Identification, in mouse macrophages and in serum, of a soluble receptor for the Fc portion of IgG (Fc{gamma}R) encoded by an alternatively spliced transcript of the Fc{gamma}RII gene

Low affinity FcR are a heterogeneous group of glycoproteinswhich exist in transmembrane (TM) as well as in soluble forms.Two membrane isoforms of the murine type II FcR, FcRilb1 andFc;Rilb2, have been described. They result from the translationof alternatively spliced premRNA, FcRilb2 lacking sequencesof the first intracytoplasmic domain (IC1). Soluble forms ofFcR (sFcR) have previously been shown to result from proteolysisof membrane receptors. We report here the identification, inmacrophages, of a mRNA derived from the FCRll gene by splicingexons encoding the TM and IC1 domains, i.e. corresponding toa TM-deleted FcRllb2 mRNA. A soluble protein possibly encodedby this mRNA was identified in macrophage supernatants. In accordancewith FcR nomenclature, we propose to name this new FcRll IsoformFcRllb3. It is the most abundant 8FcR present in serum, as comparedwith 8FcR resulting from cleavage of membrane FcR.     

Neutral Polymeric Surfactants Derived from Dextran: A Study of Their Aqueous Solution Behavior

Summary: Amphiphilic polysaccharides are obtained by hydrophobic modification of a neutral bacterial polysaccharide, dextran. By reacting the polysaccharide with aliphatic epoxides (epoxyoctane and epoxydodecane) in dimethyl sulfoxide, a series of amphiphilic polymers is obtained which covers a large range of structural parameters (length of the polysaccharide, number and nature of hydrocarbon moieties). The solution behavior of dextran derivatives is first characterized by viscometric measurements in dilute and semi‐dilute domains. The effects of molecular parameters on polymer viscosity behavior are evidenced and discussed. Information on the state of aggregation of polymers is obtained by the use of static and dynamic light scattering. The presence of aggregates in the dilute domain is clearly evidenced and their structural characteristics are estimated (size, molecular weight and number of aggregation). The aggregates are shown to account for the viscometric results in the examined concentration range, relating their chemical parameters (hydrodynamic radius and molecular weight) to the macroscopic behavior of the solutions.

     

Major histocompatibility complex class I molecules are required for the development of insulitis in non-obese diabetic mice

An early step in the development of autoimmune diabetes is lymphocyte infiltration into the islets of Langerhans of the pancreas, or insulitis. The infiltrate contains both CD4⁺ and CD8⁺ T cells and both are required for progression to diabetes in non-obese diabetic (NOD) mice. It has been thought that the CD4⁺ lymphocytes are the initiators of the disease, the islet invaders, while CD8⁺ cells are the effectors, the islet destroyers. We question this interpretation because NOD mice lacking MHC class I molecules, hence CD8⁺ T cells, do not display even insulitis when expected.     

Behavioral and neurochemical effects induced by subchronic combined exposure to toluene at 40 ppm and noise at 80 dB-A in rats

We investigated whether exposure to noise, in addition to its well-known potentiating effect on toluene-induced ototoxicity, may also exacerbate behavioral disturbances and brain neurochemical alterations produced by subchronic exposure to low toluene concentration. To test this hypothesis, we evaluated whether subchronic combined exposure (16 weeks, 104 h per week) to noise at 80 dB-A and toluene at 40 ppm potentiates the recently reported neurotoxic effects of subchronic exposure to 40 ppm toluene. Locomotor and rearing activities, sensitization to narcosis induced by acute toluene at high concentration, and tyrosine and tryptophan hydroxylase activities in the caudate-putamen and hippocampus were investigated in both male and female rats. Our results confirm that subchronic exposure to 40 ppm toluene significantly decreases rearing activity and leads to a sensitization to toluene-induced narcosis, as evaluated by loss of righting reflex, but fails to demonstrate any adverse effect of noise, alone or in combination with toluene. Given that toluene has addictive properties, the lack of potentiating behavioral and neurochemical effect of noise is discussed with regards to a recent study that has shown that methamphetamine neurotoxicity is potentiated by exposure to loud noise.     

Uncoupling between beta-adrenoceptors and adenylate cyclase in dog ischemic myocardium

Summary We evaluated the effects of ischemic injury on the myocardial adenylate cyclase system, 5 h after ligation of the left anterior descending coronary in 5 anesthetized dogs. Crude cardiac membrane preparations were isolated from control and ischemic areas of ventricular myocardium and tested for: 1. L-(¹²⁵I)iodocyanopindolol binding, in the absence and presence of ±-isoprenaline and GTP, and 2. adenylate cyclase activity. The density of beta-adrenoceptors increased by 35% in membranes from ischemic areas while the proportion of receptors in a high affinity state for ±-isoprenaline decreased from 43% to 20%. Adenylate cyclase activities in the basal state and under stimulation with NaF, forskolin, Gpp(NH)p, ±-isoprenaline and VIP were all markedly and similarly reduced, being only about 30% of comparable activities in membranes from control areas. The ±-isoprenaline subsensitivity of cardiac adenylate cyclase can, thus, be attributed to a defective enzymatic system and not to a reduction in the number of beta-adrenoceptors implying that the internal components of the system were more sensitive to acute ischemia than the outward oriented hormone receptors. It is tempting to ascribe this uncoupling to a functional depletion in the guanine nucleotide-binding regulatory protein Ns that might reflect a loss of high energy phosphate stores including GTP.Abbreviations CYP cyanopindolol - Gpp(NH)p 5-guanyl imidodiphosphate - VIP vasoactive intestinal peptide - Ns guanine nucleotide-binding regulatory protein     

A comparison between muscarinic receptor occupancy,adenylate cyclase inhibition,and inotropic response in human heart

Summary Binding to muscarinic receptors was compared with adenylate cyclase inhibition in membranes derived from human heart auricles, and with inhibition of the contraction of auricular muscle fibers.In the absence of GTP, agonists recognized two classes of receptors both of which bound antagonists with the same affinity. In the presence of GTP, both classes of receptors for agonists were converted into a single low affinity state.Carbachol and oxotremorine inhibited adenylate cyclase activity by 43%, pilocarpine being less efficient (–28%). The 3 agonists exerted similar inhibitory effects on the inotropic response, in 7 out of 9 preparations of electrically- and norepinephrine-stimulated fibers. Dose-effect curves suggested that spareness (or an amplification mechanism) was implicated in the occupancy of low affinity binding sites by carbachol and oxotremorine (but not by the partial agonist pilocarpine) and the resulting inhibition of both adenylate cyclase activity and contractile force.Abbreviations [³H] NMS, [N-methyl-³H] scopolamine methyl chloride - Gpp(NH)p guanosine 5-0-(2-3 imido) triphosphate - EGTA ethylene glycol bis (2-aminoethyl ether)-N,N,N,N-tetraacetic acid     

Postoperative assessment of nosocomial transmission of COVID-19 after robotic surgical procedures during the pandemic

ObjectivesTo assess potential nosocomial coronavirus disease-2019 (COVID-19) transmission in patients who underwent robot-assisted laparoscopic procedures during the pandemic.Material and methodsProspective study in patients undergoing robot-assisted laparoscopy in urology or gynaecology within 2 academic hospitals. Patients underwent local preoperative COVID-19 screening using a symptoms questionnaire. Patients with suspicious screening underwent coronavirus real time-polymerase chain reaction (RT-PCR) and were excluded from robotic surgery if positive. Patients with symptoms postsurgery were systematically tested for coronavirus by RT-PCR. One-month postsurgery, all patients had a telephone consultation to evaluate COVID-19 symptoms.ResultsSixty-eight patients underwent robotic surgery during the study period (median age: 63-years [IQR: 53–70], 1.8 male: female ratio). Oncology was the main indication for robotic surgery (n = 62, 91.2%) and 26 patients (38.2%) received a chest CT-scan prior to surgery. Eleven patients (16.2%) were symptomatic after surgery of whom only 1 tested positive for coronavirus by RT-PCR (1.5%) and was transferred to COVID-19 unit with no life-threatening condition. No attending surgeon was diagnosed with COVID-19 during the study.ConclusionsRobot-assisted laparoscopic surgery seemed safe in the era of COVID-19 as long as all recommended precautions are followed. The rate of nosocomial COVID-19 transmission was extremely low despite the fact that we only used RT-PCR testing in symptomatic patients during the preoperative work-up. Larger cohort is needed to validate these results.     

Increased incidence and unusual presentations of CMV disease in kidney transplant recipients after conversion to belatacept

Belatacept may increase cytomegalovirus (CMV) disease risk after conversion from CNI-based therapy. We analyzed CMV disease characteristics after belatacept conversion. Propensity score matching was used to compare CMV disease incidence in belatacept- and CNI-treated kidney transplant recipients (KTRs). CMV disease characteristics and risk factors under belatacept were analyzed. In total, 223 KTRs (median age [IQR] 59.2 years [45.4–68.5]) were converted to belatacept (median of 11.5 months [2.5–37.0] post-transplantation); 40/223 (17.9%) developed CMV disease. Independent risk factors included increased age (p = .0164), D+/R− CMV serostatus (p = .0220), and low eGFR at conversion (p = .0355). Among 181 belatacept-treated patients matched to 181 controls, 32/181 (17.7%) experienced CMV disease (vs. 5/181 controls [2.8%]). CMV disease cumulative incidences were 6.33 and 0.91/100 person-years (p-y) in belatacept and control groups, respectively. CMV disease risk was particularly high in elderly patients (converted >70 years) and those with eGFR <30 ml/min; cumulative incidences were 18.4 and 5.2/100 p-y, respectively. CMV diseases under belatacept were atypical, with late-onset disease (24/40 patients [60%]), high CMV seropositivity (27/40, 67%), increased severe and tissue-invasive disease rates (gastrointestinal involvement in 32/40 [80%]) and life-threatening diseases (4/40 [10%]). These findings should stimulate further research to secure the use of belatacept as a valuable rescue therapy in KTRs.     

Feasibility of health-related quality of life (HRQoL) assessment for cancer patients using electronic patient-reported outcome (ePRO) in daily clinical practice

Quality of Life Research - Routine Electronic Monitoring of Health-Related Quality of Life (HRQoL) (REMOQOL) in clinical care with real-time feedback to physicians could help to enhance...