High-dose sequential chemotherapy (ICE) under circulating progenitor cells (CPC) protection in patients with small cell lung carcinoma (SCLC). Preliminary report on a multicentric study

Starting in February 1994, 20 patients (pt) with a median age of 50 years(range 41-63) from 7 European centers have been included. Completedata were obtained in 16 patients so far. CPC were mobilized with chemo(Epirubicine 75 mg/m2 /d, 01 + 02) followed by G-CSF 5 p.gfkg/d for14 days. HD chemo consisted in 3 sequential courses of ICE regimen(UOs. 10 g/m2 , Carbo. 1200 mg/m2 and Etop. 1200 mg/m2 ) underCPC protection and G-CSF 5 p.g/kg/d. Out of the 16 pt, 12 completedfull program (3 cycles). One pt died of septic shock before receivingany ICE course. One pt died during the first ICE of renal insufficiency.Two pt had only 2 courses because of toxicity. Among the 16 pt, responserate (RR) was: 7 CR, 6 PR, 1 PO; 3 pt are not evaluable dueto early withdrawal (overall RR: 13/16 = 81 %). Thirty-nine cycles ofHD chemo were given with a median hematological recovery of 9 days(range 7-12) until neutro. counts> 1.0 x 109 /1 and 9 days (range 717)until thrombo. > 20 x 109 /1. No cumulative, hematological toxicitywas seen. Accrual of patients is still ongoing and updated results will bepresented.

Siofokissa, pienessä kylpypaikassa Balaton-järven etelärannalla. Lauantaina 16/6 -28

Kirje 16.6.1928

Immunology taught by lung dendritic cells.

Dendritic cells (DCs) are leukocytes specialised in the uptake, processing, and presentation of antigen and fundamental in regulating both innate and adaptive immune functions. They are mainly localised at the interface between body surfaces and the environment, continuously scrutinising incoming antigen for the potential threat it may represent to the organism. In the respiratory tract, DCs constitute a tightly enmeshed network, with the most prominent populations localised in the epithelium of the conducting airways and lung parenchyma. Their unique localisation enables them to continuously assess inhaled antigen, either inducing tolerance to inoffensive substances, or initiating immunity against a potentially harmful pathogen. This immunological homeostasis requires stringent control mechanisms to protect the vital and fragile gaseous exchange barrier from unrestrained and damaging inflammation, or an exaggerated immune response to an innocuous allergen, such as in allergic asthma. During DC activation, there is upregulation of co-stimulatory molecules and maturation markers, enabling DC to activate naïve T cells. This activation is accompanied by chemokine and cytokine release that not only serves to amplify innate immune response, but also determines the type of effector T cell population generated. An increasing body of recent literature provides evidence that different DC subpopulations, such as myeloid DC (mDC) and plasmacytoid DC (pDC) in the lungs occupy a key position at the crossroads between tolerance and immunity. This review aims to provide the clinician and researcher with a summary of the latest insights into DC-mediated pulmonary immune regulation and its relevance for developing novel therapeutic strategies for various disease conditions such as infection, asthma, COPD, and fibrotic lung disease.

Seppä Antti Kemppainen 20/10 1971

Kirje 20.10.1971

SNTL:n Korkeimman neuvoston puhemiehistön puheenjohtajan N.V. Podgornyin virallinen vierailu Suomeen 14.-18.10.1969 (Tasavallan Presidentin vastauspuhe Neuvostoliiton suurlähetystössä SNTL:n Korkeimman neuvoston puhemiehistön puheenjohtaja N.V. Podgornyin vierailun johdosta järjestetyillä päivällisillä 15.10.1969)

Puhe

L'hygiène des albuminuriques / par le Dr Maurice Springer,...

Collection : Bibliothèque d'hygiène thérapeutique

Consumption of Cinara spp. (Hemiptera, Aphididae) by Cycloneda sanguinea (Linnaeus, 1763) and Hippodamia convergens Guérin-Méneville, 1842 (Coleoptera, Coccinellidae)

Adults and larvae of coccinellids were observed feeding on populations of the giant conifer aphids Cinara spp. on Pinus spp., in Southern Brazil. The objective of this research is to evaluate the consumption capacity of Cycloneda sanguinea (Linnaeus, 1763) and Hippodamia convergens Guérin-Méneville, 1842 (Coleoptera, Coccinellidae) on these aphid species, in order to obtain information for biological control programs. Ten larvae of each predator species were fed with aphids of small size (nymphs of 1st and 2nd instars), and 10 with aphids of medium size (nymphs of 3rd and 4th instars), maintained under 15ºC, 20ºC and 25ºC, 12 h photophase and 70 ± 10% relative humidity. The aphids were counted every 24 hours, replacing those that were consumed. The total consumption of Cinara by the larvae of C. sanguinea was not statistically different at the three temperatures: 325.5; 322.2 and 324.8 of small aphids and 121.3; 140.4 and 109.9 of medium ones, respectively at 15ºC, 20ºC and 25ºC. The consumption by H. convergens was higher than by C. sanguinea and increased noticeably with temperature: 444 aphids at 15ºC; 491.3 at 20ºC and 513.3 at 25ºC, considering the small aphids, and 187.1; 205.1 and 216.6 of medium aphids at the three temperatures. The small aphids weigh about half as much as medium ones and were preferred by all larval instars probably because they are easier to manipulate than the large ones. Both predators, especially the 4th instar larvae, showed high consumption capacity on the Cinara nymphs at all temperatures and can be regarded as promising biological control agents.

Maintaining dendritic cell viability in culture.

When mouse dendritic cells (DCs) are isolated from tissues, purified and placed in a nutritive culture they die more rapidly than would be expected from their normal turnover in vivo. This can distort culture assays of DC function. We therefore tested several approaches to prolonging DC survival in culture. Of several cytokines tested granulocyte-macrophage colony stimulating factor was most effective at preserving the viability of conventional DCs (cDCs) but was ineffective for plasmacytoid DCs (pDCs). Surprisingly, Fms-like tyrosine kinase 3 ligand, crucial for DC development, produced only a marginal improvement in DC survival in culture, and interleukin-3, reported to prevent apoptosis of human pDCs, produced only a minor improvement in survival of mouse DCs. Genetic manipulation of cell death pathways was also tested, to avoid activation effects exerted by cytokine signalling. The isolation of DCs from mice overexpressing Bcl-2 was especially effective in maintaining pDC viability but gave a lesser improvement in cDC viability. DCs isolated from Bim(-/-)Noxa(-/-) mice also showed improved culture survival, but in this case with pDCs showing the least improvement.

Radiopuhe joulukuussa 1941

Puhe

Liver enzyme elevation after lamivudine withdrawal in HIV-hepatitis B virus co-infected patients: the Swiss HIV Cohort Study.

Background The principal causes of liver enzyme elevation among HIV-hepatitis B virus (HBV) co-infected patients are the hepatotoxic effects of antiretroviral therapy (ART), alcohol abuse, ART-induced immune reconstitution and the exacerbation of chronic HBV infection. Objectives To investigate the incidence and severity of liver enzyme elevation, liver failure and death following lamivudine (3TC) withdrawal in HIV-HBV co-infected patients. Methods Retrospective analysis of the Swiss HIV Cohort Study database to assess the clinical and biological consequences of the discontinuation of 3TC. Variables considered for analysis included liver enzyme, HIV virological and immunological parameters, and medication prescribed during a 6-month period following 3TC withdrawal. Results 3TC was discontinued in 255 patients on 363 occasions. On 147 occasions (109 patients), a follow-up visit within 6 months following 3TC withdrawal was recorded. Among these patients, liver enzyme elevation occurred on 42 occasions (29%), three of them (2%) with severity grade III and five of them (3.4%) with severity grade IV elevations (as defined by the AIDS Clinical Trials Group). Three patients presented with fulminant hepatitis. One death (0.7%) was recorded. Conclusions HBV reactivation leading to liver dysfunction may be an under-reported consequence of 3TC withdrawal in HIV-HBV co-infected patients. Regular monitoring of HBV markers is warranted if active therapy against HBV is discontinued.

Influência da temperatura na reprodução e longevidade do predador Orius thyestes Herring (Hemiptera, Anthocoridae)

O desenvolvimento e a fecundidade das espécies de Orius são bastante influenciados por uma série de fatores, como as condições ambientais, e em particular, pela temperatura. Esse trabalho teve como objetivo avaliar a reprodução e a longevidade de Orius thyestes Herring 1966 em diferentes temperaturas, tendo como alimento, ovos de Anagasta kuehniella (Zeller, 1879). O experimento foi conduzido em câmaras climatizadas com temperaturas de 16, 19, 22, 25, 28, 31 ± 1ºC, UR de 70±10% e fotofase de 12horas. Efeito deletério da temperatura em O. thyestes foi obtido a 16ºC, na qual apenas 40% das ninfas atingiram a fase adulta, e destes apenas 19% não apresentaram deformações morfológicas. O maior período de pré-oviposição foi observado a 19ºC (17,8 dias). Os maiores valores para a fecundidade média total foram registrados a 25 e 28ºC, com 109,2 e 128,2 ovos/fêmea, respectivamente, e o menor a 19ºC, com 22,8 ovos/fêmea. A 22 e 31ºC as fêmeas viveram mais que os machos, sendo que a 19ºC a longevidade foi maior, independente do sexo. As baixas temperaturas influenciaram a reprodução e longevidade de O. thyestes sugerindo que esta espécie poderá ter melhor performance reprodutiva em temperaturas mais elevadas, como aquelas de regiões tropicais e ou subtropicais.

Use of forensic investigations in anti-doping

The fight against doping is mainly focused on direct detection, using analytical methods for the detection of doping agents in biological samples. However, the World Anti-Doping Code also defines doping as possession, administration or attempted administration of prohibited substances or methods, trafficking or attempted trafficking in any prohibited substance or methods. As these issues correspond to criminal investigation, a forensic approach can help assessing potential violation of these rules.In the context of a rowing competition, genetic analyses were conducted on biological samples collected in infusion apparatus, bags and tubing in order to obtain DNA profiles. As no database of athletes' DNA profiles was available, the use of information from the location detection as well as contextual information were key to determine a population of suspected athletes and to obtain reference DNA profiles for comparison.Analysis of samples from infusion systems provided 8 different DNA profiles. The comparison between these profiles and 8 reference profiles from suspected athletes could not be distinguished.This case-study is one of the first where a forensic approach was applied for anti-doping purposes. Based on this investigation, the International Rowing Federation authorities decided to ban not only the incriminated athletes, but also the coaches and officials for 2 years.

Bilateral dorsal and ventral fiber pathways for the processing of affective prosody identified by probabilistic fiber tracking.

Dorsal and ventral pathways for syntacto-semantic speech processing in the left hemisphere are represented in the dual-stream model of auditory processing. Here we report new findings for the right dorsal and ventral temporo-frontal pathway during processing of affectively intonated speech (i.e. affective prosody) in humans, together with several left hemispheric structural connections, partly resembling those for syntacto-semantic speech processing. We investigated white matter fiber connectivity between regions responding to affective prosody in several subregions of the bilateral superior temporal cortex (secondary and higher-level auditory cortex) and of the inferior frontal cortex (anterior and posterior inferior frontal gyrus). The fiber connectivity was investigated by using probabilistic diffusion tensor based tractography. The results underscore several so far underestimated auditory pathway connections, especially for the processing of affective prosody, such as a right ventral auditory pathway. The results also suggest the existence of a dual-stream processing in the right hemisphere, and a general predominance of the dorsal pathways in both hemispheres underlying the neural processing of affective prosody in an extended temporo-frontal network.

Regulation of catecholamine release and tyrosine hydroxylase in human adrenal chromaffin cells by interleukin-1beta: role of neuropeptide Y and nitric oxide.

Adrenal chromaffin cells synthesize and secrete catecholamines and neuropeptides that may regulate hormonal and paracrine signaling in stress and also during inflammation. The aim of our work was to study the role of the cytokine interleukin-1beta (IL-1beta) on catecholamine release and synthesis from primary cell cultures of human adrenal chromaffin cells. The effect of IL-1beta on neuropeptide Y (NPY) release and the intracellular pathways involved in catecholamine release evoked by IL-1beta and NPY were also investigated. We observed that IL-1beta increases the release of NPY, norepinephrine (NE), and epinephrine (EP) from human chromaffin cells. Moreover, the immunoneutralization of released NPY inhibits catecholamine release evoked by IL-1beta. Moreover, IL-1beta regulates catecholamine synthesis as the inhibition of tyrosine hydroxylase decreases IL-1beta-evoked catecholamine release and the cytokine induces tyrosine hydroxylase Ser40 phosphorylation. Moreover, IL-1beta induces catecholamine release by a mitogen-activated protein kinase (MAPK)-dependent mechanism, and by nitric oxide synthase activation. Furthermore, MAPK, protein kinase C (PKC), protein kinase A (PKA), and nitric oxide (NO) production are involved in catecholamine release evoked by NPY. Using human chromaffin cells, our data suggest that IL-1beta, NPY, and nitric oxide (NO) may contribute to a regulatory loop between the immune and the adrenal systems, and this is relevant in pathological conditions such as infection, trauma, stress, or in hypertension.