[ECOVIR: Study of a primary care cohort in of patients with Acute Respiratory Infections in Normandy, an example of pluri-professional hospital-primary care coordination]. / ECOVIR : mise en place d'une cohorte en soins primaires, un exemple de coopération pluri-professionnelle ville-hôpital.

Acute Respiratory Infections (ARI) need be better understood and more effectively treated, especially insofar as they are of pivotal importance in public health, particularly during a crisis such as the SARS-CoV2 pandemic. The prospective, multicentric cohort study of viral codetections in respiratory samples study known as ECOVIR was conducted in Normandy, France during two winters (2018-2019, 2019-2020). The objective of the project was to create a biobank of respiratory tract samples from patients consulting their general practitioner (GP) for ARI symptoms. ECOVIR involved 36 GP investigators (GPI), from 8 health care centers throughout Normandy. Six hundred and eighty-five patients with ARI symptoms were included; naso-pharyngeal samples were taken by the GPIs and subsequently analyzed in virology laboratories for the purposes of viral codetection. The median of inclusions was 16 patients for each of the 31 actively participating GPIs over the two winters (CI25-75% [4.75; 27]). By D7, 92% of the patients contacted had responded to our call for participation, enabling us to obtain clinical, environmental and socio-demographic data. Through this study, we created an original functional network, thereby establishing a viable link between research and primary care, which is generally underrepresented in research protocols, even though it constitutes the cornerstone of the French health care system, especially during this prolonged period of sanitary crisis.

VIP receptors in human SUP-T1 lymphoblasts.

We characterized a new type of vasoactive intestinal peptide (VIP) receptors in the CD4+ Stanford University Pediatric (SUP)-T1 lymphoma cell line, by comparing receptor occupancy [in the presence of (125I)helodermin and (125I)(acetyl-His1)VIP] and adenylate cyclase activation (in the presence of GTP). The order of potency of peptides on both parameters was: helodermin greater than (acetyl-His1)VIP greater than (Phe1)VIP = VIP greater than PHI while secretin was ineffective. In membranes, when Gs was permanently activated by Gpp(NH)p or by ADP-ribosylation (after pretreating intact lymphoblasts for 2 h with cholera toxin), there resulted a variably increased affinity of receptors for VIP-like peptides, suggesting reduced receptor selectivity. Preexposing intact lymphoblasts to the same peptides induced, within 5 min, homologous desensitization (i.e. reduced binding capacity and even more so impaired capability to activate adenylate cyclase), whose extent correlated with the Kd of each peptide at time 0. After prolonged (16 h) exposure to 30 nM VIP that resulted in marked (75%) downregulation, 60% of the adenylate cyclase responsiveness could recover within 30-120 min even in the presence of cycloheximide, but further resensitization was cycloheximide-sensitive. To conclude, VIP receptors coupled to adenylate cyclase showed distinct specificity in human SUP-T1 lymphoblasts. Their specificity decreased when Gs was permanently activated. In intact cells exposed to VIP-like peptides, the receptors were rapidly desensitized, then down-regulated, the resensitization mechanism being not immediately inhibited by cycloheximide.

Variable stimulation of adenylate cyclase activity by vasoactive intestinal-like peptides and beta-adrenergic agonists in murine T cell lymphomas of immature, helper, and cytotoxic types.

We examined several cultured murine T cell lymphomas, induced by a radiation leukemia virus MuRadLV, including cell lines derived from immature T cells (5 clones of the BL/VL3 cell line), antigen-specific T helper cells (5 lines of the TL2 series), and one T cytotoxic cell line (NS8). With one exception (the TL2-9 cell line), these cells showed common characteristics: 1) an efficient adenylate cyclase system; 2) increased cyclic AMP production in response to at least one type of neurotransmitter, i.e., to the catecholamine isoproterenol and/or the neuropeptide VIP; 3) on the basis of adenylate cyclase stimulation, beta-adrenoceptors were of the beta 2 subtype and VIP receptors were of a "helodermin-preferring" subtype previously encountered in a human T lymphoblast cell line. Although we analyzed only a limited number of cell lines, it appeared that the immature T BL/VL3 clones responded to peptides of the VIP family with higher potency and efficacy than T helper and T cytotoxic cells. The membranes from the specific TL2-9 helper cell line were without adenylate cyclase activity in the presence of Gpp[NH]p, NaF, and GTP alone or GTP in the presence of isoproterenol or VIP. They produced cyclic AMP in the presence of Mn2+ and forskolin only, suggesting a defect in Gs as in S49 cyc- mouse lymphosarcoma cells. This was further demonstrated by the absence of cholera toxin-stimulated ADP-ribosylation in TL2-9 membranes.