid, Arachidonic acid, has been shown to enhance the proliferation of malignant prostate epithelial cells and increase the risk of advanced prostate cancer. However, its role in potentiating the migration of cancer cells is unknown. Here we show that arachidonic acid at concentrations <or=5 microM is a potent stimulator of malignant epithelial cellular invasion, which is able to restore invasion toward hydrocortisone-deprived adipocyte-free human bone marrow stroma completely. This observed invasion is mediated by the arachidonic acid metabolite prostaglandin E2 and is inhibited by the Omega-3 poly-unsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid at a ratio of 1 : 2 Omega-3 : Omega-6, and by the COX-2 inhibitor NS-398. These results identify a mechanism by which arachidonic acid may potentiate the risk of metastatic migration and secondary implantation in vivo, a risk which can be reduced with the uptake of Omega-3 poly-unsaturated fatty acids.

Arachidonic Acid↗
PubMed2006

Evaluation of the meningitis epidemics risk model in Africa.

Meningitis epidemics have a strong environmental component in Africa with the most severe epidemics occurring in the Sahelian region known as the Meningitis Belt. The objective of this study is to evaluate an ecological model based on absolute humidity and land cover type to predict the location of these epidemics. The risk model is evaluated prospectively based on epidemics occurring in Africa from January 2000 to April 2004. Seventy-one epidemics occurred during this time period affecting 22% of continental African districts. The model predicted their location with a sensitivity of 88%. The evaluation also suggests that epidemics may be extending south of the Sahel, which is consistent with environmental changes in the region. This model could be used to select priority areas for the introduction of the newly developed conjugate meningococcal vaccines. Further studies are needed to enhance our understanding of the complex relationship between meningitis epidemics and the environment.

Africa↗
PubMed2006

Bacterial killing in gastric juice--effect of pH and pepsin on Escherichia coli and Helicobacter pylori.

The susceptibility of Escherichia coli and Helicobacter pylori to pH and the effect of pepsin-mediated proteolysis were investigated. This was to establish the relative importance of their bacterial killing properties in gastric juice. Solutions in the pH range 1.5-7.4 with or without pig pepsin A were used, together with seven gastric juice samples obtained from patients undergoing routine gastric collection. Escherichia coli C690 (a capsulate strain), E. coli K-12 (a rough mutant) and Helicobacter pylori E5 were selected as the test organisms. Suspensions of bacteria (1x10(6) E. coli ml-1 and 1x10(8) H. pylori ml-1) were pre-incubated with test solutions at 37 degrees C for up to 2 h, and then cultured to establish the effect on subsequent growth. Survival of bacteria was diminished at pHs of less than 3.5, whereas killing required a pH of less than 2.5. Pre-incubation with pig pepsin at 0.5, 1.0 and 2.0 mg ml-1 at pH 3.5 reduced viable counts by 100% for E. coli 690 and E. coli K-12 after 100 min incubation. With H. pylori, the viable counts decreased to 50% of the control after 20 min incubation in 1 mg pepsin ml-1 at pH 2.5, 3.0 and 3.5. The gastric juices showed bactericidal activity at pH 3.5, and the rate of killing was juice dependent, with complete death of E. coli 690 occurring between 5 and 40 min post-incubation. Thus, killing of E. coli and H. pylori occurs optimally at pHs of less than 2.5. At pH 3.5, little effect is observed, whereas addition of pepsin alone or in gastric juice causes a marked increase in bacterial susceptibility, suggesting an important role for proteolysis in the killing of bacteria.

Colony Count, Microbial↗
PubMed2006

Characterization of a spirochaete isolated from a case of bovine digital dermatitis.

AIMS: The aim of the study was to characterize a spirochaete isolated from the lesions of a cow with digital dermatitis (DD). METHODS AND RESULTS: The characterization was on the basis of its light and electron microscopic appearance, enzymic profile and DNA sequence analysis of its flagellin and 16S rRNA genes. The spirochaete was 6-8-microm long and 0.2-0.3 microm in diameter, and possessed seven to eight periplasmic flagella, with three to five helical turns. The enzymic profile of the bacterium resembles, but is not identical to that of Treponema brennaborense. Its flagellin gene sequence was identical to that of Treponema phagedenis but distinct from that of an ovine spirochaete. Analysis of a 1477-bp region of the 16S rRNA genes indicated that this is a Treponema species and that it is indistinguishable from some isolates made from cases of bovine DD in the United States. Finally, electron microscopy revealed the presence of myovirus-like bacteriophage particles in all cultures of the treponeme examined. CONCLUSIONS: The spirochaete isolate was identified as a Treponema species closely related to some isolates from the United States (by 16S rDNA) and to T. phagedenis (by flagellin gene sequence) and is associated with bacteriophage particles. SIGNIFICANCE AND IMPACT OF THE STUDY: The fact that the isolates with the same or very similar 16S rDNA sequences have been obtained from cases of bovine DD in cattle in different countries at different times, lends further support to the hypothesis that treponemes play a role in the pathogenesis of this disease.

Animals↗
PubMed2006

Molecular epidemiology of rotavirus diarrhea among children and adults in Nepal: detection of G12 strains with P[6] or P[8] and a G11P[25] strain.

In anticipation of a rotavirus vaccine in Nepal, this study was undertaken to determine the distribution of the G and P serotypes and electropherotypes of rotaviruses in order to examine if there is any emerging serotype or unusual strain circulating in children and adults in Nepal. Of 1,315 diarrheal stool specimens, rotavirus was detected by an enzyme-linked immunosorbent assay in 116 (17%) of 666 patients less than 5 years of age, in 18 (7%) of 260 patients 5 to 14 years of age, and in 19 (5%) of 358 patients 15 years of age and older. Approximately 75% of rotavirus diarrhea occurred in children less than 5 years of age. Approximately 70% of rotaviruses found in each of the three age groups belonged to serotype G1P[8]. Interestingly, there were 29 (20%) G12 rotaviruses carrying either P[8] or P[6] and one (0.7%) G11 rotavirus carrying an unusual P[25] genotype. RNA polyacrylamide gel electrophoresis discriminated 19 strains (electropherotypes), among which there were three codominant strains carrying G1P[8] and long RNA patterns. Five electropherotypes were discriminated among G12 rotaviruses, all of which had long RNA patterns. The fact that 20% of rotaviruses were G12 strains carrying either P[8] or P[6] and had multiple electropherotypes suggest that G12 strains are not more rare strains but that they pose an emerging challenge to current and future vaccines. The presence of multiple strains as defined by electropherotypes suggests the richness of the rotavirus gene pool in Nepal, where unusual strains may continue to emerge.

Adolescent↗
PubMed2006

Molecular characterization of rotavirus gastroenteritis strains, Iraqi Kurdistan.

Of 260 children with acute diarrhea in Erbil, Iraqi Kurdistan, 96 (37%) were infected with rotavirus. Reverse transcription-polymerase chain reaction identified G1, G4, G2, G9, P[8], P[6], and P[4] as the most common genotypes. Eight G/P combinations were found, but P[8]G1 and P[4]G2 accounted for >50% of the strains.

Acute Disease↗
PubMed2006

A survey of antimicrobial prescribing and dispensing practices in rural Bangladesh.

This study was undertaken to determine the patterns of antimicrobial prescription by 64 Rural Medical Practitioners (RMPs) from Bangladesh. The antimicrobial dispensing procedures followed by the local retail drug sellers along with the purchasing capacities of the patients was also assessed. All antimicrobial agents were prescribed mainly on the patient's complaints, and all available antibiotics were prescribed in inappropriate doses and duration. In most cases, the RMPs initiated treatment with a parenteral form of antibiotic, and a different oral antibiotic usually followed. Parenteral streptomycin was used most frequently in short inadequate courses. Almost half of the antibiotics were sold without any prescriptions, and even ordinary people without any knowledge of medicine asked the drug seller for specific antibiotics. This unregulated prescribing and dispensing practice has the potential risk for the development and spread of antimicrobial resistance on a global scale.

Anti-Infective Agents↗
PubMed2005

Invasive characteristics of human prostatic epithelial cells: understanding the metastatic process.

Prostate cancer has a predilection to metastasise to the bone marrow stroma (BMS) by an as yet uncharacterised mechanism. We have defined a series of coculture models of invasion, which simulate the blood/BMS boundary and allow the elucidation of the signalling and mechanics of trans-endothelial migration within the complex bone marrow environment. Confocal microscopy shows that prostate epithelial cells bind specifically to bone marrow endothelial-to-endothelial cell junctions and initiate endothelial cell retraction. Trans-endothelial migration proceeds via an epithelial cell pseudopodial process, with complete epithelial migration occurring after 232+/-43 min. Stromal-derived factor-1 (SDF-1)/CXCR4 signalling induced PC-3 to invade across a basement membrane although the level of invasion was 3.5-fold less than invasion towards BMS (P=0.0007) or bone marrow endothelial cells (P=0.004). Maximal SDF-1 signalling of invasion was completely inhibited by 10 microM of the SDF-1 inhibitor T140. However, 10 microM T140 only reduced invasion towards BMS and bone marrow endothelial cells by 59% (P=0.001) and 29% (P=0.011), respectively. This study highlights the need to examine the potential roles of signalling molecules and/or inhibitors, not just in single-cell models but in coculture models that mimic the complex environment of the bone marrow.

Bone Marrow Cells↗
PubMed2005

Experimental infection of non-human primates with a human rotavirus isolate.

Several rotavirus candidate vaccines have been developed and are at various stages of evaluation. In order to assess the safety and efficacy of these candidate vaccines, an appropriate non-human primate model is desirable. In earlier studies, we reported the presence of naturally occurring anti-rotavirus antibodies in monkeys and demonstrated that parenteral vaccination of baboons led to production of specific rotavirus antibodies in their milk. In the present study, we assessed the possibility of developing the baboon and the vervet monkey as an animal model for rotavirus studies by inoculating them with a pathogenic human rotavirus isolate prepared from the fresh faeces obtained from a child suffering from rotavirus diarrhoea. Preliminary studies have showed excretion of rotavirus in the faeces of 5 of 5 vervets monkeys and 1 of 2 baboons, by antigen ELISA and SDS-PAGE. These results were confirmed by RT-PCR and electron microscopy. The animals also showed elevation of IgG and high titres of virus neutralising antibodies. These data indicate that baboon and vervet monkeys may be useful models for human rotavirus infection and for pre-clinical evaluation of rotavirus candidate vaccines.

Animals↗
PubMed2005

Environmental contamination with an epidemic strain of Pseudomonas aeruginosa in a Liverpool cystic fibrosis centre, and study of its survival on dry surfaces.

We conducted an environmental survey in the Liverpool adult cystic fibrosis (CF) centre in order to determine the extent of environmental contamination with an epidemic strain of Pseudomonas aeruginosa that colonizes most CF patients in Liverpool, and to identify possible reservoirs and routes of cross-infection. In addition, we studied the survival of this strain on dry surfaces, compared with that of other CF P. aeruginosa strains, to explore factors that might contribute to its high transmissibility. Samples were collected from staff, patients and the environment (drains, bath tubs, showers, dry surfaces, respiratory equipment and air) in the inpatient ward and outpatient clinic. P. aeruginosa strains were tested using a new polymerase chain reaction amplification assay specific for the Liverpool epidemic strain (LES). LES was isolated from patients' hands, clothes and bed linen. Environmental contamination with LES was only detected in close proximity to colonized patients (external surfaces of their respiratory equipment, and spirometry machine tubing and chair) and was short-lived. No persistent environmental reservoirs were found. LES was detected in the majority of air samples from inside patients' rooms, the ward corridor and the outpatient clinic. Survival of LES on dry surfaces was significantly longer than that for some other strains tested, but not compared with other strains shown not to be transmissible. Improved environmental survival on its own, therefore, cannot explain the high transmissibility of this epidemic strain. Our study suggests that airborne dissemination plays a significant role in patient-to-patient spread of LES, and confirms the need to segregate those patients colonized by epidemic P. aeruginosa strains from all other CF patients.

Adult↗
PubMed2005

Bovine digital dermatitis and severe virulent ovine foot rot: a common spirochaetal pathogenesis.

A potential pathological role for spirochaetes in bovine digital dermatitis (bovine DD) and severe virulent ovine foot rot (SVOFR) has been considered and a treponeme isolate obtained from each disease in the UK. In this work, we have investigated the hypothesis that the two diseases may have a shared (common) spirochaetal aetiology. Experiments were designed to identify serological similarities and differences between the two spirochaetes; an enzyme-linked immunosorbent assay (ELISA) was developed to detect anti-treponeme antibodies in the sera of cows and sheep against the two-treponeme isolates. Sera were further tested for antigen reactivity by Western blotting. Cattle and sheep with bovine DD and SVOFR, respectively, had increased seropositivity rates to both treponeme isolates, with different patterns of reactivity between farms. In some cattle herds, significant correlations were shown between antibodies to bovine DD treponemes and SVOFR treponemes (P<0.001). In other herds, there was no apparent cross reaction, suggesting the presence of more than one treponeme in bovine DD on some farms. There was no significant correlation between the two treponeme isolates when ELISA-tested against 58 sheep sera from SVOFR cases (P>0.05); sheep showed strong evidence of reactivity to one or the other treponeme antigens, but never to both. Western blotting against both treponeme antigens showed that they frequently displayed different antigen epitopes, although some minor bands were common to both organisms. The data suggest that there are a number of spirochaetes in UK farms, which could be involved in the pathogenesis of either bovine DD or SVOFR.

Animals↗
PubMed2005

Prevalence and genetic diversity of Campylobacter spp. in environmental water samples from a 100-square-kilometer predominantly dairy farming area.

Water samples were taken systematically from a 100-km2 area of mainly dairy farmland in northwestern England and examined for Campylobacter spp. Pulsed-field gel electrophoresis-restriction fragment length polymorphism (PFGE-RFLP) and flaA strain typing of Campylobacter jejuni and Campylobacter coli isolates were done. Data on the water source and the adjacent environment were recorded and examined as explanatory variables. Campylobacter spp. were isolated from 40.5% (n = 119) of the water samples tested. C. jejuni was isolated from 14.3%, C. coli was isolated from 18.5%, and Campylobacter lari was isolated from 4.2% of the samples. Campylobacter hyointestinalis was not isolated from any water source. The difference in prevalence between water types (trough, running, and standing) was significant (P = 0.001). C. jejuni was the species most commonly isolated from trough-water and running-water sources, while C. coli was the most frequently isolated from standing water (P < 0.001). No association was found between the presence of Escherichia coli and that of Campylobacter spp. The final multivariable logistic regression model for Campylobacter spp. included the following variables: water source, soil type, aspect, and amount of cattle fecal material in the environment (fecal pat count). Strain typing demonstrated a diverse population of C. jejuni and the presence of a common C. coli flaA type that was widely distributed throughout the area. Most of the isolates within the common flaA type were discriminated by PFGE-RFLP. These findings suggest a possible role for environmental water in the epidemiology of Campylobacter spp. in a farming environment.

Agriculture↗
PubMed2004

Prevalence of enteropathic Escherichia coli in dogs with acute and chronic diarrhoea.

Samples of faeces from 57 dogs with acute diarrhoea, 82 dogs with chronic diarrhoea, 34 clinically healthy household dogs and 88 kennelled control dogs were analysed by hybridisation, using DNA probes to detect enteropathogenic Escherichia coli (EPEC) and enterotoxigenic E coli (ETEC), verocytotoxin-producing E coli (VTEC), enterohaemorrhagic E coli (EHEC), enteroinvasive E coli (EIEC) and enteroaggregative E coli (EAggEC). Samples of duodenal juice from 60 of the 82 dogs with chronic diarrhoea were also examined. Significantly more of the dogs with diarrhoea were excreting EPEC (acute 35.1 per cent, chronic 31.7 per cent) and VTEC (acute 24.6 per cent, chronic 28 per cent) than the kennelled dogs (EPEC 17.1 per cent, VTEC 0 per cent) or the household control dogs (EPEC 6 per cent, VTEC 5.9 per cent). Enteropathic E coli was also detected in the duodenal juice of 23 of 60 (38.3 per cent) of the dogs with chronic diarrhoea. The EPEC attaching and effacing A (eaeA) gene and the verocytotoxin 1 (VR1) gene coding for VTEC were often found together. There was good agreement between in vitro studies and hybridisation for the detection of eaeA and VT1. Isolates from the dogs with diarrhoea adhered significantly more to Hep-2 cells, and VT1-positive strains from the dogs with diarrhoea consistently killed more than 50 per cent of Vero cells.

Acute Disease↗
PubMed2004

Epidemiology of rotavirus diarrhoea in Iranian children.

Human rotavirus is the most important cause of severe diarrhoea in infants and young children worldwide. We describe the aetiology of viral diarrhoea and the characteristics of rotavirus infection in Shahrekord, Iran. Two hundred and fifty nine children <5 years old admitted to Hajar Hospital, 245 children with acute diarrhoea attending primary health centres in Shahrekord, and 114 children hospitalised for elective surgery were selected from October 2001 to August 2002. Stool samples were screened for enteric viruses using EM. Rotaviruses were characterised using ELISA, reverse transcription-polymerase chain reaction (RT-PCR), and electropherotyping. One hundred and eighty six viruses were identified, of which 146 (78%) were rotavirus. The second most frequent virus was coronavirus, followed by calicivirus. Rotaviruses exhibited a marked seasonal variation, being most frequently isolated from November to February (50% of rotavirus recovered) and affected mostly children <2 years old. The RT-PCR successfully typed 139 of the 146 (95%) rotavirus G types and 124 (85%) P types. The most frequent P type was, P[8] in 108 (74%), P[4] in 16 (11%), and was P non-typeable in 22 (15%). Among the G types, G1 was identified in 120 (82%), G2 in 19 (13%), and was G-non-typeable in 7 (5%). Our results are the first report of rotavirus genotypes affecting Iranian children. The most frequent G and P types (G1, G2, P[8], and P[4]) are similar to those reported from around the world and will be covered by existing rotavirus vaccines targeting G types G1-G4.

Antigens, Viral↗
PubMed2004

Protein quantity, not protein quality, accelerates whole-body leucine kinetics and the acute-phase response during acute infection in marasmic Malawian children.

The present study compared leucine kinetics and acute-phase-protein concentrations in three groups of marasmic, acutely infected Malawian children fed one of three isoenergetic diets. These were: an enhanced-protein-quality diet (egg-white+tryptophan, providing 1.2 g protein/kg per d; n 14); an increased-protein-content diet (egg-white+tryptophan, providing 1.8 g protein/kg per d; n 14); a standard-protein diet (1.2 g milk protein/kg per d; n 25). The hypotheses tested were that children receiving a diet with more protein would have greater rates of non-oxidative leucine disposal and that children receiving an isonitrogenous diet with a higher protein quality would have lower rates of leucine oxidation. The children were studied after 24 h of therapy using standard [(13)C]leucine stable-isotope tracer techniques. The children receiving the higher-protein-content diet had greater leucine kinetic rates than those receiving the standard-protein-content diet; non-oxidative leucine disposal was 170 (sd 52) v. 122 (sd 30) mumol leucine/kg per h (P<0.01). Leucine oxidation was less in the children receiving the enhanced-protein-quality diet than in those receiving the standard-protein-quality diet; 34 (sd 12) v. 45 (sd 13) mumol leucine/kg per h (P<0.05). The children receiving the high-protein-content diet increased their serum concentration for five of six acute-phase proteins 24 h after starting therapy, while those receiving the standard-protein-content diet did not. These data suggest that there was greater whole-body protein synthesis, and a more vigorous acute-phase response associated with the higher-protein-content diet. The clinical benefits associated with a higher protein intake in marasmic, acutely infected children need further study.

Acute Disease↗
PubMed2004

Development and application of a spiral plating method for the enumeration of Escherichia coli O157 in bovine faeces.

AIM: To develop and validate a direct plating method applicable to epidemiological studies for enumerating Escherichia coli O157 in cattle faeces. METHODS AND RESULTS: The spiral plate count method was used to enumerate E. coli O157 in faecal samples. The accuracy and variation of counts was then assessed using faecal samples inoculated with E. coli O157. There was good agreement between inoculated levels of E. coli O157 and those recovered from faeces, particularly when counts were > 10(2) CFU g(-1) of faeces. The method was applied to a small study assessing short-term survival of E. coli O157 in naturally infected cattle faeces. E. coli O157 was found to survive in faeces for over 10 days at concentrations above 10(3) CFU g(-1) of faeces. Populations of E. coli O157 were also found to increase 100-fold in the first few hours after defecation. CONCLUSIONS: The enumeration method is easy to implement and enables a quick throughput of large numbers of samples. The method is accurate and reliable and enables the inherent variation in count data to be explored but needs to be used in combination with a more sensitive method for samples containing < 10(2) CFU g(-1) of faeces. SIGNIFICANCE AND IMPACT OF THE STUDY: The method described is appropriate for enumeration of E. coli O157 in cattle faeces in large-scale epidemiological studies.

Animals↗
PubMed2004

Intermittent and persistent shedding of Escherichia coli O157 in cohorts of naturally infected calves.

AIMS: We conducted two short-term studies of cohorts of naturally infected calves to determine the prevalence and concentrations of Escherichia coli O157 shed in faeces. METHODS AND RESULTS: Two cohorts of calves were sampled; in the first study 14 calves were sampled up to five times a day for 5 days; in the second study a group of 16 separate calves were sampled once or twice a day for 15 days. All cattle within the two cohorts shed E. coli O157 at some point during the respective studies. In 18% of samples, E. coli O157 could only be isolated using immunomagnetic separation after an enrichment period, suggesting concentrations <250 CFU g(-1). The highest concentrations recorded were 6.7 x 10(5) and 1.6 x 10(6) CFU g(-1) for studies 1 and 2 respectively. CONCLUSIONS: Persistent, high shedders (shedding >10(3) CFU g(-1)) were evident in both studies but, in the majority of calves, the pathogen was isolated intermittently. SIGNIFICANCE AND IMPACT OF THE STUDY: The variable patterns of shedding have important implications for the design of appropriate sampling protocols and for gaining meaningful estimates of parameters used in mathematical models of transmission.

Animals↗