RepoMed (Medizinische Hochschule Hannover)
Not a member yet
3024 research outputs found
Sort by
Recipient natural killer cells alter the course of rejection of allogeneic heart grafts in rats.
Get PDFRejection of solid organ grafts is regarded to be dependent on T cell responses. Nonetheless, numerous studies have focused on the contribution of NK cells in this process, resulting in contradictory theories. While some conclude that there is no participation of NK cells, others found an inflammatory or regulative role of NK cells. However, the experimental settings are rarely comparable with regard to challenged species, strain combinations or the nature of the graft. Thus, clear definition of NK cell contribution might be impeded by these circumstances. In this study we performed heterotopic heart transplantation (HTx) in rats, choosing one donor-recipient-combination leading to a fast and a second leading to a prolonged course of graft rejection. We intervened in the rejection process, by depletion of recipient NK cells on the one hand and by injection of activated NK cells syngeneic to the recipients on the other. The fast course of rejection could not be influenced by any of the NK cell manipulative treatments. However, the more prolonged course of rejection was highly susceptible to depletion of NK cells, resulting in significant acceleration of rejection, while injection of NK cells induced acceptance of the grafts. We suggest that, depending on the specific setting, NK cells can attenuate the first trigger of immune response, which allows establishing the regulatory activity leading to tolerance of the graft
Autoimmunity (or Not) in Atopic Dermatitis.
Get PDFAtopic dermatitis (AD), one of the most frequent inflammatory skin diseases worldwide, is believed to result from a disturbed skin barrier as well as aberrant immune reactions against per se harmless allergens. Starting mostly during childhood with a chronic, remitting relapsing course, the disease can persist into adulthood in about one fifth of patients. Immune reactions to self-proteins have been observed in AD patients already in the beginning of the Twentieth century, when human cellular extracts were shown to provoke skin lesions. However, the term "autoimmunity" has never been claimed, since AD is first and foremost an atopic disease. In contrast, this IgE-hallmarked autoreactivity was termed "autoallergy" and is ongoing discussed regarding its impact on the disease. Since severely affected patients tend to develop IgE-hypersensitivity reactions to numerous environmental allergens, the impact of immune responses to self-proteins is difficult to determine. On the other hand: any autoreactivity, irrespective of the magnitude, implicates the potential of driving the chronification of the disease while shaping the immune response. This review article revisits the observations made on autoallergy from an actual point of view and tries to approach the question whether these still point to a contribution to the disease
FGF23 and Phosphate-Cardiovascular Toxins in CKD.
Get PDFElevated levels of fibroblast growth factor 23 (FGF23) and phosphate are highly associated with increased cardiovascular disease and mortality in patients suffering from chronic kidney disease (CKD). As the kidney function declines, serum phosphate levels rise and subsequently induce the secretion of the phosphaturic hormone FGF23. In early stages of CKD, FGF23 prevents the increase of serum phosphate levels and thereby attenuates phosphate-induced vascular calcification, whereas in end-stage kidney disease, FGF23 fails to maintain phosphate homeostasis. Both hyperphosphatemia and elevated FGF23 levels promote the development of hypertension, vascular calcification, and left ventricular hypertrophy by distinct mechanisms. Therefore, FGF23 and phosphate are considered promising therapeutic targets to improve the cardiovascular outcome in CKD patients. Previous therapeutic strategies are based on dietary and pharmacological reduction of serum phosphate, and consequently FGF23 levels. However, clinical trials proving the effects on the cardiovascular outcome are lacking. Recent publications provide evidence for new promising therapeutic interventions, such as magnesium supplementation and direct targeting of phosphate and FGF receptors to prevent toxicity of FGF23 and hyperphosphatemia in CKD patients
Materielle und infrastrukturelle Einbindung von Zahn-, Mund- und Kieferzentren in Notfallkonzepte von Universitätskliniken: eine systematische Analyse
Get PDFFamiliäre Hypertrophe Kardiomyopathie: Quantifizierung und Analyse molekularer Mechanismen der allelischen Imbalance durch Mutationen des MYH7-Gens
Get PDFInterferon-free therapy of chronic hepatitis C with direct-acting antivirals does not change the short-term risk for de novo hepatocellular carcinoma in patients with liver cirrhosis
Get PDFEinfluss der Fibrocystin-Defizienz auf das Adhäsionsverhalten von Nierenepithelzellen im Einzellstadium
Get PDF
Serotonin transporter binding is increased in Tourette syndrome with Obsessive Compulsive Disorder
No full textWhile the importance of the serotonergic system in obsessive compulsive disorder
(OCD) is well established, its role in Tourette syndrome (TS) is uncertain.
Particularly in TS patients with comorbid OCD (TS + OCD), decreased serotonin
transporter (SERT) binding has been suggested. Here, we investigated for the
first time SERT binding in TS patients with and without OCD (TS - OCD) compared
to both healthy controls (HC) and OCD patients as well as the influence of
escitalopram using the potent SERT imaging ligand
[(123)I]2-((2-((dimethylamino)methyl)phenyl)thio)-5-iodophenylamine
([(123)I]ADAM) and single-photon emission tomography (SPECT). We included 33
adult subjects (10 HC, 10 TS - OCD, 8 TS + OCD and 5 OCD). In patients with OCD
and TS + OCD [(123)I]ADAM SPECT was repeated after 12-16 weeks treatment with
escitalopram. SERT binding was normal in patients with OCD and TS - OCD, but
significantly increased (p < 0.05) in those with TS + OCD, particularly in
caudate and midbrain compared to both HC and TS - OCD. Treatment with
escitalopram resulted in a significant overall reduction in SERT binding (range,
19 to 79%, p values between 0.0409 and <0.0001) without any correlation with
clinical improvement. Our results provide further evidence that alterations in
the serotonergic system in TS are related to comorbid OCD and do not represent
the primary cause of the diseas
Identification of Leishmania major UDP-Sugar Pyrophosphorylase Inhibitors Using Biosensor-Based Small Molecule Fragment Library Screening
No full textLeishmaniasis is a neglected disease that is caused by different species of the protozoan parasite Leishmania, and it currently affects 12 million people worldwide. The antileishmanial therapeutic arsenal remains very limited in number and efficacy, and there is no vaccine for this parasitic disease. One pathway that has been genetically validated as an antileishmanial drug target is the biosynthesis of uridine diphosphate-glucose (UDP-Glc), and its direct derivative UDP-galactose (UDP-Gal). De novo biosynthesis of these two nucleotide sugars is controlled by the specific UDP-glucose pyrophosphorylase (UGP). Leishmania parasites additionally express a UDP-sugar pyrophosphorylase (USP) responsible for monosaccharides salvage that is able to generate both UDP-Gal and UDP-Glc. The inactivation of the two parasite pyrophosphorylases UGP and USP, results in parasite death. The present study reports on the identification of structurally diverse scaffolds for the development of USP inhibitors by fragment library screening. Based on this screening, we selected a small set of commercially available compounds, and identified molecules that inhibit both Leishmania major USP and UGP, with a half-maximal inhibitory concentration in the 100 microM range. The inhibitors were predicted to bind at allosteric regulation sites, which were validated by mutagenesis studies. This study sets the stage for the development of potent USP inhibitor