Biomedical subjects

F W Tischendorf

Publications and source records attributed to F W Tischendorf.

At least 19 recordsLinked to original sources

PubMed2001

[Fever and exanthema after trip to the Mediterranean area--Mediterranean spotted fever (Boutonneuse fever)].

HISTORY AND CLINICAL FINDINGS: In connection with a period of residence in the Mediterranean basin (Portugal, Spain, Sicily) one woman and two men (age: 28, 31 and 40 years) got sick with fever in August and in the midst of October. In addition, they complained about headache in two cases and myalgias, arthralgia and vomiting in one case, respectively. Two of the vacationers (cases 2 and 3) had been accompanied by their dogs. One of them (case 2) was bitten of a tick. The woman (case 3) removed few days after vacation-beginning ticks from her dogs. Patients 1 and 2 appeared severely ill and presented with high fever and generalized maculopapular rash which included also the soles and palms. Patients 2 and 3 had a primarily-lesion ("eschar"). In patient 3 the eschar was pustular and associated with regional lymphadenitis. INVESTIGATIONS: All three patients showed an increased erythrocyte sedimentation rate and elevated liver enzymes. Cases 1 and 2 presented with a significantly elevated activity of lactate dehydrogenase, leukocyturia and microhematuria. Indirect immunofluorescent assay for specific antibodies directed against Rickettsia conorii revealed titers between 1:40 and 1:640 (normal: negative). DIAGNOSIS, TREATMENT AND COURSE: Diagnosis was based on the triad fever, rash and eschar as well as on epidemiological data which include a recent period of residence in the Mediterranean basin during the summer and contact with a dog. In case 1 diagnosis was difficult because of the absence of an eschar. This patient had been treated with penicillin for two days without success. Only the parenteral administration of ciprofloxacin caused complete defervescence and clinical improvement within two days. A complete defervescence within two days was reached with doxycycline also in case 2. In comparison to these cases, the course in the third patient was mild, and the patient defervesced spontaneously. CONCLUSION: Mediterranean spotted fever should be considered in the case of unclear fever and rash following a period of residence in the Mediterranean basin during summer time. An eschar may confirm this diagnosis, and early start of therapy may shorten the course of the disease and prevent complications.

Adult↗

PubMed2000

Lipopolysaccharide-like molecules derived from Wolbachia endobacteria of the filaria Onchocerca volvulus are candidate mediators in the sequence of inflammatory and antiinflammatory responses of human monocytes.

The majority of Onchocerca volvulus-infected persons show signs of cellular anergy, and long-time survival of adult and larval parasites in subcutaneous tissue is observed. The mechanisms leading to immunological hyporesponsiveness are poorly understood. Monocytes/macrophages represent a link between the innate and acquired immune system and are candidate cells to promote inflammatory and antiinflammatory processes. In the present study we have shown that products of microfilarial (O. volvulus) and adult (O. volvulus and O. ochengi) parasites affect monocytes in vitro. An early production of TNF-alpha by exposed monocytes was followed by the production of IL-10 and a reduced expression of HLA-DR and the costimulatory molecules B7-1 and B7-2, while other adhesion receptors remained unaffected. Downregulation of the functional membrane receptors failed to occur after treatment of the cells with anti-IL-10 antibodies. The engagement of CD14, a dominant membrane receptor on monocytes and major binding protein for lipopolysaccharides, was indicated by partial blocking of monocyte modulation by neutralizing antibodies to CD14 and by the antagonistic lipid A analog compound 406. Lipopolysaccharide-like molecules were detected in sterile products of O. volvulus stages which could originate from Wolbachia bacteria related to Gram-negative Rickettsiales, known to be abundant in the hypodermis and the female reproductive organs of O. volvulus. The present results indicate that the monocyte/macrophage may be a major target cell for immunomodulatory parasite-derived and intraparasitic, bacteria-derived molecules, thereby contributing to the host's cellular hyporesponsiveness.

Animals↗

PubMed2000

Humoral responses to a secretory Onchocerca volvulus protein: differences in the pattern of antibody isotypes to recombinant Ov20/OvS1 in generalized and hyperreactive onchocerciasis.

The Onchocerca volvulus secretory protein Ov20/OvS1 represents a dominant antigen expressed in the infective larvae, microfilariae and adult stages of the parasite. The humoral responses to this protein have not yet been analysed in the polar clinical and immunological forms of onchocerciasis. Analysis by ELISA of class and subclass antibodies to Ov20/OvS1 in persons with the generalized or the hyperreactive form of onchocerciasis revealed similar strong responses of IgG1, IgG4 and IgM antibody levels in both forms of onchocerciasis and significant differences were observed in the IgE and IgA antibody classes. Computation of the ratios of antibodies showed that persons with the generalized form exhibited significantly higher ratios of IgG4 to IgG1, IgG4 to IgE, and IgM to IgE than patients with the hyperreactive form. To investigate the isotype recognition of antigenic sites on Ov20/OvS1 protein, three recombinantly expressed fragments (F1-3) of Ov20/OvS1 were probed using sera which strongly reacted with intact recombinant Ov20/OvS1. Epitope(s) on F1 comprising amino acid residues 1-63 were significantly recognized by IgG1 and IgE, while IgM recognized epitopes on all three fragments. The strongest reaction of IgM occurred with epitope(s) formed by residues 108-171 (F3). In contrast, IgG4 type antibodies were not reactive with either of the three OvS1 fragments, but they reacted with intact Ov20/OvS1 protein. Generalized onchocerciasis, unable to eliminate microfilariae, and hyperreactive onchocerciasis, with a high potency to eliminate or to reduce parasite loads, can be distinguished by a distinct pattern of isotype responses to Ov20/OvS1.

Animals↗

PubMed2000

Eosinophil granule proteins in serum and urine of patients with helminth infections and atopic dermatitis.

Eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EPX) are cytotoxic molecules involved in helminth infections and allergic reactions. Hitherto most clinical chemical studies have been concerned with the analysis of serum ECP in allergic diseases. The aim of this study was to examine whether serum as well as urine levels of these proteins are useful clinical chemical parameters in helminthiases and allergic diseases such as atopic dermatitis. Comparing these diseases under the same methodological conditions, levels of ECP and EPX were generally higher in helminthiases than in atopic dermatitis and non-helminth, non-allergic diseases. The highest levels of both proteins occurred in tropical worm diseases, in particular hookworm disease and onchocerciasis. When comparing helminthiases with allergic disorder, only hookworm disease (ECP and EPX) and onchocerciasis (EPX) exhibited significantly higher eosinophil cationic protein serum levels than atopic dermatitis. In patients with schistosomiasis mansoni and egg loads of > 1000-10 000 eggs/g stool (epg) EPX serum levels were significantly higher than in patients exhibiting loads < 1000 epg. Urinary analyses revealed only EPX to be present in measurable amounts. Levels of this protein were much higher in urine of patients with hookworm disease and onchocerciasis than in those with atopic dermatitis and in healthy controls. The results suggest that besides serum EPX, urinary EPX may be a useful clinical chemical parameter in eosinophilia of helminth and allergic aetiology.

Adolescent↗

PubMed2000

Use of the recombinant Onchocerca volvulus protein Ov20/OvS1 for the immunodiagnostic differentiation between onchocerciasis and mansonelliasis and for the characterization of hyperreactive onchocerciasis (sowda).

The protein Ov20/OvS1 was used as antigen in ELISA and Western blot in order to differentiate onchocerciasis from African mansonelliasis and to characterize the hyperreactive form of Onchocerca volvulus infection (sowda). The specificity of the IgG4 Western blot was 98% for the differentiation between persons with onchocerciasis and Mansonella microfilariae (mf) carriers (125 persons with M. perstans and 92 with M. streptocerca), whereas the IgG4 ELISA showed a specificity of 81% in 137 M. perstans mf carriers and 85% in 94 M. streptocerca mf carriers. The sensitivity of Ov20/OvS1 in identifying onchocerciasis using the IgG4 ELISA was 75% for 103 O. volvulus mf carriers with the generalized and 89% for 44 patients with the sowda form of onchocerciasis. IgE antibodies against OvS1 were found in 95% of 39 patients with hyperreactive onchocerciasis but only in 15% of 47 persons with the generalized form. Thus, Ov20/-OvS1 appears a promising candidate antigen for the diagnosis of onchocerciasis and in particular for the detection of the sowda type of disease.

Adult↗

PubMed2000

Two large liver abscesses complicating Crohn's disease.

A 20-year-old woman with active Crohn's disease had an abrupt onset of high fever accompanied by an elevation of serum gamma-glutamyltransferase and alkaline phosphatase. Her past medical history included a course of corticosteroid therapy for 7.5 months and a resection of the terminal ileum and the cecum 2 months before admission. At that time an ileoascendostomy had been performed, revealing a walled-off perforation of the colon into the retroperitoneal space. Sonography revealed 2 large abscesses in the right lobe of the liver. After beginning antibiotics, ultrasound-guided percutaneous aspiration and drainage with a pigtail catheter were performed for both abscesses leading to a rapid reduction of their size and an improvement in the patients general condition. Liver abscess represents a rare complication of Crohn's disease. A review of the literature is presented.

Adult↗

PubMed1999

Eosinophils, eosinophil cationic protein and eosinophil-derived neurotoxin in serum and urine of patients with onchocerciasis coinfected with intestinal nematodes and in urinary schistosomiasis.

Eosinophils, eosinophil cationic protein (ECP), eosinophil-derived neurotoxin (EDN/EPX), myeloperoxidase (MPO) and IgE were measured in blood, serum and/or urine in Schistosoma haematobium- and Onchocerca volvulus-infected Guineans and O. volvulus- and S. haematobium-negative Guineans coinfected or infected with intestinal nematodes. The number of eosinophils and levels of eosinophil granule proteins but not of MPO were found to be strongly elevated in all Africans as compared to European controls. The highest serum ECP and serum and urinary EDN/EPX levels were observed in the hyperreactive form of onchocerciasis (sowda). Onchocerciasis patients and O. volvulus-negative Africans coinfected or infected with intestinal nematodes (hookworm and/or Ascaris lumbricoides) revealed higher serum granule protein concentrations and/or absolute eosinophil counts and urinary ECP than those without nematode infections. Statistical differences between both sections were found for the absolute eosinophil counts and for serum EDN/EPX and IgE in generalized onchocerciasis, and for urinary ECP in sowda, indicating stimulation of the eosinophil potential of O. volvulus-positive patients by coexistent hookworm infection. This worm species, in contrast to A. lumbricoides, causes especially high eosinophil counts and EDN/EPX and IgE levels. From these results it is concluded that in nematode diseases, ECP and EDN/EPX levels reflect the degree of antigenic stimulation, eosinophil activation and eosinophil turnover rates. Serum ECP and serum and urinary EDN/EPX may, therefore, serve as parameters to monitor helminth infection. Urinary ECP may be a marker of eosinophiluria secondary to urogenital manifestation of S. haematobium. It is elevated in hyperreactive onchocerciasis activated by intestinal nematodes.

Adolescent↗

PubMed1999

Analysis of renal function in onchocerciasis patients before and after therapy.

The occurrence of renal abnormalities was investigated in patients with onchocerciasis in comparison to individuals without onchocerciasis in Guinea. Serum creatinine levels, excretion of urinary marker proteins, and kidney size by ultrasound were determined. A high prevalence of glomerular as well as tubular dysfunctions was observed; however, no association with onchocerciasis could be detected. We also hypothesized that patients with hyperreactive onchocerciasis might be prone to develop immune-mediated glomerular disorders; however, this could not be verified. Following treatment with ivermectin, a slight but significant increase in the excretion of urinary albumin and alpha1-microglobulin was seen five days after treatment in all treated patients, whereas levels of proteinuria were significantly higher five days after treatment only in patients with high microfilarial densities. Our results indicate that ivermectin can cause glomerular and tubular disturbances in patients with onchocerciasis; however, these are minor and do not seem to be clinically relevant.

Adult↗

PubMed1998

Onchocerca volvulus: microfilariae secrete elastinolytic and males nonelastinolytic matrix-degrading serine and metalloproteases.

Host tissue penetration by parasitic nematodes may be mediated by both mechanical processes and proteolytic enzymes released by the parasites. Analysis of excretory-secretory (ES) products of Onchocerca volvulus microfilariae and adult stages on substrate gels demonstrated that they contain several distinct proteolytic enzymes. The analysis of the ES products of the microfilariae revealed one low and two high molecular weight proteolytic bands that degraded gelatin in substrate gels. The low molecular weight protein was found to be an elastinolytic protease cleaving soluble and insoluble elastin. ES products of males contained several high molecular weight proteases in the range of >/= 100-kDa degrading gelatin but lacked the low elastinolytic protease. The ES proteases of both developmental stages degraded the extracellular matrix proteins fibronectin, laminin, and collagen type IV, but not intact immunoglobulin G. The optimal protease activity for each of the proteases was found to be at a neutral pH. Inhibitor studies demonstrated their classification as serine and metalloproteases. Female and male extracts were able to hydrolyze azocasein but not gelatin in substrate gels. Protease activity could not be detected in ES products of females and microfilariae extract.

Animals↗

PubMed1997

Cellular and subcellular localization of cationic leukocyte antigen (CLA) in human eosinophil granulocytes.

The cellular and subcellular localization of cationic leukocyte antigen (CLA) in human peripheral blood and tissue granulocytes was investigated by immunoenzymatic labeling and by immunoelectron microscopy. Human peripheral blood granulocytes from healthy individuals and from subjects with eosinophilia of varying etiology, as well as intravascular and/or perivascular granulocytes in skin biopsies taken from patients with generalized onchocerciasis, a skin disease caused by microfilariae of Onchocerca volvulus, were studied. Controlled indirect immunoenzymatic staining for CLA in cytospin preparations of buffy coat cells and in histological sections of skin biopsies revealed that this protein was exclusively found in the cytoplasm of eosinophil granulocytes. Furthermore, immunogold labeling coupled with electron microscopy showed that CLA was specifically localized within the matrix of both the small non-crystalloid-containing pale granules and the large crystalloid-containing secondary granules of peripheral blood and tissue eosinophils. No specific gold labeling was observed in other organelles of eosinophils, in neutrophils, basophils, lymphocytes or monocytes.

Antigens, Differentiation, T-Lymphocyte↗

PubMed1996

Serum levels of eosinophil cationic protein, eosinophil-derived neurotoxin and myeloperoxidase in infections with filariae and schistosomes.

The serum levels of three major granulocyte proteins were measured in patients with onchocerciasis, bancroftian filariasis and intestinal schistosomiasis and compared to controls from patients with malaria, Africans living in areas not endemic for these infections and healthy Germans. The investigation comprised the determination of the eosinophil granule proteins eosinophil cationic protein (ECP) and eosinophil-derived neurotoxin (EDN/EPX), and the neutrophil/monocyte granule protein myeloperoxidase (MPO). ECP and EDN/EPX levels were found elevated only in the three helminth infections that are associated with eosinophilia, while MPO was found elevated in all tested disease groups. The levels of eosinophil granule proteins observed in the helminth diseases by far exceeded those described for bronchial asthma and atopic dermatitis. ECP, EDN/EPX and MPO serum levels reflect the ongoing disease and are related to functional activity of the respective leukopoetic system. ECP and EDN/EPX appear to be markers of the eosinophil effector system and MPO a marker of the neutrophil and/or monocyte/macrophage effector system. Significantly higher ECP levels in chronic hyperreactive onchodermatitis (sowda) versus generalized onchocerciasis seem to reflect an augmented degree of antigenic stimulation, eosinophil activation and eosinophil turnover rates, indicating a more active mechanism of parasite clearance in sowda patients.

Africa↗

PubMed1994

Lymph nodes of onchocerciasis patients after treatment with ivermectin: reaction of eosinophil granulocytes and their cationic granule proteins.

Lymph node and skin biopsies from Liberian patients with generalized and localized (sowda) onchocerciasis were studied 12-68 hours after oral administration of ivermectin at a single dose of 150 micrograms/kg body weight. Electron microscopic examination and immunohistochemical staining with antibodies against two different forms of eosinophil cationic protein (ECP EG1, ECP EG2), eosinophil peroxidase (EPO) and cationic leukocyte antigen (CLA) were performed. Following their disappearance from the skin, a large number of microfilariae was found in the regional lymph nodes. The lymph nodes from treated patients had over ten times more eosinophils compared to those from untreated persons with a peak of eosinophil density at 40-48 hours after treatment. Degenerating microfilariae in the lymph nodes were encircled by eosinophils, which showed positive immunostaining for ECP, EPO or CLA. Intra- and extracellular eosinophil granules revealed a great variation in their condition. In some specific granules a variety of structural alterations in the crystalloid cores occurred while in others different stages of deficiency in the matrix electron density were observed. The frequent necrosis of eosinophils in the immediate vicinity and at some distance from the microfilariae, with subsequent release of granules and the deposition of toxic cationic granule proteins onto the microfilarial cuticle during the eosinophil-parasite adherence reaction, demonstrated the function of these proteins in the ivermectin-reinforced killing of microfilariae in lymph nodes.

Animals↗

PubMed1993

Modulatory effects of antifilarial drugs ivermectin, CGP 6140 and CGP 20376 on the oxidative burst of eosinophilic granulocytes.

Three recently introduced anthelmintic agents, the macrocyclic lactone, ivermectin, the amoscanate derivative CGP 6140 and the benzothiazole compound CGP 20376, were investigated for their in vitro modulatory effects on eosinophilic effector cells. The investigation comprised studies on the generation of the toxic oxygen intermediates superoxide anion and hydrogen peroxide which are major effector products of granulocytes. Eosinophils were obtained from 19 patients infected with the filarial parasite Onchocerca volvulus. Inhibitory effects on the generation of toxic oxygen intermediates were demonstrated for ivermectin and CGP 20376 at concentrations higher than 200 ng/ml (0.5 microM) and for CGP 6140 at concentrations higher than 1000 ng/ml (2.7 microM). An increased production of the reactive oxygen metabolites was demonstrated at low doses of ivermectin (20-40 ng/ml; corresponding to 0.02-0.04 microM) and CGP 6140 (40-100 ng/ml; 0.1-0.3 microM), respectively. The results reveal a dual, dose-dependent modulatory in vitro effect of the investigated anthelmintic drugs on the respiratory burst of eosinophilic effector cells indicating that these compounds may modulate host defense in vivo.

Eosinophils↗

PubMed1993

Improved Randolph stain for direct leukocyte differentiation and determination of total eosinophil count in a hemocytometer.

Identification and quantification of eosinophilic granulocytes are commonly performed indirectly by total leukocyte count and white cell differentiation in smears or cytocentrifuge preparations. Using a combination of four dyes, phloxine, Biebrich scarlet, methylene blue, and crystal violet, at 50-800 micrograms/ml, we have substantially improved an earlier method for differentiating leukocytes in a hemocytometer. This direct method allowed a rapid and reliable enumeration of eosinophils and their differentiation from neutrophils, lymphocytes and monocytes in peripheral blood and leukocyte fractions. The results obtained using this stain correlated with the leukocyte counts calculated from May-Grünwald-Giemsa stained smears in 100 patients with eosinophilia of various etiologies (r = 0.95; p < 0.01). This simple method is a useful improvement for eosinophil enumeration in field studies and biological experiments where the purity of cell suspensions must be evaluated without delay. The method cannot be substituted for the commonly used indirect technique which also allows the identification of other leukocyte lineages and their precursors.

Blood Cell Count↗

PubMed1991

Eosinophil-larval-interaction in onchocerciasis: heterogeneity of in vitro adherence of eosinophils to infective third and fourth stage larvae and microfilariae of Onchocerca volvulus.

Adherence of eosinophilic granulocytes from patients with onchocerciasis to microfilariae (Mf), third (L3) and fourth (L4) stage larvae of Onchocerca volvulus was studied in vitro. Native and heat-inactivated sera from patients with onchocerciasis (OS), from endemic controls without signs of the disease (ECS), from healthy Caucasians (NS) or foetal calf serum (FCS) served as sources for adherence mediating factors. In FCS-supplemented medium eosinophils did not adhere to any larvae. None of the sera mediated the adherence of eosinophils to L4. Eosinophils adhered to L3 in the presence of OS, ECS and NS, whereas OS exclusively mediated adherence to Mf. Reduced adherence rates of eosinophils to L3 occurred in heat-inactivated or zymosan-activated OS, ECS or CS. Eosinophils bound to the L3 cuticle of moulting stage but not to the newly exposed L4 cuticle. A single adherent layer of effector cells was found around cast L3 cuticle, multiple layers were found around intact L3 leading to subsequent paralysis of the larvae and to an amplification of the toxic effector potential by homotypic intereosinophilic adhesion. Our experiments document heterogeneity of in vitro effector cell adherence to the three larval stages of O. volvulus and indicate that complement-dependent as well as independent mechanisms are operative in eosinophil-larval-interaction. The results emphasize the importance of the invading infective larval stages of O. volvulus as possible targets for vaccine production.

Animals↗

PubMed1990

Ultrastructural study of the interaction between eosinophilic granulocytes and third and fourth stage larvae of Onchocerca volvulus.

The interaction in vitro between eosinophil effector cells and third and fourth stage larvae of Onchocerca volvulus was studied by electron microscopy. The morphological observations demonstrated different mechanisms of attack of eosinophil cells that are dependent upon the time of incubation. Rapid adherence to the cuticle of the target, flattening, secretion of granule contents, vacuole formation and, finally, complete degranulation of the eosinophils were seen after incubation with third stage larvae and moulting stages. Alterations of the epicuticular and cuticular structures could be found near the attachment site of the cells. The eosinophils, however, showed no interactions with fourth stage larvae of this filarial parasite.

Animals↗

PubMed1989

[The effects of the intake of cod liver oil on the blood lipid level, the lipoprotein profile and bleeding time].

In a research study performed over eight months with five female and six male subjects (age 35-67 years) the effect of cod liver oil on the lipoprotein composition in the blood was tested. The main goal was to prove that the regular administration of so-called highly unsaturated omega-3-fatty acid components in fish oil (4 g per day over six months) may lead to a reduction of triglyceride and total cholesterol values. Furthermore, any changes in HDL and LDL cholesterol fractions as well as the bleeding time were registered. The average values of all subjects showed an essential reduction of the triglyceride and cholesterol values. The control examination after 8 months even showed a continuous trend. The LDL fractions on an average remained unchanged. It can be taken for granted that the administration of unsaturated fatty acids in cod liver oil shows a successful therapeutic effect by the reduction of triglyceride and cholesterol values. The anti-atherosclerotic and the anti-platelet aggregational effect of fish oil has been described in many publications.

Adult↗

PubMed1988

[Effect of cod liver oil administration on blood lipid levels, lipoprotein profile and bleeding time].

Adult↗