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Query: HUMANGGP:036187 (gut)
 73,132 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Male ICR Swiss mice (2 to 3 months old) were fed Candida albicans in their drinking water for 3 days, followed by no treatment, antibiotics in their drinking water (daily), or immunosuppressants given by intraperitoneal injection (two to three times weekly) over a 3- to 4-week period. The organs of animals were processed to determine the numbers of C. albicans and total aerobic bacteria per g of tissue. Untreated animals had mean Candida counts during the 1-month period of 10(2.3) CFU/g of cecum. Animals in six of eight antibiotic-treated groups had mean cecal Candida counts higher than those of control animals (P less than 0.05), with clindamycin-gentamicin producing the highest counts (10(4.7) CFU/g). Cyclophosphamide produced counts (10(4.3) CFU/g) which were higher (P less than 0.05) than those resulting from methotrexate (10(3.0) CFU/g) or steroid (10(2.7) CFU/g) treatment. Cyclophosphamide-clindamycin-gentamicin treatment was associated with the highest (P less than 0.05) levels of Candida colonization (10(6.5) CFU/g). Mice receiving immunosuppressants plus clindamycin-gentamicin were more likely to disseminate C. albicans than were mice receiving antibiotics alone (P less than 0.001). Our findings suggest that colonization of the guts of mice by C. albicans can be facilitated by manipulating the aerobic, anaerobic, or both types of gut flora. The combined effect of immunosuppressants on both Candida gut colonization and dissemination appears multifactorial and deserves further investigation.
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PMID:Factors affecting colonization and dissemination of Candida albicans from the gastrointestinal tract of mice. 359

Mice fed ovalbumin develop specific systemic hyporesponsiveness. This oral tolerance is abrogated by cyclophosphamide pretreatment, and the mechanism of abrogation could be either via T suppressor cells or via damage to the gut epithelium. A serum transfer protocol was used to examine the site of action of cyclophosphamide in this system. Serum was collected from ovalbumin-fed mice and transferred into recipients which were then parenterally immunized with ovalbumin in Freund's complete adjuvant. Serum transfer suppressed the delayed-type hypersensitivity (DTH) responses but not the antibody responses of the recipients. Cyclophosphamide pretreatment (100 mg/kg) of recipients (but not of donors) abrogated this suppressor effect. Parenteral administration of ovalbumin in a range of doses did not induce immunological hyporesponsiveness. It is suggested that absorption across the gut mucosa leads to generation of fragments of ovalbumin that induce suppressor cells selective for DTH.
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PMID:Immunological responses to fed protein antigens in mice. II. Oral tolerance for CMI is due to activation of cyclophosphamide-sensitive cells by gut-processed antigen. 686 21

Frequencies of baseline and cyclophosphamide-induced sister chromatid exchanges (SCE) were measured in mouse maternal and fetal cells between days 11 and 19 of gestation. Baseline levels of SCE did not vary as a function of gestational age in either the mother or fetus. Cyclophosphamide-induced SCE frequencies remained constant in maternal cells but declined dramatically in the fetus throughout the latter half of development. Because cyclophosphamide is a metabolically activated mutagen, a direct-acting drug, mitomycin C, was given on days 11 and 15 to determine if the decline in induced SCE levels seen with gestational results from alterations in activating enzymes. A similar decline in mitomycin C-induced SCE levels was noted in fetal tissues as a function of gestational age. Dose-response curves to cyclophosphamide performed on day 13 of gestation showed increases in SCE as a function of cyclophosphamide concentration in both the mother and the fetus. When mutagen-induced SCE levels were compared in different fetal organs, the direct-acting drugs (mitomycin C and daunomycin) were found to induce similar levels in all tissues. Cyclophosphamide, which is metabolically activated, induced higher SCE levels in fetal liver than in lung or gut. Whereas cyclophosphamide induced similar SCE levels in fetal and maternal cells on day 13 of gestation, daunomycin produced fetal SCE levels that were approximately 50% of maternal levels. Simultaneous measurement of the distribution of [14C]cyclophosphamide and [3H]daunomycin in maternal and fetal cells revealed that the lower SCE induction by daunomycin was probably due to decreased ability to cross the placental barrier.
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PMID:In utero analysis of sister chromatid exchange: alterations in suscptibility to mutagenic damage as a function of fetal cell type and gestational age. 693 26

Feeding of a protein antigen to adult mice results in reduced humoral and cell-mediated immune (CMI) responses when that antigen is subsequently presented, and also causes activation of suppressor cells in the gut-associated lymphoid tissues (GALT). We have attempted to abrogate this tolerance to fed antigen by pretreating mice with 100 mg/kg cyclophosphamide before oral immunization and challenge with ovalbumin. Cyclophosphamide-pretreated mice did not develop serum haemagglutinating antibodies, nor systemic CMI (as assessed by skin testing) after ovalbumin feeding. However, evidence that CMI had been induced in the GALT was provided by the significant inhibition of migration and mesenteric lymph node cells from cyclophosphamide-pretreated animals, but not from other control groups. in the presence of ovalbumin. Our previous work on CMI reactions in the small intestine has shown that the cell production rate in the crypts of Lieberkuhn and the intraepithelial lymphocyte count are reliable although indirect measures of mucosal CMI. Cyclophosphamide-pretreated, ovalbumin-immunized animals, which had been fed 0 . 1 mg ovalbumin daily for 10 days before killing, had increased crypt cell mitoses, and increased intraepithelial lymphocyte counts, indicating the presence of mucosal CMI response to ovalbumin. Mechanisms whereby cyclophosphamide pretreatment leads to abrogation of tolerance and induction of mucosal CMI are discussed.
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PMID:Hypersensitivity in the small intestinal mucosa. V. Induction of cell-mediated immunity to a dietary antigen. 728 93

Cyclophosphamide (CY) is used in many animal studies, including models of bacteraemia, to deplete peripheral neutrophils and induce a compromised state. Although CY also influences lymphocyte function, the protective role of lymphocytes in bacteraemia is unclear. Therefore, CY (200 mg/kg) was administered to ddY mice and its influence on the number, cellular composition, and function of lymphocytes in the spleen and Peyer's patches was examined. A single dose of CY reduced the number of lymphocytes in a time-dependent fashion. Flow cytometry showed that B cells carrying B220 antigen decreased significantly. The production of IgA in Peyer's patches, as measured by enzyme-linked immunosorbent assay, was also suppressed in a time-dependent fashion. Blastogenic responses of splenic lymphocytes to Concanavalin-A, lipopolysaccharide and heat-killed Pseudomonas aeruginosa were suppressed 48 h after CY administration. The results suggest that CY suppresses the number and function of lymphocytes, especially B cells. This may lead to bacterial overgrowth in the gut and result in bacteraemia. Intravenous transfusion of normal lymphocytes or oral inoculation of IgA to mice with P. aeruginosa D4 endogenous bacteraemia significantly increased survival rates, indicating that lymphocytes and their products have a protective role in bacteraemia in mice.
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PMID:A protective role for lymphocytes in cyclophosphamide-induced endogenous bacteraemia in mice. 762 54

Myripritis sp. (squirrelfish) has been assessed for toxicity by 1) the stick-enzyme immunoassay (S-EIA); 2) mouse toxicity bioassay; and 3) guinea pig atrial assay. Analysis of Myripristis flesh with MAb-CTX and MAb-OA showed that with every fish examined, the reaction with MAb-OA was considerably higher. The mean S-EIA value for MAB-OA was 2.9 +/- 0.8 while the mean for MAb-CTX was 1.7 +/- 0.5. The data strongly suggests that Myripristis sp. appear to contain okadaic acid-like toxins and/or mixed with CTX. Five fractions of the flesh extracts were obtained by silica gel chromatography. These included 100% CHC1(3), 10% MeOH/CHC1(3), 50% MeOH-CHC1(3), 100% MeOH, and 80% MeOH/H2O. The 100% CHC1(3) eluate proved to be the most toxic (mouse killed in 32 minutes) and the 10% MeOH-CHC1(3) fraction killed in approximately 48 hours. The remaining fractions showed a significantly lower toxicity level in mice. In the guinea pig atria examinations, extracts of Myripristis flesh, gut, and crustacea (from the gut) were studied. Extracts of the gut and crustacea showed strong sodium channel blockage, while the flesh extracts showed a weak inotropic effect, characteristic of okadaic acid. The latter response was only blocked by verapamil, but not with tetrodotoxin (10(-5) M) or the adrenergic blockers (10(-5)M). The data from this study suggest toxic compound(s) not previously reported, in the non-polar fraction of Myripristis flesh having a sodium channel blockage effect.
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PMID:Characterization of marine toxin(s) in Myripristis sp. by immunological, mouse toxicity, and guinea pig assays. 842 72

Graft versus host disease (GVHD) is one of the obstacles encountered in allogeneic bone marrow transplantation (alloBMT) and has a direct impact on the transplant outcome and survival. In this report, we summarized the incidence of acute and chronic GVHD among 71 HLA matched and 9 HLA mismatched sibling alloBMTs performed for various hematological malignancies, mainly leukemias seen at Ibn-i Sina Hospital. Fifty-five were male and 25 were female Turkish patients. Median age was 29 (12-48). Cyclophosphamide(CY)+total body irradiation (TBI)(12), CY+total lymphatic irradiation (TLI)(6), busulfan (BU)+CY(58) and ALG/ATG+CY(4) were the regimens used for conditioning. Cyclosporin A (CsA)+short term methotrexate were given for GVHD prophylaxis except for two syngeneic transplants who both received only CsA. In 22 of the patients ABO and in 30 patients sex mismatched bone marrow was given. Thirty-one (38.8%) patients showed acute GVHD (grade I-II: 22, grade III-IV: 9) and 8 (11.6%) showed chronic GVHD. In HLA matched and mismatched patients acute GVHD incidence were 33.7% and 44.4% respectively. All of the HLA mismatched patients that showed acute GVHD were in advanced stage. Of the patients with acute GVHD, 28 (96.5%) disclosed skin, 22 (75.9%) hepatic and 14 (48.3%) gut involvement. In the chronic form three patients had mild limited, two limited, two moderate and one advanced GVHD. Seven of the patients were lost due to GVHD. To determine the graft versus leukemia effect of alloBMT, we compared the disease free survival (DFS) of the 68 leukemia patients. Although the patients who had grade I-II acute GVHD showed a better DFS than the patients who did not have acute GVHD, it did not reach to a significance (15.9 vs 13.6 months: p = 0.43).
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PMID:Incidence of graft vs host disease in allogeneic bone marrow transplantation in a single center study from Turkey. 926 89

To evaluate the role of tumour necrosis factor (TNF) in gut-derived sepsis, mice were given Pseudomomas aeruginosa strain D4 by bacterial suspension in their drinking water during which time ampicillin (200 mg/kg) was given to disrupt the normal indigenous bacterial flora. Cyclophosphamide was additionally administered to induce bacterial translocation of the P. aeruginosa that had colonized the gastrointestinal tract, and thereby to cause gut-derived sepsis. In this model, TNF-alpha was detected in serum from the next day after the second cyclophosphamide administration, increasing to level of 3 ng/ml in lethal conditions. Average serum TNF-alpha level was significantly higher in mice with bacteraemia than in those without bacteraemia. Treatment with 0.8 microg/kg of recombinant human TNF-alpha (rhTNF-alpha) did not affect the mortality, whereas administration of either 4 and 20 microg/kg of rhTNF-alpha significantly increased the mortality rate in comparison with saline-treated mice. Bacterial counts in liver and blood were significantly higher in 20 microg/kg of rhTNF-alpha treated mice than in saline-treated mice. Treatment with murine anti-TNF-alpha monoclonal antibody significantly reduced the mortality from septic infection. We conclude that TNF-alpha may facilitate bacterial translocation and causes deterioration of gut-derived sepsis due to P. aeruginosa in mice.
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PMID:Adverse effects of tumour necrosis factor in cyclophosphamide-treated mice subjected to gut-derived Pseudomonas aeruginosa sepsis. 934 9

A 47-year-old man had been given a diagnosis of mixed connective tissue disease (MCTD) on 1987 when he had presented with Raynaud's phenomenon, polyarthralgia, sclerodactyly, and a high titre of anti-RNP antibody. Once his symptoms had improved following the administration of prednisolone orally and the treatment was discontinued since 1995. He noticed dyspnea and chest pain in February 1997. The bilateral pleural effusion was pointed out in the local hospital and he was admitted to our hospital in March 1997 for further examination. In addition to pleural effusion and ascites, laboratory studies revealed hypoalbuminemia and low serum levels of complements. Renal and liver function tests were normal and the urine gave a trace test for protein. The presence of protein loss in the gut was confirmed by an elevated alpha 1-antitrypsin clearance and 99mTc-albumin scintigraphy showing abnormal radioactivity in the gastrointestinal tract. Although endoscopic examination showed no abnormal findings macroscopically and gastrointestinal biopsies revealed nonspecific inflammation only, immunofluorescent studies demonstrated deposits of C 3, C 4 and IgG in the stomach, colon, and pleura. These findings supported the pathogenesis that immune deposits in tissues caused protein-losing gastroenteropathy (PLGE) in MCTD. Intravenous administration of cyclophosphamide started since July 1997, while the high-dose corticosteroid therapy including methylprednisolone pulse therapy were not effective. Hypoalbuminemia and low serum levels of complements improved remarkably and the pleural effusion and ascites disappeared after cyclophosphamide pulse therapy four times monthly. Cyclophosphamide pulse therapy should be considered as a possibly effective treatment for PLGE in association with collagen disease resistant to corticosteroid therapy.
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PMID:[A case of protein-losing gastroenteropathy in association with mixed connective tissue disease which was successfully treated with cyclophosphamide pulse therapy]. 1004 20

We evaluated the effect of antiflagellar human monoclonal antibody on gut-derived Pseudomonas aeruginosa sepsis. Mice were given a suspension of P. aeruginosa SP10052 in their drinking water and were simultaneously treated with ampicillin (200 mg/kg of body weight) to disrupt the normal bacterial flora. Cyclophosphamide was then administered to induce leukopenia and translocation of the P. aeruginosa that had colonized the gastrointestinal tract, thereby producing gut-derived generalized sepsis. In this model, intraperitoneal injection of 100 microg of antiflagellar human monoclonal antibody (SC-1225) per mouse for 5 consecutive days significantly (P < 0.01) increased the survival rate compared with that for mice treated with bovine serum albumin (BSA). Treatment with SC-1225 significantly reduced the average number of viable bacteria in portal blood, liver, and heart blood compared with the average number after treatment with BSA. Furthermore, the presence in serum of the inflammatory cytokines tumor necrosis factor alpha and interleukin 6 were evaluated as markers of severity of infection, and the results showed that the levels of these cytokines in mice treated with SC-1225 were significantly decreased in comparison with those in BSA-treated control mice. Although there was no significant difference in the number of bacteria that colonized the intestine, SC-1225 treatment significantly increased bacterial opsonophagocytosis by cultured peritoneal macrophages from mice with or without cyclophosphamide pretreatment. Our results indicate that antiflagellar human monoclonal antibody SC-1225 protects mice against gut-derived sepsis caused by P. aeruginosa and suggest that such an effect is due to its opsonophagocytic activity and the reduced motility of the translocated bacteria once the bacteria move from the intestine into the bloodstream.
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PMID:Effect of antiflagellar human monoclonal antibody on gut-derived Pseudomonas aeruginosa sepsis in mice. 1039 58


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