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Biomedical subjects

M J Hudson

Publications and source records attributed to M J Hudson.

At least 37 records · Page 2Linked to original sources

Product development horizons--a view from industry.

Against the background of what appears to be an increasing incidence of many allergic disorders, the production of safe, effective 'hypoallergenic' diets on a commercial scale has become of increasing importance. Combining knowledge of protein biochemistry and immunology with clinical science has provided not only a greater understanding of what is required for effective treatment of allergic disorders, but is also facilitating a unique insight into the use of dietary management in allergy prevention. Infants who have become sensitised to intact proteins either in utero or during early feeding usually require a diet with significantly reduced allergenicity for a period of time. One of the most effective methods of allergen avoidance has traditionally been achieved by subjecting dairy proteins to extensive hydrolysis until virtually no antigenic epitopes remain recognisable to the infant's immune system (Sampson, Bernhisel-Broadbent, Yang et al., 1991). This 'hypoallergenic' protein base can then be used together with other non-sensitizing ingredients, to create a formula feed which will meet the essential nutritional requirements of infants during the specified period for recovery--usually the first 12 months of life or beyond.

Dietary Proteins↗

Elevation in anti-Proteus antibodies in patients with rheumatoid arthritis from Bermuda and England.

OBJECTIVE: To determine whether patients with rheumatoid arthritis (RA) from Bermuda and England have an increased anti-Proteus antibody titer when compared to healthy Bermudian and English controls, and to ascertain whether any increase in antibody titer is specific by testing 4 other microbes, Escherichia coli and 3 normal anaerobic bowel bacteria. METHODS: Antibody titers were measured by ELISA and indirect immunofluorescence (IIFA) under coded conditions. RESULTS: Elevated titers of anti-Proteus antibodies were demonstrated in 34 patients with active RA from Bermuda when compared to 33 healthy Bermudian controls by ELISA (p < 0.001) and IIFA (p < 0.001). An elevation of anti-Proteus antibodies was also observed in 34 patients with RA from England when compared to 30 healthy English controls again by ELISA (p < 0.001). A similar antibody elevation in 31 patients with RA from England was observed when compared to 30 healthy controls when measured by IIFA (p < 0.001). However, there was no significant elevation in antibody titers against E. coli or the 3 normal bowel flora isolates in the patients with RA from both countries compared to their respective controls, when measured by ELISA. CONCLUSION: A specific elevation in the immune response to Proteus mirabilis has been demonstrated in patients with RA from both Bermuda and England. However, this study cannot distinguish between antibody association with disease per se and association with disease activity. The role of Proteus in RA and the effect of anti-Proteus therapy in patients with RA merits further study.

Adult↗

The targeting of immunoliposomes to tumour cells (A431) and the effects of encapsulated methotrexate.

Immunoliposomes have been prepared from lipid mixtures of dipalmitoylphosphatidylcholine, wheat germ phosphatidylinositol and a reactive lipid (the m-maleimidobenzoyl-N-hydroxysuccinimide derivative of dipalmitoylphosphatidylethanolamine) which was conjugated to the N-succinimidyl-S-acetylthioacetate (SATA) derivative of a monoclonal antibody (H17E2) raised to human placental alkaline phosphatase (PLAP). The immunoliposomes were prepared by the extrusion technique (VETs) and by reverse phase evaporation (REVs) and were found to effectively target to immobilised PLAP and to PLAP or PLAP-like enzyme on the surface of a tumour cell line (A431) using an ELISA and autoradiography. The extent of binding to immobilised PLAP was a function of immunoliposomal lipid concentration, the weight-average number of antibody molecules per liposome (Pw) and the liposome size. The effectiveness of methotrexate-loaded immunoliposomes in inhibiting the proliferation of A431 cells was investigated relative to equivalent levels of the free drug. The immunoliposomes prepared by the extrusion technique (VETs) inhibited growth of A431 cells but had no effect on the growth of a normal human fibroblastic cell line. Immunoliposomes prepared by reverse phase evaporation (REVs) were less effective in inhibiting A431 cell proliferation. The immunoliposomes probably enter the tumour cells largely by receptor-mediated endocytosis although other mechanisms of uptake cannot be excluded.

Alkaline Phosphatase↗

Adhesive and hydrophobic properties of Escherichia coli from the rectal mucosa of patients with ulcerative colitis.

The adherent properties and hydrophobicity of Escherichia coli isolates have been compared from the rectal mucosa of patients with active and inactive ulcerative colitis and from a control patient group. Patients with active colitis were colonised less frequently and with lower numbers of E coli than were control patients. Mannose resistant adhesion to HEp-2 cells was determined for 124 isolates of E coli and surface hydrophobicity was estimated by salt agglutination in 96 of these isolates. There was no significant difference in the distribution of adherent strains between the colitis patient groups or with disease activity. E coli from the control patients were marginally less adhesive than those from colitics. The hydrophobicity of isolates did not differ significantly between colitic and control groups nor were there significant differences correlated with disease activity. Furthermore, for these mucosal E coli isolates, hydrophobicity and mannose resistant adhesion were unrelated characteristics.

Agglutination Tests↗

Breath methane excretion and intestinal methanogenesis in children and adults in rural Nigeria.

Breath methane excretion was measured in 274 healthy subjects from 2 rural communities in northern Nigeria. Studies in 24 adults showed a normal faecal flora with no enteric pathogens. Breath methane was detected in 122 (77%) of 159 adults, 19 (40%) of 47 older children (2-6 years), and 4 (8%) of 68 young children (< 2 years). Women were slightly more commonly breath methane-positive than men (82% versus 75%, respectively). Hyperventilation did not influence the specificity of the breath methane assay, although levels were circa 30% lower after deliberate hyperventilation. Methanogens were estimated by enrichment culture of faeces from 49 subjects. Of the subjects 76% had faecal methanogens estimated at > or = 10(2)/g, 45% at > or = 10(4)/g, and 16% at > or = 10(6)/g. There was no significant difference in distribution of methanogenic cultures between different age or tribal groups, and there were no obvious correlations between breath methane excretion and either the faecal carriage of methanogens per se or numbers present.

Adult↗

The rectal mucosa-associated microflora in patients with ulcerative colitis.

The rectal mucosa-associated flora (MAF) of patients with ulcerative colitis has been studied in 25 patients with newly diagnosed disease, 20 with relapse of existing disease, and 44 who were in remission. Patients with active disease were re-examined twice during treatment. The MAF was simpler and less dense than the microflora of faeces. Obligate anaerobes usually predominated in the MAF although the ratio of obligate anaerobes to facultative species was lower than that found in faeces. Viable counts of the total flora and of its constituent genera varied considerably between patients. Counts of the total flora, of obligate anaerobes (including bifidobacteria, eubacteria and clostridia), and facultative organisms and micro-aerobes (enterobacteria and lactobacilli) were reduced in patients with active disease compared with those with inactive disease; corresponding carriage rates were also lower. Counts and carriage rates increased during treatment and approached those found in quiescent disease. The alterations in the MAF were especially marked in patients experiencing their first attack of ulcerative colitis. The relationship between these alterations and the aetiology and pathogenesis of this disease remains unclear.

Bacterial Infections↗

Search for enteric microbial pathogens in patients with ulcerative colitis.

Microbial pathogens were sought in faeces of patients with active ulcerative colitis and again after 3 months treatment. 64 patients were examined during their first episode of ulcerative colitis and 30 with relapse of chronic disease. At presentation, bacterial pathogens were not found; 1 patient had cryptosporidiosis. In 10 patients treatment appeared to result in some loss of colonisation resistance as evidenced by colonisation with beta-haemolytic streptococci, Staphylococcus aureus, candida and Clostridium difficile. Unidentified cytotoxic activity was present in the faeces of 4 patients at presentation and 2 patients during or after treatment. We conclude that enteric infection is an uncommon finding in patients with active ulcerative colitis.

Colitis, Ulcerative↗

Antigenic conservation of the ureases of spiral- and helical-shaped bacteria colonising the stomachs of man and animals.

A monoclonal antibody, CP11, has been produced which is directed against the ureas of Campylobacter pylori. This antibody has been used to look for antigenic cross-reactivity, in other ureolytic and non-ureolytic campylobacters, by immunohistological techniques. It has also been used to investigate the helical-shaped organisms found in the stomach of the human, monkey and cat (CS1) and the ileum of the rat (ST1). Interestingly the antibody cross-reacted with the gastric helical organisms from the human, monkey and cat but not with the rat helical organism. No cross-reactivity was observed with C. mustelae or the other ureolytic campylobacters, C. nitrofigilis and the urease positive thermophilic campylobacters. These results are discussed in relation to the phylotaxonomy of these organisms.

Animals↗

Isolation of a gastric campylobacter-like organism from the stomach of four rhesus monkeys, and identification as Campylobacter pylori.

Campylobacter-like organisms, isolated from the gastric antrum of Rhesus monkeys, were compared with Campylobacter jejuni and C. pylori. They were similar to C. pylori by light microscopy, in ultrastructural morphology, in enzymic, fatty-acid-methyl-ester, and protein-profile analysis, and in antigenic reactivity with rabbit antisera to C. jejuni and C. pylori and with C. pylori-specific monoclonal antibody. Because this natural infection of the Rhesus monkey is associated with chronic gastritis, resembling the disease in humans colonised with C. pylori, we recommend the animal as a model for the investigation of human gastritis.

Animals↗

Iatrogenic superior mesenteric arteriovenous fistula. Report of a case and review of the literature.

Bowel resection can result in the formation of an arteriovenous fistula at the point of intersection of the feeding vessels. Iatrogenic arteriovenous fistula of the superior mesenteric vessels is rare, with only 11 cases reported in the English language literature. We report a case after small bowel resection, which was done because of adhesions from a laparoscopic sterilization. An anatomic classification of the fistulas into H and U types is suggested, with its significance for management. A review of the literature is included.

Arteriovenous Fistula↗

Relationship of CDC group EO-2 and psychrobacter immobilis.

Thirty strains of microorganisms previously classified in the CDC group EO-2 were studied to determine the relationship of this group and the recently proposed Psychrobacter immobilis. Results of transformation studies indicated that 9 of the 30 studied strains should be reclassified as P. immobilis. While transformation studies should be used to identify the Psychrobacter genus definitively, some presumptive characteristics useful in differentiating the CDC group EO-2 and P. immobilis were observed. The Psychrobacter genus, compared with the CDC group EO-2, grew well at 25 degrees C, lightly or not at all at 35 degrees C, and not at all at 42 degrees C, grew in nutrient broth without NaCl and with only one exception grew in 6% NaCl, usually did not produce acid from adonitol, dextrin, fructose, or D-mannitol, did not demonstrate the O-shaped cellular morphology, and usually possessed an odor resembling that noted from a phenylethyl alcohol blood agar plate.

DNA, Bacterial↗

Colonic bacterial proteases to IgA1 and sIgA in patients with ulcerative colitis.

The colonic faecal and mucosal associated bacterial populations of five patients with ulcerative colitis and four control patients were studied in detail to assess their ability to produce IgA1-proteases. A total of 330 bacterial strains were isolated from the patients with ulcerative colitis and IgA1-protease activity was unable to be reliably shown in any. It is therefore unlikely that such enzyme production by colonic bacteria plays a significant role in the pathogenesis of ulcerative colitis.

Bacteria↗

Rectal spirochaetosis in homosexual men: characterisation of the organism and pathophysiology.

Microbiological and electron microscopy studies were carried out on rectal biopsy specimens and faecal samples from eight practising male homosexuals and five heterosexual controls. Rectal spirochaetosis was present in five of the eight homosexual men. The organism was cultured and morphologically identified as a large anaerobic host associated treponeme. The degrees of infestation and depletion of microvilli were also measured. The results are discussed in relation to the possible clinical importance of rectal spirochaetosis.

Adult↗

The microbial flora of the rectal mucosa and faeces of patients with Crohn's disease before and during antimicrobial chemotherapy.

The faecal flora and mucosa-associated flora (MAF) of rectal biopsy material from 12 patients with active Crohn's disease were studied before and during treatment with a combination of metronidazole and cotrimoxazole given orally for at least 2 weeks. The total faecal flora was greater than the MAF although the proportions of bacterial groups were similar. The changes observed during treatment were: obligate anaerobes such as Bacteroides spp. decreased in faeces (p less than 0.05) and in MAF (p less than 0.02); the total count of facultative bacteria increased in the faeces (p less than 0.002) but not in the MAF. Streptococci, predominantly enterococci, increased significantly in faeces (p less than 0.001) and in MAF (p less than 0.02) such that they became predominant components of these florae. Facultative gram-negative bacilli were unaltered in faeces but significantly reduced in the MAF (p less than 0.05). Sporing clostridia were infrequently isolated from the MAF but were significantly reduced in the faeces (p less than 0.01). During the treatment period, eight of the 12 patients showed clinical improvement, but this could not be related to the site or extent of disease or to specific changes in faecal flora or MAF. This combination of antibacterial agents causes profound alterations to the bacterial flora of mucosa and faeces and these changes may help to define the role of bacteria in the pathogenesis of Crohn's disease.

Adult↗