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Monoclonal antibodies against fimbrial subunits of colonization factor antigen I (CFA/I) inhibit binding to human enterocytes and protect against enterotoxigenic Escherichia coli expressing heterologous colonization factors.

Enterotoxigenic Escherichia coli (ETEC) bind to enterocytes in the small intestine by means of antigenically distinct colonization factors (CFs). By immunizing with isolated subunits of CFA/I fimbriae we have previously produced monoclonal antibodies (MAbs) that cross-react immunologically in vitro with several CFs. Two of these MAbs [S(subunit)-CFA/ I 17:8 and S-CFA/I 5:6] were found to significantly inhibit the binding of ETEC strains expressing either homologous or heterologous CFs, i.e. CFA/I and CS4, to isolated human jejunal enterocytes. The two MAbs also conferred passive protection against fluid accumulation in rabbit ileal loops caused by CFA/I-as well as CS4-expressing ETEC strains. Immunoelectron microscopy studies showed that both MAbs bound specifically to CFA/I as well as to CS4 fimbriae expressed on bacteria. These results indicate the possibility to induce anti-CF antibodies that can protect against ETEC infection caused by bacteria expressing not only homologous but also heterologous CFs, by immunizing with fimbrial subunits.

Adhesins, Bacterial↗

["Field cancerization"--an additional phenomenon in development of colon tumors? K-ras codon 12 mutations in normal colonic mucosa of patients with colorectal neoplasms].

INTRODUCTION: The c-K-ras2-gene (K-ras) encodes the p21ras protein, which participates in the transduction of mitogenic signals from the cell surface to the nucleus. About 40-50% of colorectal cancers bear a point mutation of the K-ras codon 12 within exon I, leading to activation of the K-ras oncogene. METHODS: Using a polymerase chain reaction (PCR)-based two-step restriction fragment length polymorphism (2sRFLP)-technique, we assessed the frequency of point mutations in the first or second base of K-ras codon 12 in patients suffering from colorectal carcinoma, adenoma, and their normal colon mucosa, respectively. RESULTS: Similar to other investigators, we found mutations in 7 out of 17 (41%) colorectal carcinomas and 1 out of 4 (25%) adenomas. Using this very sensitive 2sRFLP technique (detection level = 0.2% of mutated cells), we were able to find K-ras codon 12 mutations in normal mucosa in 4 out of 18 (22.2%) patients with colorectal neoplasia. CONCLUSIONS: This result can be explained by the phenomenon of "field cancerization" or by a local micrometastasis of K-ras-positive tumor cells.

Adenocarcinoma↗

Studies of introital colonization in women with recurrent urinary infection. VI. Analysis of segmented leukocytes on the vaginal vestibule in relation to enterobacterial colonization.

Segmented leukocytes on the vaginal vestibule were quantitated in 93 specimens from 27 women with recurrent bacteriuria (1.03 times 10(5) plus or minus 4.9 times 10(5) cells per ml.) and compared to 251 specimens from 26 control women who had never had bacteriuria (8.0 times 10(4) plus or minus 1.7 times 10(5)). There was no significant difference (p more than 0.6). Leukocyte counts accompanying colonization with more than 100 Enterobacteriaceae per ml. (6.4 times 10(4) plus or minus 1.0 times 10(5) cells per ml). were no different from those unaccompanied by Enterobacteriaceae (8.7 times 10(4) plus or minus 3.3 times 10(5) cells per ml., p more than 0.9). No distinctive pattern was observed in excretion of vaginal leukocytes during the menstrual cycles of 21 premenopausal, control volunteers.

Adult↗

Infection with colonization factor antigen I-expressing enterotoxigenic Escherichia coli boosts antibody responses against heterologous colonization factors in primed subjects.

Enterotoxigenic Escherichia coli (ETEC) adhere to the intestinal mucosa by a number of fimbrial colonization factors (CFs) that have been claimed to induce only type-specific immunity. However, adult Bangladeshi patients infected with CFA/I-expressing bacteria, developed significant plasma IgA antibody responses, as determined by enzyme-linked immunosorbent assay, not only against the homologous fimbriae but also against several heterologous CFs, i.e. CS1, CS2, CS4 and PCFO166 fimbriae. In contrast, North American volunteers, who had probably not been infected by ETEC previously, responded with serum IgA against CFA/I fimbriae but not against any other CFs after symptomatic infection with CFA/I-expressing ETEC. Thus, infection with CFA/I-expressing bacteria may boost immune responses against CFs with a related amino acid sequence in previously primed subjects.

Adult↗

Effect of ovalbumin aerosol exposure on colonization of the porcine upper airway by Pasteurella multocida and effect of colonization on subsequent immune function.

Seventy-three piglets were weaned at 1 week of age, randomly assigned to 10 groups (A to J), accommodated in stainless steel exposure chambers, and exposed continuously to a controlled environment containing aerosolized ovalbumin. The concentrations of ovalbumin dust were as follows (milligrams per cubic meter): A and F, 16.6; B and G, 8.4; C and H, 4.2; D and I, 2.1; E and J, 0. At weekly intervals, the pigs were bled via venipuncture and anesthetized for nasal lavage and tonsilar biopsies performed for subsequent bacteriologic analysis. At 2 weeks of age, the pigs in groups A to E were challenged with toxigenic Pasteurella multocida (10(8) CFU pig(-1)), and at 6 weeks of age, the pigs were euthanatized. At postmortem, the extent of turbinate atrophy was assessed on the snout sections by using a morphometric index. Exposure to aerial ovalbumin resulted in a dose-dependent increase in serum antiovalbumin immunoglobulin G (IgG; P < 0.001) and serum antiovalbumin IgA (P < 0.001). Exposure also caused a significant increase in the numbers of P. multocida organisms isolated from the upper respiratory tract (P < 0.001) and a corresponding increase in turbinate atrophy, as judged by the morphometric index (P < 0.001). Concurrent challenge with P. multocida and ovalbumin resulted in a significant decrease in both the IgG and IgA responses to ovalbumin (P < 0.001). These results show that ovalbumin exposure increases pig susceptibility to P. multocida colonization and that toxigenic P. multocida modifies the serum IgG and IgA responses to ovalbumin in the pig. Both of these effects may enhance the virulence of this respiratory pathogen and so influence the pathogenesis of atrophic rhinitis in pigs.

Aerosols↗

Colonic inflammatory bowel disease. Medical therapies for colonic Crohn's disease and ulcerative colitis.

Advances in the treatment of inflammatory bowel disease (IBD) in the past decade include 5-aminosalicylic preparations with fewer adverse effects; new, rapidly metabolized corticosteroids; and new agents targeted at refractory or complicated IBD. Dr Tung and Dr Warner discuss the use of these and more traditional drugs in patients with colonic Crohn's disease and ulcerative colitis, stressing the need for individualized treatment.

Colitis, Ulcerative↗

Intermittent volvulus of the sigmoid colon.

Three patients in the younger age group are described who are thought to have had intermittent volvulus of the sigmoid colon. Successful treatment was effected by sigmoid colectomy and end-to-end anastomosis. The incidence and aetiology of sigmoid volvulus are reviewed, with particular reference to its occurrence in younger patients.

Adult↗

Crohn's disease of the colon. V. Retroperitoneal lumbocrural abscess in Crohn's disease involving the colon.

Retroperitoneal lumbocrural abscess occurred in 12 patients of 231 with Crohn's colitis or ileocolitis. Although all patients with this complication fell within the group of 175 ileocolitis patients, at least four originated in fistulous tracts of the colon. Eleven of the 12 abscesses developed spontaneously as the first major complication of the disease. The prominent clinical features included pain radiating down the thigh, hip joint flexion, difficulty in walking, hydronephrosis and hydroureter. Internal and external fistulas were significantly more common in the abscess group of 12 patients than in the 219 patients without retroperitoneal abscess. Radiological evidence of granulomatous disease was found in all patients; fistulous tract formation was characteristic and the development of extraperitoneal gas bubbles, in four patients, pathognomonic of abscess with gast-forming organisms. In the presence of established retroperitoneal abscess, the surgical sequence suggested is drainage synchronous with, or followed by diversion and ultimately definitive resection. Resection with anastomosis should not be carried out in the presence of an acute inflammatory process with frank abscess or free pus communicating with the peritoneal cavity. The spontaneous development of retroperitoneal abscess is a serious development in the natural history of Crohn's (ileo) colitis. It frequently heralds the first of a series of operative procedures to deal with the abscess. It sequels are enterocutaneous fistulas and further extension of the disease process.

Abscess↗

Endoscopic colonic decompression of toxic megacolon, placement of colonic tube, and steroid colonclysis.

A case of inflammatory bowel disease with toxic megacolon decompressed by colonoscopy, placement of an indwelling colonic tube through which steroid solution was administered. Toxic megacolon was alleviated, thus suspending the impending surgery. Literature search did not reveal any similar approaches of treating toxic megacolon. This procedure, however, should not replace the proper surgical management of toxic megacolon of inflammatory bowel disease.

Colitis, Ulcerative↗

Colonization of soil by Histoplasma capsulatum: II. Effect of bat guano added to an area of reduced colonization.

Application of bat guano to an area with reduced but detectable colonization by Histoplasma capsulatum had no quantitative effect on the fungus. After seeding the guano treated area and an untreated area with a soil culture of the fungus, a quantitative effect was noted in the treated area but the period of survival did not appear to be extended. Twenty-four months after seeding, the fungus was no longer detectable in the study areas and they have remained negative for more than a year.

Animals↗