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Biomedical subjects

J Knop

Publications and source records attributed to J Knop.

At least 235 records · Page 13Linked to original sources

Antibody cross-linking as a factor in immunity to cholera in infant mice.

Several antibody preparations were tested for their ability to reduce adsorption of Vibrio cholerae to isolated intestinal epithelial cells, and this ability was related to agglutination and protective activity in infant mice. The results demonstrate that (1) the reduction in adsorption of V. cholerae to epithelial cells correlates with the degree of agglutination for given antibody preparation; (2) intact tantibodies protect infant mice from cholera only at concentrations that agglutinate the bacteria; and (3) purified antibodies to flagellar antigens protect infant mice from cholera. These results indicate that cross-linking of bacteria by antibody causes a reduction in the number of organisms adsorbed to the intestinal wall. Thus antibody cross-linking plays an important role in immunity to cholera in infant mice.

Adsorption↗

The effect of lysozyme on the complement-dependent bactericidal action of different antibody classes.

Preparations of rabbit, dog and sheep IgA, IgA and IgM were examined for their antibacterial effects using a complement-dependent bactericidal assay. IgM and IgG were efficient bactericidal antibodies in the presence of complement; IgA, however, contained negligible activity. Except for sheep IgG no enhancement of bactericidal activity was observed in the presence of added lysozyme.

Animals↗

Dendritic cell-based genetic immunization in mice with a recombinant adenovirus encoding murine TRP2 induces effective anti-melanoma immunity.

BACKGROUND: The induction of cellular immune responses to melanocyte-specific enzymes such as the tyrosinase family of proteins is the goal of various clinical studies for the immunotherapy of melanoma. Tyrosinase-related protein-2 (TRP2) is an attractive model antigen for preclinical studies in C57BL/6 mice because it is naturally expressed by the murine B16 melanoma and can be recognized by self-reactive cytolytic T lymphocytes (CTL). Here we describe efforts to develop genetic immunization with dendritic cells (DC) for the immunotherapy of melanoma in this clinically relevant system. METHODS: Recombinant adenoviruses encoding green fluorescent protein (Ad-EGFP) and murine TRP2 (Ad-mTRP2) were constructed using Cre-loxP-mediated recombination. DC were generated in vitro from precursors in bone marrow and transduced with Ad-EGFP or Ad-mTRP2. Mice were immunized by direct injection of adenovirus or by injection of Ad-transduced DC. Induction of tumor immunity was assessed by intravenous challenge with B16 melanoma cells and enumeration of experimentally induced lung metastases. RESULTS: Flowcytometric analysis of DC transduced with Ad-EGFP demonstrated endogenous fluorescence due to cytoplasmatic expression of EGFP in 30-60% of cells. Ad-EGFP-transduced DC simultaneously displayed the DC-specific marker NLDC145 and high levels of MHC and costimulatory molecules on their cell surface. Transduction of DC with Ad-mTRP2 resulted in strong intracellular expression of TRP2 which could be readily detected by immunostaining. Importantly, immunization of mice with cultured Ad-mTRP2-transduced DC completely prevented the development of lung metastases following an intravenous challenge with B16 melanoma cells. This striking protective effect was observed with both the intravenous and the subcutaneous route of DC immunization. In vivo depletion of T-cell subsets suggested that the protective effect of an immunization with Ad-mTRP2-transduced DC involved both CD8+ and CD4+ T-cells. CONCLUSIONS: Our results demonstrate that DC-based genetic immunization of mice with TRP2, a clinically relevant melanocyte-specific self-antigen, induces effective cellular immunity and prevents metastatic growth of B16 melanoma cells in vivo.

Adenoviridae↗

[Cardiomyopathy after osteosarcoma treatment: a contribution to the cardiotoxicity of adriamycin].

The frequency and severity of clinical and subclinical heart damage were studied in patients who had been treated with adriamycin (ADR) as part of the Cooperative Osteosarcoma Studies (COSS). The study charts of 785 patients from 63 participating institutions were reviewed: The overall incidence of drug-induced congestive heart failure was 2.2% (17 cases, 5 fatal). Late left ventricular function was studied in 29 tumor free survivors 81 +/- 41 month after treatment with 342 +/- 113 mg/m2 ADR. A detailed history and physical exam for signs of overt heart disease were obtained. M-mode echocardiography (ECHO, 29 cases) with evaluation of the fractional shortening rate (FS) and radionuclide ventriculography (RNV, 18 cases) with determination of the systolic ejection fraction at rest (EF) were used to screen for subclinical cardiac disease. Impaired cardiac function leading to pathological values was documented in close to one half of these patients. The frequency and severity of clinical and subclinical heart damage increased with cumulative adriamycin and time since cessation of anthracycline therapy.

Adolescent↗

[Nuclear medicine prediction of histologic tumor response of osteosarcoma].

The prediction of histologic tumor response to preoperative chemotherapy was assessed by quantitative scintigraphic follow-up examinations of 54 osteosarcomas. Tumor/non-tumor scintimetry using 99mTc labeled diphosphonates allowed accurate prediction of tumor response in 28 of 30 tumors (accuracy = 93%) after completion and in 10 of 12 osteosarcomas (accuracy = 83%) at the half-way stage of preoperative chemotherapy evaluating only those tumors which showed convergent changes of tumor/non-tumor ratios in the perfusion and the mineral phase. At the half-way stage, however, evaluation of chemotherapy effects was complicated in 12 of 23 osteosarcomas by diverging T/NT ratios. In contrast, quantification and mapping of the tumor plasma volume and 99mTc MDP plasma clearance predicted the histologic tumor response to chemotherapy in 12 of 13 tumors (accuracy = 92%) after completion and in all 11 cases (accuracy = 100%) at the half-way stage.

Antineoplastic Combined Chemotherapy Protocols↗

[Osteonecrosis of the femur head. Comparative studies on methods for early diagnosis].

Compared to the computerized tomography and bone scintigraphy with additional single photon emission tomography the Magnetic-Resonance-Tomography shows early pre-radiological stages in cases of femoral head necrosis which cannot be seen neither by computerized tomography nor by usual x-ray. Compared to this the bone scintigraphy shows early stages similarly, but the topographic coordination and specific diagnosis is impossible.

Femur Head↗

Cellular and molecular mechanisms in the induction phase of contact sensitivity.

During the induction phase of contact sensitivity, hapten-specific Th1 cells are primed by epidermal Langerhans cells. These Langerhans cells present hapten on MHC class II molecules and provide costimulatory signals. This presentation discusses the induction of cytokines in Langerhans cells and keratinocytes by haptens and their regulatory effects on contact sensitivity. Haptens were painted on the skin of normal BALB/c mice and epidermal cells were prepared at various times thereafter. Langerhans cell-derived interleukin (IL)-1 beta mRNA was observed as early as 15 min after hapten paining. In keratinocytes, tumor necrosis factor-alpha, IL-1 alpha, IP-10, MIP-2 and IL-10 were found to be up-regulated. IL-1 beta appeared to be a 'master' cytokine since it was able to mimic the effects of haptens, such as the increase of MHC class II expression in Langerhans cells and activation of the cytokine cascade. Injection of anti-IL-1 beta monoclonal antibody prior to hapten application completely prevented epicutaneous sensitization. In vivo application of IL-10 by intradermal injection prior to epicutaneous application of TNCB induced antigen-specific tolerance and impeded the induction of proinflammatory cytokines.

Animals↗