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Biomedical subjects

P Kern

Publications and source records attributed to P Kern.

At least 91 records · Page 5Linked to original sources
PubMed1998

Clinical efficacy of and immunologic alterations caused by interferon gamma therapy for alveolar echinococcosis.

Alveolar echinococcosis (AE) is a rare and often fatal disease characterized by a tumorlike expansion of the metacestode Echinococcus multilocularis in the liver. Because of the severe side effects of therapy with benzimidazoles, we treated a patient with recombinant interferon gamma at a dose of 250 microg over a 3-day period once a month. Disease progression was not detected during the observed period of 18 months. Following stimulation with crude Echinococcus antigen, mRNA from interleukin 5 was still detected in peripheral blood mononuclear cells by means of reverse transcriptase polymerase chain reaction analysis, and expression of interleukin 10 in T lymphocytes (as measured by fluorescence-associated cell sorting of intracellular cytokines) was elevated. These results indicate that bolus therapy with interferon gamma has some clinical effect but does not result in a change in the T helper 2 lymphocyte-dominated immune response to this parasite.

Cytokines↗
PubMed1998

HLA and alveolar echinococcosis.

Evidence in animal intermediate hosts that susceptibility to larval infection with Echinococcus multilocularis is restricted to individual host factors prompted us to investigate the susceptibility markers in humans. Because antigens of the extracellular parasite E. multilocularis are possibly presented by MHC molecules in a restricted way, we speculated that MHC polymorphism may influence resistance of the host towards infection and course of disease. We studied HLA-A, -B, -DRB1, -DQB1 and -DPB1 polymorphism in 151 patients with alveolar echinococcosis. Patients with an observation period of more than 2 years were grouped according to the clinical follow-up into cured (no recurrence following surgery) patients and patients with regressive or progressive forms of disease during benzimidazole chemotherapy. By comparing phenotypic frequency between patients with alveolar echinococcosis and healthy controls, HLA-DRB1*11 was associated with a reduced risk for disease development (odds ratio=0.55, 95% confidence interval=0.34-0.88; P=0.01). HLA-DQB1*02 was more frequent in patients with progressive disease when compared with patients with regressive disease (54.3% vs 28.3%, P=0.02). The result suggests that HLA-DRB1*11 might confer protection against alveolar echinococcosis and that HLA-DQB1*02 may indicate a risk for progressive disease development. The findings may facilitate the search for immunodominant T-cell epitopes of E. multilocularis.

Animals↗
PubMed1997

[Hyperferritinemia in Still syndrome in the adult and reactive hemophagocytic syndrome].

This report describes the fatal outcome of a case of adult onset Still's disease in a 46-year old man. The diagnosis was made according to the 1992 criteria, proposed by Yamaguchi. Nine months after the initial disease manifestations a rapid deterioration with progressive hepatosplenomegaly developed. In parallel, pancytopenia and marked hyperferritinemia could be detected. Transjugular liver biopsy revealed the presence of a hemophagocytic syndrome. The course of the disease was refractory to any form of treatment and the patient died from disseminated intravascular coagulation, hepatic and pulmonary failure. Pathogenetic mechanisms and possible associations between Still's disease and reactive hemophagocytic syndrome are discussed.

Adult↗
PubMed1997

T-lymphocyte cytokine mRNA expression in cystic echinococcosis.

In the present study we investigated cytokine mRNA expression by peripheral blood mononuclear cells (PBMC) from patients with cystic echinococcosis (CE) after stimulation with different antigens. By using reverse transcriptase polymerase chain reaction (RT-PCR) we could demonstrate that restimulation with crude Echinococcus granulosus antigen (Eg-Ag) induced or enhanced Th2 cytokine mRNA expression, especially IL-5 (by using antigen from sheep cyst fluid) in 23 out of 26 investigated CE patients and IL-10 (by using antigen from camel cyst fluid) in 10 out of 10 investigated CE patients. In contrast, IL-5 mRNA expression was absent in PBMC of healthy controls after Eg-Ag stimulation. To determine the specificity of this reaction we stimulated PBMC from 11 CE patients with crude Echinococcus multilocularis antigen (Em-Ag) and PBMC from 8 CE patients with Toxocara canis antigen (Tc-Ag). We found that the PBMC of patients showed a similar mRNA cytokine pattern on stimulation with Em-Ag when compared with Eg-Ag stimulation. The cytokine mRNA pattern on stimulation with Tc-Ag, however, resembled the cytokine mRNA pattern of unstimulated PBMC. Furthermore, the stimulation of PBMC with crude Mycobacterium tuberculosis antigen (H37Ra) and purified protein derivative (PPD) of M. tuberculosis revealed distinct IL-5 mRNA expression in all investigated CE patients, whereas in healthy controls IL-5 mRNA expression was very weak or totally absent. Thus, our results indicate an induction of Th2 cytokine mRNA expression in CE patients, which is frequently observed in parasite infections. Interestingly, this response persists after stimulation with tuberculosis antigens, which normally induce Th1 response.

Adolescent↗
PubMed1997

Bone and soft tissue manifestations of alveolar echinococcosis.

OBJECTIVE: The present study demonstrates the osseous and soft tissue manifestations of alveolar echinococcosis (AE). PATIENTS: We report on eight patients with AE with bone or soft tissue involvement confirmed at biopsy or needle cytology. RESULTS: All eight patients showed hepatic involvement. Four exhibited infiltration of the spine as a result of direct spread of the hepatic primary lesion; distant metastases were observed in only three of these patients. Calcifications, which are typical for hepatic manifestations of the disease, were observed in soft tissue in only two of eight cases (25%); we observed no instances of endovesicular daughter cysts. CONCLUSIONS: AE manifests itself in the vertebral column as a form of spondylitis and in soft tissue presents similar to an abscess. Since in most of these cases spread of the disease per continuitatem from the liver is present, the diagnosis is easily made from the characteristic hepatic findings.

Adult↗
PubMed1997

Affinity and kinetics of the interactions between an alphabeta T-cell receptor and its superantigen and class II-MHC/peptide ligands.

Immune activation is mediated by a specific interaction between the T-cell receptor (TCR) and an antigenic peptide bound to the major histocompatibility complex (MHC). T-cell activation can also be stimulated by superantigens which bind to germline-encoded variable domain sequences of certain TCR beta-chains. We have used a surface plasmon resonance biosensor to characterize the molecular interactions between a class II-restricted alphabeta TCR and its superantigen and MHC/peptide ligands. The extracellular domains of the murine D10 TCR (Valpha2, Vbeta8.2) were expressed in insect cells and secreted as a disulfide-linked heterodimer. In the absence of MHC class II, purified soluble D10 TCR bound to Staphylococcus aureus enterotoxin C2 with an association rate of 1.69+/-0.12 x 10(4)M(-1) sec(-1) and a dissociation rate of 1.9+/-0.47 x 10(-2) sec(-1), giving a dissociation constant of 1.1 microM. Binding of the TCR to S. aureus enterotoxin B was barely detectable and could not be measured accurately due to the rapid dissociation rate. Soluble D10 TCR also bound to a soluble murine MHC class II I-A(k) molecule containing a fused antigenic conalbumin peptide and complementary leucine zipper sequences to facilitate efficient chain pairing. The purified I A(k) chimera specifically stimulated proliferation of the D10 T-cell clone, and bound to immobilized soluble D10 TCR with an association rate of 1.07+/-0.19 x 10(4)M(-1)sec(-1) and a dissociation rate of 2.2+/-0.65 x 10(-2) sec(-1), giving a dissociation constant of 2.1 microM.

Animals↗
PubMed1997

IL-5 expressed by CD4+ lymphocytes from Echinococcus multilocularis-infected patients.

IL-5 is a major factor inducing differentiation of B lymphocytes into immunoglobulin-producing cells as well as a main regulator of eosinophils. Recently, we have shown that peripheral blood mononuclear cells (PBMC) from patients with alveolar echinococcosis (AE) express IL-5 mRNA after stimulation with crude Echinococcus multilocularis (E.m.) antigen. To characterize the observed response in lymphocyte subpopulations, we cultured patients' PBMC in the presence of E.m. crude antigen for 18 h. PBMC were separated from seven patients by fluorescence-activated cell sorting (EPICSorter) into CD4+ and CD8+ subpopulations and from an additional seven patients by magnetic cell sorting (MACS) into CD4+, CD8+ and the CD4+/CD8+ depleted fractions. mRNA was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) for the cytokines IFN-gamma, IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, as well as for beta-actin as control. IL-4 and IFN-gamma expression was positive in all of the patients in the stimulated CD4+ subgroup. IL-5 mRNA expression was detected in eight out of 14 CD4+ samples (58%) and not observed in the other subpopulations, or the unstimulated and healthy controls. Co-expression of other Th2 cytokines in the eight patients expressing IL-5 mRNA was found in five patients for IL-3 and in seven for IL-10. Expression of IL-5 and both Th2 cytokines (IL-3 and IL-10) was only observed in patients judged as critically ill. Out of the six patients who were regarded as cured after radical operation or as stabilized with or without chemotherapy, only two expressed IL-5. Out of those eight patients considered as critically ill, six expressed IL-5 mRNA and five of these co-expressed IL-3 and IL-10. Thus, we conclude that specific antigenic challenge of PBMC from patients with active or previous AE induces an IL-5 response of CD4+ lymphocytes. The expression of Th2-type interleukin mRNA is significantly more frequent in patients clinically judged as progressive. Furthermore, IgE was elevated only in patients regarded as critically ill (six out of eight). In none of the patients were eosinophils elevated. These data support a Th2-type immune response in patients with chronic E. multilocularis infection.

Actins↗
PubMed1997

Subclass-specific serological reactivity and IgG4-specific antigen recognition in human echinococcosis.

Immunoglobulin (Ig) subclass-specific antibody responses and isotype-specific recognition of E. multilocularis (Em) and E. granulosus (Eg) antigens (Ag) were evaluated in both alveolar echinococcosis (AE) and cystic echinococcosis (CE). AE patients were divided into 3 groups by clinical and therapeutic criteria according to their actual state of infection, i.e. elimination of parasite, and regression or progression of disease, CE patients were either before or after surgery, of in continuous chemotherapy due to parasite persistence. Total IgE was highly elevated in progressive AE cases (7/11), but not in the cases with eliminated infection or regression. In AE patients with active disease, EmAg-specific IgE, total IgG, IgG1, IgG2 and IgG4 were particularly high. Similarly, in 9 of 30 CE patients, total IgE was raised above reference values, indicating progressive disease. CE patients" sera antibody cross-reacted with crude EmAg, and detectable Ig levels of the same isotype were also measured by ELISA. In both AE and CE, parasite-specific antigen recognition was dominated by IgG1 and IgG4. In AE patients with progressive disease, IgG4 distinctively recognized low molecular weight EmAg of Ar 26 kD, 18 kD, 16 kD and 12 kD. As prominent IgG4 and IgE responses develop with chronic helminth infections only, these serological parameters may indicate successful parasite infestation and severe outcome of disease. In summary, analyses of immunoglobulin isotype responses in AE patients by ELISA in combination with immunoblotting are a useful approach for post-treatment follow-up of patients at risk of developing recrudescent disease.

Adult↗
PubMed1997

Systemic infection with Mycobacterium genavense following immunosuppressive therapy in a patient who was seronegative for human immunodeficiency virus.

We describe, to our knowledge, the first case of disseminated Mycobacterium genavense infection in a patient who was seronegative for human immunodeficiency virus. The patient, a 47-year-old woman, had been previously treated with immunosuppressive drugs for 9 months to control an unclassified immunologic disorder characterized by intermittent fever and inflammatory pulmonary, hepatic, and dermal infiltrates. Antemortem and postmortem examinations revealed the presence of numerous mycobacteria in the bone marrow, spleen, kidneys, and lungs; these organisms failed to grow in vitro and were identified as M. genavense by 16S rRNA gene sequencing. This case illustrates that systemic M. genavense infections are not restricted to patients with AIDS but can also occur in otherwise immunocompromised patients.

Female↗
PubMed1997

Human CD30+ cells are induced by Mycobacterium tuberculosis and present in tuberculosis lesions.

CD30 is a member of the tumor necrosis factor/nerve growth factor receptor family and evidence has been presented that activated CD4+ CD45Ro+ T cells of Th2 type selectively express CD30. Mycobacterium tuberculosis, a facultative intracellular bacterium capable of replicating in resting macrophages, is a potent inducer of IFN-gamma secretion by Th1 cells. We find increased CD30 expression by M. tuberculosis-stimulated alpha beta and gamma delta T cells, and elevated numbers of CD30+ alpha beta T cells in tuberculosis pleuritis and affected lung tissue. Furthermore, surface CD30 was associated with intracytoplasmic IFN-gamma expression and IFN-gamma production by M. tuberculosis-stimulated alpha beta and gamma delta T cells. Thus, our results indicate that M. tuberculosis is a potent inducer of CD30 expression in Th1 cells and argue against exclusive correlation of CD30 expression with Th2 cell responses.

Animals↗
PubMed1997

Detection of restricted junctional diversity of peripheral T cells in SLE patients by spectratyping.

Analysis of somatic mutations revealed that anti-double-stranded DNA (dsDNA) autoantibodies from patients with systemic lupus erythematosus (SLE) share features of a T cell dependent, antigen driven immune response. Therefore we analysed the length diversity of the complementarity determining region 3 (CDR3) of T cell receptor (TCR) by high resolution gel electrophoresis of 16 V beta family specific RT PCR products (spectratyping). To enable statistical analysis we developed a quantitative scoring method for the histograms. We investigated 16 V beta gene families in peripheral T cells of SLE patients (n = 9) with active (n = 5) and inactive (n = 4) disease as well as normal healthy blood donors (NHD; n = 9). Analysis of TCR V beta spectratypes (active SLE, n = 59; inactive SLE, n = 51 and NHD n = 97) revealed statistically significant differences of CDR3 length distribution between SLE patients and NHD (P < 0.0001 (active SLE/NHD) and P = 0.0034 (inactive SLE/NHD). These results suggest that spectratyping is able to detect clonal activation of peripheral T cells which correlates to disease activity in SLE patients. We conclude that peripheral T cells from SLE patients display features of a secondary antigen driven immune response.

Adolescent↗
PubMed1997

Musculoskeletal involvement in cystic echinococcosis: report of eight cases and review of the literature.

OBJECTIVE: Our purpose was to describe the morphologic appearance of musculoskeletal lesions in patients with cystic echinococcosis shown by CT and MR imaging. CONCLUSION: Patients with musculoskeletal lesions of cystic echinococcosis typically have cystic structures in adjacent soft tissues. These cysts morphologically resemble abscesses, with peripheral uptake of contrast medium and variable signal intensities on T1-weighted MR images. The absence of calcifications or endovesicular daughter cysts does not exclude the diagnosis of cystic echinococcosis.

Adult↗
PubMed1997

Serum PCR of Pneumocystis carinii DNA in immunocompromised patients.

The detection of Pneumocystis carinii DNA in serum, a potentially useful and attractive tool for the diagnosis of P. carinii infection and for monitoring the success of therapeutic interventions, remains a controversial issue. In a prospective study of 29 immunocompromised patients, including 16 with HIV infection undergoing bronchoscopy and bronchoalveolar lavage, we examined 32 bronchoalveolar lavage fluids and multiple serum samples for the presence of P. carinii DNA by using mitochondrial rRNA gene fragments pAZ102-E as pAZ102-H as primers. Samples from 7 immunocompetent patients were analysed as a control. 13/32 bronchoalveolar lavage fluids of immunocompromised patients (41%), but none of the controls, had both microscopic evidence of P. carinii cysts as well as P. carinii DNA detection. In none of these patients were serum samples obtained before therapy positive for P. carinii DNA, while in 1 patient (8%), P. carinii DNA was detected in 2/5 serum samples obtained during therapy. Interestingly, PCR detected P. carinii DNA in sera of 3/15 immunocompromised patients without detection of P. carinii DNA or organisms in BAL. Two of these 3 patients were taking secondary prophylactics for P. carinii pneumonia. In conclusion, PCR for P. carinii DNA in serum, at least in certain circumstances, may be of little value for the diagnosis of P. carinii pneumonia.

Adult↗
PubMed1997

Supportive pentoxifylline in falciparum malaria: no effect on tumor necrosis factor alpha levels or clinical outcome: a prospective, randomized, placebo-controlled study.

Pentoxifylline (POF) may suppress overproduction of tumor necrosis factor alpha (TNF alpha), which is thought to contribute to complications of human falciparum malaria. However, POF is believed to improve impaired capillary blood flow, which can be impaired in falciparum malaria. To test whether POF affects TNF alpha serum levels or other variables in this disease, we administered POF (20 mg/kg/day intravenously in 150 ml of saline for five days) randomized versus placebo (150 ml of saline without POF) in addition to standard antimalarial therapy. After recruitment of 51 patients with Plasmodium falciparum malaria, those receiving POF had more nausea and abdominal discomfort than the placebo group, as expected. Eleven of 27 patients receiving POF and three of 24 patients receiving placebo requested termination of the study medication (P < 0.05). Pentoxifylline did not change the decrease of TNF alpha levels or affect the clinical course in a significant way. Since POF failed to improve the clinical situation or to impact numerous laboratory parameters (including TNF alpha, thrombin-antithrombin III, thrombomodulin, and human neutrophil elastase), the study was terminated earlier than planned. While this study does not specifically address cerebral complications of malaria, the results suggest that POF is not useful as a routine adjunct to the standard therapy of falciparum malaria.

Acetaminophen↗
PubMed1997

[Interactions between biospecific polymers and MCF7 cells: modulation of cellular proliferation and expression of estrogen receptors].

Numerous studies on interactions between insoluble polymers and cell membrane receptors indicated modulation of cellular proliferation and cell phenotype by these polymers considered as biospecific. We synthesized several biospecific polymers in order to investigate the interactions between polymers and intracellular receptors as estrogen receptors considered as tumoral indicator of breast cancer. Biospecific polymers were obtained by random substitutions of crosslinked polystyrene beads with suitable chemical groups (sulfonate and amino acid sulfamides). These polymers were used as microcarriers for culture of MCF7 cells, a cellular model of human breast cancer. Quantification of MCF7 cell estrogen receptors was determined by radioligand binding assay for different days of cellular proliferation. The data obtained with MCF7 cells cultured on biospecific polymers show an inverse relationship between polymer induced inhibition of cell proliferation and polymer induced increase of estrogen receptors. Similar inverse relationship was obtained with MCF7 cell cultured on standard polystyrene tissue culture plates. The various interaction between insoluble polymers and MCF7 cells could be related to the proportion and the nature of the substitutive chemical groups. These biospecific polymers could presents sites of interaction with cell membrane receptors leading to modulation of cell biological activity. The different insoluble polymers were used as preliminary models: a practical application could be a methodology of cellular selection using soluble biospecific polymers (for example chemically modified dextrans).

Binding, Competitive↗