Osteosarkom – Apoptose und Proliferation Untersuchung zur bcl-2-Expression

Zusammenfassung Bei zahlreichen epithelialen Geweben konnte ein Zusammenhang zwischen Tumorwachstum und der Expression des Protoonkogens Bcl-2 nachgewiesen werden. Eine bcl-2-Expression ist verbunden mit verl?ngertem Zellüberleben infolge einer Apoptoseinhibition. Hingegen ist über die bcl-2-Expression und deren m?gliche Bedeutung in mesenchymalen Tumoren wenig bekannt. Da die heterogene Gruppe der Osteosarkome mit den derzeitigen methodischen Mitteln nicht hinreichend charakterisierbar ist, wurde die bcl-2-Expression untersucht. Immunhistologisch wurden 47 Osteosarkompr?parate von 36 Patienten unterschiedlicher Subtypen analysiert. Von den 36 F?llen zeigten in der Biopsie 16 F?lle (46 %) eine stark positive und 13 F?lle (35 %) eine mittelgradig positive bcl-2 Expression. Sieben F?lle (19 %) waren bcl-2-negativ. Die heterogene, fehlende bis starke bcl-2-Expression deutet darauf hin, da? in Osteosarkomen die Bcl-2-gesteuerte Regulation des programmierten Zelltodes einen Faktor in der zellul?ren Wachstumskinetik darstellt. Zus?tzlich wurde die Proliferationsrate, anhand des gegen das Ki-67-Antigen gerichteten monoklonalen Antik?rper MIB-1 bestimmt. Aus den Daten zur bcl-2-Expression und Proliferationsrate ergibt sich eine Einteilung, die eine übereinstimmung mit der histologischen Klassifikation aufweist. Welche Bedeutung die Apoptose in der Genese mesenchymaler Tumoren hat und ob die bcl-2-Expression einen pr?diktiven Wert für die Prognose von Osteosarkomen besitzt, bedarf weiterer Untersuchungen.      

Fibroblastic reticular cells provide a supportive niche for lymph node–resident macrophages

The lymph node (LN) is home to resident macrophage populations that are essential for immune function and homeostasis, but key factors controlling this niche are undefined. Here, we show that fibroblastic reticular cells (FRCs) are an essential component of the LN macrophage niche. Genetic ablation of FRCs caused rapid loss of macrophages and monocytes from LNs across two in vivo models. Macrophages co-localized with FRCs in human LNs, and murine single-cell RNA-sequencing revealed that FRC subsets broadly expressed master macrophage regulator CSF1. Functional assays containing purified FRCs and monocytes showed that CSF1R signaling was sufficient to support macrophage development. These effects were conserved between mouse and human systems. These data indicate an important role for FRCs in maintaining the LN parenchymal macrophage niche.     

The effect of β-adrenergic blockade on infarct size following experimental coronary occlusion

Summary The effect of Pindolol on myocardial infarct size was studied in 10 open chest dogs. In each animal a sequential occlusion and reperfusion of 2 medium-sized branches of the left coronary artery was performed in the same heart. After occlusion and reperfusion of the control artery the initial dose of Pindolol (0.25 mg/kg body weight) was administered. Thereafter the test artery was occluded, followed by a maintenance dose of Pindolol (0.3 mg/kg body weight).The drug caused a significant decrease in LVP and LV-dp/dt but no change in heart rate. MVO₂ also decreased significantly. Regional myocardial blood flow was measured with the tracer microsphere method. Collateral flow in the perfusion area of the control artery was 11.2±5.9% and in the area of the test artery 10.0±4.4% of normal. No change in the endo/epi ratio as a result of treatment was observed.The area of infarction (p-nitroblue tetrazolium-reaction) was divided by the area of perfusion (angiography). Infarct size, expressed as the percentage of the perfusion area. was 48.2±22.2% in the region of the control artery and 43.0±23.9% in the region of the test artery. The difference was statistically not significant.With 1 table     

Frühe Hilfen aus der Distanz – Chancen und Herausforderungen bei der Unterstützung psychosozial belasteter Familien in der COVID-19-Pandemie

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Kontaktbeschränkende Maßnahmen waren zur Eindämmung des SARS-CoV-2-Infektionsgeschehens ab Frühjahr 2020 in...     

Prophylactic antibiotic treatment is superior to therapy on-demand in experimental necrotising pancreatitis

Introduction

High morbidity and mortality rates in patients with severe acute pancreatitis are mainly caused by bacterial superinfection of pancreatic necrosis and subsequent sepsis. The benefit of early prophylactic antibiotics remains controversial because clinical studies performed to date were statistically underpowered. Thus, the aim of this study was to evaluate on-demand versus prophylactic antibiotic treatment in a standardised experimental model.

Methods

Treatment groups received meropenem either therapeutically 24 hours after induction of necrotising pancreatitis or prophylactically before development of pancreatic superinfection. At 24 and 72 hours, pancreatic injury was investigated by histology and translocation by bacterial cultures of pancreatic tissue and mesenteric lymph nodes. Septic complications were evaluated by blood cultures and survival.

Results

Without antibiotic treatment, pancreatic superinfection was observed in almost all cases after induction of necrotising pancreatitis. The 72-hour-mortality rate was 42.9% and bacterial infection of mesenteric lymph nodes and bacteraemia was found in 87.5% of the surviving animals. Therapeutic administration of meropenem on-demand reduced bacteraemia to 50% and mortality to 27.3%. However, prophylactic antibiotic treatment significantly reduced bacteraemia to 25.0% (p = 0.04) and pancreatic superinfection as well as mortality to 0% (p < 0.001 and p = 0.05, respectively) compared with controls.

Conclusions

In the present study both prophylactic and delayed antibiotic treatment on-demand reduced septic complications in a standardised setting of experimental necrotising pancreatitis. However, pancreatic superinfection, bacteraemia and mortality rates were reduced significantly by early treatment. Thus, in the absence of statistically relevant and well-designed clinical trials, the study demonstrates that prophylactic antibiotic treatment is superior to antibiotic treatment on-demand.     

Ways to obtain a breast cancer diagnosis,consistency of information,patient satisfaction,and the presence of relatives

Goals of work What physicians told breast cancer patients about their diagnosis, who informed them, and how this information was conveyed were examined in this study. Finally, the relatives’ role in this communication process was considered. Materials and methods Women with primary breast cancer (N = 222) below the age of 70 were interviewed after surgery and after they were informed about their diagnosis. Main results One hundred twenty-one women consulted their primary gynecologist first, then they were referred to a radiologist, and finally to the secondary care gynecologist. Forty-seven women omitted the radiologist and only five went directly to the hospital for treatment. In most cases (N = 199), the general practitioner was not involved. Receiving inconsistent information was associated with patient dissatisfaction. This also applies to women who received their diagnosis on the phone. Women awaiting a worse diagnosis were more likely to be accompanied by another person. Conclusions Future studies should focus on the possible involvement of family doctors and relatives during the diagnostic process. Giving inconsistent information should be avoided.     

The twin-arginine translocation pathway is a major route of protein export in Streptomyces coelicolor

The twin-arginine translocation (Tat) pathway is a protein transport system for the export of folded proteins. Substrate proteins are targeted to the Tat translocase by N-terminal signal peptides harboring a distinctive R-R-x-Phi-Phi "twin-arginine" amino acid motif. Using a combination of proteomic techniques, the protein contents from the cell wall of the model Gram-positive bacterium Streptomyces coelicolor were identified and compared with that of mutant strains defective in Tat transport. The proteomic experiments pointed to 43 potentially Tat-dependent extracellular proteins. Of these, 25 were verified as bearing bona fide Tat-targeting signal peptides after independent screening with a facile, rapid, and sensitive reporter assay. The identified Tat substrates, among others, include polymer-degrading enzymes, phosphatases, and binding proteins as well as enzymes involved in secondary metabolism. Moreover, in addition to predicted extracellular substrates, putative lipoproteins were shown to be Tat-dependent. This work provides strong experimental evidence that the Tat system is used as a major general export pathway in Streptomyces.