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Biomedical subjects

G Wiedermann

Publications and source records attributed to G Wiedermann.

At least 73 records · Page 4Linked to original sources

Immune response in patients with amoebiasis: evaluation of IgG-subclasses.

In order to evaluate the immune response with respect to IgG-subclasses (IgG1-IgG4) in patients with extraintestinal amoebiasis, an ELISA technique was established. It was the aim of this pilot study to quantify the IgG subclass response and to compare the resulting pattern with other systemic protozoal infections. Our results give evidence that IgG4 contributes to more than one third of the total immune response, followed by IgG2, IgG3 and IgG1. Regarding the IgG4 response in patients with Plasmodium falciparum malaria or Chagas disease, IgG4 plays only a minor role in these systemic protozoal infections. The interpretation of a prognostic value of the high IgG4 titres in our patients is not possible at present. However, in patients with a prolonged clinical course of extraintestinal amoebiasis, extremely high IgG4 titres were observed.

Amebiasis↗

Interaction of different strains of Entamoeba histolytica with target cells: characterization of electrophysiological and morphological features.

Two strains of Entamoeba histolytica with pathogenic zymodemes (SFL3, HK9), one strain with non-pathogenic zymodeme ("Bru") and one non-pathogenic Entamoeba sp. strain ("cold strain"), were investigated with respect to their interaction with target cells. Three test systems were used: 1) direct microscopical observation and qualitative as well as quantitative evaluation of contact and binding events with MDCK cells as targets, 2) kinetics of cytotoxic activity as measured by means of chromium release from 51Cr-labelled K562 cells, and 3) electrophysiological observations with freshly prepared mouse liver cells. We observed that the non-pathogenic cold strain interacted only shortly with target cells (statistical events, interaction type "I"), but did not induce morphological changes, chromium release or depolarization of targets. Non-pathogenic and avirulent strain "Bru" showed, apart from type "I"-binding, the ability to establish tight (type "II") and long-lasting contact (type "III") with targets, but again without cytotoxic effects. The pathogenic but avirulent strain HK9 tightly interacted (type "II") and sometimes long-lasting with target cells, but morphological changes and chromium release were of a moderate degree during the first 20 min, and depolarization was only a rare event. In contrast, strain SFL3 produced tight and long-lasting contacts (type "III" binding), leading to cell death in 83% (type "IV" interaction) within 20 min, substantial chromium release within 10 min and rapid depolarization ("electric collapse") of target cells.

Animals↗

In vitro drug sensitivity of Plasmodium falciparum in Acre, Brazil.

In Acre, the westernmost state of Brazil in the Amazon region, the sensitivity of Plasmodium falciparum to chloroquine, amodiaquine, mefloquine, quinine and sulfadoxine/pyrimethamine was determined in vitro by the Rieckmann microtechnique. The study was performed between January and June 1987; the in vitro parasite responses to all antimalarial drugs were determined according to the recommendations of WHO. Of 83 isolates of P. falciparum, all were sensitive to mefloquine and of 87 isolates of P. falciparum, 84 (97%) were sensitive to quinine. The EC50 for mefloquine was 0.27 mumol/l and for quinine 4.60 mumol/l. In contrast, 65 of 89 (73%) and 70 of 83 (84%) isolates were resistant to amodiaquine and chloroquine, respectively; 11 isolates even grew at 6.4 mumol chloroquine/l. The EC50 for amodiaquine was 0.34 mumol/l and for chloroquine 0.73 mumol/l. Sulfadoxine/pyrimethamine resistance was seen in 23 of 25 (92%) cases. These data clearly indicate that in the western part of the Amazon region the 4-aminoquinolines, as well as sulfadoxine/pyrimethamine, can no longer be recommended for the treatment of P. falciparum infections.

Adolescent↗

Tolerability of long-term malaria prophylaxis with the combination mefloquine + sulfadoxine + pyrimethamine (Fansimef): results of a double blind field trial versus chloroquine in Nigeria.

A randomized double blind study in long term malaria chemoprophylaxis was performed to compare the tolerability of Fansimef (1 tablet containing 250 mg mefloquine + 500 mg sulfadoxine + 25 mg pyrimethamine per week) with chloroquine (300 mg per week). 211 Austrian industrial workers and their families in Warri, Nigeria, participated in this study; 101 received Fansimef and 110 chloroquine for 3-18 months (mean 41 weeks). Prophylaxis was discontinued because of adverse effects in 7 volunteers in the Fansimef group (mainly insomnia, palpitations, dizziness, nausea and headache) and in 2 volunteers of the chloroquine group (headache and loss of hair in one volunteer, nausea, dizziness and vomiting in the other). Most of the adverse effects could be due to the mefloquine component. A few minor complaints of burning eyes, nausea and gastric pain were reported in both groups. Laboratory checks performed at 3-monthly intervals showed a slight, transient and clinically irrelevant (but statistically significant) increase of serum glutamic-oxalacetic transaminase and gamma-glutamyl transpeptidase at month 3 in the Fansimef group. An attack of acute Plasmodium falciparum malaria occurred in one volunteer 6 weeks after discontinuation of prophylaxis with Fansimef. Antibodies against blood stage parasites could be demonstrated by the indirect immunofluorescence test at different stages of the study, indicating that these two antimalarials are not causal prophylactic agents.

Adolescent↗

Tolerability and immunogenicity of a polyvalent Pseudomonas aeruginosa extract vaccine in human volunteers.

A polyvalent 16 serotype Pseudomonas extract vaccine was administered to normal volunteers to ascertain tolerability, immunogenicity and immunisation schedule. Four groups of nine volunteers were immunised with 0.8 X 10(9) bacterial equivalents (BE), 1.2 X 10(9) BE, 1.6 X 10(9) BE or placebo, respectively, on days 0, 14 and 21. A further six volunteers were immunised with 1.6 X 10(9) BE on days 0 and 28. Tolerability was excellent, slight side effects were unrelated to vaccine concentration and decreased with the number of injections. All concentrations of vaccine gave a significantly increased titre 14 days after the first immunisation. Reimmunisation did not increase the titre, which reached a plateau at day 14. Individuals with high pre-immunisation-titres produced very high post-immunisation-titres with a conversion factor of 6.5 whilst those with low pre-immunisation-titres had a higher conversion factor of 13 but produced lower final titres. ELISA titre did not always correlate with biological activity (mouse protection assay) suggesting that effective protective antibodies are only part of the total specific antibody measured by ELISA with the polyvalent whole-cell vaccine antigen.

Adult↗

Lack of induction of IgE and IgG antibodies to yeast in humans immunized with recombinant hepatitis B vaccines.

Yeast-derived hepatitis B vaccines (partially purified or highly purified) at different dosages and a plasma-derived hepatitis B vaccine (control) were injected into 50 young volunteers 3 times at monthly intervals. Before and 4 weeks after this series of immunizations, blood samples were drawn and tested for presence of IgE and IgG antibodies against yeast antigens. No rise in IgE antibodies against Saccharomyces cerevisiae antigens nor in IgG antibodies against Candida albicans antigens was found. Together with former clinical results this underlines the experience that type I and type III reactions against putative yeast contaminants apparently play no major role after immunization with recombinant hepatitis B vaccines.

Adult↗

Defective intralesional interferon-gamma activity in patients with lepromatous leprosy.

Cryostat sections of full-thickness skin biopsies from 21 patients along the whole spectrum of leprosy were subjected to immunohistological examination with special regard to defective lymphokine production. There was an inverse relationship between intra-lesional IL-1 reactivity and IL-2R expression, in that the latter was markedly observed in tuberculoid lesions. Whenever epithelioid cell containing granulomas were present in paucibacillary forms, significant reactivity within the central phagocytic cells with the monoclonal antibody directed against interferon-gamma was detectable. The keratinocytes covering tuberculoid lesions abundantly expressed class II alloantigens (HLA-DR antigens), indicating high intra-lesional interferon-gamma activity. In contrast, multibacillary forms revealed significant anti-IL-1 reactivity within the cellular infiltrate. IL-2R bearing cells were virtually absent as was anti-HLA-DR reactivity of the keratinocytes, underlining a defective intra-lesional interferon-gamma activity.

Epidermal Cells↗

Multicentre dose range study of a yeast-derived hepatitis B vaccine.

Healthy young adult volunteers, 778 in number, without HBV markers were randomly distributed into groups and administered different lots of a yeast-derived hepatitis B vaccine (YDV) at different dose levels or a commercial plasma-derived vaccine (PDV), according to a 0, 1, 2, 12-month vaccination schedule. The YDV proved to be safe and well tolerated, even when partly purified lots were given. Reactions were mild and transient, comparable to those observed after PDV. One month after three YDV doses, 0-7% of subjects overall had failed to seroconvert; all those evaluated one month after the booster dose had seroconverted. No significant difference was found between the two vaccine types as far as seroconversion rates were concerned. Geometric mean anti-HBs levels following three vaccine doses were higher in seroconverters of the PDV groups. However, a booster dose of YDV resulted in high anti-HBs levels in all groups varying from 11,474 to 51,404 IU l-1 (purified YDV lot), 4915 to 18,832 IU l-1 (partly purified YDV lots) and 11,008 to 15,805 IU l-1 (PDV lots). Of seroconverters to the purified lots of YDV 93% attained 1000 IU l-1 after the booster dose, thus ensuring protection for a number of years. Dose-response studies provided a basis for the selection of 20 micrograms of highly purified YDV as the standard dose.

Adult↗

Reactogenicity and immunogenicity of different lots of a yeast-derived hepatitis B vaccine.

Several lots of a yeast-derived hepatitis B vaccine at different doses and a 20 micrograms dose of plasma-derived vaccine were tested in young healthy adults and compared with respect to risk of hypersensitivity reactions, reactogenicity, and immunogenicity. No signs of hypersensitivity either pre-existing or vaccine-induced were observed. Reactogenicity was low and similar in all vaccine groups. It was not dose related and unaffected by the number of injections. Immunogenicity was evaluated for a 0, 1, 2, and 12 month vaccination schedule. Seroconversion rates (greater than or equal to 10 IU/l) were not significantly different between the purified yeast- and plasma-derived vaccines one month after the second vaccination whereas the percentage of seroconversion was slightly lower in the groups receiving only partly purified recombinant vaccines. Although geometric mean titres induced by the plasma-derived vaccine were somewhat higher after the first months, the antibody titres induced by the recombinant vaccine were at least as high as those elicited by a plasma-derived vaccine following the booster dose.

Antigens↗

Persistence of vaccine-induced antibodies to hepatitis B surface antigen and the need for booster vaccination in adult subjects.

Protection against hepatitis B virus infection can be achieved by the induction of neutralizing antibodies against the hepatitis B surface antigen (HBsAg). An antibody concentration of 10 IU/l, as measured by radioimmunoassay, is considered to be protective. HBsAg can be produced either from the plasma of chronic carriers or by DNA recombinant technology in yeast cells. Plasma- and yeast-derived vaccines have been compared in several studies and their immunological properties were found to be similar, including the persistence of antibodies induced by either type of vaccine. Finally, yeast-derived hepatitis B vaccine can boost anti-HBs responses initially elicited by either plasma- or yeast-derived vaccine equally and effectively. In order to maintain protective immunity after hepatitis B vaccination, antibody determination and, if necessary, booster vaccination should be performed, particularly in high-risk persons.

Adult↗

Interaction of serum components with the cytotoxic action of Entamoeba histolytica.

Native normal human serum is capable of inhibiting the cytotoxic action of Entamoeba histolytica against K562 tissue culture target cells assessed by a 51Cr-release test. It is suggested that a part of the inhibitory activity on amoebae's cytotoxic action is represented by the complement system which is known to lyze trophozoites by activation of the alternative pathway. For the rest of the serum's inhibitory activity on amoebic cytotoxic action molecule(s) is (are) responsible which act(s) independently of Mg2+ and Ca2+. The serum components have to act before the trophozoites have come in contact with the target cells. The opsonization of trophozoites with antiamoebic antibodies led to an inhibition of amoebae's cytotoxic action (ACA) in a dose-dependent manner. The inhibitory components of normal human serum and antiamoebic antibodies potentiated each other in their capacity to inhibit ACA. It is suggested that opsonization of amoebae with C3b via its metastable binding site leads to redistribution phenomena on the amoebae's surface similar to the effects observed with antiamoebic antibodies, both events leading to inhibition of ACA.

Animals↗

Studies on the influence of BCG vaccination on infantile leukemia.

In the situation of low and decreasing risk of tuberculosis the possible non specific effect of BCG vaccination against leukemia becomes more and more important. To answer this question several studies using epidemiological and clinical data of children up to 5 years were performed in Austria. The following parameters which might be influenced by a possible protective effect of BCG vaccination were checked: leukemia mortality, case fatality, age of manifestation, frequency of different kinds of leukemia and the distribution of tuberculin reactions in leukemic and non leukemic children. All these parameters showed significant differences between vaccinated and non vaccinated leukemic and non leukemic children respectively making a protective effect of BCG vaccination against leukemia highly probable.

Austria↗

[Split tetanus vaccine. Studies on its efficacy and tolerance as compared to adsorbed vaccine].

A tetanus split vaccine consisting of the purified C fragment of tetanus toxin was compared with normal adsorbed toxoid vaccine with respect to local reactions and immunogenicity. Altogether, 200 volunteers with primary vaccination against tetanus were vaccinated. Local reactions were studied in 170 persons, the immune response in 87. Immunogenicity, expressed as mean conversion factor, was identical for both groups. Local reactions, including frequency, duration and intensity of symptoms, were reduced by 60% in the subjects given split vaccine. In both groups a positive correlation between preimmunization antibody titer and the mean extent of the local reaction was observed.

Adult↗

[Pneumococcal vaccination in geriatrics].

Pneumococcal vaccination may be recommended for certain risk groups according to Landesman and Schiffman such as people with heart and pulmonary diseases, sickle cell anemia, condition after splenectomy, M. Hodgkin, multiple myeloma, immune suppression. The vaccination is also indicated in elderly people (above 60 years). 14 oder 17-valent polysaccharide-vaccines are available which are well tolerated although mild side effects are possible. The immunogenicity is good in young as well as elderly people, antibody levels as high as 250-300 ng antibody nitrogen/ml are protective according to Landesman and Schiffman. A field trial performed in elderly people revealed a preferential influence on the case-fatality rate. The vaccination shall not be repeated within 4-5 years because of possible local reactions due to local antigen-antibody union.

Aged↗