Ground-Based Mobile Measurements to Track Urban Methane Emissions from Natural Gas in 12 Cities across Eight Countries.

To mitigate methane emission from urban natural gas distribution systems, it is crucial to understand local leak rates and occurrence rates. To explore urban methane emissions in cities outside the U.S., where significant emissions were found previously, mobile measurements were performed in 12 cities across eight countries. The surveyed cities range from medium size, like Groningen, NL, to large size, like Toronto, CA, and London, UK. Furthermore, this survey spanned across European regions from Barcelona, ES, to Bucharest, RO. The joint analysis of all data allows us to focus on general emission behavior for cities with different infrastructure and environmental conditions. We find that all cities have a spectrum of small, medium, and large methane sources in their domain. The emission rates found follow a heavy-tailed distribution, and the top 10% of emitters account for 60-80% of total emissions, which implies that strategic repair planning could help reduce emissions quickly. Furthermore, we compare our findings with inventory estimates for urban natural gas-related methane emissions from this sector in Europe. While cities with larger reported emissions were found to generally also have larger observed emissions, we find clear discrepancies between observation-based and inventory-based emission estimates for our 12 cities.

Colo-rectal endoscopic full-thickness resection (EFTR) with the over-the-scope device (FTRD®): A multicenter Italian experience.

BACKGROUND AND AIM: Endoscopic full-thickness resection(EFTR) with FTRD® in colo-rectum may be useful for several indications.The aim was to assess its efficacy and safety. MATERIAL AND METHODS: In this retrospective multicenter study 114 patients were screened; 110 (61M/49F, mean age 68 ±â€¯11 years, range 20-90) underwent EFTR using FTRD®. Indications were:residual/recurrent adenoma (39), incomplete resection at histology (R1 resection) (26), non-lifting lesion (12), adenoma involving the appendix (2) or diverticulum (2), subepithelial lesions(10), suspected T1 carcinoma (16), diagnostic resection (3). Technical success (TS: lesion reached and resected), R0 resection (negative lateral and deep margins),EFTR rate(all layers documented in the specimen) and safety have been evaluated. RESULTS: TS was achieved in 94.4% of cases. EFTR was achieved in 91% with lateral and deep R0 resection in 90% and 92%. Mean size of specimens was 20 mm (range 6-42). In residual/recurrent adenomas, final analysis revealed: low-risk T1 (11), adenoma with low-grade dysplasia (LGD) (24) and high-grade dysplasia (HGD) (3), scar tissue (1). Histology reports of R1 resections were: adenoma with LGD (6), with HGD (1), low-risk (6) and high-risk (1) T1, scar tissue (12). Non-lifting lesions were diagnosed as: adenoma with HGD (3), low-risk (7) and high risk (2) T1. Adverse clinical events occurred in 12 patients (11%),while adverse technical events in11%. Three-months follow-up was available in 100 cases and residual disease was evident in only seven patients. CONCLUSIONS: EFTR using FTRD® seems to be a feasible, effective and safe technique for treating selected colo-rectal lesions. Comparative prospective studies are needed to confirm these promising results.

Influence of long-range atmospheric transport pathways and climate teleconnection patterns on the variability of surface 210Pb and 7Be concentrations in southwestern Europe.

The variability of the atmospheric concentration of the 7Be and 210Pb radionuclides is strongly linked to the origin of air masses, the strength of their sources and the processes of wet and dry deposition. It has been shown how these processes and their variability are strongly affected by climate change. Thus, a deeper knowledge of the relationship between the atmospheric radionuclides variability measured close to the ground and these atmospheric processes could help in the analysis of climate scenarios. In the present study, we analyze the atmospheric variability of a 14-year time series of 7Be and 210Pb in a Mediterranean coastal city using a synergy of different indicators and tools such as: the local meteorological conditions, global and regional climate indexes and a lagrangian atmospheric transport model. We particularly focus on the relationships between the main pathways of air masses and sun spots occurrence, the variability of the local relative humidity and temperature conditions, and the main modes of regional climate variability, such as the North Atlantic Oscillation (NAO) and the Western Mediterranean Oscillation (WeMO). The variability of the observed atmospheric concentrations of both 7Be and 210Pb radionuclides was found to be mainly positively associated to the local climate conditions of temperature and to the pathways of air masses arriving at the station. Measured radionuclide concentrations significantly increase when air masses travel at low tropospheric levels from central Europe and the western part of the Iberian Peninsula, while low concentrations are associated with westerly air masses. We found a significant negative correlation between the WeMO index and the atmospheric variability of both radionuclides and no significant association was observed for the NAO index.

Analysis of the vertical radon structure at the Spanish "El Arenosillo" tower station.

This paper presents an analysis of one year of hourly radon and meteorological measurements at 10 m and 100 m a.g.l. at El Arenosillo tall-tower station, in the south-west of the Iberian Peninsula. Whole-year and seasonal composites of the diurnal radon cycle show the expected behaviour, with larger concentrations at 10 m than at 100 m during the night, due to poor vertical mixing, and similar concentrations at both heights during the daylight hours. Wind speed and wind direction analyses by sector show the prevailing contributions for each season. Sectors with air which has spent a longer period over the ocean and high wind speeds will lead to low concentrations at both levels, whereas inland sectors show a clear increase of the concentrations with similar overall averages for the two levels. The Sierra Morena, Guadalquivir and Bethics System sectors (continental pathways) are the sectors that show higher concentrations for mild to large wind speeds. The daily evolution of radon concentration differences at both heights has been grouped into four clusters by using a K-means algorithm method. The four clusters have been selected so that they sufficiently describe different characteristics in terms of stability. The temporal evolution of the mixing height (MH) and of the bulk diffusivity parameter (Kb) during the nocturnal period has been calculated by using the temporal variation of (222)Rn concentration at 10 m and the concentration gradient with height, respectively.

Toll-like receptor 4 and ß2 glycoprotein I interaction on endothelial cells.

Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by thrombotic events and/or pregnancy morbidity in the persistent presence of antiphospholipid antibodies (aPL). aPL targeting ß2 glycoprotein I (anti-ß2GPI Abs) provide the main pathogenic autoantibody subset. In monocytes, platelets and endothelial cells (ECs), the interaction of circulating aPL with membrane-bound ß2GPI results in cell activation, and EC perturbation provides an important player in clotting. Several receptors have been suggested to mediate ß2GPI/EC binding. AnnexinA2 provides a high-affinity binding site for ß2GPI but, since it does not span the cell membrane, an adaptor protein is required to trigger signal. Consistent evidence supports the role of Toll-like receptor (TLR) 4 as co-receptor for ß2GPI on ECs. ß2GPI was recently reported to behave as lipopolysaccharide (LPS) scavenger. In monocytes, TLR4 activation was shown to be apparent, due to LPS/ß2GPI complexes. Conversely, our findings in ECs demonstrate that ß2GPI interacts directly with TLR4, and that such interaction may contribute to ß2GPI-dependent aPL-mediated EC activation. LPS enhanced anti-ß2GPI Ab binding to EC only at cell-activating concentrations, able to up-regulate TLR4. This in vitro model may explain why LPS behaves as a second hit increasing the expression of ß2GPI in vascular tissues and triggering aPL-mediated thrombosis in vivo.

International standards for IgG and IgM anti-ß2glycoprotein antibody measurement.

International standards for anti-beta2 glycoprotein I (anti-ß2GPI) testing are needed. We evaluated the suitability of polyclonal/monoclonal candidate reference materials (RM) for the assay. IgG/IgM anti-ß2GPI were affinity-purified (AP) from high-positive antiphospholipid syndrome sera and IgG from HCAL clone supernatant. Igs were tested for purity by SDS-PAGE, pooled, concentrated, sterile-filtered and the protein concentration determined. One unit was defined as the binding activity of 1 µg/ml of AP anti-ß2GPI Ig. IgG/IgM RM were each assigned a unit value using the respective AP material as a calibrator. Polyclonal/monoclonal RM and 30 samples were evaluated for linearity, unit equivalency and commutability. Polyclonal AP material was assigned a value of 100 U IgG and 15 U IgM anti-ß2GPI, respectively. IgG-RM had a value of 270 IgG and the IgM-RM of 220.3 IgM anti-ß2GPI U. The linearity (R (2)) of each RM curve for the various assays ranged from 0.96 to 0.99. Commutability samples fit very well within 95% prediction intervals and had excellent correlation when comparing assays. IgG and IgM polyclonal and IgG monoclonal RM displayed excellent linearity and commutability, being good candidates for better standardization of anti-ß2GPI immunoassays.

Immune parameters identify Italian centenarians with a longer five-year survival independent of their health and functional status.

Centenarians are rare and exceptional individuals characterized by a peculiar phenotype. They are the best example of healthy aging in humans as most of them have escaped or substantially delayed the onset of major age-related diseases. Within this scenario, the purpose of the present work was to understand if immune status is associated with survival and health status in centenarians. To this aim, 116 centenarians were concomitantly characterized for their immunological, health and functional status, and followed-up for five-year survival. On the basis of previous knowledge we focused on a core of fundamental and basic immune parameters (number of leukocytes, monocytes, total lymphocytes, CD3(+) T lymphocytes, CD4(+) helper T lymphocytes, CD8(+) cytotoxic T lymphocytes, CD19(+) B lymphocytes and plasma levels of IgM), and the most important findings can be summarized as follows: i. a hierarchical cluster analysis was able to define Cluster1 (88 centenarians) and Cluster2 (28 centenarians) characterized by low and high values of all these immune parameters, respectively; ii. centenarians of Cluster2 showed a statistically longer five-year survival and more favorable values of other important immune (naïve, activated/memory and effector/memory T cells) and metabolic (glycemia, insulin and HOMA-IR) parameters, in accord with previous observations that centenarians have a peculiar immune profile, a preserved insulin pathway and a lower incidence of type 2 diabetes; and iii. unexpectedly, parameters related to frailty, as well as functional and cognitive status, did not show any significant correlation with the immune clustering, despite being capable per se of predicting survival. In conclusion, high values of basic immunological parameters and important T cell subsets correlate with five-year survival in centenarians, independent of other phenotypic characteristics. This unexpected biological scenario is compatible with the general hypothesis that in centenarians a progressive disconnection and loss of biological coherence among the different functions of the body occur, where survival/mortality result from the failure of any of these domains which apparently follow an independent age-related trajectory.

Obstetric and vascular APS: same autoantibodies but different diseases?

Beta2 glycoprotein I (ß2GPI)-dependent antiphospholipid antibodies (aPLs) are the main pathogenic autoantibody population and at the same time the laboratory diagnostic tool for the antiphospholipid syndrome (APS). These antibodies are responsible for both the vascular and the obstetric manifestations of the syndrome but the pathogenic mechanisms behind these manifestations are not the same. For example, thrombotic events do not appear to play a major role in APS miscarriages and a direct reactivity of ß2GPI-dependent aPLs on decidual and trophoblast cells was reported. A local expression of ß2GPI on these tissues was reported both in physiological conditions and in APS women, thus explaining the local tropism of the autoantibodies. The two hit hypothesis was suggested to explain why the vascular manifestations of APS may occur only occasionally in spite of the persistent presence of aPLs. This is not apparently the case for the obstetric variant of the syndrome, making the difference even more striking. A different pathogenesis may also provide the rationale for the well-known fact that the vascular and the obstetric manifestations may occur independently although in a minority of cases.

Influence of the Fukushima Dai-ichi nuclear accident on Spanish environmental radioactivity levels.

This paper presents measurements of the effect of the atmospheric radioactive release from the Fukushima Dai-ichi nuclear power station at three sites belonging to the Spanish environmental monitoring system. Measured values varied depending on the locations of the sites in Spain and their respective climatic characteristics. (134)Cs, (136)Cs, (137)Cs, (131)I, and (132)Te activity concentrations in filter samples were studied and associated levels of (131)I fallout were estimated from wet and dry deposition. Particulate aerosol activity concentrations ranges, in µBq/m(3), were 1.63-3080 ((131)I), 2.8-690 ((137)Cs), 1.3-620 ((134)Cs) and 3.6-330 ((132)Te), while the associated (131)I fallout was roughly estimated to be less than 20 Bq/m(2), Gaseous (131)I was also detected and the (131)I-gaseous/(131)I-total ratio increased at the three stations from approximately 0.75 at the end of March to 0.85-0.9 during the first few days of April. Finally, the presence of (131)I in some crucial parts of the food chain was also studied. (131)I was detected in samples from goat's and cow's milk (maximum levels of 1.11 Bq/L) and in broadleaf plants (maximum level 1.42 Bq/kg).

Climatology of salt transitions and implications for stone weathering.

This work introduces the notion of salt climatology. It shows how climate affects salt thermodynamic and the potential to relate long-term salt damage to climate types. It mainly focuses on specific sites in Western Europe, which include some cities in France and Peninsular Spain. Salt damage was parameterised using the number of dissolution-crystallisation events for unhydrated (sodium chloride) and hydrated (sodium sulphate) systems. These phase transitions have been calculated using daily temperature and relative humidity from observation meteorological data and Climate Change models' output (HadCM3 and ARPEGE). Comparing the number of transitions with meteorological seasonal data allowed us to develop techniques to estimate the frequency of salt transitions based on the local climatology. Results show that it is possible to associate the Köppen-Geiger climate types with potential salt weathering. Temperate fully humid climates seem to offer the highest potential for salt damage and possible higher number of transitions in summer. Climates with dry summers tend to show a lesser frequency of transitions in summer. The analysis of temperature, precipitation and relative output from Climate Change models suggests changes in the Köppen-Geiger climate types and changes in the patterns of salt damage. For instance, West Europe areas with a fully humid climate may change to a more Mediterranean like or dry climates, and consequently the seasonality of different salt transitions. The accuracy and reliability of the projections might be improved by simultaneously running multiple climate models (ensembles).

Toll-like receptors: another player in the pathogenesis of the anti-phospholipid syndrome.

The anti-phospholipid syndrome (APS) is a systemic autoimmune disease characterized by an adaptive immune response against self phospholipid (PL)--binding proteins. Although APS is considered as an autoantibody-mediated disease, there is now evidence that anti-phospholipid antibodies (aPL) are necessary but not sufficient to trigger some of the clinical manifestations of the syndrome. For example, mediators of the innate immunity are recognized to be additional second hits able to induce the thrombotic events in the presence of aPL. Finally, environmental agents - in particular infectious ones - were reported to act as triggers for the production of autoantibodies cross-reacting with PL-binding proteins as well as inflammatory stimuli that potentiate the aPL thrombogenic effect. Altogether, these findings suggest a role for the innate immunity in APS pathogenesis. Toll-like receptors (TLR) are receptors that induce prompt inflammatory responses and mediate functional activation in immune effector cells. There is evidence that aPL, and in particular anti-beta(2) glycoprotein I (beta(2)GPI) antibodies, may activate endothelial cells and monocytes through TLR-4-dependent signalling. Whether or not TLR may behave as surface receptors for beta(2)GPI is still matter of research. Drugs or molecules able to interfere with TLR involvement may represent new therapeutic approaches for APS.

Differential activation of mitogen-activated protein kinase signalling pathways in the hippocampus of CRND8 transgenic mouse, a model of Alzheimer's disease.

Transgenic Centre for Research in Neurodegenerative Diseases 8 (TgCRND8) mice expressing a double mutant form of human amyloid precursor protein represent a good model of Alzheimer's disease, and can be useful to clarify the involvement of mitogen-activated protein kinases (MAPK) dysregulation in the pathophysiology of this neurodegenerative disorder. Activation of extracellular regulated kinase (ERK) 1/2, jun kinase (JNK) and p38MAPK was studied in the hippocampus of 7-month-old TgCRND8 mice by immunohistochemistry and Western blot analysis using antibodies selective for the phosphorylated, and thus active, forms of the enzymes. We demonstrated that the three main MAPK pathways were differentially activated in cells of the hippocampus of TgCRND8 mice in comparison to wild type (Wt) littermates, p38MAPK and JNK being more activated, while ERK less activated. p38MAPK was significantly activated in microglia, astrocytes and neurons, around and distant from the plaques. JNK was highly activated in cells closely surrounding the plaques. No difference was observed in the activation of the two major bands of JNK, at a molecular weight of 46 kDa and 54 kDa. These data indicate the possible involvement of p38MAPK and JNK pathways dysregulation in the pathogenesis of Alzheimer's disease. The ERK2 isoform of the ERK pathway was less activated in the hippocampal dentate gyrus of Tg mice in basal conditions. Furthermore activation of the ERK pathway by ex vivo cholinergic stimulation with carbachol caused significantly higher activation of ERK in the hippocampus of Wt mice than in Tg mice. These findings may pose a molecular basis for the memory disruption of Alzheimer's disease, since proper functioning of the basal forebrain cholinergic neurons and of ERK2 is critical for memory formation.

CD1d expression on B-precursor acute lymphoblastic leukemia subsets with poor prognosis.

Acute lymphoblastic leukemia (ALL) is the most frequent malignancy of childhood. Although therapeutical advances have been achieved, some ALL subgroups still fare poorly. CD1d is a monomorphic molecule that provides a suitable target for immunotherapy in view of the characterization of a glycolipid, alpha-galactosylceramide (alpha-GalCer), capable of being presented to CD1d-restricted T cells with cytotoxic potential. We investigated CD1d expression in 80 pediatric B-cell precursor (BCP) ALL cases defined according to immunophenotype, cytogenetic features and age at onset. CD1d was detected on ALL cells in 15% of the patients. CD1d+ ALLs were significantly associated with infant leukemia, pro-B phenotype and mixed-lineage leukemia (MLL)/AF4 gene rearrangement. Accordingly, overall survival of patients with CD1d+ ALL was significantly shorter. CD1d+ leukemic blasts were able to present alpha-GalCer via CD1d to cytotoxic CD1d-restricted T cells, which induced apoptosis of ALL cells that was inhibited by mAb to CD1d. CD1d+ blasts loaded with alpha-GalCer elicited cytokine secretion by CD1d-restricted T cells. Analysis of bone marrow (BM) cells derived from normal donors revealed that CD19+/CD1d+ cells were mostly mature B lymphocytes. However, a minority of BCPs expressed CD1d. Thus, expression of CD1d in ALL cases heralds an adverse prognosis but may provide a therapeutic tool.

Role of Helicobacter pylori serology in atrophic body gastritis after eradication treatment.

BACKGROUND: It has been reported that 50% of patients with atrophic body gastritis have positive Helicobacter pylori antibody titres only. In atrophic body gastritis, a decrease in H. pylori antibodies after eradication treatment has been reported, suggesting that serology may indicate an active H. pylori infection. AIM: To investigate the time course of H. pylori antibodies and gastric inflammation after eradication treatment in patients with atrophic body gastritis, and to determine whether serology alone can be considered as a valid tool to assess the efficacy of eradication treatment in patients with atrophic body gastritis. METHODS: Twenty-seven patients with atrophic body gastritis (12 serologically H. pylori-positive only, ABG-S+; 15 H. pylori-positive at histology and serology, ABG-H+) were included in the treatment group, and 17 patients (all ABG-S+) in the no treatment group. All patients had gastroscopy plus biopsies evaluated according to the updated Sydney system and H. pylori immunoglobulin G determination: in the treatment group, at baseline and 6 and 24 months after eradication (bismuth-based triple regimens); in the no treatment group, at baseline and after 3 years. RESULTS: In the treatment group, in ABG-S+ patients, H. pylori antibodies decreased significantly 6 months after treatment [37.5 U/mL (16-100 U/mL) vs. 15 U/mL (0--100 U/mL), P < 0.01], but 2 years after treatment no further decrease occurred. In addition, in ABG-H+ patients, a significant decrease in H. pylori antibodies occurred 6 months after treatment [45 U/mL (12.5-100 U/mL) vs. 31 U/mL (0-65 U/mL), P < 0.01], but a further decrease was also observed 2 years after treatment [20 U/mL (0-56 U/mL), P < 0.01]. In ABG-S+ patients, no correlation was observed between the H. pylori antibodies and gastric inflammation score, whereas, in the ABG-H+ group, this correlation was extremely significant (r=0.5991, P < 0.0001). In the no treatment group, at follow-up, a significant decrease in H. pylori antibodies was observed [26 U/mL (15-100 U/mL) vs. 22 U/mL (0-53 U/mL), P < 0.05], but the gastric body inflammation remained unchanged. CONCLUSIONS: This study shows that, in ABG-S+ patients after eradication treatment, serology does not keep in step with gastric inflammation. This suggests that, in patients with atrophic body gastritis, serology alone may not be valid for the assessment of the efficacy of eradication treatment.

Two-thirds of atrophic body gastritis patients have evidence of Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori is involved in the induction of atrophic body gastritis (ABG). During the progression of atrophic gastritis the disappearance of H. pylori has been documented and in time serology is the only sign that indicates a previous infection. It has been shown that a positive serology, in ABG patients without histological evidence of infection, indicates an active H. pylori infection. AIM: To investigate in a population of patients with ABG the prevalence of H. pylori infection on the basis of histology and serology. PATIENTS: A total of 150 consecutive outpatients with atrophic body gastritis were diagnosed on the basis of a screening system. METHODS: All patients had a detailed assessment including measurement of specific anti-H. pylori antibodies, parietal cell antibodies, and fasting gastrin, gastroscopy with biopsies from gastric antrum and body. RESULTS: 24.6% of patients were histologically and serologically negative (Group A). 52.7% H. pylori was not detected on histology but IgG to H. pylori were in all these patients elevated (Group B). 22.6% of patients were found to be positive at histology in the corpus mucosa; all but one of these patients had elevated circulating IgG to H. pylori (Group C). Mean corporal atrophy score in Group B patients was statistically lower than in Group A patients (2.43 +/- 0.08 vs. 2.75 +/- 0.09; p <.05), but was statistically higher than in Group C patients (1.79 +/- 0.11; p <.001). Thus, in corporal mucosa a gradient of atrophy was shown: Group C < Group B < Group A. A similar gradient was observed for the presence of pernicious anemia being lowest in Group C 11.8% increasing to 45.6% in Group B and being highest in Group C 75.6%. A statistical correlation was obtained (r =.04791, p <.05) between the histological score of corporal atrophy and the titer of antibodies to parietal cells and an inverse correlation was obtained (r = -.2322, p <.0001) between the histological score of corporal atrophy and IgG to H. pylori. CONCLUSION: This study shows that two-thirds of ABG patients have evidence of H. pylori infection. This suggests that atrophic gastritis of the corpus is a spectrum of damage where H. pylori is a key agent able to induce gastric atrophic damage and also gastric autoimmunity.

CD85/LIR-1/ILT2 and CD152 (cytotoxic T lymphocyte antigen 4) inhibitory molecules down-regulate the cytolytic activity of human CD4+ T-cell clones specific for Mycobacterium tuberculosis.

Antigen-specific cytolytic CD4+ T lymphocytes control Mycobacterium tuberculosis infection by secreting cytokines and by killing macrophages that have phagocytosed the pathogen. However, lysis of the latter cells promotes microbial dissemination, and other macrophages engulf the released bacteria. Subsequently, CD4+ T-cell-mediated killing of macrophages goes on, and this persistent process may hamper control of infection, unless regulatory mechanisms maintain a subtle balance between lysis of macrophages by cytolytic CD4+ cells and activation of cytolytic CD4+ cells by infected macrophages. We asked whether inhibitory molecules expressed by CD4+ cytolytic T lymphocytes could play a role in such a balance. To this end, human CD4+ T-cell clones specific for M. tuberculosis were produced that displayed an autologous major histocompatibility complex class II-restricted lytic ability against purified protein derivative (PPD)-pulsed antigen-presenting cells. All T-cell clones expressed CD152 (cytotoxic T-lymphocyte antigen 4 [CTLA-4]) and CD85/leukocyte immunoglobulin-like receptor 1 (LIR-1)/immunoglobulin-like transcript 2 (ILT2) inhibitory receptors, but not CD94 and the killer inhibitory receptor (or killer immunoglobulin-like receptor [KIR]) p58.2. CD3-mediated activation of the clones was inhibited in a redirected killing assay in which CD152 and CD85/LIR-1/ILT2 were cross-linked. Specific antigen-mediated proliferation of the clones was also sharply reduced when CD152 and CD85/LIR-1/ILT2 were cross-linked by specific monoclonal antibody (MAb) followed by goat anti-mouse antiserum. In contrast, blockade of the receptors by specific MAb only increased their proliferation. Production of interleukin 2 (IL-2) and gamma interferon (IFN-gamma) by the T-cell clones was also strongly reduced when CD152 and CD85/LIR-1/ILT2 were cross-linked. The lytic activity of the T-cell clones against PPD-pulsed autologous monocytes or Epstein-Barr virus-activated B cells was increased by blockade and decreased by cross-linking of the receptors. These results indicate that CD152 and CD85/LIR-1/ILT2 play a role in the regulation of the antigen-specific activity of CD4+ cytolytic T lymphocytes against PPD-presenting cells.

Comparison between single and double internal mammary artery grafts: results over ten years.

BACKGROUND: In view of the superior patency of the internal mammary artery (IMA), grafting of this vessel to the left anterior descending artery is advantageous in terms of survival and quality of life; the benefits of using both the mammary arteries remain unproved. METHODS: Among the patients operated upon during the period 1988-1990, we randomly selected 150 patients in whom one IMA (group 1) was grafted and 150 patients in whom both IMAs (group 2) were grafted. The survival and event free curves of these two groups of patients were designed using the Kaplan-Mayer method; the log-rank test was used to assess the statistical difference between the curves and to determine whether, in the long term, benefits were superior in patients in whom both IMAs were grafted. RESULTS: Patients in group 1 were older (p = 0.002). In this group there were more patients with diabetes (p = 0.004) and with peripheral vascular disease (p = 0.047). There were more female patients in group 2 (p < 0.02) and more coronary vessels were grafted (p = 0.03). Follow-up was complete (100%) and equivalent in duration for both groups (109 +/- 30 months for group 1 and 110 +/- 33 months for group 2, p = NS). The survival rate at 10 years was equal for both groups (82.5 +/- 3.4% for group 2 vs 82.9 +/- 3.2% for group 1, p = NS) and so was the freedom from cardiac death. The provocative test for myocardial ischemia was more frequently positive in group 1 than in group 2 (21 vs 10 cases, p = 0.054). Freedom from new myocardial infarction (p = NS), angina recurrence (p = NS) and reoperation (p = NS) was equally distributed during follow-up. Group 2 patients more frequently necessitated coronary angioplasty but the difference was not significant (p = 0.17). Survival free from angina recurrence, new myocardial infarction, coronary angioplasty and reoperation was more frequent in group 2 (respectively 74.6 +/- 3.8 vs 70.7 +/- 4.1%) but the difference was not statistically significant (p = NS). CONCLUSIONS: After 12 years of follow-up, patients submitted to grafting of a single IMA more frequently presented with inducible myocardial ischemia, but neither survival nor the quality of life were superior in the patients in whom both IMAs were grafted.

Adhesion molecule expression, clinical features and therapy outcome in childhood acute lymphoblastic leukemia.

In view of the relevance of adhesion molecule expression for the mechanisms of homing, trafficking and spreading of malignant cells, we have investigated the expression of surface adhesion molecules in lymphoblasts from 57 acute lymphoblastic leukemia (ALL) cases and tried to correlate the adhesive phenotype with immunological typing, prognostic factors at diagnosis and clinical follow-up. Blasts from all cases expressed adhesion molecules at high rates. Beta1 integrin chain (CD18) was consistently found on blasts from most ALL cases: among integrins of the beta2 family. LFA-1 was detected in 58% of cases, in the virtual absence of other alpha chains. CD54 and CD58 were expressed in variable proportions by ALL blasts and CD44 was detected in the majority of the malignant cells, whereas the CD62L selectin was only present in 24% of cases. B-lineage ALL's displayed similar adhesion molecule phenotypes irrespective of maturational stages of the leukemic cells. We found a significantly reduced expression of beta2 alphaL integrins in the hybrid ALL cases (CD13 and/or CD33 positive). However, these cases did not show differences in clinical presentation and behaviour in comparison with patients of other groups. We did not find a significant correlation between adhesion molecule expression and well established risk factors (age, white blood cell count, central nervous system involvement, chromosomal abnormalities), with the exception of splenomegaly, that was significantly associated with CD18 expression. In the follow-up, no evidence of significant correlation between adhesive phenotype and adverse events such as leukemic relapse and death was found. In conclusion, although expression of adhesion molecules on lymphoblasts confirms the phenotypic heterogeneity of ALL, it appears that this is not relevant for the clinical aspects of the disease and for prognosis.

Signaling through CD38 induces NK cell activation.

Human CD38 is a signal transduction molecule, and, concurrently, an ectoenzyme catalyzing the synthesis and degradation of cyclic ADP-ribose (cADPR), a potent Ca2+ mobilizer. One facet of CD38 that has not yet been addressed is its role in NK cells. To this end, the events triggered by CD38 ligation with agonistic mAb were analyzed on freshly purified human NK cells. Ligation was followed by (i) a significant rise in the intracellular level of Ca2+, (ii) increased expression of HLA class II and CD25, and (iii) tyrosine phosphorylation of discrete cytoplasmic substrates. The phosphorylation cascade involved CD3-zeta and FcepsilonRIgamma chains, zeta-associated protein (ZAP)-70 and the proto-oncogene product c-Cbl. NK effector functions were then analyzed: CD38 signaling was able (iv) to induce release of IFN-gamma and, more prominently, of granulocyte macrophage colony stimulating factor, as assessed by measuring both mRNA and protein products; and, lastly, (v) to induce cytolytic effector functions on target cells after IL-2 activation, as shown both by cytotoxicity assays and ultrastructural changes. The tyrosine-phosphorylated substrates and all the effects mediated by CD38 were similar to those observed following triggering via CD16 (FcgammaRIIIA); moreover, Ca2+ mobilization via CD38 no longer operated in NK-derived cell lines lacking CD16. These results suggest that the activation signals transduced by CD38 in NK cells elicit relevant cellular events. The effects are similar to those elicited via CD16 and possibly rely on common signaling pathways.