[Sexual and reproductive health of adolescents living with HIV in pediatric care programs in Abidjan : Structured provision of care and perceptions of health care workers in 2019]. / Santé sexuelle et reproductive des adolescent(e)s vivant avec le VIH dans les programmes de prise en charge pédiatrique à Abidjan : offre de services des structures et perceptions des professionnels de santé en 2019.

INTRODUCTION: The majority of adolescents living with HIV (ALHIV) reside in sub-Saharan Africa, with sexual and reproductive health (SRH) needs to be met. The health care facilities and professionals involved have a major role to assume in the quality of SRH services offered to these teenagers. OBJECTIVE: To investigate the SRH services offered to ALHIV subjects in pediatric facilities in Abidjan, Ivory-Coast. METHODS: In 2019 we conducted an exploratory cross-sectional study using qualitative and quantitative methods in three pediatric facilities caring for ALHIV subjects (CIRBA, CTAP and CePReF) and participating in the IeDEA (International epidemiologic databases to Evaluate AIDS project) in Abidjan, Ivory Coast. This study included: (1) an inventory of SRH services, using a questionnaire and direct observation, describing their adaptation to the teenagers' needs and their inclusion in provision of care; (2 an assessment by means of semi-structured interviews of 14 health professionals' perceptions of the SRH needs of the ALHIV subjects with whom they worked. Quantitative data were expressed in percentages and qualitative data from the interviews were analyzed through inductive thematic analysis. RESULTS: The care provided in the three facilities was poorly adapted to the teenagers' needs. Few SRH services were effectively provided to the ALHIV subjects in the different centers. The services essentially consisted in condom distribution and organization of SRH-based focus groups. Exceptionally, hormonal contraception was offered to teenage girls. Barriers to the services were largely due to poorly equipped facilities, particularly in terms of SRH offer, health professionals' experience, and support provided for ALHIV subjects and their parents. The health professionals were desirous of SRH skill-building programs enabling them to deliver optimal, adequately contextualized SRH services to the teenagers. CONCLUSIONS: In pediatric programs addressed to ALHIV subjects in three Abidjan facilities, the teenagers' SRH needs remain unmet. It is urgently necessary to strengthen the health facilities by means of improved equipment, enhanced awareness of teenagers' needs, and training programs enabling the health professionals to provide more adapted sexual and reproductive health services.

Re-emergence of genotype I of African swine fever virus in Ivory Coast.

In July 2014, an outbreak of severe haemorrhagic disease in a domestic pig population, was reported in San-Pedro, the second seaport city of Ivory Coast. Animals of all age groups developed clinical signs consistent with African swine fever (ASF). Tissue and serum samples from dead pigs were sent to the laboratory for diagnostic confirmation and molecular characterization based on the partial B646L (p72), the full E183L (p54) gene and the central variable region of the B602L gene. The PCR results confirmed the outbreak of ASF. Phylogenetic analyses based on p72 and p54 sequences showed that the San-Pedro 2014 outbreak virus strain belongs to p72 genotype I. The Analysis of the tetrameric amino acid repeat regions of the B602L gene showed two repeat signatures which differ by an extra A = CAST in the second signature. The ASFV sequence of the San-Pedro 2014 outbreak strain is closely related to historical and recent ASFV strains collected in Angola and Cameroon whose ships have repeatedly visited the seaport of San-Pedro from March to June 2014. The 2014 viruses are distinct from the strains involved in the previous ASF wave in 1996 in Ivory Coast.

The DSM5/RDoC debate on the future of mental health research: implication for studies on human stress and presentation of the signature bank.

In 2008, the National Institute of Mental Health (NIMH) announced that in the next few decades, it will be essential to study the various biological, psychological and social "signatures" of mental disorders. Along with this new "signature" approach to mental health disorders, modifications of DSM were introduced. One major modification consisted of incorporating a dimensional approach to mental disorders, which involved analyzing, using a transnosological approach, various factors that are commonly observed across different types of mental disorders. Although this new methodology led to interesting discussions of the DSM5 working groups, it has not been incorporated in the last version of the DSM5. Consequently, the NIMH launched the "Research Domain Criteria" (RDoC) framework in order to provide new ways of classifying mental illnesses based on dimensions of observable behavioral and neurobiological measures. The NIMH emphasizes that it is important to consider the benefits of dimensional measures from the perspective of psychopathology and environmental influences, and it is also important to build these dimensions on neurobiological data. The goal of this paper is to present the perspectives of DSM5 and RDoC to the science of mental health disorders and the impact of this debate on the future of human stress research. The second goal is to present the "Signature Bank" developed by the Institut Universitaire en Santé Mentale de Montréal (IUSMM) that has been developed in line with a dimensional and transnosological approach to mental illness.

Asp ou echographie dans l'exploration de la douleur abdominale aigue de l'enfant a Ouagadougou

Objectif : Evaluer l'apport de l'ASP et de l'echographie dans le diagnostic etiologique des douleurs abdominales aigues de l'enfant. Methodologie : Etude prospective transversale comparative du 30 janvier 2007 au 30 avril 2008. Ont ete inclus 153 enfants ages de 1 a 180 mois dont 60 de garcons; recus dans les services d'imagerie des CHU de Ouagadougou pour exploration radiologique de douleurs abdominales aigues non traumatiques (DAANT). Ces patients ont beneficie de la radiographie de l'abdomen sans preparation (ASP) et de l'echographie abdominale. La synthese radiologique etait obtenue a partir des resultats de l'ASP et de l'echographe. Les diagnostics finaux etaient obtenus apres confrontation radio clinique. Resultats : L'ASP etait anormale dans 35;3 des cas et l'echographie l'etait dans 79;1. Les diagnostics finaux etaient entre autre l'appendicite; la lithiase urinaire; les pneumopathies aigues; la peritonite; l'invagination intestinale aigue (IIA) et les occlusions intestinales aigues (OIA). Le diagnostic de l'ASP etait concordant au diagnostic final dans 17;6 des cas et celui de l'echographique dans 67;3. L'association ASP - echographie a permis d'aboutir au diagnostic etiologique dans 69;3 des cas

[A new focus of human paragonimosis discovered in Côte d'Ivoire (West Africa): the case of the Lauzoua Island]. / Un nouveau foyer de paragonimose humaine découvert en Côte d'Ivoire (Afrique de l'ouest): le cas de l'île de Lauzoua.

Fifteen cases of human paragonimosis were detected in Ivory Coast from 1974 to 1999. Since no further cases have been reported, an epidemiological survey was carried out in local health centers. The purpose of this paper is to described a new focus of paragonimosis discovered on Lauzoua Island. Clinical and parasitological examinations were performed on 17 patients presenting chronic cough, haemoptysis and/or epilepsy. Stools belonging to cats, dogs and pigs as well as river crustaceans were also examined to identify parasite eggs and metacercariae respectively. Paragonimus eggs were found in stools and/or sputum of five patients. Measurements of these eggs after fixation in formalin allowed division into three groups. Stools from cats, dogs and pigs were negative. Small Paragonimus metacercariae (mean: 277 to 323 microm) were found in three Callinectes marginatus crabs (out of 15 caught near the island). No metacercariae were found in local prawns. The presence of these three Paragonimus egg groups as well as of infected crabs near the island will require further study to identify the species and determine the prevalence of each in human infection.

Un nouveau foyer de paragonimose humaine découvert en Côte d'Ivoire (Afrique de l'Ouest): le cas de l'île de Lauzoua

Quinze cas de paragonimose humaine ont été détectés en Côte d'Ivoire de 1974 à 1999. Comme aucun autre cas n'a été trouvé depuis cette dernière date, une étude épidémiologique a été réalisée dans les centres locaux de santé. La présente note rapporte un nouveau foyer de paragonimose dans l'île de Lauzoua. Des examens cliniques et parasitologiques ont été effectués chez 17 patients souffrant de toux chronique, d'hémoptysie ou d'épilepsie. Des fèces de chats, de chiens et de porcs de même que des crustacés de rivière ont été également examinés pour y trouver les oeufs du parasite ou des métacercaires respectivement.Des oeufs de Paragonimus ont été trouvés dans les selles ou les expectorations de cinq patients. Les dimensions des oeufs (fixés dans du formol)permettent de caractériser trois groupes. L'examen des fèces provenant des chats, des chiens et des porcs s'est révélé négatif.Desmétacercaires de Paragonimus,de petite taille (de 277 à 323 µm en moyenne), ont été trouvées dans trois crabes (sur les 15 Callinectes marginatus capturés autour de l'île) tandis que l'examen des crevettes locales était négatif. La présence de trois types d'oeufs pour Paragonimus et celle des crabes parasités autour de l'île nécessitent d'autres études pour déterminer les espèces de ces parasites et la prévalence de l'infestation humaine pour chaque espèce

[Persistence of a paragonimosis focus in the department of Lakota, Côte d'Ivoire (West Africa)]. / Persistance d'un foyer de paragonimose dans le département de Lakota, Côte d'Ivoire (Afrique de l'Ouest).

A field survey was carried out from March to August 2006 in three villages around the town of Lakota (Côte d'Ivoire) to verify the presence of paragonimosis in local people, wild vertebrates, and crabs. Out of the 92 patients who were recruited because of their chronic cough, haemoptysis and/or epilepsy, 3 had Paragonimus eggs in their stools and/or sputa. Examination of stools belonging to 24 wild mammals and a reptile revealed the presence of eggs in three civets (Viverra civetta) and a mongoose (Crossarchus obscurus). Six local crabs (out of the 30 Liberonautes latidactylus dissected) harboured Paragonimus metacercariae having low diameters (299 to 315 pm). The presence of several paragonimid species (at least 2) in the district of Lakota was hypothesized. However, the existence of quantitative variations in metacercarial diameters for the same species of Paragonimus cannot be excluded.

The effects of antimalarial drugs on ventricular repolarization.

Cardiotoxicity has become a major concern during treatment with antimalarial drugs. Lengthening of the QTc and severe cardiac arrhythmia have been observed, particularly after treatment with halofantrine for chloroquine-resistant Plasmodium falciparum malaria. The purpose of this prospective study was to evaluate whether antimalarial agents alter dispersion of the QTc and ventricular repolarization dynamicity. Sixty patients with uncomplicated falciparum malaria were randomly allocated in four groups of 15 patients and treated with quinine, mefloquine, artemether, or halofantrine at recommended doses. Patients in treatment groups were compared with a group including 15 healthy controls with no history of malaria and/or febrile illness within the last month. QTc dispersion was measured on surface electrocardiograms. Repolarization dynamicity was analyzed from Holter recordings, which allow automatic beat-to-beat measurement of QT and RR intervals. Plasma drug concentration was determined by reversed-phase high-performance liquid chromatography. No change in QTc dispersion was observed after treatment with quinine, mefloquine, or artemether. Treatment with halofantrine was followed by a significant increase in QTc dispersion at 9 hours (P < 0.0001) and 24 hours (P < 0.01). Assessment of QT heart rate variability by QT/RR nychtohemeral regression slope demonstrated no significant difference between the artemether (mean +/- SEM = 0.170 +/- 0.048), mefloquine (0.145 +/- 0.044), and the control groups (0.172 +/- 0.039). A significant decrease in the Q-eT/RR slope was observed in the quinine group compared with the control and artemether groups (0.135 +/- 0.057; P < 0.04). With halofantrine, a significant increase in the QT/RR regression slope (0.289 +/- 0.118) was observed (P < 0.0002). QTc interval, QT dispersion, and QT regression slope were significantly correlated with halofantrine and quinine plasma concentration. Mefloquine and artemether did not alter ventricular repolarization. Quinine induced a significant decrease in QT/RR slope of the same order of magnitude as those previously observed with quinidine. Both QTc dispersion and QT/RR slope were significantly modified by halofantrine. These repolarization changes were related to a class-III antiarrhythmic drug effect and may explain the occurrence of ventricular arrhythmia and/or sudden deaths reported after halofantrine intake.

Transcriptional mechanisms for induction of 5-HT1A receptor mRNA and protein in activated B and T lymphocytes.

Serotonin (5-HT) up-regulates B and T lymphocyte proliferation by activating mitogen-induced cell surface 5-HT(1A) receptors. The mechanism of 5-HT(1A) receptor induction by B and T cell mitogens at the mRNA and protein levels in mouse splenocytes was addressed. Quantitation by RNase protection assay showed maximal increases of 3.4-, 3.0-, 3.8-, and 4.9-fold in relative 5-HT(1A) mRNA levels after 48 h of stimulation of splenocytes with lipopolysaccharide, phytohemagglutinin, concanavalin A, or phorbol 12-myristate 13-acetate plus ionomycin, respectively, as compared with unstimulated cells. Mitogens did not alter 5-HT(1A) mRNA stability (t(12) = 26 h), but induction of 5-HT(1A) mRNA was blocked by the transcriptional inhibitor actinomycin D (10 microgram/ml) and by inhibition of nuclear factor-kappaB signaling. Additionally, mitogenic stimulation of transcription was paralleled by increased cell surface 5-HT(1A) receptor immunoreactivity in splenocytes. Thus, mitogen-induced 5-HT(1A) receptor expression appears to involve transcriptional regulation by the nuclear factor-kappaB signaling cascade. Increased expression of the 5-HT(1A) receptor in activated B and T lymphocytes may enhance the immune response and provide therapeutic target for tissue inflammation and immune stimulation.

Conjugation of blocked ricin to an anti-CD19 monoclonal antibody increases antibody-induced cell calcium mobilization and CD19 internalization.

CD19 (B4) is a signal transduction molecule restricted to the B-cell lineage and the target of the immunotoxin anti-B4-blocked ricin (anti-B4-bR), which is composed of the monoclonal antibody (MoAb) anti-B4 and the modified plant toxin blocked ricin. To explore the influence of conjugation of blocked ricin to anti-B4 on functional activation of CD19, we investigated the effects of anti-B4-bR, and that of unconjugated anti-B4, on intracellular calcium mobilization and ligand/receptor internalization. The data showed that anti-B4-bR was more potent than anti-B4 in triggering cell calcium mobilization. Two other immunotoxins that bind to the B-cell surface, anti-CD20-bR and anti-CD38-bR, were devoid of the calcium increasing effect of anti-B4-bR. Furthermore, anti-B4 conjugated to ricin A-chain was also without effect in Namalwa cells, indicating that the ricin B-chain component was required for anti-B4-bR effect. Anti-B4-bR-induced calcium mobilization was inhibited in the presence of lactose, yet the calcium response induced by cross-linking anti-B4-bR with a second step antibody was not affected. The extent of CD19 modulation induced by anti-B4-bR was higher than that induced by anti-B4, and lactose dampened the effect of the immunotoxin down to that of the MoAb. Moreover, the number of internalized immunotoxin molecules was higher than that of unconjugated MoAb. Although a mechanism involving dimerization of the immunotoxin cannot be excluded, our findings suggest that the residual binding activity of the blocked ricin B-chain to cell surface molecules plays an important role in the greater calcium fluxes and greater internalization rate of anti-B4-bR, and is of functional significance in the mechanism of intoxication of cells by the immunotoxin.

Serotonin upregulates mitogen-stimulated B lymphocyte proliferation through 5-HT1A receptors.

Serotonin is a well-known neurotransmitter and neuroimmunomodulator which has been reported to modulate T cell and NK cell proliferation. In this study we investigated whether serotonin could regulate mitogen-stimulated proliferation of the mature B lymphocyte. Mouse and rat spleen cells were cultured with serotonin in the presence or absence of a combination of Escherichia coli lipopolysaccharide and dextran sulfate, and proliferation was assessed by [3H]thymidine uptake or propidium iodide staining of DNA. Serotonin alone had no effect on spleen cell proliferation, while it increased mitogen-stimulated B cell proliferation in a dose- and time-dependent manner. These effects were reproduced by the selective 5-HT1A receptor agonist 8-OH-DPAT. Serotonin- or 8-OH-DPAT-induced increase in proliferation could be blocked by the 5-HT1A receptor antagonists (+)WAY 100135 and propranolol. Moreover, lipopolysaccharide-activated mouse spleen cells expressed specific binding sites for [3H]8-OH-DPAT. These results show that serotonin upregulates mitogen-stimulated B lymphocyte proliferation through 5-HT1A receptors, thus providing an important link between this neurotransmitter and the immune system.

Activation of human monocyte chemiluminescence response by acylpoly(1,3)galactosides derived from Klebsiella pneumoniae.

The stimulating activity of several preparations isolated from a membrane proteoglycan of a nonencapsulated smooth strain of Klebsiella pneumoniae (Kp-MPG) on the oxidative burst of human blood monocytes was assessed by luminol-enhanced chemiluminescence (CL). Five Kp derivatives were studied: a 34-kd acylpoly(1,3)galactoside (APG), obtained by drastic alkaline hydrolysis and purified by chromatography; an APG preparation subjected to acid hydrolysis that removed the core part and all fatty acids, leaving intact the galactose chain of APG (GC-APG); an APG preparation subjected to mild oxidation (ox APG); a preparation obtained by mild alkaline hydrolysis of Kp-MPG, containing additional ester-linked C14 and C16 fatty acids bound to the APG molecule (EFA-APG); and a polymer of the latter compound, APG pol. EFA-APG directly stimulated monocyte CL, whereas Kp-MPG, APG pol, and the whole bacterial cells had little or no activity. APG itself and ox APG induced a weaker response than EFA-APG. Polymyxin B sulfate completely inhibited the CL response to bacterial lipopolysaccharide (LPS) but not to EFA-APG. The stimulating action of EFA-APG on blood monocytes was dependent on the extracellular levels of both calcium and magnesium. Preincubation of monocytes with monoclonal antibody anti-Mac-1 directed against CD11b, the alpha chain of complement receptor type 3 (CR3; CD11b/CD18), strongly inhibited CL activation by EFA-APG and to a lesser extent CL activation by unopsonized zymosan and rough LPS. Altogether, these findings provide indirect evidence for the contribution of the CD11b/CD18 integrin in the functional interaction of EFA-APG with monocyte membranes. They demonstrate the role of fatty acids in the triggering of monocyte oxidative burst, while the polysaccharide chain itself does not contribute to induction of the CL response in this model. In keeping with the effects of EFA-APG and APG, we show that the monocyte CL response was triggered by bacterial LPS from the rough strain of Salmonella minnesota Re 595 and its lipid A, but not by LPS from smooth strains, again suggesting a critical role for the lipid moiety.

Binding of a membrane proteoglycan from Klebsiella pneumoniae and its derivatives to human leukocytes.

The binding of a membrane proteoglycan from a non-encapsulated strain of Klebsiella pneumoniae (Kp-MPG) and four derivatives thereof, to human leukocytes, was investigated by indirect immunofluorescence using biotinylated F(ab')2 fragments of anti-Kp-MPG antibodies and the streptavidin-phycoerythrin amplification system in flow cytometry. Four Kp-MPG derivatives were studied: 1/ an acylpoly(1,3)galactoside (APG), 2/ an APG preparation submitted to acid hydrolysis which removed all fatty acids, but left intact the galactose chain of APG (GC-APG), 3/ a preparation obtained by mild alkaline hydrolysis, containing additional ester-linked C14 and C16 fatty acids bound to the APG molecule (EFA-APG) and 4/ a polymer of the latter compound (APG pol). Kp-MPG, APG and EFA-APG were shown to bind exclusively to monocytes at the lowest concentrations (from 0.15 to 3 microM APG). At higher concentrations, these compounds interacted with polymorphonuclear leukocytes, and with lymphocyte subsets in the following decreasing order: B cells, NK cells, CD8+ and CD4+ lymphocytes. Neither APG pol or GC-APG nor K. pneumoniae smooth LPS showed significant binding to leukocytes. However Kp-LPS treated by drastic alkaline hydrolysis displayed binding properties similar to those of APG. Removal of the ester-linked C14 and C16 fatty acids from EFA-APG did not affect the binding of the molecule. The capacity of cells from the myelomonocytic lineage to bind Kp-MPG and APG was very low in phenotypically immature cell lines (HL60 and U937) as compared with monocytes or polymorphonuclear cells. Treatment of U937 cells with interferon-gamma up-regulated their APG binding capacity along with the expression of the integrin CD 11 b and the CD 14 molecule, whereas monocytes exposed to interferon-gamma showed an increased binding of APG associated with an elevated expression of the galactose specific lectin Mac-2. The data demonstrate a preferential binding of Kp-MPG and APG to cells of the monocyte/macrophage lineage. APG binding does not involve the poly (1,3) galactose chain and the ester-linked C14 and C16 fatty acids but requires the presence of the hydrophobic part of the molecule.

Binding of a bacterial acylpoly(1,3)galactoside to human blood leucocytes.

The binding of a 34-kDa (mol. wt.) acylpoly(1,3)galactoside (APG) extracted from a membrane proteoglycan of Klebsiella pneumoniae to human blood leucocytes was investigated. APG is made of a long poly(1,3)galactose chain, a core-like region and a lipid moiety which comprises two glucosamine residues bound to a phosphate group and two beta OH myristic acids. Fluoresceinated APG was shown to bind preferentially to monocytes and to a lesser extent to polymorphonuclear neutrophils, as determined by flow cytometry. Binding of fluoresceinated APG was inhibited by unlabelled APG; it was concentration dependent, but not saturable, with rapid kinetics. It occurred at +4 degrees C but was markedly increased at 37 degrees C. It involved trypsin-sensitive molecules on the membrane of monocytes. Neither the parent proteoglycan nor lipopolysaccharide from K. pneumoniae or Salmonella minnesota competed for APG binding. A minor non-specific binding to lymphocytes, occurring predominantly on B cells, was observed. Unlike that of lipopolysaccharide, the APG binding was not blocked by polymyxin B sulphate. Interaction between the galactose chain of APG and the galactose receptor does not account for the binding of APG to monocytes because the galactose receptor (Mac-2) is expressed at high density on activated macrophages but not on monocytes. Despite its strong binding to human blood monocytes, APG displayed a much weaker activity than K. pneumoniae membrane proteoglycan with respect to induction of monocyte cytokine synthesis. When administered as a Technetium 99 conjugate, APG was shown to label inflammatory foci in experimental animals, and its property as a marker of macrophages is currently being evaluated in clinical trials.

Differential regulation of mouse B-cell activation by beta-adrenoceptor stimulation depending on type of mitogens.

We investigated the effects of the beta-adrenoceptor agonist isoproterenol (ISO) and the alpha- and beta-adrenoceptor agonist norepinephrine (NE) on murine B-cell activation. Cells were stimulated either by anti-mouse mu-chain antibodies (anti-mu), or by lipopolysaccharide (LPS), or a membrane proteoglycan of Klebsiella pneumoniae (Kp MPG), a T-independent polyclonal activator distinct from LPS, which induces B-cell proliferation and Ig synthesis. ISO and NE enhanced LPS- and Kp MPG-induced B-cell proliferation and maturation into IgM-, IgG- and IgA-secreting cells. The enhancement was prevented by prior addition of the beta-adrenoceptor antagonist propranolol but not by the alpha-adrenoceptor antagonist phentolamine. Earlier events in the LPS- and Kp MPG-stimulated B-cell activation, such as increases in Ia antigen expression and RNA synthesis, were not modified by the catecholamines. Unlike ISO and NE, the membrane-permeant cyclic adenosine 3',5'-monophosphate (cAMP) analogue dibutyryl cAMP (dbcAMP), and the potent adenylate cyclase activator forskolin did not enhance but even inhibited DNA synthesis and Ig secretion stimulated by LPS and Kp MPG. In addition, ISO and NE did not enhance but strongly inhibited anti-mu-induced B-cell proliferation, and these effects were mimicked by dbcAMP and forskolin. Collectively, the data demonstrate that beta-agonists differently modulate B-cell activation depending upon the polyclonal activator, and provide additional evidence for distinct biochemical mechanisms of B-cell activation by anti-mu and LPS. Moreover, our results indicate that beta-adrenergic stimulation up-regulates B-cell responses to LPS and Kp MPG by a novel and cAMP-independent pathway.

Elevation of cyclic adenosine monophosphate levels independently down regulates IL-1, IL-2, and IL-2 receptor (CD25) syntheses.

In view of the central involvement of interleukin-1 (IL-1) in T-cell functions and the negative effects exerted by cyclic adenosine monophosphate (cAMP) on T-cell responses, we wondered whether these inhibitions rely on defects in IL-1 generation. We investigated the effect of a known cAMP elevating agent, cholera toxin (CT), on the generation of IL-1 from peripheral blood adherent cells as well as the role of IL-1 whenever IL-2 synthesis and IL-2 receptor (CD25 antigen) expression are inhibited. While augmenting intracellular cAMP concentration, CT inhibits from 20 to 40% the generation of IL-1 activity from E. coli lipopolysaccharide (LPS)-stimulated adherent cells. Theophylline (TH), a cAMP degradation blocking agent, induces the same decrease in IL-1 activity. The B chain of CT, devoid of cAMP activating potency, is not inhibitory. In systems where CT and TH dramatically inhibit the generation of IL-2 activity (80%), addition of exogenous IL-1 does not restore the ability of T-cells to produce or release IL-2. Moreover, CT- and dibutyryl (db)cAMP-induced inhibition of CD25 antigen expression is not overcome by exogenous IL-1, IL-2, nor by both interleukins. It is concluded that inhibition of IL-1 and IL-2 production are independent and that inhibition of CD25 antigen expression is independent of IL-1 and IL-2 modulation. Cholera toxin and cAMP influences on interleukin synthesis are discussed.

Cyclic AMP can enhance mouse B cell activation by regulating progression into the late G1/S phase.

This study demonstrates that several substances which raise intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels in different ways were able to enhance both RNA and DNA synthesis in mouse purified B cells co-stimulated by the protein kinase C activator phorbol 12-myristate 13-acetate and the Ca2+ ionophore ionomycin, while earlier activation events were not modified. These included early changes in cell size and chromatin decondensing demonstrated by light scatter properties at narrow and 90 degrees angles, increase in Ia expression and loss of surface IgD. We concluded that cAMP can up-regulate mouse B cell activation by controlling progression into the late G1 (G1B)/S phase, but not transition from G0 to early G1 (G1A). Furthermore, because cAMP could synergize with ionomycin but not with phorbol 12-myristate 13-acetate to induce RNA and DNA synthesis, we proposed that the cAMP effects in this model may be related to the protein kinase C pathway.

Opposite effects of the catecholamines dopamine and norepinephrine on murine polyclonal B-cell activation.

The effects of dopamine (DA) and norepinephrine (NE) on polyclonal B-cell activation induced in vitro by lipopolysaccharide (LPS) and on cyclic AMP response in BALB/c mouse lymphocytes were investigated. DA at non-cytotoxic concentrations (5 x 10(-5) M and 10(-4) M) inhibited, but NE (5 x 10(-6) M to 5 x 10(-5) M) enhanced LPS-stimulated proliferation and Ig synthesis by lymphocytes from spleen, mesenteric lymph nodes and Peyer's patches. Depletion of adherent cells and T lymphocytes did not prevent the respective effects of DA and NE, and the drug effects were reproduced on nude (nu+/nu+) spleen cell proliferation and differentiation stimulated by LPS. The inhibitory effect of DA persisted even if the drug was added as late as 48 h after the mitogen. In contrast, NE was no longer stimulatory if added 2 h later than LPS. The effect of DA was blocked neither by DA1 or DA2 dopaminergic antagonists (SCH 23390 and sulpiride respectively), nor by alpha- or beta-adrenoceptor antagonists (phentolamine and propranolol respectively). Enhancement by NE was antagonized by propranolol, but not by phentolamine. Both DA and NE raised the level of cyclic AMP in unfractionated spleen cells as well as in B-enriched spleen cells but DA was less potent than NE. Pre-incubation of spleen lymphocytes with LPS for 1-24 h did not alter their cyclic AMP response to NE but it prevented the loss of sensitivity to DA after 4 or 24 h of in vitro incubation. The lysosomotropic agent chloroquine induced suppression of LPS-stimulated proliferation and Ig production with a dose-response profile similar to that of DA. Altogether, these results indicate that the catecholamines can exert opposite effects on polyclonal B-cell activation by acting directly on B lymphocytes.

Induction of murine B cell proliferation and immunoglobulin synthesis by some bacterial ribosomes.

Ribosomal preparations from Klebsiella pneumoniae, Haemophilus influenzae, Streptococcus pyogenes, and Streptococcus pneumoniae were investigated with respect to their activating capacity towards murine lymphoid cells. The proliferation of BALB/c spleen cells was induced in a dose-dependent fashion (from 1 to 100 micrograms/ml) by ribosomes of K. pneumoniae, H. influenzae, and S. pyogenes with a peak activity at 48 or 72 hr of culture. The majority of the blast cells induced by these ribosomal preparations were positive for surface-immunoglobulin (S-Ig) and negative for Thy 1.2. Furthermore, K. pneumoniae, H. influenzae, and S. pyogenes ribosomes induced the synthesis of IgM and some IgA. Cell proliferation and induction of IgM production were also demonstrated with the 3 ribosomal preparations using spleen cells from athymic nude (nu+/nu+) mice, Lyb-5-defective CBA/N spleen cells, B cell-enriched and T cell-depleted BALB/c spleen cell suspensions, as well as spleen cells from the Ips gene-deficient C3H/HeJ strain. Cell culture supernatants contained specific anti-ribosome IgM antibodies. Antibodies of other specificities (anti-sheep erythrocytes) were also demonstrated in supernatants from K. pneumoniae-stimulated cultures. Evidence against a possible role of contamination of K. pneumoniae and H. influenzae ribosomes by lipopolysaccharide- or lipid A-associated proteins in this effect is discussed. Ribosomes from S. pneumoniae did not induce 3H-thymidine incorporation nor Ig production. None of the 4 ribosomal preparations was found to stimulate T cell blastogenesis or to induce interleukin-2 production by naive BALB/c spleen cells. Finally, ribosomes from H. influenzae, S. pyogenes, S. pneumoniae but not those of K. pneumoniae stimulated interleukin-1 production by adherent spleen cells, from BALB/c mice.