Biomedical subjects

K Steinbrink

Publications and source records attributed to K Steinbrink.

30 records · Page 2Linked to original sources

PubMed1995

Expression of murine VCAM-1 in vitro and in different models of inflammation in vivo: correlation with immigration of monocytes.

VCAM-1 (vascular cell adhesion molecule-1) is a cytokine-inducible adhesion molecule which is known to mediate adhesion of mononuclear cells to endothelial cells in vitro via binding to the integrin VLA-4 (very late antigen-4). To further elucidate the role and regulation of VCAM-1 in vitro, we compared in vitro and in vivo expression of VCAM-1 in response to cytokines and investigated immunohistochemically the expression of VCAM-1 in three murine models of experimental inflammation. These models differed with regard to the pathogenetic mechanism, and the subsesquent infiltrate: allergic contact dermatitis (ACD) to DNFB as a T cell-controlled, DTH type of inflammation, cutaneous infection with Leishmania major as a chronic granulomatous inflammation and the cauterized cornea as a model for acute inflammation. VCAM-1 was found to be markedly enhanced on vascular endothelia in all types of inflammation and after subcutaneous administration of LPS and TNF-alpha. Administration of IL-4, however, failed to induce VCAM-1 both in vivo and in vitro. The increased VCAM-1 expression in the inflammatory models correlated with the appearance of infiltrating monocytes/macrophages. A concomitant influx of CD4-positive/CD8-positive lymphocytes was only observed in ACD and Leishmaniasis.

Animals↗

PubMed1994

Macrophages and angiogenesis.

Macrophages are supposed to play a key role in inflammatory and tumor angiogenesis. Their importance derives from (1) their ubiquitous presence in normal and especially inflamed tissues, (2) their potential to become activated in response to appropriate stimuli, and (3) their repertoire of secretory products. By release of proteases, growth factors (bFGF, GM-CSF, TGF-alpha, IGF-I, PDGF, VEGF/VPF, TGF-beta), and other monokines (IL-1, IL-6, IL-8, TNF-alpha, substance P, prostaglandins, interferons, thrombospondin 1), activated macrophages have the capability to influence each phase of the angiogenic process, such as alterations of the local extracellular matrix, induction of endothelial cells to migrate or proliferate, and inhibition of vascular growth with formation of differentiated capillaries. This review describes macrophage physiology and the influence of macrophage secretory products on the different phases of angiogenesis in vitro and in vivo.

Animals↗

PubMed1994

Expression of murine VCAM-1 in vitro and in different models of inflammation in vivo: correlation with immigration of monocytes.

VCAM-1 (vascular cell adhesion molecule-1) is a cytokine-inducible adhesion molecule which is known to mediate adhesion of mononuclear cells to endothelial cells in vitro via binding to the integrin VLA-4 (very late antigen-4). To further elucidate the role and regulation of VCAM-1 in vivo, we compared in vitro and in vivo expression of VCAM-1 in response to cytokines and investigated immunohistochemically the expression of VCAM-1 in three murine models of experimental inflammation. These models differed with regard to the pathogenetic mechanism and the subsequent infiltrate: allergic contact dermatitis (ACD) to DNFB as a T cell-controlled, DTH type of inflammation, cutaneous infection with Leishmania major as a chronic granulomatous inflammation and the cauterized cornea as a model for acute inflammation. VCAM-1 was found to be markedly enhanced on vascular endothelia in all types of inflammation and after subcutaneous administration of LPS and TNF-alpha. Administration of IL-4, however, failed to induce VCAM-1 both in vivo and in vitro. The increased VCAM-1 expression in the inflammatory models correlated with the appearance of infiltrating monocytes/macrophages. A concomitant influx of CD4-positive/CD8-positive lymphocytes was only observed in ACD and Leishmaniasis.

Animals↗

PubMed1993

Resistance of mice to experimental leishmaniasis is associated with more rapid appearance of mature macrophages in vitro and in vivo.

Resistance to murine leishmaniasis has been related to the propagation of specific Th cell subsets (Th1 and Th2). This study shows that there are differences between resistant and susceptible mice in the initial myelomonocytic infiltrate, which precede the specific T cell response. After subcutaneous injection of 2 x 10(7) Leishmania major into footpads of resistant C57Bl/6 and susceptible BALB/c mice we performed immunohistochemical studies on the infiltrate. Two days after infection the percentage of more mature, F4/80-positive macrophages in the lesion increased faster in C57Bl/6 mice (63%) than in BALB/c mice (29%). The same strain-specific differences were observed after infection of corresponding strains of athymic mice (57.2% in C57Bl/6 nu/nu; 33.6% in BALB/c nu/nu), thus excluding a T cell-controlled phenomenon. After 1 wk the infiltrate in susceptible mice began to reveal significantly more cells containing MRP14, which is expressed by granulocytes and less mature monocytes but not by mature macrophages. No corresponding differences were found between athymic strains, suggesting that at this point organization of the infiltrate falls under control of protective T cells. In bone marrow cultures of BALB/c and C57Bl/6 mice, the percentage of F4/80-positive macrophages was also increasing faster in C57Bl/6 mice than in BALB/c mice. Increased expression of the F4/80 Ag was associated with higher leishmanicidal activity of C57Bl/6 macrophages. MRP14-positive bone marrow cells on the other hand were rarely infected by parasites. We suggest 1) that the earlier appearance of leishmanicidal macrophages in lesions of C57Bl/6 mice could influence propagation of either Th1 or Th2 cells by reduction of parasite load or by differential secretion of decisive cytokines and 2) that the diffuse accumulation of granulocytes and inflammatory monocytes in susceptible mice facilitates spread of disease.

Animals↗

PubMed1990

The saddle prosthesis for salvage of the destroyed acetabulum.

We report the 12 to 74 month results of our mark I saddle prosthesis after its use as a salvage device for gross loss of pelvic bone stock in 76 patients with failed hip arthroplasties. The implant transmits load between iliac bone and bare polish chrome-cobalt. Our clinical and radiological results indicate that a useful and stable articulation can be achieved in most cases, provided that continued deep infection can be avoided. The appearance of radiological sclerosis at the bearing site in successful cases seems to indicate that significant late migration will not occur. Based on our experience with the mark I prosthesis we have designed and developed a mark II model which has freedom of axial rotation of the saddle. Our early results in 40 cases show a significant improvement over the results which could have been predicted for the mark I device.

Acetabulum↗

PubMed1990

The case for revision arthroplasty using antibiotic-loaded acrylic cement.

For managing infected joint implants, revision arthroplasty using antibiotic-loaded acrylic cement (ALAC) has proven to be superior to other methods of treatment that are currently available. Ablation of the implant, cement, and necrotic tissue is essential. Further refinement of the ALAC method is possible. Analysis of complications shows that disarticulation and a permanent Girdlestone can become rare surgical procedures.

Anti-Bacterial Agents↗

PubMed1989

[Value of irrigation-suction drainage in the treatment of early infection of joint implants].

The analysis of follow-up examinations on 77 patients at the Endo-Klinik who were treated with suction irrigation drainage for acute postoperative infection after joint replacement surgery during the last 12 years showed a success rate up to a maximum of 60%. The success of this treatment increased, the earlier and more thoroughly it was performed. Only when the suction irrigation drainage is combined with radical excision of infected soft tissue this operation can save the implant and prolong its service life.

Arthritis, Infectious↗

PubMed1987

[Procedure in extensive or complete loss of bone substance of the femur following shaft loosening].

We reviewed our present method of treatment in cases of femoral bone loss. Our clinical experience with the method is based on 800 exchange operations performed at the Endo-Klinik per year. The review showed that in cases of proximal bone deficiency, custom-made protheses are increasingly required. Cemented implants are used in septic and aseptic cases but we also have had experience with a small number of cases in which reconstructive surgery was carried out using allografts and cementless shaft components. In 1.4% of revision cases total femoral replacement is required. We have had more than 12 years experience with this type of prostheses, which is available as a modular system. So far there has been no disarticulation as a result of implant failures but in some instances failure occurred due to persistent deep infections.

Bone Cements↗

PubMed1983

[Modular system for the total replacement of the femur--Endo-model].

Total femur replacement may offer a useful solution in cases of severe trauma or neoplasia and in revision arthroplasty after failed total joint replacement when gross losses of bone have resulted in an unloadable femur and all other methods of treatment would fail to provide the patient with a stable leg. Until recently, total femur components were custom-made, but now we have a comprehensive modular total femur implant available reducing problems of preoperative preparation and simplifying the manufacture of custom-made designs. The new device can be shaped and adapted to the conditions encountered at the time of operation. The "push-through" type of prosthesis can be mounted step by step and converted into a total femur replacement with either a conventional head or a saddle at the proximal end and a total axial rotating knee prosthesis at the distal end. Elongation of the entire system is feasible.

Adult↗

PubMed1982

The total femoral prosthesis. A preliminary report.

The use of a total femoral prosthesis can offer a realistic alternative to amputation or disarticulation. The limited indications for such a prosthesis in the surgical management of primary bone tumours and pathological fractures still exist. In this specialised clinic there is an increased need to replace the entire femur where repeated procedures have failed, from loss of bone stock with infection or because of non-union in the presence of a prosthesis. Over the past eight years, four basic models have been developed. The most recent designs allow for the preservation of non-involved bone or for stable support where there is complete acetabular destruction.

Adult↗

PubMed1979

[Injury to pelvic vessels in total hip replacement surgery].

Massive bleeding of the pelvic vessels during an alloarthroplastic operation on the hip joint should be suspected in cases of abnormal anatomic conditions. Therefore, the operative procedure should be meticulously planned including extensive X-ray investigations such as angiography and computer-tomography. Surgical preparation and procedures in case of vascular complications are described. Hints on operative techniques are given to prevent vascular complications during and after surgical intervention of the hip joint.

Adult↗

PubMedDate not supplied

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↗