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Biomedical subjects

L P Andersen

Publications and source records attributed to L P Andersen.

At least 73 records · Page 4Linked to original sources
PubMed1993

Activation of human phagocytes by Helicobacter pylori. A novel interaction with neutrophils and monocytes distinct from that of N-formylated oligopeptides.

Sonicate proteins from Helicobacter pylori activate human neutrophils and monocytes for chemotactic and oxidative burst responses. The molecular nature of this activity and its interaction with the phagocyte membrane is unknown. Cross-stimulation experiments were performed with human neutrophils and monocytes preincubated in H. pylori sonicate and subsequently stimulated with the established and characterised stimuli N-f-methionyl-leucyl-phenylalanine (fMLP), the complement split product C5a (in zymosan-activated serum, ZAS), and phorbol-myristate-acetate (PMA). Checkerboard experiments confirmed the sonicate to be truly chemotactic, whereas no chemokinetic activity was demonstrated. At high concentrations of sonicate (1 mg/ml), a depressed chemotactic and oxidative burst response was observed, whereas the viability was > 98%. At lower concentrations (0.01-0.1 mg/ml), only weak deactivation could be induced for monocytes, i.e. the cells had a normal function. With neutrophils, even low concentrations of sonicate depressed the oxidative burs responsiveness. However, the reduced activity was unrelated to the stimulus applied indicating that H. pylori protein(s) activate human neutrophils and monocytes by a membrane binding site distinct from that of previously described receptors.

Chemotaxis, Leukocyte↗
PubMed1993

Comparison of four second generation kits for detection of IgG antibodies against Helicobacter pylori in adults.

Four serological kits for detection of IgG antibodies against H. pylori were tested on 132 adult patients with dyspeptic symptoms. Presence of H. pylori infection was established when either culture or microscopy of gastric biopsies were positive. The prevalence of H. pylori infection was 55% in the test population. With Anti-H. pylori MTP-assay (Roche), Pylori stat test kit (Whittaker), HM-CAP (Enteric Products Inc.) and Pyloriset EIA-G (Orion) the sensitivities were 97%, 95%, 81% and 68% respectively, the specificities were 53%, 56%, 71% and 69% respectively, the positive predictive values 72%, 74%, 79% and 74% respectively and the negative predictive values were 94%, 92%, 79% and 64% respectively.

Adolescent↗
PubMed1993

Evaluation of eight commercial kits for Helicobacter pylori IgG antibody detection.

Eight commercial kits and an in-house ELISA for detection of IgG antibodies against Helicobacter pylori were evaluated for their use in diagnosis of H. pylori infection and in epidemiological research: Helico-GTM (Porton-Cambridge), G. A. P. test (Bio-Rad), H. pylori antibodies ELISA (Biometra), Anti-H. pylori IgG EIA (Roche), 2nd generation H. pylori EIA (Roche), Anti-H. pylori MTP-assay (Roche), Pylori stat test kit (Whittaker), Pyloriset latex agglutination kit (Orion), and the in-house ELISA based on heat-stable antigens. Fifty-four patients with dyspepsia (31 H. pylori positive by culture or microscopy) and 68 asymptomatic persons were tested. Sensitivities for the eight kits were 71%, 77%, 90%, 84%, 87%, 94%, 90%, 87%, and 87%, specificities were 74%, 65%, 74%, 74%, 83%, 83%, 70%, 65%, and 65%, respectively. For epidemiological use the estimated seroprevalence varied within approximately 15% in all age groups. Sensitivities and specificities obtained in different studies reveal as great differences in the results with the same kit as between results obtained with different kits in the same study. Kits with the highest sensitivities tend to be the same in all studies. It is therefore more important to test a kit in the population to which it is to be applied than to choose a specific kit.

Adolescent↗
PubMed1993

Peptic ulcer: an infectious disease?

Since the ingestion studies by Marshall and Morris, Helicobacter pylori has been known to cause both acute and chronic infection in the human stomach activating both the cellular and the humoral immune system. It is of little or no value to evaluate the causative relationship of an infectious agent using Koch's criteria. The more recent criteria for causative relationships used in the science of epidemiology are more useful. These criteria include: (i) the characteristic of the association which is fulfilled for most cases of both duodenal and gastric ulcer; (ii) the temporal relationship which is fulfilled for duodenal ulcer and has not been investigated for gastric ulcer; (iii) the biological gradient which has been fulfilled for duodenal ulcer in a few studies but not investigated for gastric ulcer; (iv) the biological plausibility which is easily fulfilled for both duodenal and gastric ulcer; (v) the effect of an intervention which has been fulfilled for duodenal ulcer and in a few studies for gastric ulcer; and (vi) the coherence of these data with what is known about the disease which is fulfilled for both duodenal and gastric ulcer. Even though there is no need for all criteria to be fulfilled, further studies are necessary to confirm the temporal relationship between H. pylori and peptic ulcer, and the biological gradient of H. pylori in relation to the gastric ulcer. Even so, there is a strong indication that most of the peptic ulcers, apart from those caused by non-steroid anti-inflammatory drugs and Zollinger-Ellison-like syndromes, are caused by H. pylori infection.

Chronic Disease↗
PubMed1993

Survival and ultrastructural changes of Helicobacter pylori after phagocytosis by human polymorphonuclear leukocytes and monocytes.

Few studies have been carried out on the phagocytosis and killing of Helicobacter pylori by both polymorphonuclear leukocytes (PMNs) and monocytes. In this study, H. pylori was incubated for up to 60 min either alone or with phagocytes in the presence or absence of human serum. Both non-immune serum and immune serum were used. Reduction in the number of H. pylori, which corresponds to the killing of H. pylori, was analysed by a colony count and ultrastructural changes were studied by electron microscopy. No reduction in the number of H. pylori was found when the bacteria were incubated alone or with phagocytes in the absence of serum. It is remarkable that unopsonized H. pylori was phagocytosed. When immune serum was added to the suspensions of bacteria and phagocytes, the killing rate of H. pylori was found to depend on the ratio of H. pylori to phagocytes. Thus an excess of monocytes reduced the number of H. pylori, whereas an excess of PMNs resulted in complete killing of H. pylori. On incubation with PMNs and serum, ultrastructural changes were observed in the majority of the bacteria whether they were phagocytosed or not. Controls without serum did not show any changes in the morphology of H. pylori, indicating that components in the serum play an important role in the phagocytosis and killing of H. pylori. In contrast, several of the phagocytosed bacteria were found to be unaffected after incubation with monocytes and serum. Such preparations often contained large aggregates of platelets surrounding unaffected H. pylori. In the gastric mucosa, H. pylori is often found in excess as compared to the phagocytes. If these results can be compared to the situation in vivo, the phagocytes seem to be ineffective in the killing of H. pylori, and other immune mechanisms may therefore be of importance for the elimination of H. pylori from the gastric epithelium. The possible intracellular survival of H. pylori should be taken into account when treatment regimes for H. pylori infections are chosen.

Helicobacter pylori↗
PubMed1992

Activation of human phagocyte oxidative metabolism by Helicobacter pylori.

A characteristic feature of chronic antral gastritis is the abundant inflammatory response in close association with Helicobacter pylori, but the immunopathological mechanisms of tissue damage are unknown. Because reactive oxygen radicals have been implicated in the tissue damage of other chronic inflammatory disorders, we investigated the potential ability of H. pylori sonicate to influence the oxidative burst responsiveness of human polymorphonuclear leukocytes and monocytes. For both cell types, a dose-dependent stimulation in a chemiluminescence system was observed. Furthermore, preincubation in sonicate caused a marked priming of the cells to subsequent stimulation with the oligopeptide N-f-methionyl-leucyl-phenylalanine and phorbol-myristate-acetate. The sonicate activity was nondialysable, completely destroyed by proteinase and resistant to heat treatment. However, dialysis of boiled sonicate significantly reduced the activity, suggesting the breakdown of a larger molecule(s) to smaller fragments still biologically active. Preliminary experiments suggest that the activity is 25-35 kilodaltons. The demonstration of a protein with stimulatory activity for production of reactive oxygen radicals by human phagocytes may contribute to the understanding of the immunopathology associated with H. pylori infection.

Adult↗
PubMed1992

Immunoglobulin G antibodies to Helicobacter pylori in patients with dyspeptic symptoms investigated by the western immunoblot technique.

Helicobacter pylori is a gram-negative, curved, rod-shaped bacterium known to cause gastritis and to be an important factor in the pathogenesis of peptic ulcers. Serological testing has recently been proposed as an aid in diagnosis of H. pylori infections. In this study, we used the Western immunoblot technique to evaluate the possibility of using one or more of the antigens from H. pylori for this purpose. Thirteen major bands and about 30 minor bands could be identified by Western blotting when sera from 53 consecutive dyspeptic patients, 27 healthy children, and 25 blood donors were evaluated. Antibodies against most of the major bands were found significantly more frequently in patients with H. pylori infections than in patients without such infections. However, antibodies against a single polypeptide were not produced by all patients with H. pylori infection. Polypeptides with molecular masses of 120, 50, and between 19 and 36 kDa seem to be the most specific polypeptides for the diagnosis of H. pylori infections. This study showed only minor differences in antigenic composition between different clinical isolates of H. pylori, and serological cross-reactions with other bacteria were limited. Major serological cross-reactions were found only with Campylobacter jejuni and with bacterial lipopolysaccharide. However, one band at 60 kDa reacted with antiserum to the Legionella micdadei common antigen, which may indicate a cross-reaction with common antigen from several other bacteria. This study demonstrates that a number of bands may be useful as antigens in serological tests after isolation and purification.

Adolescent↗
PubMed1992

Chemotactic activity of Helicobacter pylori sonicate for human polymorphonuclear leucocytes and monocytes.

The immunopathology of Helicobacter pylori associated active chronic gastritis, which is characterised by predominance of polymorphonuclear leucocyte infiltration, is largely unknown. To evaluate the role of bacterial components as inflammatory mediators ultracentrifuged sonicated preparations were made of clinical isolates of Helicobacter pylori. The crude sonicates were shown to exhibit chemotactic activity for human polymorphonuclear leucocytes and blood monocytes in a concentration dependent fashion. The potency was comparable with previously described bacterial derived cytotaxins. The cytotaxin(s) was non-dialysable and completely destroyed by proteinase. Heat treatment did not decrease the chemotactic activity, but in sonicate subjected to 100 degrees C for 15 minutes all activity disappeared after dialysis suggesting the breakdown of a larger protein to small fragments that are still biological active. By ammonium sulphate precipitation at increasing concentrations the cytotaxin(s) was selectively found in 10% ammonium sulphate saturation, and by further molecular gel separation the chemotactic activity was found in the molecular size range from 25 to 35 kDa. The demonstration of a polymorphonuclear leucocyte and monocyte cytotaxin from Helicobacter pylori sonicate may help in understanding the mucosal immune response in gastric inflammatory diseases.

Bacterial Proteins↗
PubMed1992

Prevalence of antibodies against heat-stable antigens from Helicobacter pylori in patients with dyspeptic symptoms and normal persons.

Heat-stable antigens from Helicobacter pylori were investigated for the detection of serum IgG, IgA and IgM antibodies against H. pylori by an ELISA technique. Antibody titers against H. pylori were measured in 167 dyspeptic patients, of whom 96 were H. pylori positive confirmed by culture or microscopy, and in 482 controls (0-98 years). Increased IgG antibody titers were found significantly more often in dyspeptic patients with active chronic gastritis than in patients with normal morphology, as well as in H. pylori-positive patients as compared to H. pylori-negative patients, independent of the endoscopic findings. The heat-stable antigens were compared with acid glycine-extracted antigens and a high degree of concordance was found in the results obtained with the two antigen preparations. The differences in the IgA antibody titers against H. pylori between H. pylori-positive and H. pylori-negative dyspeptic patients were significant and may be useful to confirm a borderline IgG result. No differences were found in IgM antibody titer between H. pylori-positive and -negative patients. The greatest age-dependent increase in IgG and IgA antibody titers was found in children, and if a lower cut-off level is used for children than for adults, as has been proposed, the proportion of people with increased antibody titers against H. pylori would be almost constant from the age of between five and 10 years until the time between 61 and 80 years. Comparison of H. pylori IgG antibodies with IgG antibodies against Campylobacter jejuni and total antibodies against cytomegalovirus (CMV) showed a greater similarity between H. pylori and C. jejuni (R = 0.51) than between H. pylori and CMV (R = 0.22). This may possibly be caused by cross-reactions between H. pylori and C. jejuni. The H. pylori heat-stabile antigen seems not to be very different from other crude H. pylori antigens like acid glycine-extracted antigens, but purification and characterization of the antigens are needed to improve antibody assays.

Adolescent↗
PubMed1992

IgG subclass antibodies against Helicobacter pylori heat-stable antigens in normal persons and in dyspeptic patients.

Measurement of serum IgG antibodies against Helicobacter pylori seems to be useful in the diagnosis of H. pylori infections. IgG subclass antibodies against H. pylori have, however, not been investigated thoroughly. In this study IgG1, IgG2, IgG3 and IgG4 antibody levels against H. pylori were measured using an ELISA technique in 187 normal adult persons and in 174 patients with dyspeptic symptoms, of whom 99 patients were H. pylori positive. None of the IgG subclass antibody levels were better than the total IgG level for the diagnosis of H. pylori infection. The discrimination between H. pylori-positive and H. pylori-negative patients was better with IgG1, IgG2 and IgG4 antibody levels than with IgG3 antibody level. IgG2 was the IgG subclass antibody that mainly contributed to the age-dependent increase in the IgG antibody level. This sustains the suspicion that cross-reactions between lipopolysaccharide (LPS) from H. pylori and LPS from other Gram-negative bacteria may occur.

Adult↗
PubMed1991

Effect of selected neuroleptic agents and stereo-isomeric analogues on virus and eukaryotic cells.

Chlorpromazine, cis(Z)-chlorprothixene (Truxal), and the non-neuroleptic trans(E)-chlorprothixene and trans(E)-flupenthixol were studied in vitro for possible antiviral effect on Herpes simplex virus 2 and for toxic effect on human diploid fibroblasts. Based on an enzyme-linked immunosorbent assay (ELISA) antiviral activity was demonstrated for all the compounds in the concentration range 0.39 micrograms/ml-25 micrograms/ml. A cell-toxic effect was shown in the higher concentration range for all the compounds except cis(Z)-chlorprothixene. A cell-stimulatory effect was also detected at the lower concentration range (about 3.13 micrograms/ml) for all compounds. Thus both cell stimulation and antiviral effect can be found for the same agent within the same concentration range. The results point to the possibility of creating different antiviral drugs--which would also include a cell-stimulatory activity--among psychopharmacological drugs and their stereoisomeric analogues.

Antipsychotic Agents↗
PubMed1991

The Helicobacter (Campylobacter) pylori-colonized duodenal mucosa and gastric metaplasia.

Biopsies were obtained from non-ulcerated sites of the duodenum from 100 dyspeptic patients. Helicobacter (Campylobacter) pylori was cultivated from 19 of these biopsies. Active chronic duodenitis (ACD) was found in 17 biopsies and more than 5% gastric metaplasia in 20 biopsies. H. pylori as well as ACD occurred with a significantly increased frequency when more than 5% gastric metaplasia was found in the duodenal biopsies. H. pylori on metaplastic tissue without ACD was, however, seen in two cases. H. pylori was cultivated from 9% and ACD was found in 5% of the biopsies with less than 5% gastric metaplasia. Gastric metaplasia in the duodenum was found significantly more frequently in patients with endoscopic duodenitis or duodenal ulceration than in patients with normal endoscopy. No association between gastric metaplasia in the duodenum and gastric pH or serum antibodies against H. pylori was seen. This study indicates that there is an established, but not exclusive, connection between gastric metaplasia and the colonization of the duodenum by H. pylori, the most important role being played by the antral gastric mucosa rather than the duodenum.

Biopsy↗
PubMed1990

Possible evidence of invasiveness of Helicobacter (Campylobacter) pylori.

Gastric/duodenal biopsy material from 52 patients was examined immunohistochemically for Helicobacter (Campylobacter) pylori. Specimens from 34 of the patients harboured Helicobacter pylori along the mucosal surface and 13 of these featured, in addition, immunopositive material within the lamina propria. The remaining 18 biopsies were non-reactive. This observation suggests that Helicobacter pylori can penetrate the epithelium and its basement membrane, resulting in the production of specific systemic antibodies.

Antibodies, Bacterial↗
PubMed1990

Long-term suppression of severe recurrent genital herpes simplex infections with oral acyclovir: a dose-titration study.

Twenty immunocompetent patients, four females and 16 males, with severe recurrent genital herpes (median number of recurrences the previous year 16, range (8-24] entered an open continuous long-term suppressive treatment with oral acyclovir (ACV) for 12 months. The study included a dose-titration schedule: (ACV, 200 mg x 4/1-3 months, ACV, 400 mg x 2/4-6 months, ACV, 200 mg x 2/7-9 months, and ACV, 400 mg x 1/10-12 months). Patients with recurrences on steps two and three received an alternative dose of ACV, 200 mg x 3. Otherwise patients entered the previous dose-step. Five (20%) of patients were completely free of symptoms (recurrences and abortive lesions) during the four dose-reduction periods. A further nine patients (50%) could be dose-reduced to 200 mg x 3 without symptoms. Isolates from three patients showed a decrease in virus sensitivity after ceasing treatment. In conclusion, 14/20 of treated patients could be dose reduced to 200 mg x 2-3 without selection of HSV strains showing clinically important decreases in sensitivity towards ACV.

Acyclovir↗
PubMed1989

Trimipramine and other antipsychotics inhibit Campylobacter pylori in vitro.

A series of conventional anti-ulcer drugs, tricyclic antidepressants and neuroleptics (and some CNS non-active isomers) were tested in vitro for possible inhibition of Campylobacter pylori. These bacteria are claimed to play an etiological role in peptic ulcer disease, at least in gastritis B. While cimetidine, famotidine, ranitidine and pirenzepine were inactive, all the antipsychotic agents and their isomeric derivatives were active to various degrees with IC50 of 26-59 microM. Of special interest is trimipramine (Surmontil) that has been demonstrated to be effective against duodenal ulcers in some trials. The activity of the non-neuroleptic stereo-isomers of clopenthixol and chlorprothixene may lead to investigation in patients with peptic ulcer disease of this kind of agents. However, a firm connection between the antimicrobial activity of these compounds, their possible anti-ulcer effect and the etiological role of Campylobacter pylori in peptic ulcer disease must first be established.

Anti-Ulcer Agents↗
PubMed1989

Oral acyclovir suppressive therapy in severe recurrent genital herpes. A double-blind, placebo-controlled cross-over study.

A randomised, double-blind, placebo-controlled cross-over study was conducted in 24 patients, nine females and 15 males, with a history of more than eight recurrences of genital herpes in the past year. The patients received a first treatment course with 400 mg acyclovir or matching placebo by mouth, twice daily, for 12 weeks. After cross-over patients received alternative medication for another 12 weeks. The patients were followed without treatment for a further three-month period. During acyclovir therapy, recurrences were completely prevented in 17 patients (71%) and the remaining seven patients had nine recurrences as compared to 18 recurrences while receiving placebo. The placebo treatment did not reduce the recurrence rate. No adverse effects were attributable to the acyclovir treatment period. All virus isolates tested after treatment remained sensitive to acyclovir. Acyclovir prophylaxis of recurrent genital herpes is effective and safe. A continuous suppressive therapy with acyclovir offers a basis for a normal sexual life to those patients severely incapacitated by their disease, but once medication is stopped, patients shed virus as before suppression.

Acyclovir↗
PubMed1988

[Drug fever].

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Drug Hypersensitivity↗