Biomedical subjects

M J Hudson

Publications and source records attributed to M J Hudson.

At least 19 recordsLinked to original sources

PubMed2003

The infectious intestinal disease study of England: a prospective evaluation of symptoms and health care use after an acute episode.

The sequelae of Infectious Intestinal Disease (IID) in a population-based sample of cases and matched controls were investigated for a period of 3 months following the initial infection. Incident cases of IID presenting to GPs or occurring in the community and controls were studied at 3 weeks and over a 3-month follow-up period. Cases were six times more likely than controls to have gastrointestinal symptoms, particularly diarrhoea, at 3 weeks. Ten per cent of cases consulted their GP in the 3 months after episode and 2.3% were referred to hospital. GP presentation rates were twice as high in cases. Gastrointestinal symptoms persist after IID, leading to an increased likelihood of GP consultation and hospital referral. Diagnosis of irritable bowel syndrome may be more likely following IID. The burden of IID is likely to be considerable given its high incidence and the frequency of such sequelae.

Adolescent↗

PubMed2002

Novel in vitro functional assays for the determination of anthrax toxin components.

The characterisation and evaluation of the UK licensed human anthrax vaccine depends on several in vivo tests that determine its safety and potency. Assays for the determination of functionally active and/or immunoreactive toxin components and S-layer proteins have been developed and applied to the characterisation of anthrax vaccine. These technologies may support production of consistent and effective vaccines, and may ultimately reduce the requirements for in vivo testing.

Adenylyl Cyclases↗

PubMed2001

Formulation and characterisation of Bordetella pertussis fimbriae as novel carrier proteins for Hib conjugate vaccines.

Haemophilus influenzae type b (Hib) capsular polysaccharide (polyribosylribitol phosphate, PRP) is the active component of conjugate vaccines that have proven successful in preventing invasive Hib disease. Conjugation of PRP to a protein carrier greatly improves its immunogenicity providing protection in infants and subsequent antibody maturation upon boosting. In this study, fimbriae isolated from Bordetella pertussis have been assessed as novel carrier proteins. These proteins are components of some acellular pertussis vaccines and clinical trials have indicated that fimbriae could be important protective antigens against whooping cough. Fimbriae (Fim2 and Fim3) purified from B. pertussis were dissociated in 6 M guanidine hydrochloride, pH 10.5, to produce proteins of defined size and to facilitate the production and characterisation of the conjugates. Both carbodiimide-mediated coupling and reductive amination were used to conjugate PRP to dissociated fimbriae. Efficiency of conjugation was determined by size exclusion chromatography followed by protein and polysaccharide analysis of fractionated components. Immunisation of rabbits with dissociated fimbriae-PRP conjugates (D.fim-PRP) produced high anti-fimbrial and anti-PRP IgG titres. Use of a D.fim-PRP conjugate could protect against Hib disease and may also augment protection against B. pertussis.

Animals↗

PubMed2001

Human MUC1 mucin: a potent glandular morphogen.

Human MUC1 mucin is a high-molecular-weight transmembrane glycoprotein, which is apically expressed in the majority of glandular epithelia. During embryonic development, changes in the pattern of MUC1 mucin expression coincide with the onset of glandular differentiation. This mucin is also frequently overexpressed and aberrantly glycosylated in carcinomas. To investigate the potential role of MUC1 mucin in morphogenesis, a full length MUC1 cDNA was transfected into murine mammary adenocarcinoma (410.4) and Madin-Darby canine kidney (MDCK) cells. This generated four clonal cell lines. Western blotting, FACS analysis, and immunohistochemistry confirmed expression of MUC1. All four MUC1-expressing clones demonstrated altered morphogenesis when cultured in three-dimensional type I collagen gels. While parental and vector control 410.4 cells formed compact spherical structures, the MUC1-expressing clones formed complex branching structures. Similarly, while parental and vector control MDCK cells formed small circumscribed colonies with a central lumen, the MUC1-expressing clones formed elongated tubules. MUC1 expression was also associated with reduced cellular cohesion and enhanced migration on type I collagen-coated surfaces for all except one of the clones, which expressed only low levels of MUC1 on the cell surface. These results show that MUC1 expression stimulates morphogenetic changes in two distinct epithelial cell lines. Taken together with previous observations on MUC1 expression in embryonic development and carcinomas, this finding suggests that MUC1 may induce changes in tissue architecture in both normal development and cancer.

Adenocarcinoma↗

PubMed2001

A study of infectious intestinal disease in England: risk factors associated with group A rotavirus in children.

OBJECTIVE: To identify risk factors for infectious intestinal disease (IID) due to rotavirus group A in children aged under 16 years. METHODS: Case-control study of cases of IID with rotavirus infection presenting to general practitioners (GPs) or occurring in community cohorts, and matched controls. RESULTS: There were 139 matched pairs. In children under 16 years the following risk factors were significantly associated with rotavirus IID: living in rented council housing (adjusted OR = 3.78, P = 0.022), accommodation with more than five rooms (OR = 0.72, P = 0.002), contact with someone ill with IID (OR = 3.45, P < 0.001). Some foods were associated with decreased risk. In infants, bottle feeding with or without breast feeding was associated with increased risk (OR = 9.06, P < 0.05). CONCLUSIONS: Contact with persons with IID, living in rented council housing and accommodation with fewer rooms, were significant risk factors for sporadic rotavirus IID in children whereas breast feeding is protective in infants.

Adolescent↗

PubMed2001

The study of infectious intestinal disease in England: risk factors for cases of infectious intestinal disease with Campylobacter jejuni infection.

This is a case-control study aimed at identifying risk factors for intestinal infection with Campylobacter jejuni. Cases were defined as subjects with diarrhoea occurring in community cohorts or presenting to General Practitioners (GPs) with Campylobacter jejuni in stools. Controls were selected from GP lists or cohorts, matched by age, sex, and GP practice. Travel abroad and consumption of chicken in a restaurant were statistically significantly associated with being a case. There was no statistically significant risk associated with consumption of chicken other than in restaurants nor with reported domestic kitchen hygiene practices. Consumption of some foods was associated with a lower risk of being a case. Most cases remained unexplained. We suggest that infection with low numbers of micro-organisms, and individual susceptibility may play a greater role in the causation of campylobacter infection than previously thought. It is possible that in mild, sporadic cases infection may result from cross contamination from kitchen hygiene practices usually regarded as acceptable. Chicken may be a less important vehicle of infection for sporadic cases than for outbreaks, although its role as a source of infection in both settings requires further clarification in particular in relation to the effect of domestic hygiene practices. The potential effect of diet in reducing the risk of campylobacteriosis requires exploration.

Campylobacter Infections↗

PubMed2001

Bordetella pertussis fimbriae are effective carrier proteins in Neisseria meningitidis serogroup C conjugate vaccines.

Serogroup C meningococcal conjugate vaccines generally use diphtheria or tetanus toxoids as the protein carriers. The use of alternative carrier proteins may allow multivalent conjugate vaccines to be formulated into a single injection and circumvent potential problems of immune suppression in primed individuals. Bordetella pertussis fimbriae were assessed as carrier proteins for Neisseria meningitidis serogroup C polysaccharide. Fimbriae were conjugated to the polysaccharide using modifications of published methods and characterised by size exclusion chromatography; co-elution of protein and polysaccharide moieties confirmed conjugation. The conjugates elicited boostable IgG responses to fimbriae and serogroup C polysaccharide in mice, and IgG:IgM ratios indicated that the responses were thymus-dependent. High bactericidal antibody titres against a serogroup C strain of N. meningitidis were also observed. In a mouse infection model, the conjugate vaccine protected against lethal infection with N. meningitidis. Therefore, B. pertussis fimbriae are effective carrier proteins for meningococcal serogroup C polysaccharide and could produce a vaccine to protect against meningococcal disease and to augment protection against pertussis.

Animals↗

PubMed2001

A comparison study of different methods used in the detection of Giardia lamblia.

OBJECTIVE: The purpose of this study was to compare results obtained using a single fecal specimen for O&P examination, direct immunofluorescent assay (DFA), and three immunodiagnostic techniques. DESIGN: Sixty-eight human fecal specimens were collected and examined by each method. The O&P and the DFA were used as the reference method. SETTING: The study was performed at the research laboratory in the Medical Technology Department at The University of Southern Mississippi. PATIENTS OR OTHER PARTICIPANTS: The fecal specimens were collected from individuals with a suspected Giardia lamblia infection. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The amount of agreement and disagreement between methods. 1. The sensitivity and specificity of each method. 2. The working time and cost per specimen for each method. RESULTS: There was complete agreement among methods on 52 specimens (21 positive, 31 negative). Eight specimens were positive by all immunologic methods, but negative by O&P. The remaining eight specimens (12%) demonstrated discrepancies among methods. Sensitivity and specificity of each assay ranged from 91% to 100% and 89% to 100%, respectively. The cost per specimen ranged from $11.62 for the DFA method to $32.54 for the O&P method. The average cost per specimen for ELISA and EIA averaged $26.86. CONCLUSION: The study supported findings of other investigators who concluded that immunologic methods have the greater sensitivity. The immunologic methods were more efficient, quicker, and economical than the conventional O&P method.

Animals↗

PubMed2000

Crystallographic, X-ray absorption, and IR studies of solid- and solution-state structures of tris(nitrato) N,N,N',N'-tetraethylmalonamide complexes of lanthanides. Comparison with the Americium complex.

To fine-tune the design of optimized donor ligands for nuclear waste actinide selective extraction, both electronic and molecular structures of the actinide complexes that are formed must be investigated. In particular, to achieve the selective complexation of transplutonium 3+ ions versus lanthanide 3+ ions is one of the major challenges, given the chemical similarities between these two f-element families. In this work, the structure of solvent-phase M(NO3)3(TEMA)2 complexes (Ln = Nd, Eu, Ho, Yb, Lu, Am; TEMA = N,N,N',N'-tetraethylmalonamide) was investigated by liquid-phase spectroscopic methods among which extended X-ray absorption fine structure played a major role. In addition, the crystal structures of the species Nd(NO3)3(TEMA)2 and Yb(NO3)3(TEMA)2 have been determined by X-ray diffraction. Nd(NO3)3(C11N2O2H22)2 crystallizes in the monoclinic system (P2(1) space group; a = 11.2627(4) A, b = 20.5992(8) A, c = 22.2126(8) A; alpha = gamma = 90 degrees, beta = 102.572(1) degrees; Z = 6), and Yb(NO3)3(C11N2O2H22)2 crystallizes in the orthorhombic system (P2(1)2(1)2(1) space group; a = 9.3542(1) A, b = 18.1148(2) A, c = 19.7675(2) A; alpha = beta = gamma = 90 degrees; Z = 4). In the solvent phase, the metal polyhedron was found to be similar to that of the solid-state complex Nd(NO3)3(TEMA)2 for M = Nd to Ho. For M = Yb and Lu, a significant elongation of one nitrate oxygen bond was observed. Comparison with measurements on the Am(NO3)3(TEMA)2 complex in ethanol has shown the similarities between the Nd3+ and Am3+ coordination spheres.

Journal Article↗

PubMed1999

Study of infectious intestinal disease in England: rates in the community, presenting to general practice, and reported to national surveillance. The Infectious Intestinal Disease Study Executive.

OBJECTIVE: To establish the incidence and aetiology of infectious intestinal disease in the community and presenting to general practitioners. Comparison with incidence and aetiology of cases reaching national laboratory based surveillance. DESIGN: Population based community cohort incidence study, general practice based incidence studies, and case linkage to national laboratory surveillance. SETTING: 70 general practices throughout England. PARTICIPANTS: 459 975 patients served by the practices. Community surveillance of 9776 randomly selected patients. MAIN OUTCOME MEASURES: Incidence of infectious intestinal disease in community and reported to general practice. RESULTS: 781 cases were identified in the community cohort, giving an incidence of 19.4/100 person years (95% confidence interval 18.1 to 20.8). 8770 cases presented to general practice (3.3/100 person years (2.94 to 3.75)). One case was reported to national surveillance for every 1.4 laboratory identifications, 6.2 stools sent for laboratory investigation, 23 cases presenting to general practice, and 136 community cases. The ratio of cases in the community to cases reaching national surveillance was lower for bacterial pathogens (salmonella 3.2:1, campylobacter 7.6:1) than for viruses (rotavirus 35:1, small round structured viruses 1562:1). There were many cases for which no organism was identified. CONCLUSIONS: Infectious intestinal disease occurs in 1 in 5 people each year, of whom 1 in 6 presents to a general practitioner. The proportion of cases not recorded by national laboratory surveillance is large and varies widely by microorganism. Ways of supplementing the national laboratory surveillance system for infectious intestinal diseases should be considered.

Adolescent↗

PubMed1999

A study of infectious intestinal disease in England: plan and methods of data collection.

The Committee on the Microbiological Safety of Food, set up in 1989 by the Department of Health in response to national epidemics of foodborne infection, considered the available evidence and commissioned a study of infectious intestinal disease (IID) in England. Seventy practices (with 489,500) patients overall) recruited from the Medical Research Council's General Practice Research Framework between August 1993 and January 1995 collected data for one year. The practice populations were representative of practices in England by area and urban/rural location, but with fewer small and affluent practices. There were five main components. i) A population cohort of 9776 (40% of those eligible) were enrolled to estimate the incidence and aetiology of IID in the community, and a large proportion were followed up. A median of 10% of patients on practice age-sex registers had moved away or died. ii) A nested case control component based on cases ascertained in the cohort was used to identify risk factors for IID in the community. iii) In a case control component used to identify risk factors and to estimate the incidence and aetiology of IID presenting in 34 general practices 70% of the 4026 cases returned risk factor questionnaires, 75% submitted stools, and matched controls were found for 75% of cases. iv) An enumeration component was used to estimate the incidence of IID presenting to general practitioners (GPs) in 36 practices and the proportion of specimens sent routinely for microbiological examination. v) In a socioeconomic costs component used to estimate the burden of illness of IID in the community and presenting to GPs 63% of those who returned a risk factor questionnaire also returned a socioeconomic questionnaire and were representative by age, sex, and social class. Despite variable enrolment and compliance the study sample had sufficient power for the multivariable analysis. The characteristics associated with low enrollment and compliance must be considered in the interpretation of the main study results.

Case-Control Studies↗

PubMed1999

A study of infectious intestinal disease in England: microbiological findings in cases and controls.

A study was undertaken to identify the microorganisms and toxins in stool specimens associated with infectious intestinal disease (IID) among cases in the community and presenting to general practitioners (GPs) and in asymptomatic controls. Population based cohorts were recruited from practice lists in 70 practices and followed for 26 weeks (cohort component). Seven hundred and sixty-one cases of IID identified from the cohorts, 2893 cases who presented to GPs in 34 of the practices (GP component), and age/sex matched control subjects (555 and 2264, respectively) submitted stool specimens by post for comprehensive microbiological examination. Campylobacter spp (12.2% of stools tested), rotavirus group A (7.7%), and small round structured virus (SRSV) (6.5%) were the organisms most commonly detected in the GP component. SRSV was identified in 7.0% of cases in the community cohort. No target microorganisms or toxins were identified in 45.1% and 63.1% of cases in the two components. Aeromonas spp, Yersinia spp, and some enterovirulent groups of Escherichia coli were detected as frequently in controls as in cases. The higher frequency of detection of campylobacter, salmonella, and rotavirus among cases who presented to GPs than among those in the community suggests that those pathogens cause more severe illness. No enteropathogens were detected from a large proportion of cases although comprehensive standard methods were used to seek them.

Case-Control Studies↗

PubMed1998

Loss of AP-2 results in up-regulation of MCAM/MUC18 and an increase in tumor growth and metastasis of human melanoma cells.

MCAM/MUC18 is a cell-surface glycoprotein of 113 kDa, originally identified as a melanoma antigen, whose expression is associated with tumor progression and the development of metastatic potential. We have previously shown that enforced expression of MCAM/MUC18 in primary cutaneous melanoma led to increased tumor growth and metastatic potential in nude mice. The mechanism for up-regulation of MCAM/MUC18 during melanoma progression is unknown. Here we show that up-regulation of MCAM/MUC18 expression in highly metastatic cells correlates with loss of expression of the transcription factor AP-2. The MCAM/MUC18 promoter contains four binding sites for AP-2, and electrophoretic mobility shift assay gels demonstrated that the AP-2 protein bound directly to the MCAM/MUC18 promoter. Transfection of AP-2 into highly metastatic A375SM melanoma cells (AP-2-negative and MCAM/MUC18-positive) inhibited MCAM/MUC18 promoter-driven chloramphenicol acetyltransferase reporter gene in a dose-dependent manner. MCAM/MUC18 mRNA and protein expression were down-regulated in AP-2-transfected but not in control cells. In addition, re-expression of AP-2 in A375SM cells inhibited their tumorigenicity and metastatic potential in nude mice. These results indicate that the expression of MCAM/MUC18 is regulated by AP-2 and that enforced AP-2 expression suppresses tumorigenicity and metastatic potential of human melanoma cells, possibly by down-regulating MCAM/MUC18 gene expression. Since AP-2 also regulates other genes that are involved in the progression of human melanoma such as c-KIT, E-cadherin, MMP-2, and p21(WAF-1), we propose that loss of AP-2 is a crucial event in the development of malignant melanoma.

Animals↗

PubMed1998

Experimental campylobacter infection and diarrhoea in immunodeficient mice.

The responses of previously untested immunodeficient mouse strains to campylobacter infection are described. Three strains of adult immunodeficient mice (SCID-Beige, C.B-17-SCID-Beige and RAG-2) were inoculated intragastrically with Campylobacter jejuni NCTC 11168. All mice became heavily colonised, but none developed clinical signs of disease. Immunocompetent BALB/c mice inoculated similarly had much lower colonisation levels. The co-administration of iron dextran had no effect on colonisation levels nor the development of clinical signs of disease. In contrast, C.B-17-SCID-Beige mice, when inoculated with one of a series of 10 clinical isolates of C. jejuni, were more heavily colonised for extended periods (up to 5 months) and approximately 10-20% of the mice became ill with diarrhoea. C. jejuni was detected in mouse faeces throughout at levels of 10(7)-10(9) cfu/g. All mice killed whilst ill with diarrhoea displayed histopathological lesions typical of human campylobacteriosis. Severe pathology was limited to the large intestine and was suggestive of an acute, bacteria-induced inflammation. Although blood was detected in the diarrhoeal stools, no evidence of mucosal epithelial cell invasion was found by immunohistology. No pathology was detected in tissue sections from any of the animals that had not developed signs of disease following C. jejuni inoculation. These immunodeficient mouse strains are readily, and heavily, colonised as adults by C. jejuni. The diarrhoea, although sporadic, was reproducibly produced, and could provide the basis for pathogenicity studies.

Animals↗

PubMed1997

Antibody responses to gut bacteria in ankylosing spondylitis, rheumatoid arthritis, Crohn's disease and ulcerative colitis.

Specific immunoreactive anti-Klebsiella antibodies are found in patients with ankylosing spondylitis (AS), a significant proportion of whom have occult inflammatory bowel disease. Molecular mimicry between Klebsiella or other bacterial antigens and HLA-B27 has been suggested in the pathogenesis of AS. The specificity of increased immunoreactivity against Klebsiella remains to be assessed against the abundant anaerobic bacterial flora, present either in healthy controls or in patients with ulcerative colitis (UC) and Crohn's disease (CD). Total immunoglobulin (Ig; IgG, IgA, IgM) immunoreactivity was measured by ELISA against Klebsiella pneumoniae, Proteus mirabilis, Escherichia coli and ten anaerobic isolates of the predominant normal bowel flora in 35 patients with active AS, 60 patients with inflammatory bowel disease (30 CD, 30 UC), 60 patients with active rheumatoid arthritis (RA) and 60 healthy controls. Ig immunoreactivity to K. pneumoniae was significantly elevated in AS (P < 0.001), CD (P < 0.001) and UC (P < 0.001) patients compared with RA patients and healthy controls. Furthermore, Ig immunoreactivity to P. mirabilis was significantly elevated only in RA patients, compared with the other inflammatory groups (P < 0.001) and controls (P < 0.001). There was no significant antibody response against E. coli or the ten obligate anaerobes in any of the test groups. The data suggested an increased immune response to Klebsiella in patients with AS, UC, CD and to Proteus in patients with RA. The specificity of these responses in some patients supported a possible role for enteric Klebsiella in the pathogenesis of AS and Proteus in RA. The role of Klebsiella in inflammatory bowel disease requires further study.

Adult↗

PubMed1997

Flotation removal of As(V) onto goethite.

Arsenic oxyanions, considered as priority pollutants, were removed from dilute aqueous solutions by sorption onto synthetic goethite, a typical inorganic adsorbent. Flotation was subsequently applied as an effective solid/liquid separation method. The combined process produced a foam concentrate, containing the arsenic-loaded goethite particles. The dispersed-air flotation technique was used for the generation of fine gas bubbles. The main parameters affecting the process were studied and promising results, in terms of arsenic removal and of goethite separation, were obtained.

Journal Article↗

PubMed1996

Sulphasalazine treatment and the colorectal mucosa-associated flora in ulcerative colitis.

AIM: To study the influence of sulphasalazine treatment on the mucosa-associated bacterial flora of rectal biopsy tissue specimens in patients with ulcerative colitis. PATIENTS: Twenty-four patients had newly diagnosed active ulcerative colitis; 20 patients had acute relapse of ulcerative colitis (10 not taking maintenance sulphasalazine); (40 patients had quiescent ulcerative colitis; 21 not taking maintenance sulphasalazine). The influence of 3 weeks of sulphasalazine treatment on the mucosa-associated flora was studied in the patients presenting with active disease. RESULTS: Comparison of patients according to sulphasalazine usage revealed few differences in the mucosal flora. In patients with quiescent ulcerative colitis, Escherichia coli was found at lower counts in patients taking maintenance sulphasalazine; however, this effect was not evident in patients with active disease. Inconsistent changes in other facultatives were seen between the two active disease groups, particularly for a miscellaneous group of unidentified Gram-positive rods. Three patients, all receiving sulphasalazine, were colonized with Clostridium difficile, but this did not appear to influence their disease. CONCLUSION: Sulphasalazine treatment in ulcerative colitis causes only minor disturbance to the populations of bacteria colonizing the colorectal mucosa.

Adult↗

PubMed1996

MUC1 expressed in PanC1 cells decreases adhesion to type 1 collagen but increases contraction in collagen lattices.

A subline of human pancreatic cells (PanC1) that expresses low levels of cytokeratins 8 and 18 but not MUC1 mucin was transfected with both 3.5-kb and 3.9-kb full-length MUC1 cDNA. The MUC1-positive clone expressing the larger mucin was shown to express increased levels of cytokeratins 8 and 18 compared with the parental line or vector controls. Growth of these MUC1-transfected cells in type I collagen gels produced marked gel contraction that could be significantly reduced by the synthetic peptide SRGDTG or by growth in serum and fibronectin-depleted media. Cellular binding to type I collagen was found to be reduced by two- to four-fold in cells expressing the MUC1 mucin, for which the greatest inhibition was observed in cells expressing the larger form. No difference in cellular binding to fibronectin was observed. From these data we conclude that the human MUC1 mucin modifies the differentiated state of human pancreatic cells by altering cytokeratin expression and reducing adhesion to type I collagen but paradoxically enhancing the cellular contractile phenotype, effects that appear to be mediated by integrin expression and/or function.

Adenocarcinoma↗