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T Midtvedt

Publications and source records attributed to T Midtvedt.

At least 73 records · Page 4Linked to original sources
PubMed1994

Role of the bowel flora for development of immunity to hsp 65 and arthritis in three experimental models.

An infectious aetiology in rheumatoid arthritis (RA) has for long been suggested, although no conclusive evidence for this is at present available. Lately a large interest has been devoted to the involvement of heat shock proteins (hsps) in autoimmune disorders due to their conserved structure and immunogenic properties. Immunity to hsps has been observed both in human autoimmune conditions and in experimental models of autoimmune disease. We have studied the role of the bacterial flora and hsp immunity in the arthritic response in three experimental models of arthritis; type II collagen arthritis (CIA), adjuvant arthritis (AA) and oil induced arthritis (OIA); by using germ free and conventional DA rats. A high incidence of severe arthritis developed in all the models evaluated irrespectively of whether the animals were in the conventional or germ free state. This confirms earlier results which show a minor effect of the bacterial flora in CIA and AA in high responder strains. These results also show that a severe OIA can develop in germ free animals. Despite the severe arthritic response induced, no serum antibody levels to hsp 65 could be detected in the germ free animals, which was in contrast to the conventional animals where a positive anti-hsp 65 serum response was seen in 35-80% of the animals with CIA, AA or OIA. These results show that development of a humoral response to hsp 65 in these models of arthritis is dependent on the presence of a bacterial flora. Further, the lack of humoral immunity in germ free animals despite a severe arthritic response indicates that humoral immunity to hsp 65 is not involved in development of disease in these three models of experimental arthritis.

Animals↗
PubMed1994

Differential cell kinetics in the ileum and colon of germfree rats.

Our aim was to study the cell kinetics and epithelial structure in the ileum and colon of conventional and germfree AGUS rats by means of a classic stathmokinetic technique. A slight hyperplasia was observed in the villi of germfree animals (p < 0.05), associated with a comparatively short cell cycle time. The crypt cell production rate was reduced in the colon of germfree rats (p < 0.05), and their crypts contained fewer cells than those of conventional animals (p < 0.05). It is concluded that intraluminal bacteria influence cell proliferation in the colon. The absence of microflora prolongs the cell cycle time and reduces the proliferative activity in the colonic crypts, which contributes to a steady state that is different from that of conventional animals.

Animals↗
PubMed1994

Abnormal colonic microbial function in patients with rheumatoid arthritis.

The aim of this study was to examine the microflora-associated characteristics (MACs) of faecal samples of patients with rheumatoid arthritis (RA) and to evaluate the actions of sulphasalazine (SASP) on these MACs. The conversion of cholesterol to coprostanol, the production of urobilinogen, the degradation of faecal tryptic activity (FTA) and of beta-aspartylglycine were measured in faecal samples from 19 patients treated with SASP and 21 patients not treated with this medication. A control group of 21 healthy subjects was sex- and age-matched with the untreated patients. The conversion of cholesterol to coprostanol showed a bimodal distribution. The frequency of high converters in patients without SASP treatment was higher than in healthy subjects (p < 0.05). Treatment with SASP markedly increased the FTA and reduced the urobilinogen values, as compared to the untreated patients (p < 0.05). Beta-aspartylglycine was not found in any faecal samples. The results indicate that patients with RA have an abnormal formation of coprostanol, which is ascribed to alterations in the function of the Eubacteria species. In patients with RA, SASP treatment induces disturbances in the metabolism of the microflora.

Aged↗
PubMed1993

Intestinal bacteria and endogenous production of malonaldehyde and alkylators in mice.

Association of intestinal bacteria with endogenous production of some reactive compounds was studied by determination of adducts to haemoglobin in blood from germ-free and corresponding control mice. N-terminal valines in haemoglobin were analysed with regard to adducts from malonaldehyde (MA), ethene/ethylene oxide, propene/propylene oxide and methylating agents. It was found that the adduct levels from MA were 1.65 and 3.32 nmol/g globin in germ-free and control mice, respectively. The levels of adducts from ethylene oxide and propylene oxide were 10.8 and 10.3 pmol/g globin, respectively, in germ-free and 21.7 and 17.7 pmol/g globin, respectively, in control mice. The level of adducts from endogenous methylating agents was higher in germ-free mice than in controls (473 and 408 pmol/g globin, respectively). These differences in adduct levels between germ-free and conventional mice are statistically significant. The causes of the observed variations are so far not identified. This study confirms earlier findings on background levels of adducts in unexposed individuals and supports the hypothesis that these adducts reflect the occurrence of reactive intermediates in vivo that may constitute cancer risks in background cancer incidence. The present study also shows that intestinal bacteria may be an important determinant of such endogenous risk factors.

Alkylating Agents↗
PubMed1993

Conversion of cholesterol to coprostanol by the intestinal microflora during the first two years of human life.

The establishment of the conversion of cholesterol to coprostanol by the intestinal microflora was followed in 25 healthy Swedish children by gas-chromatographic analysis of fecal samples taken at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months of age. In 15 children, the microbial conversion of cholesterol to coprostanol started during the second half of the first year of life. During the second year of life, a sequestered distribution of the conversion rate could be distinguished. At the end of the study, 13 of the children were stable high converters, 3 were stable low converters, and 6 were unstable converters while the conversion pattern of three children could not be determined. The initiation of the establishment of conversion was delayed by breast-feeding, and only one child had coprostanol in feces while still being breast-fed. Those children exclusively breast-fed for more than 4 months or weaned after 6 months of age had significantly lower conversion rates at 12 months of age than did the other children (p < 0.05). Once conversion started, previous breast-feeding tended to result in a stable, later high rate of conversion of cholesterol. Between 6 and 15 months of age, the conversion rate increased with age, but after standardization for the period of exposure to foods other than breast milk, no age factor could be identified.

Age Factors↗
PubMed1993

Small intestinal bacterial overgrowth in patients with rheumatoid arthritis.

OBJECTIVES: To examine the microflora of the upper small intestine in patients with seropositive rheumatoid arthritis (RA) using a combination of microbial cultivation and tests for microbial metabolic activity. METHODS: Twenty five patients with seropositive RA, 12 achlorhydric control subjects, and 11 control subjects with normal gastric acid secretion were investigated. Disease activity was evaluated in the patients with RA by three different indices. Eight (32%) of the patients with RA had hypochlorhydria or achlorhydria. The acid secretory capacity was determined with pentagastrin stimulation. A modified Crosby capsule was used to obtain biopsy specimens and samples of intestinal fluid from the proximal jejunum; aerobic and anaerobic microbial cultivation of mucosal specimens/intestinal fluid was carried out, and gas production and microflora associated characteristics in jejunal fluid were determined. Additionally, a bile acid deconjugation breath test was performed. RESULTS: Subjects with at least one of the following findings were considered to have bacterial overgrowth: positive bile acid deconjugation test; growth of Enterobacteriaceae; positive gas production; or low tryptic activity. By these criteria half of the patients with RA with hypochlorhydria or achlorhydria and half of the achlorhydric controls had bacterial overgrowth. Thirty five per cent of the patients with RA with normal gastric acid secretion had bacterial overgrowth compared with none of the normal controls. Disease activity indices and rheumatoid factor titres were significantly higher in patients with RA with bacterial overgrowth than in those without. CONCLUSIONS: A high frequency of small intestinal bacterial overgrowth was found in patients with RA; it was associated with a high disease activity and observed in patients with hypochlorhydria or achlorhydria and in those with normal acid secretion.

Achlorhydria↗
PubMed1993

Functional alterations of the microflora in patients with ulcerative colitis.

The aim of the study was to examine microflora-associated characteristics in patients with inactive ulcerative colitis, receiving sulphasalazine, in relation to the spread of the disease. The conversion of cholesterol to coprostanol, the production of urobilinogen, and the degradation of tryptic activity (FTA) and beta-aspartylglycine were measured in faecal samples from patients with proctitis or left-sided or total ulcerative colitis and in age- and sex-matched controls. No significant differences in the results were observed in patients with various degrees of extension of inflammatory bowel disease. However, the coprostanol ratio and the urobilinogen level were lower and the FTA was higher in patients with colitis than in the controls (p < 0.05). Beta-aspartylglycine was not found in any faecal sample. The results indicate that patients with ulcerative colitis taking sulphasalazine have a microflora with abnormal metabolic characteristics.

Adult↗
PubMed1992

[Cholera].

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Cholera↗
PubMed1992

Cytokine responsiveness in germfree and conventional NMRI mice.

We have investigated the proliferative response of thymocytes from different mouse strains to cytokines in vitro. Interleukin 2 (IL-2), IL-4 and IL-7 induced proliferation of thymocytes from NMRI/KI (a locally bred NMRI mouse strain), NMRI/H ('traditional' NMRI mice), C3H/HeJ and C3H/HeN mice. NMRI/KI thymocytes showed the most prominent proliferation in response to IL-1 alpha and IL-1 beta. IL-3, IL-5, IL-6, IL-8, IL-10, tumour necrosis factor alpha (TNF-alpha), interferon gamma (IFN-gamma), inhibin and lipopolysaccharide (LPS) induced no thymocyte proliferation. Germfree NMRI/KI mouse thymocytes showed a significantly lower proliferation in response to IL-1 alpha and IL-1 beta than conventional mice. Rat tissues, previously shown to contain lymphocyte activating factors (LAFs), were also tested. Skin, tongue, esophagus, proventricular stomach, testis and placenta were all positive in the LAF assay utilizing NMRI/KI thymocytes, whereas none of the tissue extracts could induce proliferation in NMRI/H thymocytes. The higher cytokine responsiveness in conventional mice compared with germfree might suggest that exposure to microflora induces a higher state of activation of the immune system. The LAF assay, utilizing NMRI/KI thymocytes, is a highly sensitive IL-1 bioassay with a detection level of 1 pg/ml for IL-1 beta and 2 pg/ml for IL-1 alpha. The specificity of the assay is increased by utilizing NMRI/H mice to exclude the presence of IL-2, IL-4 and IL-7.

Animals↗
PubMed1992

Production of short chain fatty acids by the intestinal microflora during the first 2 years of human life.

We have followed the establishment of one group of intestinal microflora-associated characteristics, namely, the production of short chain fatty acids (SCFAs), in 30 healthy children, by gas chromatography analysis of fecal samples taken at 0, 1, 3, 6, 9, 12, 15, 18, 21, and 24 months of age. Acetic and propionic acids were the principal SCFAs at 1 and 3 months. Successively, the production of iso- and n-butyric, valeric, and caproic acids was established. At 2 years, the absolute amounts of all SCFAs with the exception of n-valeric acid had reached adult values. However, not all children had achieved a typically adult range of stool SCFAs by the end of the study. Both absolute and relative amounts of SCFAs were influenced by exposure to foods other than breast milk and exposure to antibiotic therapy. After standardization for exposure to foods other than breast milk, a positive age factor could be seen between 0 and 1 month of age for total amounts produced of SCFAs, acetic, propionic, and n-butyric acids. After this time, however, no clear age factor could be distinguished.

Age Factors↗
PubMed1992

The role of the gastrointestinal microflora in postsurgical adhesion formation--a study in germfree rats.

The elucidation of the pathogenesis of postsurgical adhesion formation is still lacking. In this study experimental adhesion formation was studied in germfree (i.e. void of bacteria) and conventional rats (intestinal flora comprising over 400 species) using a caecal crush model. The germfree rats responded significantly weaker to the same stimuli, forming adhesions in only 20% of the cases as compared to the conventional rats 87.5% (p = 0.0076). The findings indicate that the bowel flora is of importance but not essential for postsurgical adhesion formation in rats.

Abdomen↗
PubMed1992

E2 prostaglandins modulate cell proliferation in the small intestinal epithelium of the rat.

Groups of Sprague-Dawley rats were administered 1 mg/kg indomethacin subcutaneously, indomethacin subcutaneously plus 200 micrograms/kg oral 15-R-15 methyl-prostaglandin E2 (MePGE2) or oral MePGE2 twice daily for 10 days. The animals were treated with antibiotics to prevent mortality. Two control groups were used: control 1 was given placebo and control 2 was treated with antibiotics. All rats were killed 4 h after injection of a metaphase blocker, and the proliferative activity of the distal small intestine was examined in histological sections by means of the cumulative mitotic index (MI). A reduction in the number of villous cells was observed in the rats given antibiotics (p < 0.05 vs. control 1). The small intestinal villi of the rats treated with indomethacin had fewer cells than those of both control groups (p < 0.05) whereas the crypts contained more cells (p < 0.05) and had a higher MI than those of the controls (p < 0.05 vs. controls 1 and 2). These changes were reverted by the prostaglandin analogue. The number of cells of the small intestinal crypts and the cumulative MI in the rats who received indomethacin and the prostaglandin analogue were similar to controls, and they were significantly lower than the values observed in the animals treated with indomethacin (p < 0.05). The animals treated with the prostaglandin analogue and placebo developed a marked hyperplasia of the small intestinal villi (p < 0.05 vs. both control groups), but the atrophy of the villi induced by indomethacin was not prevented by simultaneous administration of the analogue.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Intestinal mucin of germ-free rats. Biochemical and electron-microscopic characterization.

Purified germ-free rat intestinal mucin was found by chemical analysis to contain 25% protein, enriched in serine, threonine, and proline, 75% carbohydrate, and no nucleic acid. It was analyzed by darkfield electron microscopy and found to consist of long filamentous molecules with a maximum length of approximately 740 nm, a mean length of 456 nm, and a mean width of 7 nm. Given reasonable assumptions derived from earlier work on other well-characterized mucins, the molecular weight of the peptide, calculated by the length from electron microscopy, was 200,000, and, given the chemical composition, the molecular weight of the entire mucin molecule was calculated to be approximately 800,000.

Amino Acids↗
PubMed1991

[Antibiotics and ecology in the Third World].

Infectious diseases are more common in developing than in developed countries, as in inapropriate use of antibiotics, and antibioticresistant microbes. Problems connected to misuse of antibiotics and resistance to these substances, and the ecological disturbances following use of such drugs, are of global importance. The author underlines the need for improvements.

Anti-Bacterial Agents↗
PubMed1991

Establishment of Lactobacillus and Bifidobacterium species in germfree mice and their influence on some microflora-associated characteristics.

Germfree mice were inoculated with both Lactobacillus acidophilus A10 and Bifidobacterium bifidum B11. Both strains were established and present in more than 10(8) cells per g of cecum and colon contents. Furthermore, L. acidophilus A10 was established in high numbers in stomach and small intestine. Contents from different parts of the intestine were investigated with regard to the following microflora-associated characteristics: degradation of mucin, beta-aspartylglycine and tryptic activity, conversion of cholesterol to coprostanol and bilirubin to urobilinogen, deconjugation of bilirubin glucuronides, and reduction of the cecum size. In spite of being established, the microbes were not able to mediate any alterations of the parameters investigated. All animals retained values as found in their germfree counterparts.

Actinomycetales Infections↗