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Biomedical subjects

R Stoll

Publications and source records attributed to R Stoll.

At least 55 records · Page 3Linked to original sources

13C-urea breath test for detection of Helicobacter pylori and its correlation with endoscopic and histologic findings.

The urea breath test (UBT) reflects the intragastric urease activity and thus the extent of H. pylori (H.p.) burden of the mucosa. We compared UBT results with gastroscopic and histologic findings in 174 patients. H.p.density, grade and activity of the chronic gastritis type B were semiquantitatively assessed. 46% of patients were H.p.-positive. A type B gastritis was significantly (p < 0.01) associated with H.p. colonization. UBT-results significantly correlated with the grade (r = 0.53) and the activity (r = 0.45) of gastritis. They correlated better with grade and activity of the inflammation than did the H.p.-density in histology (r = 0.38 and r = 0.37). There is a considerable interindividual variability in UBT-results for the same degree of gastritis indicating that besides the number of bacteria other factors must be of significance for the severity of inflammation. Endoscopic findings apart from ulcers do not predict the presence of H.p.

Breath Tests↗

Chromosome polymorphisms close to the cm-ADE1 locus of candida maltosa.

The imperfect yeast Candida maltosa has an ill-defined genetic constitution; it is nominally diploid, but probably highly aneuploid, in nature. We report on polymorphisms specifically affecting those chromosomes which bear the cm-ADE1 gene. This gene encodes phosphoribosylaminoimidazole-succino-carboxamide synthetase, an enzyme in the adenine biosynthetic pathway. By electrophoretic karyotype analysis, three differently sized chromosomes were demonstrated to carry cm-ADE1; the size (but not the number) of these chromosomes was also found to vary, both between strains and during the mitotic growth of a single strain. Four different alleles of cm-ADE1 have been cloned and sequenced from one prototrophic strain. DNA sequence divergence between these different alleles is as high as 8%, with the greatest divergence being found in the upstream region. Mitotic recombination events that led to changes in the karyotype were followed by using cm-ADE1 DNA as an hybridization probe. A recombination hot-spot in the neighbourhood of the gene appears to be responsible for the instability of the chromosomes on which it residues.

Alleles↗

Action of testosterone on the estradiol-induced feminization of the male chick embryo.

The early treatment of male chick embryos with estradiol induces the feminization of their sex tract, i.e. both their gonads and müllerian tract exhibit female features. The additional treatment of estrogenized male embryos with testosterone propionate antagonizes the effects of estradiol on both gonads and müllerian ducts. Our data give further support to the view that testosterone and estrogens act respectively as agonist and antagonist modulators of the secretion of the anti-müllerian hormone.

Androgen-Insensitivity Syndrome↗

Immunohistochemical demonstration of the calcium-binding proteins MRP8 and MRP14 and their heterodimer (27E10 antigen) in Crohn's disease.

Monospecific antibodies against the calcium-binding proteins MRP8 and MRP14 and their heterodimer MRP8/14 (epitope 27E10) were used to investigate immunohistochemically the distribution of these proteins in routinely processed small and large bowel tissues from patients with Crohn's disease. MRP8, MRP14, and complex MRP8/14 were demonstrated in most granulocytes and macrophages in active Crohn's disease. Additionally, a strong complex MRP8/14 immunoreactivity was present in epithelial cells of the terminal ileum adjacent to ulcerative and fissuring lesions, whereas epithelial cells in large bowel tissues were consistently negative. Our results morphologically confirm the clinical finding of increased MRP8/14 serum levels in patients with active Crohn's disease; there is evidence that the serum MRP8/14 increase is caused by active secretion from granulocytes, monocytes, and epithelial cells.

Antibodies, Monoclonal↗

Elevated levels of activities of beta-hexosaminidase and alpha-mannosidase in human immunodeficiency virus-infected patients.

To determine their value as markers of the clinical stage of human immunodeficiency virus (HIV) disease, plasma activities of lysosomal glycosidases were determined in the plasma of 97 HIV-infected patients: molecular forms of cathepsin D were characterized by Western blot to examine the mode of enzyme release. In patients with Centers for Disease Control and Prevention stage II and III of HIV disease, plasma activity of beta-hexosaminidase was significantly increased. In patients with stage III infection, alpha-mannosidase activity was also significantly increased and cathepsin D was elevated and present only in its premature form. Thus, determination of plasma activities of beta-hexosaminidase and alpha-mannosidase in HIV-positive persons may be useful for distinguishing the clinical stage of disease. The elevation of precursors of cathepsin D in patients with stage III HIV disease indicates that secretion of lysosomal enzymes rather than leakage of enzymes from damaged cells is markedly elevated.

Cathepsin D↗

Circulating antiinflammatory cytokine IL-10 in patients with inflammatory bowel disease (IBD).

IBD is characterized by increased serum concentrations of different cytokines. IL-10 inhibits the production of proinflammatory cytokines such as IL-1, tumour necrosis factor-alpha (TNF-a), interferon-gamma (IFN-gamma) and IL-6 through inhibitory action on Th1 cells and macrophages, and it is thought to be a suppressor type cytokine. In the present study we determined serum concentrations of IL-10 in patients with ulcerative colitis (UC) and Crohn's disease (CD). We measured human IL-10 by our own newly established ELISA system using PharMingen antibodies. Serum antibodies were assessed in 44 patients with UC, 40 patients with CD, and in 30 healthy controls. Human IL-10 serum levels were significantly increased in patients with active UC (144 +/- 34 pg/ml (mean +/- s.e.m.), P < 0.001) and in active CD (132 +/- 32 pg/ml, P < 0.001) compared with healthy controls (44 +/- 9.5 pg/ml). Only patients with active CD and active UC presented with significantly increased IL-10 serum levels, while patients with inactive disease did not show any significant increase. There was no statistically significant difference between IL-10 serum levels in patients with CD or UC. Compared with clinical disease activity indices there was a significant correlation between IL-10 serum concentration and CDAI in patients with CD (r = 0.45, P < 0.01) and CAI in UC patients (r = 0.39, P < 0.05). Comparing IL-10 serum levels with serum concentrations of other proinflammatory cytokines there was a significant correlation to serum levels of sIL-2R (r = 0.417, P < 0.05) and IL-6 (r = 0.387, P < 0.05) in patients with CD. Serum cytokine levels in patients with UC did not show any significant correlation to IL-10 serum concentration. IL-10 is elevated in serum of patients with active CD and UC, suggesting that IL-10 acts as a naturally occurring damper in the acute inflammatory process of IBD.

Acute Disease↗

Serum 27E10 antigen: a new potential marker for staging HIV disease.

MRP8 and MRP14 are myeloic related proteins expressed by most circulating and emigrated neutrophils and monocytes. Their composite molecule MRP8/14 (27E10 antigen) was shown to exhibit striking antimicrobial properties. The aim of the present study was to assess the value of MRPs as markers for detection of the different stages of HIV infection (Centres for Disease Control and Prevention, 1993). By employing the ELISA technique we measured serum concentrations of these proteins in samples from 122 HIV patients at the various stages of disease, and the results were compared with those for healthy controls. Serum levels of the heterodimeric molecule 27E10 were significantly increased (P < 0.001) in patients with CDC stages II and III, with the highest levels being in patients with stage III and acute ongoing opportunistic infections. For the single component MRP14, significantly raised levels (P < 0.05) were only found in HIV stage III individuals with acute clinical events. Similar associations were not found for MRP8 alone. Increase was not related to CD4+ cell count. There was a significant correlation between 27E10 antigen serum concentrations and levels of neopterin in patients with HIV stages II and III without acute concurrent illness. Patients being treated with Zidovudine showed no statistically significant variation in levels of 27E10 and its single components MRP8 and MRP14 compared with untreated patients. These findings suggest that elevation of MRP14 levels occurs in HIV+ individuals at later stages post-HIV infection, after the onset of opportunistic infections. 27E10 antigen is concluded to be a potential marker for the different stages of HIV disease.

AIDS-Related Opportunistic Infections↗

The myeloic related protein MRP8/14 (27E10 antigen)--usefulness as a potential marker for disease activity in ulcerative colitis and putative biological function.

MRP8, MRP14 and their heterodimer MRP8/14 (27E10 antigen) are myeloic related proteins which have been shown to have a major role in inflammatory and immunological responses. In the present study monospecific antibodies against MRPs were used to investigate immunohistochemically the distribution of these proteins in routinely processed bowel tissues from 23 patients with ulcerative colitis (UC). MRP8, MRP14 and their heterocomplex MRP8/14 were demonstrated in the majority of granulocytes and macrophages in tissues of patients with active UC. Furthermore by employing the ELISA technique we measured MRP8/14 serum levels in 62 patients with UC and the results were compared with those for healthy controls. Disease activities were determined by established clinical activity indices. Serum MRP8/14 concentrations were significantly (P < 0.0001) increased in patients with active ulcerative colitis. No enhancement of serum levels were found for MRP14 and MRP8 alone, respectively. The follow-up of individual patients with initially active disease showed a decrease of MRP8/14 serum levels in parallel with clinical improvement following the start of therapy. It is thus concluded that MRP8/14 accurately reflects the degree of disease activity in UC. Further, possible biological function of MRPs seems to be associated with the heterodimeric form (27E10 antigen) rather than with individual proteins. Our morphological results confirm the finding of enhanced MRP8/14 serum levels in patients with active UC.

Adrenal Cortex Hormones↗

Immunohistochemical distribution and serum levels of the Ca(2+)-binding proteins MRP8, MRP14 and their heterodimeric form MRP8/14 in Crohn's disease.

In previous histochemical studies the distribution of the two Ca(2+)-binding proteins MRP8 and MRP14 as well as their heterocomplex MRP8/14 has been demonstrated in different inflammatory diseases. Monoclonal antibodies against MRP8 and MRP14 and their heterodimer MRP8/14 (27E10 epitope) were used to investigate immunohistochemically the distribution of these proteins in routinely processed small and large bowel tissues from patients with Crohn's disease (CD). Furthermore, we used a sandwich immunoassay to measure serum concentrations of MRPs in 62 patients were simultaneously assessed by the Crohn's disease activity index (CDAI) and the severity activity index of Goebell (SAI). In our immunohistochemical study, MRP8, MRP14 and heterocomplex MRP8/14 were demonstrated in the majority of granulocytes and macrophages in active CD. Additionally, a strong complex MRP8/14 immunoreactivity was present in epithelial cells adjacent to ulcerative and fissuring lesions in the bowel. Serum MRP8/14 concentrations were significantly (p < 0.0001) increased in patients with active CD (CDAI > 150, SAI > 120). No correlations were found for level of MRP14 and MRP8 alone, respectively. The follow-up of individual patients with initially active CD showed a further increase in MRP8/14 levels during acute attacks of the inflammatory process. We suggest that our assay for MRP8/14 discriminates well between active and inactive CD and may have considerable potential in the analysis of clinical disease activity in CD patients. Our morphological results confirm the finding of increased MRP8/14 serum levels in patients with active CD.

Acute-Phase Proteins↗

Monoclonal antibody 1F10 immunoreactivity in inflammatory bowel disease: a new marker specific only for continuous endothelial cells.

OBJECTIVE: To investigate in detail the immunohistochemical properties of the two endothelial-specific markers 1F10 (continuous endothelia) and MS-1 (discontinuous endothelia) in bowel tissues of patients suffering from chronic inflammatory bowel disease (IBD). METHOD: Immunohistochemical techniques were employed to study the morphology and phenotypic expression of these two proteins in routinely processed bowel tissues from 27 patients with Crohn's disease, 18 patients with ulcerative colitis, and 20 normal controls. RESULTS: All patients with IBD and controls showed a low to moderate 1F10 immunohistochemical staining restricted to the lamina propria and submucosa. In contrast to ulcerative colitis patients and healthy controls, 1F10 immunoreactivity was strongly upregulated in the muscularis propria of the small and large bowel in Crohn's disease patients regardless of the histological severity of the inflammatory process. We did not observe immunoreactivity for MS-1 on endothelial surfaces in either Crohn's disease or ulcerative colitis. CONCLUSIONS: We conclude that endothelia in patients with IBD do not undergo metaplasia. The high immunoreactivity of 1F10 antigen in the muscularis propria in Crohn's disease indicates a state of tropical immunological activation and may be important in the maintenance of chronic inflammation by facilitating leukocyte migration into sites of Crohn's disease involvement. Further studies of the factors controlling endothelial cell differentiation in the bowel of Crohn's disease patients may help to explain the features observed in this study.

Adolescent↗

Stimulus-secretion coupling in rat parietal cells is affected by extracellular magnesium.

We investigated the effects of extracellular magnesium on stimulus-secretion coupling in isolated rat parietal cells. A high concentration of extracellular magnesium (10 mM) decreased basal and carbachol-stimulated calcium levels, whereas low magnesium levels (0.2 mM) had the opposite effect. The calcium-triggered acid secretion was influenced in the same manner. Basal and carbachol-stimulated acid secretion could be enhanced by incubation in a buffer of low magnesium concentration, whereas a high magnesium concentration totally suppressed the carbachol-induced acid secretion. These results demonstrate that magnesium plays a modulative role in calcium-dependent stimulus-secretion coupling in rat parietal cells.

Aminopyrine↗

Action of testosterone on the anti-müllerian activity of the chick embryonic testis assayed in vivo by organotypic grafting.

The implantation of embryonic testis grafts into female chick embryos induces the regression of their müllerian ducts (MDs) in a certain number of cases. The treatment of either the grafts or the grafted females with testosterone propionate (TP) results in a significant increase in the number of MD regressions observed. Our data are interpretable in terms of a direct activation by TP of the anti-müllerian activity of the embryonic testis. We discuss a possible mechanism accounting for the synergistic action of testosterone and anti-müllerian hormone.

Animals↗

Host restriction in the productive cycle of avian polyomavirus budgerigar fledgling disease virus type 3 depends on a single amino acid change in the common region of structural proteins VP2/VP3.

The three avian polyomaviruses budgerigar fledgling disease virus types 1 to 3 (BFDV-1 to -3) contain genomes of identical size, 4981 bp. With differences of up to only 15 bp between the three genomes, these viruses show distinct tropism for cultured cells of various avian species: infection of chicken embryo (CE) cells with BFDV-1 and -2 results in virus propagation, whereas BFDV-3 is not replicated; all three viruses replicate, with different efficiencies, in infected Muscovy duck cells. Transfection of CE cells with BFDV-3 DNA results in a single productive cycle. As shown by construction of hybrid virus genomes and site-directed mutagenesis, a single amino acid difference (glycine instead of valine or alanine) within the common region of the minor structural proteins VP2/VP3 is responsible for this type of abortive infection of CE cells. Further experiments indicate a defect in one of the early steps during infection, at or prior to uncoating.

Animals↗

Mucosal adaptation to aspirin induced gastric damage in humans. Studies on blood flow, gastric mucosal growth, and neutrophil activation.

The gastropathy associated with the ingestion of non-steroidal anti-inflammatory drugs (NSAIDs) such as aspirin is a common side effect of this class of drugs, but the precise mechanisms by which they cause mucosal damage have not been fully explained. During continued use of an injurious substance, such as aspirin, the extent of gastric mucosal damage decreases and this phenomenon is named gastric adaptation. To assess the extent of mucosal damage by aspirin and subsequent adaptation the effects of 14 days of continuous, oral administration of aspirin (2 g per day) to eight healthy male volunteers was studied. To estimate the rate of mucosal damage, gastroscopy was performed before (day 0) and at days 3, 7, 14 of aspirin treatment. Gastric microbleeding and gastric mucosal blood flow were measured using laser Doppler flowmeter and mucosal biopsy specimens were taken for the estimation of tissue DNA synthesis and RNA and DNA concentration. In addition, the activation of neutrophils in peripheral blood was assessed by measuring their ability to associate with platelets. Aspirin induced acute damage mainly in gastric corpus, reaching at day 3 about 3.5 on the endoscopic Lanza score but lessened to about 1.5 at day 14 pointing to the occurrence of gastric adaptation. Mucosal blood flow increased at day 3 by about 50% in the gastric corpus and by 88% in the antrum. The in vitro DNA synthesis and RNA concentration, an index of mucosal growth, were reduced at day 3 but then increased to reach about 150% of initial value at the end of aspirin treatment. It is concluded that the treatment with aspirin in humans induces gastric adaptation to this agent, which entails the increase in mucosal blood flow, the rise in neutrophil activation, and the enhancement in mucosal growth.

Adaptation, Physiological↗

Role of cholecystokinin in the control of gastric emptying and secretory response to a fatty meal in normal subjects and duodenal ulcer patients.

BACKGROUND: Exogenous cholecystokinin (CCK) is known to affect gastric motor and secretory activities, but its physiologic role in the control of gastric functions is unknown. METHODS: In this study involving 10 young healthy subjects and 10 duodenal ulcer (DU) patients, 500 ml of a standard meal without or with addition of 15% soybean oil was given, and the gastric emptying rate and the pH profile and plasma levels of gastrin, CCK, pancreatic polypeptide (PP), and somatostatin were determined in separate tests with placebo or with antagonism of type-A CCK receptors (loxiglumide, 1200 mg orally). RESULTS: In healthy controls and DU patients the emptying half-time was 44 and 34 min, respectively, and the addition of oil prolonged the emptying by about 50%. Pretreatment with loxiglumide significantly reduced fat-induced retardation of gastric emptying in both healthy controls and DU patients. A standard meal in healthy subjects resulted in an immediate rise in median gastric pH to about 6.0, and this was followed by gradual decrease within about 3 h to premeal values of about 2.0. After the meal, plasma gastrin rose by 57%, CCK by 177%, PP by 100%, and somatostatin by 39%. Addition of fat significantly attenuated and prolonged the pH decrease after the meal while reducing the increment in plasma gastrin and enhancing plasma CCK and PP levels. Loxiglumide significantly reduced the median postprandial pH (from control 4.8 to 2.5) and reversed the changes in the pH profile caused by the addition of fat. The increments in plasma gastrin and CCK were markedly augmented, whereas those of somatostatin and PP were significantly attenuated. DU patients showed lower postprandial pH (3.0) in tests with or without fat and higher increments in plasma gastrin. CCK antagonism failed to affect significantly the pH profile or the increments in plasma gastrin in DU patients. CONCLUSIONS: These results indicate that endogenous CCK released by a fatty meal delays gastric emptying and inhibits gastric acid and plasma gastrin responses in healthy subjects, but in DU patients the inhibitory effect of CCK is less pronounced, suggesting a defect in the action of this hormone on gastrin release and gastric acid secretion.

Adult↗