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Biomedical subjects

K Zwingenberger

Publications and source records attributed to K Zwingenberger.

At least 37 records · Page 2Linked to original sources
PubMed1992

Hepatosplenic schistosomiasis: comparison of sonographic findings in Brazilian and Sudanese patients--correlation of sonographic findings with clinical symptoms.

Twenty-seven Brazilian and 32 Sudanese patients with hepatosplenic schistosomiasis from areas where the disease is endemic were examined with ultrasound (US). Hyperechoic periportal areas indicating periportal fibrosis (PPF) were present in all patients irrespective of their origin. Nonspecific findings were splenomegaly (all patients), gallbladder wall thickening (81% and 92%, respectively, in Brazilian and Sudanese patients), portal vein (74% and 87%, respectively) and splenic vein (59% and 70%, respectively) enlargement, and portosystemic vascular shunts (62% and 61%, respectively). The hepatic alterations were congruent and the frequency of their occurrence was similar in both patient groups. With a standardized grading system, it was shown that grade of PPF was significantly correlated with a history of bleeding from endoscopically proved esophageal varices and with distention of the portal vein as measured with US. It was concluded that sonographic grading may be used in patients with hepatosplenic Schistosoma mansoni infection who originate from completely different endemic areas.

Adolescent↗
PubMed1991

Generation of cytokines in human visceral leishmaniasis: dissociation of endogenous TNF-alpha and IL-1 beta production.

The role of TNF-alpha in visceral leishmaniasis is ambivalent, the eventual outcome of this infection, cure or generalization, being determined by the relative amounts of cytokines produced in vivo. Since release, by monocytes/macrophages, of TNF-alpha and interleukins 1 beta (IL-1 beta) and IL-6 is important in both the induction and effector phases of the immune responses, these mediators were determined in sera and cell culture supernatants of seventeen L. donovani infected patients in Brazil. The results are compared to those of a local control group. Circulating immunoreactive TNF-alpha in patients (median, 140 pg ml-1) was increased ten-fold over controls (median 16 pg ml-1, p less than or equal to 0.0001). In contrast, serum IL-1 beta was less than 20 pg ml-1 in all patients, although detectable in sera of 3/16 Brazilian controls (chi 2 = 3.5, p less than 0.1). Mitogen induced in vitro release of IL-1 beta and IL-6 by patients' circulating mononuclear cells was significantly reduced, and the capacity of patients' peripheral monocytes for H2O2 generation in response to opsonized zymosan was significantly diminished. In the patients, serum TNF-alpha levels were inversely related to IL-1 beta release in vitro (rho = -0.57, p less than or equal to 0.01).

Adolescent↗
PubMed1991

Impaired balance of interleukin-4 and interferon-gamma production in infections with Schistosoma mansoni and intestinal nematodes.

In chronic infection with Schistosoma mansoni, IL-4 and IFN-gamma are co-modulated in opposite directions. This was shown when testing sera and cell culture supernatants from 31 Brazilian patients with schistosomiasis before, and three months after treatment with praziquantel. Thorough examinations were undertaken to account for polyparasitism with intestinal nematode infections involving tissue migrating larval stages that may induce analogous changes. Controls free of S. mansoni included a group (n = 17) matching the schistosomiasis patients' parasitation by intestinal nematodes and a group (n = 16) free of helminths other than T. trichiura. Serum IL-4 was greater than 20 pg/ml in 81% of schistosomiasis patients but in only 35 and 25%, respectively, of controls with and without intestinal nematodes. IL-4 data correlated inversely with the mitogen-induced IFN-gamma synthesis. Generation of IL-4 in response to phorbol esters was related to the intensity of infection by schistosomes and intestinal nematodes. The parasitological status three months after therapy with either praziquantel or mebendazole revealed a dichotomy: whereas the ratio of IFN-gamma to IL-4 generated in vitro was identical in uninfected controls and in patients who cleared the parasites, failure to eliminate the parasites was associated with lower IFN-gamma/IL-4 ratios generated in vitro.

Female↗
PubMed1990

Determinants of the immune response in visceral leishmaniasis: evidence for predominance of endogenous interleukin 4 over interferon-gamma production.

Accumulating evidence points toward an antagonism between TH1 and TH2 focused immune responses decisive for the outcome of parasitic infections with leishmaniae. Interferon-gamma (IFN-gamma) and interleukin 4 (IL4), the principal cytokines involved in these pathways, as well as IgE and the IgG subclasses differentially modulated by these cytokines, were therefore assessed in 18 Brazilian patients with visceral leishmaniasis. The results are compared to those of a local control group. IL4 was detected in all patient sera but in only one control. Low concentrations of IFN-gamma where detectable in 50% of the Brazilian controls but in only two patients. While group medians of mitogen-induced in vitro synthesis of IL4 and IFN-gamma were similar, release of these lymphokines correlated inversely in patients (Spearman's rho = -0.84). Elevations of serum IgE complement the lymphokine data to indicate prominent TH2 type responses in clinical infections with Leishmania donovani.

Adolescent↗
PubMed1990

Re-infection in human schistosomiasis mansoni: a prospective field study 18 months after praziquantel therapy.

Twenty-eight Zairean patients with Schistosoma mansoni infection were investigated and treated with praziquantel. Of these, 22 were re-examined 18 months later and 13 were found to be re-infected. Eighteen uninfected Zaireans were monitored concurrently to control for variations unrelated to schistosomiasis. Pathophysiological changes related to liver fibrosis were assessed by the determination of serum cholylglycine and procollagen-III-peptide. Circulating T-cell subsets were quantitated, and shedded T-cell antigens were measured in sera. In patients initially presenting with hepatomegaly, the biochemical indicators for egg-induced immunopathology became normal after therapy and remained normal even after re-infection, when the parasite load attained about 50% of the pretreatment level. Among T-cell phenotypes, CD4+ cells transiently increased by three months after treatment, but after 18 months the CD4/CD8 ratios both in patients then re-infected and in those not re-infected had reverted to the respective balances which had been observed at the start of the investigation. Both soluble CD8 antigen and interleukin 2 receptor in patients' sera were significantly elevated throughout the study period. The results indicate a dissociation of factors regulating fibrogenesis and immunomodulation after treatment and re-infected.

Adolescent↗
PubMed1990

Tumour necrosis factor in hepatosplenic schistosomiasis.

Periportal fibroplasia is the dominating feature of hepatosplenic schistosomiasis. Since monokines play an important role in the regulation of fibroplasia, tumour necrosis factor (TNF) and interleukin 1 beta (IL-1 beta) were assessed in sera and cell culture supernatants from patients with intestinal and hepatosplenic schistosomiasis before and 3-6 months after treatment with praziquantel. Uninfected controls were from the study area in Alagoas, Brazil. TNF was measured using an L-M mouse fibroblast bioassay and radioimmunoassays specific for TNF-alpha. Whereas TNF-alpha was elevated threefold in the patients' sera, three- to five-fold reductions of TNF were observed by radioimmunoassay and bioassay, respectively, in cell culture supernatants of hepatosplenic schistosomiasis patients. Significant deviations, in opposite directions, from TNF levels in control sera and supernatants are most plausible in the event of a sequestration of TNF-alpha-producing cells from the circulation. This process may be disease stage-specific since a dichotomy between incipient and advanced cases of hepatosplenic schistosomiasis became apparent in the amplitude and kinetics of changes during the follow-up after treatment.

Adolescent↗
PubMed1990

Altered generation of interleukin 1 in chronic human schistosomiasis mansoni.

Chronic schistosomiasis mansoni is associated with impaired cell-mediated immune responsiveness (CMI). To assess co-stimulatory factors essential in the induction phase of CMI, interleukin 1 (IL-1) concentration was determined in the sera and cell culture supernatants of Schistosoma mansoni-infected patients, and circulating monocytes were phenotyped, labelling membrane IL-1 and HLA-DP. In addition, adherent cell oxidative-burst capacity was investigated. Since involvement of IL-1 beta in the pathogenesis of severe granulomatous lesions could not be ruled out, 17 patients with intestinal schistosomiasis and 17 patients with hepatosplenic schistosomiasis were matched for intensity of infection and monitored 3-6 months after praziquantel therapy. Seventeen age- and sex-matched uninfected residents of the study area in Alagoas, Brazil, acted as controls. Whereas schistosomiasis patients and controls did not differ in the expression of monocyte surface antigens and the capacity of adherent cells to generate H2O2, IL-1 beta release by monocytes in vitro was significantly reduced in both intestinal and hepatosplenic patients. Low concentrations of circulating IL-1 beta were detected in comparable frequencies in untreated patients and controls. Three months after therapy, IL-1 beta was detectable in serum in an increased proportion of intestinal schistosomiasis patients. IL-1 release in vitro gradually increased in all patients and reached control values 6 months after therapy.

Adolescent↗
PubMed1989

Effects of intradermal gamma-interferon in cutaneous leishmaniasis.

The clinical and immunological evolution of lesions in cutaneous leishmaniasis was assessed after treatment with human recombinant gamma interferon (rIFN-gamma). 3 weeks after rIFN-gamma treatment of lesions due to Leishmania braziliensis guyanensis, 12/13 had become smaller compared with 6/13 control lesions; only 4 treated lesions were free of parasites. 9 of 13 L tropica lesions treated with rIFN-gamma resolved completely within 4-8 weeks of treatment. An acute inflammatory reaction around treated lesions was more common in lesions due to L tropica. There were no other local or systemic adverse reactions. Histological and immunohistochemical studies indicate that local application of rIFN-gamma enhances cell-mediated immune responses and thus promotes healing of cutaneous leishmaniasis.

Acute Disease↗
PubMed1989

Presence of circulating anodic antigen in serum of Schistosoma intercalatum-infected patients from Gabon.

The presence of the schistosome circulating anodic antigen (CAA) in serum of Schistosoma intercalatum-infected patients from Gabon has been investigated using an enzyme-linked immunosorbent assay (ELISA). Blood samples were collected from 10 endemic controls, 29 patients which excreted viable S. intercalatum eggs in rectal mucosa and stool, six persons in which only non-viable eggs were found in rectal biopsy specimens and one person in which besides non-viable eggs a small number of viable eggs was found in the rectal biopsy specimen. CAA, a genus-specific antigen, could be demonstrated in 58.6% of the patients with S. intercalatum eggs in their stools. In comparison to S. mansoni infections, very light infections (0.6 eggs per gram faeces) could be detected by the ELISA. A strong correlation between parasite burden (eggs per gram faeces) and antigen-level (CAA-titer) was found (Spearman's rho = 0.65). Only one positive ELISA-results was found in the group with solely non-viable eggs in rectal tissue. As no false positive results were detected for the negative controls, the present results suggest, in accordance with results earlier obtained for schistosomiasis mansoni, that only in active S. intercalatum infections is antigen demonstrable.

Animals↗
PubMed1989

T cell phenotype alterations in hepatosplenic schistosomiasis mansoni normalize after chemotherapy.

Peripheral blood T cell phenotypes, CD3-induced mitogenesis and soluble IL 2 receptor and CD8 in sera were studied in intestinal and hepatosplenic Schistosomiasis mansoni before and three to six months after therapy with praziquantel. Fifteen pairs matched for intensity of infection were analyzed and compared with local, non-infected age-matched controls. CD3+ cell counts were lower in untreated hepatosplenic schistosomiasis (median 1040 cells/microliters; 95% confidence interval 608-1269) compared to controls (1534; 1264-1620). This difference was largely accounted for by immature CD1+/CD3-cells circulating in these patients (median 388/microliters, 252-474). The frequency of CD1+ T cells in circulation decreased drastically after chemotherapy. Similar, but less marked, alterations were seen in intestinal schistosomiasis. Lymphocyte proliferation initiated by agonistic anti-CD3 monoclonal antibody was severely impaired in hepatosplenic patients, who had suffered haemorrhagic complications, but not in the cases of incipient hepatomegaly. Soluble CD8 antigen circulated in increased amounts in hepatosplenic schistosomiasis. Remarkably, a negative correlation between CD3-induced mitogenesis and circulating levels of CD8 was noted in these patients. Whereas CD3-induced mitogenesis in hepatosplenic schistosomiasis normalized after therapy, circulating IL 2R and CD8 antigen in hepatosplenic patients still exceeded control levels. The results demonstrate disturbances of CD3 and CD8 expression and/or T cell maturation in hepatosplenic schistosomiasis. Imbalanced CD4/CD8 ratios and an increased IL 2R/CD8 turnover may reflect an inhibitory circuit within the T cell compartment.

Adolescent↗
PubMed1989

Release of interleukin 2 and gamma interferon by peripheral mononuclear cells in human Schistosoma mansoni infection normalizes after chemotherapy.

Interleukin 2 (IL-2) and gamma interferon (IFN-gamma) were determined in supernatants of mitogen- and antigen-driven cell cultures from patients with hepatosplenic or intestinal schistosomiasis. Skin reactivity was tested using a panel of eight recall antigens. Results were compared with those of uninfected local controls. In both schistosomiasis groups, IL-2 activity was reduced before treatment. In less than one third of the patients, schistosomal antigens elicited detectable IL-2 activity. IFN-gamma production was reduced more severely in hepatosplenic cases, in particular after stimulation by anti-CD3 monoclonal antibodies. After anti-schistosomal therapy with praziquantel, mitogen-induced IL-2 and IFN-gamma activities became normal within 3 months in intestinal schistosomiasis, and within 6 months in the hepatosplenic patient group. Results of in vivo delayed-type hypersensitivity tests paralleled those of in vitro lymphokine production. In conclusion, evidence is presented for severe, antigen-unspecific suppression of lymphokine production and skin reactivity against recall antigens. Anti-parasitic chemotherapy is shown to reverse the impairment of cell-mediated immune responses at the cytokine level.

Adolescent↗
PubMed1989

New approaches to the measurement of morbidity in intestinal schistosomiasis.

New approaches for the assessment of morbidity due to schistosomiasis infection include the substitution of egg counts by quantitative assays for circulating schistosomal antigens, simple parameters for global immune responsiveness and functional hepatic alterations, and ultrasonography as an imaging technique. Quantification of circulating schistosome antigens in sera of S. mansoni, S. haematobium or S. intercalatum infected patients by sensitive immunoassays provides an exact measure for the individual worm burden. The effect of chemotherapy on immunomodulation was assessed by a panel of cutaneous recall antigens. Non-specific cell-mediated immune responses returned to subnormal pretreatment levels in the event of reinfection. Immunological morbidity can be monitored in this way. Pathophysiological alterations of the liver in S. mansoni infection can be assessed by the determination of unconjugated bile acids in the systematic circulation. The regression of intrahepatic vascular lesions in schistosomiasis with hepato(spleno)megaly can be detected earlier by this parameter than by ultrasonography. Ultrasonography provides characteristic, if not pathognomonic, images of Symmers fibrosis, and may be of value in the long-term evaluation of hepatic fibrosis.

Animals↗
PubMed1988

Liver involvement in human schistosomiasis mansoni. Assessment by immunological and biochemical markers.

In 20 patients with hepatic or hepatosplenic schistosomiasis and 82 individuals infected with S. mansoni, but without liver enlargement, serum parameters reflecting the fibrotic process and hemodynamic alterations as well as immunomodulation were examined. Included as controls were 35 age- and sex-matched healthy individuals from the study region in Northeast Brazil. Peripheral blood cholylglycine levels in patients with hepatomegaly, reflecting the spillover of portal blood into the systemic circulation, were elevated 12-fold over values of patients without liver involvement. Procollagen-III-peptide, a cleavage product of collagen synthesis, was elevated in patients with hepatomegaly (P less than 0.001) but normal in uncomplicated cases. Immunomodulation was assessed by in vivo delayed hypersensitivity to recall antigens and by serum beta 2-microglobulin and neopterin, substances released in the context of lymphocyte activation. Neopterin, predominantly a macrophage product, was elevated most strikingly in hepatomegalic cases (P less than 0.001). The possible interrelation between altered immune responses and excess fibrogenesis is discussed.

Adolescent↗
PubMed1988

Liver involvement in human schistosomiasis mansoni. Regression of immunological and biochemical disease markers after specific treatment.

Peripheral blood cholyglycine and procollagen-III-peptide were measured in 22 Zairean patients with hepatomegaly caused by S. mansoni before and after treatment with praziquantel. Circulating T-cell subsets and cutaneous in vivo delayed type hypersensitivity were assessed; serum neopterin and beta 2-microglobulin served as indicators for macrophage/lymphocyte activation. The results were compared to age and sex matched patients with S. mansoni infection limited to the intestinal tract and schistosomiasis free controls with equal socioeconomic background. Abnormal serum cholyglycine and neopterin levels and alterations of circulating T-cell subset frequencies were associated with hepatomegaly in schistosomiasis. Normalization of these parameters reflected a regression of egg-induced immunopathology as early as two months after specific chemotherapy. Serum procollagen-III-peptide concentrations rose significantly after treatment, suggesting release of propeptide previously incorporated without cleavage into tissue collagen. The combination of these biochemical and immunological parameters may allow assessment of the pathophysiological mechanisms responsible for liver disease in individual patients.

Adolescent↗
PubMed1988

Interleukin 2 receptor in patients with localized and systemic parasitic diseases.

An enzyme-linked immunosorbent assay was used to quantify soluble interleukin 2 receptor (IL-2R) in the serum of patients with helminthic and protozoal infections. The results demonstrated that levels of IL-2R were normal in patients with helminthic infections limited to the intestinal tract (ascariasis, trichuriasis), but significantly elevated in patients with systemic or long-lasting infections (strongyloidiasis, schistosomiasis, fascioliasis, opisthorchiasis). In patients infected with Schistosoma mansoni levels of IL-2R were higher in those with the hepatosplenic than in those with the intestinal form of the disease. Patients with malaria also showed increased serum levels of IL-2R, irrespective whether the infection was caused by Plasmodium falciparum or P. vivax. No difference was observed between patients with acute or history of malaria. The highest levels of IL-2R were observed in patients with visceral leishmaniasis. Interestingly, in these patients the concentration of IL-2R correlated to specific antibody titre. The results are discussed in the context of preferential activation of T lymphocytes, B lymphocytes and/or macrophages during the course of the different parasitic infections investigated.

Enzyme-Linked Immunosorbent Assay↗
PubMed1987

Antibodies of the IgE and IgG isotype, serum IgE and circulating immune complexes in schistosomiasis intercalatum.

Individuals in an advanced phase of infection by Schistosoma intercalatum in whom viable ova are still present in the rectal mucosa but not excreted in detectable quantity, can be distinguished clinically from a younger group of individuals excreting S. intercalatum ova in their faeces. This clear-cut distinction is underlined by findings in parameters of humoral response. The ratio of anticercarial to anti-adult worm antibodies was higher in the group excreting eggs with probably more recent infection. Levels of total serum immunoglobulin were higher in this group, with the exception of serum IgA, which was lower as long as eggs were being excreted. In a later stage of the disease, relatively more IgG seems to be bound in circulating immune complexes. It is postulated that these stage specific patterns of humoral immune response represent the evolution of the host-parasite relationship during the infection.

Adolescent↗