Author
Michael Müller-Steinhardt
Other affiliations: University of Lübeck, German Red Cross
Bio: Michael Müller-Steinhardt is an academic researcher from Heidelberg University. The author has contributed to research in topics: Cytokine & Whole blood. The author has an hindex of 22, co-authored 50 publications receiving 1242 citations. Previous affiliations of Michael Müller-Steinhardt include University of Lübeck & German Red Cross.
Papers published on a yearly basis
Papers
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TL;DR: These findings are valuable for further assessment of normal variations and maturation processes in immune cell responses and for the clinical–therapeutic monitoring of immunological status in various childhood diseases.
Abstract: The functional differentiation of immune cells at early age plays a central role in immune physiology, e.g. for the sufficient eradication of pathogens. However, imbalances in effector cell responses may also have an impact in the pathophysiology of childhood diseases such as atopy and autoimmune disorders. As information on immune cell responses in infancy and early childhood is scarce, we conducted an observational, cross-sectional study in healthy newborns (n = 18), infants and young children (n = 54) aged 1-96 months and adult controls (n = 19) to assess cytokine mRNA and protein expression upon phorbol 12-myristate 13-actate/ionomycin stimulation and LPS-induced IL-12 expression in monocytes. The intracellular expression of interferon (IFN)-gamma, tumour necrosis factor (TNF)-alpha (R = 0.748, P < 0.0001; R = 0.784, P < 0.0001, respectively) and interleukin (IL)-2 protein expression (R = 0.384, P = 0.008) was demonstrated to increase progressively with age. While a correlation between IL-4 protein expression and age was noted (R = 0.342, P = 0.007), the levels of IL-5 and IL-10 protein expression tended to be regulated on an individual basis during infancy and early childhood. An age correlation was also observed for intracellular IL-12 expression (R = 0.331, P = 0.009) in monocytes. These findings are valuable for further assessment of normal variations and maturation processes in immune cell responses and for the clinical-therapeutic monitoring of immunological status in various childhood diseases.
135 citations
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TL;DR: The data demonstrate the need for data on the impact of ex vivo variation in order to extract reliable and consistent information, particularly when cytokine mRNA expression data from healthy blood donors are included in clinical studies.
121 citations
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TL;DR: Though evidence was found of a reduced immunologic response after SynerGraft implantation this (unexpectedly) did not translate into any hemodynamic advantage, and factors other than rejection appear as the main contributions to the observed functional changes.
Abstract: BACKGROUND AND AIM OF THE STUDY Rejection is thought to contribute to the degeneration of valved homografts. A novel cryopreserved decellularized homograft valve (SynerGraft; CryoLife, Inc.) offers the unique opportunity to gain new insight into the immunology of homograft implantation and its significance for valve function. METHODS Twenty-four patients (group I; mean age 37 +/- 11 years) underwent implantation of a pulmonary SynerGraft and were examined at one and six months postoperatively; 22 patients (group II; mean age 41 +/- 17 years) with conventional homografts served as controls. Temperature, C-reactive protein (CRP) levels and white blood cell count (WBC) were studied perioperatively. Follow up included echocardiography and anti-human leukocyte antigen (HLA) class I antibody determination. RESULTS Significantly lower temperatures were measured in group I (p = 0.019). CRP level and WBC each increased postoperatively, but did not differ between groups. During follow up, none of the SynerGraft patients became positive for anti-HLA antibodies, compared with 66% of controls (p = 0.011). Homograft diameter and valve orifice area were decreased significantly at one month after surgery in groups I and II (25 +/- 1 versus 18 +/- 3 mm; 25 +/- 1 versus 19 +/- 2 mm, respectively; p <0.001 both groups). Transvalvular pressure gradients significantly increased during follow up. CONCLUSION Implantation of the SynerGraft pulmonary homograft appeared safe, and though evidence was found of a reduced immunologic response after SynerGraft implantation this (unexpectedly) did not translate into any hemodynamic advantage. Hence, factors other than rejection appear as the main contributions to the observed functional changes.
61 citations
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TL;DR: Evidence is provided that during a 5-year period, antibody persistence against tetanus toxoid is better than that against diphtheria toxoid, therefore, detection of individual antibody concentrations may be indicated to decide on revaccination.
59 citations
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TL;DR: A delayed increase in cytokine mRNA expression during T-cell costimulation may represent a sensitive effect of immunosuppression and the parameter "area of cytokineRNA expression over time", which should include absolute cytokine RNA values at two different time points of mRNA kinetics is suggested.
Abstract: Background: Because cyclosporin A (CsA) and glucocorticoids inhibit the production of interleukin-2 (IL-2) and other cytokines, quantitative analysis of cytokine mRNA might constitute a pharmacodynamic measure for immunosuppressive drug effects. We investigated whether immunosuppressive drugs influence cytokine mRNA expression kinetics during T-cell costimulation.
Methods: We used a human whole blood assay to determine basal (unstimulated) IL-2, IL-4, and tumor necrosis factor-α (TNF-α) mRNA concentrations and expression kinetics after anti-CD3/anti-CD28 monoclonal antibody costimulation in kidney transplant recipients undergoing CsA-based immunosuppressive triple therapy and in healthy controls (ex vivo study I). The effect of CsA on IL-2 mRNA expression kinetics was also determined ex vivo in patients undergoing CsA monotherapy (ex vivo study II) and after in vitro addition of CsA.
Results: In ex vivo study I, basal TNF-α mRNA but not IL-2 and IL-4 mRNA was decreased in kidney transplant patients. We observed shifts in peak IL-2 and IL-4 (from 8 to 24 h) and TNF-α (from 4 to 8 h of costimulation) mRNA expression in kidney transplant patients after T-cell costimulation. In patients undergoing CsA monotherapy (ex vivo study II), the inhibitory effect of CsA was detectable as an individually delayed increase in IL-2 mRNA during costimulation. In vitro addition of CsA also induced a dose-independent displacement of IL-2 mRNA expression kinetics (i.e., a delay).
Conclusions: A delayed increase in cytokine mRNA expression during T-cell costimulation may represent a sensitive effect of immunosuppression. The single analysis of one absolute or peak mRNA value could be misleading. For prospective studies involving measurement of cytokine mRNA, we therefore suggest the parameter “area of cytokine mRNA expression over time”, which should include absolute cytokine mRNA values at two different time points of mRNA kinetics.
56 citations
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TL;DR: The real-time RT-PCR technique is very accurate and sensitive, allows a high throughput, and can be performed on very small samples; therefore it is the method of choice for quantification of cytokine profiles in immune cells or inflamed tissues.
1,426 citations
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TL;DR: This review presents a comprehensive overview of the various applications of collagen-based biomaterials developed for tissue engineering, aimed at providing a functional material for use in regenerative medicine from the laboratory bench to the patient bedside.
Abstract: Collagen is the most widely distributed class of proteins in the human body. The use of collagen-based biomaterials in the field of tissue engineering applications has been intensively growing over the past decades. Multiple cross-linking methods were investigated and different combinations with other biopolymers were explored in order to improve tissue function. Collagen possesses a major advantage in being biodegradable, biocompatible, easily available and highly versatile. However, since collagen is a protein, it remains difficult to sterilize without alterations to its structure. This review presents a comprehensive overview of the various applications of collagen-based biomaterials developed for tissue engineering, aimed at providing a functional material for use in regenerative medicine from the laboratory bench to the patient bedside.
946 citations
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TL;DR: Professor Titmuss, an eminent English social theorist, believes that man is inherently altruistic and that the duty of government is to create that social and economic climate which best channels man's drive to work together for the common good.
Abstract: Professor Titmuss, an eminent English social theorist, believes that man is inherently altruistic and that the duty of government is to create that social and economic climate which best channels man's drive to work together for the common good. In support of this belief, he has written a book about the procurement, distribution, and transfusion of human blood, a medical topic which he employs as an illustrative social and economic microcosm. The conclusion he reaches is foregone: "The voluntary socialized system in Britain is economically, professionally, administratively and qualitatively more efficient than the mixed, commercialized, and individualistic American system" (Titmuss, R.M: "Why Give to Strangers?" Lancet 1 :123-125, 1971). As the book was written with a bias, so will it be read with bias. My own bias is that of an American and a blood-banker. I am only too conscious of many deficiencies in the American complex of arrangements—it isn't
924 citations
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TL;DR: Given the strong association between proinflammatory cytokines and complications common in end-stage renal disease, such as vascular calcification and wasting, the potential role of both general and targeted anticytokine treatment strategies in ESRD patients needs further evaluation.
830 citations
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TL;DR: Current concepts in the pathophysiology of tissue valve calcification are summarized, including emerging concepts of endogenous regulation, progress toward prevention of calcification, and issues related to calcification of the aortic wall of stentless bioprosthetic valves.
651 citations