Atherosclerotic plaques vulnerable for rupture are characterised by e.g., a large lipid pole, a high concentration of inflammatory cells and a thin fibrous cap. Recent research has showed that vuln ...
ABSTRACT Background Epigenetic alterations upon microbial challenge have been described as both a defence strategy and a result of pathogenic manipulation. While most COVID-19 studies focus on inflammatory and immune-mediated responses, little is known about epigenetic modifications in response to SARS-CoV-2 infection. Methods Epigenome-wide DNA methylation patterns from COVID-19 convalescents were compared to uninfected controls from before and after the pandemic. Peripheral blood mononuclear cell (PBMC) DNA was extracted from uninfected controls, COVID-19 convalescents and symptom-free individuals with SARS-CoV-2-specific T cell-responses, as well as from PBMCs stimulated in vitro with SARS-CoV-2. Subsequently, the Illumina MethylationEPIC 850K array was performed, and statistical/bioinformatic analyses comprised differential DNA methylation, pathway over-representation and module identification analyses. Results Differential DNA methylation patterns distinguished COVID-19 convalescents from uninfected controls, with similar results in an experimental SARS-CoV-2 infection model. A SARS-CoV-2-induced module was identified in vivo , comprising 66 genes of which six ( TP53, INS, HSPA4, SP1, ESR1 and FAS ) were present in corresponding in vitro analyses. Over-representation analyses revealed involvement in Wnt, muscarinic acetylcholine receptor signalling and gonadotropin-releasing hormone receptor pathways. Furthermore, numerous differentially methylated and network genes from both settings interacted with the SARS-CoV-2 interactome. Conclusions Altered DNA methylation patterns of COVID-19 convalescents suggest recovery from mild-to-moderate SARS-CoV-2 infection leaves longstanding epigenetic traces. As in vitro SARS-CoV-2 infection corroborated in vivo exposure results, this indicates DNA methylation is involved in immune cell responses to challenge with this virus. Future studies should determine whether this reflects host-induced protective antiviral defence or targeted viral hijacking to evade host defence.
Abstract The functional state of vasomotor nerves to skeletal muscle vessels was studied in anesthetized cats treated with reserpine. The effects of the vasoconstrictor nerves could be completely blocked by reserpine while the responses of the vasodilator nerves seemed to be unaffected. The results are consonant with the view that there are two types of vasomotor nerves to the skeletal muscle vessels; namely, adrenergic vasoconstrictor nerves and cholinergic vasodilator nerves. The cardiovascular changes evoked by reserpine are discussed.
Hellström, K., Rosén, A. & Söderlund, K. 1970. The Gastrointestinal Absorption and the Excretion of H3-Butylscopolamine (Hyoscine Butylbromide) in Man. Scand. J. Gastroent. 5, 585-592.H3-butylscopolamine (hyoscine butylbromide) in doses of 50-100 mg and an unabsorbable marker (polyethylene glycol, PEG) were administered orally or by intra-intestinal infusion to 6 healthy subjects. By comparison of the amount of radioactivity per mg PEG in intestinal aspirates and in the test solution, it appeared that only a small percentage of administered tritium was absorbed during passage through the upper small intestine. No radioactivity could be detected in plasma. The urinary and fecal excretion of label amounted to 2 and 90 per cent of the given dose, respectively. Electrophoretic analyses of small intestinal contents showed no evidence of a metabolic change of the drug. After intravenous injection of 8 mg butylscopolamine to 1 subject, 42 per cent of the administered radioactivity was eliminated in the urine and 37 per cent in the feces.
A sensitive target binding assay has recently been shown to detect natural killer (NK) cells in the mouse. Preincubation of NK cells with detergent-solubilized cell-surface proteins of YAC lymphoma cells prevented subsequent binding to intact YAC targets. The NK target structures (NK-TS) consisted of three molecular species tentatively assigned molecular weights of 130,000, 160,000, and 240,000 based on electrophoretic mobility in sodium dodecyl sulfate/polyacrylamide gels. Moloney cell surface antigen (MCSA), gp71, p30, H-2, and NK-TS were localized in distinct fractions of gels. The NK-TS bound to concanavalin A-Sepharose columns and could be eluted with the specific sugar, suggesting that the target structures may be glycosylated. NK-TS molecules could not be detected in gels of NK-insensitive target cells such as P815, A9HT, YWA, or EL-4. The quantity obtained from the gels varied directly with the NK sensitivity of YAC which is more sensitive when grown in vitro than when grown in vivo . The NK-TS molecules specifically inhibited the binding of NK cells but not alloimmune T cells to their appropriate targets. Additional NK-sensitive tumor cells also expressed some or all of the target molecules exhibited by YAC. Some of these structures shared specificities in the case of MPC-11 or were unique in the case of Molt-4 and K562, as shown by cross-inhibition studies. These results suggest that NK-sensitive cell lines express distinct target structures with possible relevance to natural tumor resistance.
Fetale Ovarialzysten werden vereinzelt im dritten Schwangerschaftstrimenon als echoleere zumeist einseitige glattwand ige Raumforderungen gesehen. Die Diagnose erfordert üblicherweise keine Änderungen des geburtshilflichen Managements. Wir berichten über einen Fall einer akuten Stieldrehung einer fetalen Ovarialzyste in der 32. SSW mit gleichzeitig auftretenden hochsuspekten CTG-Veränderungen. Die Differentialdiagnose und das Management in diesem Fall werden diskutiert.
Abstract The Epstein‐Barr virus (EBV) nuclear antigen 2 (EBNA‐2) is the only one of the EBNA proteins to have been implicated as an EBV‐encoded transforming protein. More detailed studies of this protein have been hampered by the lack of EBNA‐2‐specific monoclonal antibodies (MAbs) and of purified protein. To overcome these problems, we isolated 5 hybridomas producing MAbs reactive with an 18 residue synthetic peptide corresponding to the carboxyterminus of EBNA‐2. Four of the 5 MAbs were specifically reactive with EBNA‐2 in its denatured form on immunoblots. The 5th antibody (IISE) was reactive with the native form of EBNA‐2. By using a one‐step immunoaffinity purification method with II5E cross‐linked to protein‐A‐Sepharose, we purified EBNA‐2 to homogeneity, i. e., more than 1,200‐fold, from Burkitt lymphoma cell extracts. A major 32‐kDa associated protein and a less abundant 17‐kDa protein were co‐purified with EBNA‐2. Immunoprecipitation with 115E from 35 S‐methionine‐labelled cell extracts showed that the 32‐kDa protein co‐precipitated with EBNA‐2 from EBV‐positive cells, but was not detectable in immunoprecipitates of EBV‐negative cells. When the immunoprecipitates or the purified proteins were immunoblotted with EBV‐immune sera, only EBNA‐2 was reactive, indicating that the associated proteins are of cellular origin. Immunoprecipitation of cells labelled with 32 P‐orthophosphate showed that EBNA‐2, but not the associated proteins, is a phosphoprotein. The expression level of EBNA‐2 varied between different EBV‐carrying cell lines, as measured by a 2‐site ELISA based on antibody II5E. In indirect immunofluorescence, the II5E MAb gave an EBNA‐2‐specific characteristic granular staining pattern. These characteristics of EBNA‐2 resemble those of other viral transforming proteins.
This study investigated the impact of a low-cost, pregnancy-specific self-help smoking-cessation program on patient smoking behavior both pre- and postpartum. The population consisted of 274 English-speaking women enrolled in a large health maintenance organization who reported smoking at the time of the baseline survey or had quit within the previous 3 months. A control group receiving standard obstetric care was compared with two experimental groups, one receiving the self-help materials and standard care and the other receiving the materials plus brief regular clinician interactions and counseling about smoking. Smoking data were obtained from two additional self-reported surveys conducted at 6 months' gestation and approximately 8 weeks postpartum. Self-reported smoking behavior was verified using a urine cotinine test, which revealed no significant differences between the groups. Among baseline smokers, although neither intervention yielded significantly higher 6-month nonsmoking rates compared with controls, both interventions significantly increased the proportion of women who were not smoking postpartum. Among those who had quit smoking at baseline, only the more intensive intervention significantly increased maintenance of non-smoking postpartum. Brief counseling, a simple charting system, and improved access to educational materials allowed the program to be integrated easily into routine prenatal care at a cost of $50-111 per patient.
