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John Connolly

Publications and source records attributed to John Connolly.

18 recordsLinked to original sources
PubMed2007

Convergence patterns and multiple species interactions in a designed plant mixture of five species.

It is known that convergence and divergence can occur in complex plant communities, but the relative importance of biotic and abiotic factors driving these processes is less clear. We addressed this issue in an experiment using a range of mixed stands of five species that are common in Swiss fens (Carex elata, C. flava, Lycopus europaeus, Lysimachia vulgaris and Mentha aquatica) and two levels of water and nutrients. One hundred and seventy-six experimental mixtures were maintained in large pots (75 l) for two consecutive growing seasons in an experimental garden. The stands varied systematically in the initial relative abundance of each of the five species and in overall initial stand abundance. The changes in biomass over 2 years were modelled as linear functions of treatments and the initial biomass of each species. The dynamics of the system were mainly driven by differences in the identity of species and by a negative feedback mechanism but also by different abiotic conditions. In all mixtures, C. elata became more dominant over time, which caused an overall convergence of community composition. In addition, the rate of change of each species' biomass was negatively related to its own initial abundance. Thus, a negative feedback further contributed to the convergence of communities. Species responded differently to water level and nutrient supply, causing community dynamics to differ among treatments. However, the different abiotic conditions only slightly modified the overall convergence pattern. Competitive interactions between more than two species were weaker than the negative feedback but still significantly influenced the species' final relative abundance. The negative feedback suggests that there is niche partitioning between the species, which permits their coexistence.

Biomass↗
PubMed2006

Seasonal influences on fungal community structure in unimproved and improved upland grassland soils.

Seasonal and management influences on the fungal community structure of two upland grassland soils were investigated. An upland site containing both unimproved floristically diverse (U4a) and improved mesotrophic (MG7b) grassland types was selected. Samples from both grassland types were taken at five times in one year. Soil fungal community structure was assessed using fungal automated ribosomal intergenic spacer analysis (ARISA), a DNA-profiling approach. A grassland management regime was found to strongly affect fungal community structure, with fungal ARISA profiles from unimproved and improved grassland soils differing significantly. The number of fungal ribotypes found was higher in unimproved than improved grassland soils, providing evidence that improvement may reduce the suitability of upland soil as a habitat for specific groups of fungi. Seasonal influences on fungal community structure were also noted, with samples taken in autumn (October) more correlated with change in ribotype profiles than samples from other seasons. However, seasonal variation did not obscure the measurement of differences in the fungal community structure that were due to agricultural improvement, with canonical correspondence analysis indicating grassland type had a stronger influence on fungal profiles than did season.

Analysis of Variance↗
PubMed2005

Upon viral exposure, myeloid and plasmacytoid dendritic cells produce 3 waves of distinct chemokines to recruit immune effectors.

Host response to viral infection involves distinct effectors of innate and adaptive immunity, whose mobilization needs to be coordinated to ensure protection. Here we show that influenza virus triggers, in human blood dendritic-cell (DC) subsets (ie, plasmacytoid and myeloid DCs), a coordinated chemokine (CK) secretion program with 3 successive waves. The first one, occurring at early time points (2 to 4 hours), includes CKs potentially attracting effector cells such as neutrophils, cytotoxic T cells, and natural killer (NK) cells (CXCL16, CXCL1, CXCL2, and CXCL3). The second one occurs within 8 to 12 hours and includes CKs attracting effector memory T cells (CXCL8, CCL3, CCL4, CCL5, CXCL9, CXCL10, and CXCL11). The third wave, which occurs after 24 to 48 hours, when DCs have reached the lymphoid organs, includes CCL19, CCL22, and CXCL13, which attract naive T and B lymphocytes. Thus, human blood DC subsets carry a common program of CK production, which allows for a coordinated attraction of the different immune effectors in response to viral infection.

Antigen-Presenting Cells↗
PubMed2005

Seasonal and management influences on bacterial community structure in an upland grassland soil.

Floristically diverse Nardo-Galion upland grasslands are common in Ireland and the UK and are valuable in agricultural, environmental and ecological terms. Under improvement (inputs of lime, fertiliser and re-seeding), they convert to mesotrophic grassland containing very few plant species. The effects of upland grassland improvement and seasonality on soil microbial communities were investigated at an upland site. Samples were taken at five times in one year in order to observe seasonal trends, and bacterial community structure was monitored using automated ribosomal intergenic spacer analysis (ARISA), a DNA-fingerprinting approach. Differences in soil chemistry and bacterial community structure between unimproved and improved grassland soils were noted. Season was also found to cause mild fluctuations in bacterial community structure, with soil samples from colder months (October and December) more correlated with change in ribotype profiles than samples from warmer months. However, for the majority of seasons clear differences in bacterial community structures from unimproved and improved soils could be seen, indicating seasonal influences did not obscure effects associated with improvement.

Bacteria↗
PubMed2005

Sustained expansion of NKT cells and antigen-specific T cells after injection of alpha-galactosyl-ceramide loaded mature dendritic cells in cancer patients.

Natural killer T (NKT) cells are distinct glycolipid reactive innate lymphocytes that are implicated in the resistance to pathogens and tumors. Earlier attempts to mobilize NKT cells, specifically, in vivo in humans met with limited success. Here, we evaluated intravenous injection of monocyte-derived mature DCs that were loaded with a synthetic NKT cell ligand, alpha-galactosyl-ceramide (alpha-GalCer; KRN-7000) in five patients who had advanced cancer. Injection of alpha-GalCer-pulsed, but not unpulsed, dendritic cells (DCs) led to >100-fold expansion of several subsets of NKT cells in all patients; these could be detected for up to 6 mo after vaccination. NKT activation was associated with an increase in serum levels of interleukin-12 p40 and IFN-gamma inducible protein-10. In addition, there was an increase in memory CD8+ T cells specific for cytomegalovirus in vivo in response to alpha-GalCer-loaded DCs, but not unpulsed DCs. These data demonstrate the feasibility of sustained expansion of NKT cells in vivo in humans, including patients who have advanced cancer, and suggest that NKT activation might help to boost adaptive T cell immunity in vivo.

Adult↗
PubMed2005

Spontaneous proliferation and type 2 cytokine secretion by CD4+T cells in patients with metastatic melanoma vaccinated with antigen-pulsed dendritic cells.

We observed the induction of spontaneous, i.e., without adding exogenous antigen, in vitro proliferation of PBMCs from patients with stage IV melanoma who underwent repeated vaccinations with antigen-loaded dendritic cells (DCs) derived from CD34(+) hematopoietic progenitors (CD34-DCs). Proliferating cells are CD4(+)T cells. Their proliferation is dependent on (1) CD11c(+) myeloid DCs, since their depletion from PBMCs abolishes it; and (2) IL-2, as it can be blocked by neutralizing anti-IL-2 antibodies. Spontaneous proliferation is associated to the secretion of type 2 cytokines. To analyze the frequency of spontaneous proliferation induction in the cohort of 18 vaccinated patients, an index of spontaneous proliferation was defined as a ratio of PBMCs proliferation from post- vs pre-DC vaccination blood samples. Ten out of sixteen analyzed patients showed an index > 2. The index of spontaneous proliferation correlates with antigen-specific PBMC proliferation to the vaccine antigen KLH. Furthermore, both spontaneous- and antigen-specific proliferation in PBMC cultures are dependent on blood myeloid DCs.

Antigen Presentation↗
PubMed2005

Human dendritic cell subsets for vaccination.

Protective immunity results from the interplay of antigen (Ag)-nonspecific innate immunity and Ag-specific adaptive immunity. The cells and molecules of the innate system employ non-clonal recognition pathways such as lectins and TLRs. B and T lymphocytes of the adaptive immune system employ clonal receptors recognizing Ag or peptides in a highly specific manner. An essential link between innate and adaptive immunity is provided by dendritic cells (DCs). As a component of the innate immune system, DC organize and transfer information from the outside world to the cells of the adaptive immune system. DC can induce such contrasting states as active immune responsiveness or immunological tolerance. Recent years have brought a wealth of information regarding DC biology and pathophysiology that shows the complexity of this cell system. Thus, presentation of antigen by immature (non-activated) DCs leads to tolerance, whereas mature, antigen-loaded DCs are geared towards the launching of antigen-specific immunity. Furthermore, DCs are composed of multiple subsets with distinct functions at the interface of the innate and adaptive immunity. Our increased understanding of DC pathophysiology will permit their rational manipulation for therapy such as vaccination to improve immunity.

Antigen Presentation↗
PubMed2005

Impact of lime, nitrogen and plant species on fungal community structure in grassland microcosms.

A microcosm-based approach was used to study impacts of plant and chemical factors on the fungal community structure of an upland acidic grassland soil. Seven plant species typical of both unimproved and fertilized grasslands were either left unamended or treated with lime, nitrogen or lime plus nitrogen. Fungal community structure was assessed by a molecular approach, fungal automated ribosomal intergenic spacer analysis (FARISA), while fungal biomass was estimated by measuring soil ergosterol content. Addition of nitrogen (with or without lime) had the largest effect, decreasing soil pH, fungal biomass and fungal ribotype number, but there was little corresponding change in fungal community structure. Although different plant species were associated with some changes in fungal biomass, this did not result in significant differences in fungal community structure between plant species. Addition of lime alone caused no changes in fungal biomass, ribotype number or community structure. Overall, fungal community structure appeared to be more significantly affected through interactions between plant species and chemical treatments, as opposed to being directly affected by changes in individual improvement factors. These results were in contrast to those found for the bacterial communities of the same soils, which changed substantially in response to chemical (lime and nitrogen) additions.

Calcium Compounds↗
PubMed2004

Assessing determinants of community biomass composition in two-species plant competition studies.

A method is proposed for assessing the relative importance of species identity, neighbour species influence and environment as determinants of change in community biomass composition in two-species short-term competition experiments. The method is based on modelling the differences in relative growth rates (RGR) of species (hence called the RGRD method). Using a multiple regression approach it quantifies the effects of initial species' abundance, species identity and environment on RGRD and hence on change in community biomass composition. The RGRD approach is relatively simple to use and deals readily with statistical difficulties associated with correlated responses between species from the same stand. It can be easily adapted to analyse sequential harvest data. An example based on data from two-species mixtures of the annual species Stellaria media and Poa annua is used to illustrate the method. The main determinant of change in community biomass composition was species identity, reflected in the difference in growth rates between the species. Change in community composition was not, in general, significantly affected by the influence of neighbours or fertiliser level. The unimportance of the influence of neighbours in affecting the composition of these communities contrasts with the strong role of intra- and interspecific competition in determining the size of individuals of both species (Connolly et al. in Oecologia 82:513-526, 1990).

Biomass↗
PubMed2004

Impact of lime, nitrogen and plant species on bacterial community structure in grassland microcosms.

A microcosm-based approach was used to study impacts of plant and chemical factors on the bacterial community structure of an upland acidic grassland soil. Seven perennial plant species typical of both natural, unimproved (Nardus stricta, Agrostis capillaris, Festuca ovina and F. rubra) and fertilized, improved (Holcus lanatus, Lolium perenne and Trifolium repens) grasslands were either left unamended or treated with lime, nitrogen, or lime plus nitrogen in a 75-day glasshouse experiment. Lime and nitrogen amendment were shown to have a greater effect on microbial activity, biomass and bacterial ribotype number than plant species. Liming increased soil pH, microbial activity and biomass, while decreasing ribotype number. Nitrogen addition decreased soil pH, microbial activity and ribotype number. Addition of lime plus nitrogen had intermediate effects, which appeared to be driven more by lime than nitrogen. Terminal restriction fragment length polymorphism (TRFLP) analysis revealed that lime and nitrogen addition altered soil bacterial community structure, while plant species had little effect. These results were further confirmed by multivariate redundancy analysis, and suggest that soil lime and nitrogen status are more important controllers of bacterial community structure than plant rhizosphere effects.

Analysis of Variance↗
PubMed2003

Clinical outcomes during the first three months posttransplant in renal allograft recipients managed by C2 monitoring of cyclosporine microemulsion.

BACKGROUND: MO2ART (monitoring of 2-hr absorption in renal transplantation) is the first prospective, multicenter trial of cyclosporine (CsA) blood level 2 hr postdose (C2) monitoring in de novo kidney recipients receiving CsA microemulsion (ME) (Neoral; Novartis, Basel, Switzerland). Efficacy and safety results from the first 3 months are presented here. METHODS: MO2ART is a 12-month, open-label, randomized study involving 296 patients. In all patients, the dose of CsA-ME was adjusted to achieve protocol-defined C2 targets of 1.6 to 2.0 microg/mL for the first month, with subsequent tapering. Randomization into two target groups occurred at 3 months. All patients received steroids and mycophenolate mofetil (89%) or azathioprine. For patients with delayed graft function, the protocol permitted reduced C2 targets and prophylactic administration of antibodies. RESULTS: At 3 months, overall incidence of biopsy-proven acute rejection was 11.5%. Median serum creatinine was 132 micromol/L. Patient and graft survival were 96.6% and 91.2%, respectively. C2 levels greater than 1.6 microg/mL were achieved within 5 days by 60.6% of patients with immediate graft function and 19.5% of patients with delayed graft function. Prophylactic antibodies were used in 15% of the total population. Twenty-four patients (8.1%) experienced serious adverse events with a suspected relation to CsA, and 26 patients (8.8%) discontinued the study because of adverse events (n=15) or after a switch in immunosuppression after rejection episodes (n=11). CONCLUSIONS: Patient management by C2 monitoring resulted in a low incidence of biopsy-proven acute rejection in standard risk de novo kidney recipients, 85% of whom did not receive prophylactic antibodies. CsA-ME with C2 monitoring provides excellent short-term efficacy and safety among de novo renal transplant patients.

Adult↗
PubMed2002

Production of allergenic pollen by ragweed (Ambrosia artemisiifolia L.) is increased in CO2-enriched atmospheres.

BACKGROUND: The potential effects of global climate change on allergenic pollen production are still poorly understood. OBJECTIVE: To study the direct impact of rising atmospheric CO2 concentrations on ragweed (Ambrosia artemisiifolia L.) pollen production and growth. METHODS: In environmentally controlled greenhouses, stands of ragweed plants were grown from seed through flowering stages at both ambient and twice-ambient CO2 levels (350 vs 700 microL L(-1)). Outcome measures included stand-level total pollen production and end-of-season measures of plant mass, height, and seed production. RESULTS: A doubling of the atmospheric CO2 concentration stimulated ragweed-pollen production by 61% (P = 0.005). CONCLUSIONS: These results suggest that there may be significant increases in exposure to allergenic pollen under the present scenarios of global warming. Further studies may enable public health groups to more accurately evaluate the future risks of hay fever and respiratory diseases (eg, asthma) exacerbated by allergenic pollen, and to develop strategies to mitigate them.

Carbon Dioxide↗
PubMedDate not supplied

Immune and clinical outcomes in patients with stage IV melanoma vaccinated with peptide-pulsed dendritic cells derived from CD34+ progenitors and activated with type I interferon.

Twenty-two HLA A*0201 patients with stage IV melanoma were enrolled in a phase 1 safety and feasibility trial using a composite dendritic cell (DC) vaccine generated by culturing CD34 hematopoietic progenitors and activated with IFN-alpha. The DC vaccine was loaded with peptides derived from four melanoma tissue differentiation antigens (MART-1, tyrosinase, MAGE-3, and gp100) and influenza matrix peptide (Flu-MP). Twenty patients were evaluable, 14 of whom received vaccination with peptide-pulsed DCs without keyhole limpet hemocyanin (KLH) and 6 of whom received vaccination with KLH-loaded DCs. Patients were vaccinated until disease progression or until they had received eight vaccinations. None of the analyzed patients showed the expansion of melanoma-peptide-specific circulating effector memory T cells that secrete IFN-gamma in direct ELISPOT. Melanoma-peptide-specific recall memory CD8 T cells able to secrete IFN-gamma and to proliferate could be detected in six of the seven analyzed patients. There were no objective clinical responses. The estimated median overall survival was 12 months (range 2-38), and the median event-free survival was 4 months (range 1-12). There was no statistically significant survival advantage in patients who received KLH-loaded vaccines. As of March 2005, four patients remained alive, 26+, 28+, 28+, and 36+ months. Three of them had received KLH-loaded vaccines and all of them had had additional therapy. Overall, these results suggest that IFN-alpha-activated CD34-DCs are safe but elicit only limited immune responses, underscoring the need to test different DC maturation factors.

Adult↗
PubMedDate not supplied

Dendritic cells loaded with killed allogeneic melanoma cells can induce objective clinical responses and MART-1 specific CD8+ T-cell immunity.

Dendritic cells (DCs) loaded with killed allogeneic tumors can cross-prime tumor-specific naive CD8 T cells in vitro, thereby providing an option to overcome human leukocyte antigen restriction inherent to loading DC vaccines with peptides. We have vaccinated 20 patients with stage IV melanoma with autologous monocyte-derived DCs loaded with killed allogeneic Colo829 melanoma cell line. DCs were generated by culturing monocytes with granulocyte macrophage-colony stimulating factor (granulocyte macrophage-colony stimulating factor) and interleukin (IL-4) and activated by additional culture with tumor necrosis factor and CD40 ligand. A total of 8 vaccines were administered at monthly intervals. The first patient was accrued December 2002 and the last November 2003. Fourteen patients were alive at 12 months, 9 patients were alive at 24 months, and 8 patients are alive as of January 2006. The estimated median overall survival is 22.5 months with a range of 2 to 35.5 months. Vaccinations were safe and tolerable. They induced, in 2 patients who failed previous therapy, durable objective clinical responses, 1 complete regression (CR) and 1 partial regression (PR) lasting 18 and 23 months, respectively. Three out of 13 analyzed patients showed T-cell immunity to melanoma antigen recognized by autologous T cells (MART-1) tissue differentiation antigen. Two of 3 patients showed improved immune function after vaccinations demonstrated by improved secretion of interferon (IFN)-gamma or T-cell proliferation in response to MART-1 derived peptides. In one of these patients, vaccination led to elicitation of CD8 T-cell immunity specific to a novel peptide-derived from MART-1 antigen, suggesting that cross-priming/presentation of melanoma antigens by DC vaccine had occurred. Thus, the present results justify the design of larger follow-up studies to assess the clinical response to DC vaccines loaded with killed allogeneic tumor cells in patients with metastatic melanoma.

Adult↗