Cytokine polymorphism and its possible impact on cancer

Human cancer is an unpredictable disease as is its response to therapy. The intrinsic genetic heterogeneity and instability of cancer cells could in part explain such behavior. However, it is possible that, individual variation in the genetic make-up of humans may affect the relationship between host and cancer cells and, therefore, be, at least in part responsible for this extraordinary variation. Human gene polymorphism has been shown indeed to play a role in immune responses; among the immune-related genes, cytokines are often polymorphic. Some polymorphisms of cytokine and cytokine receptor may have direct functional significance by altering directly and indirectly the level of gene expression and/or its function; other may only demarcate a genetic linkage to a particular haplotype associated with a given clinical condition. The majority of polymorphisms found in cytokines or their receptors are located in the promoter, intronic and 3′ untranslated regions. These sequence variations can still affect gene expression and function. In this review will we summarize the current knowledge about the role of cytokine polymorphism in disease and more specifically in cancer.     

A one-year follow-up on the effects of raloxifene on thyroid function in postmenopausal women

OBJECTIVE: Estrogens increase serum thyroxine-binding globulin (TBG) and total thyroxine (TT4) concentrations. Serum free thyroxine (FT4) concentrations, however, remain normal. Raloxifene (RAL) is a selective estrogen receptor modulator used to treat postmenopausal osteoporosis. Data on the long-term effects of RAL on thyroid physiology are scanty. We evaluated the effects of RAL administration for 1 year on thyroid function in osteopenic, postmenopausal women. DESIGN: Fifty osteopenic, postmenopausal women were randomly assigned to receive either RAL (60 mg/day, n = 25) or placebo (PL, n = 25) for 1 year, in a double-blind study. Measurements of serum TBG, TT4, FT4, thyroid-stimulating hormone (TSH), thyroid hormone-binding ratio (THBR), FT4 index (FT4-I) and TT4/TBG ratio were carried out at baseline and after 4 and 12 months of therapy. RESULTS: Baseline values were similar in both treatment groups. Serum TBG concentrations were increased during RAL treatment from baseline values of 29.60 +/- 0.9 microg/mL to 31.45 +/- 1.33 and 32.34 +/- 1.37 microg/mL at 4 months and 1 year, respectively (P < 0.05, baseline v 1-year values) but were unchanged during PL treatment. A small, insignificant increase in TT4 and TSH concentrations occurred in the RAL group and no changes in the PL group. All other values were unchanged during either treatment. CONCLUSIONS: These results demonstrate that RAL significantly increased serum TBG levels, but the changes were small and not accompanied by changes in FT4-I, FT4, or TSH concentrations, suggesting that long-term RAL treatment is unlikely to clinically affect the thyroid status in euthyroid, postmenopausal women.     

Strategic control and medial frontal negativity: beyond errors and response conflict

Errors in timed choice tasks typically produce an error-related negativity (ERN) in the event-related potential (ERP). The error specificity of the ERN has been challenged by studies showing a correct response negativity (CRN). Forty-five participants engaged in a flanker task in which both compatibility between flankers and target and the probability of compatible flankers were manipulated. Correct responses elicited a CRN, the amplitude of which increased with the degree of mismatch between the presence of conflict and conflict probability, even on low-conflict (compatible) trials. The fronto-central N2 component was larger on high-conflict (incompatible) correct response trials. However, in contrast to some recent accounts, this N2 was largest for highly probable stimuli. These findings suggest revision to models of the effects of conflict on response-related negativity to account for strategic adjustments made in preparation for the response.     

Ranking institutional settings based on publications in community psychology journals

Two primary outlets for community psychology research, the American Journal of Community Psychology and the Journal of Community Psychology, were assessed to rank institutions based on publication frequency and scientific influence of publications over a 32‐year period. Three specific periods were assessed (1973–1983, 1984–1994, 1995–2004). Findings indicate that there were a large group of institutions that published articles during these periods. Those academic institutions that had the most published articles as well as the largest influence, based on citations by other authors, were identified. Using archival data from the community psychology literature represents one approach for identifying those settings that made substantial contributions to the development and growth of the field. © 2007 Wiley Periodicals, Inc. J Comm Psychol 35: 967–979, 2007.     

Vector competence of Mexican and Honduran mosquitoes (Diptera: Culicidae) for enzootic (IE) and epizootic (IC) strains of Venezuelan equine encephalomyelitis virus

Experimental studies evaluated the vector competence of Ochlerotatus taeniorhynchus (Wiedemann), Culex cancer Theobald, Culex pseudes (Dyar and Knab), Culex taeniopus Dyar and Knab, and a Culex (Culex) species, probably Culex quinquefasciatus Say, and Culex nigripalpus Theobald from Chiapas, Mexico, and Tocoa, Honduras, for epizootic (IC) and enzootic (IE) strains of Venezuelan equine encephalomyelitis (VEE) virus. Culex pseudes was highly susceptible to infection with both the IC and IE strains of VEE (infection rates >78%). Patterns of susceptibility to VEE were similar for Oc. taeniorhynchus collected in Mexico and Honduras. Although Oc. taeniorhynchus was highly susceptible to the epizootic IC strains (infection rates > or = 95%, n = 190), this species was less susceptible to the enzootic IE strain (infection rates < or = 35%, n = 233). The Culex (Culex) species were refractory to both subtypes of VEE, and none of 166 contained evidence of a disseminated infection. Virus-exposed Cx. pseudes that refed on susceptible hamsters readily transmitted virus, confirming that this species was an efficient vector of VEE. Although Oc. taeniorhynchus that fed on hamsters infected with the epizootic IC strain transmitted VEE efficiently, only one of six of those with a disseminated infection with the enzootic IE virus that fed on hamsters transmitted virus by bite. These data indicate that Cx. pseudes is an efficient laboratory vector of both epizootic and enzootic strains of VEE and that Oc. taeniorhynchus could be an important vector of epizootic subtypes of VEE.     

Increased matrix metalloproteinase-9 with elastolysis in nocturnal asthma.

BACKGROUND: Matrix metalloproteinase-9 (MMP-9) is capable of degrading elastin, whereas tissue inhibitor of metalloproteinase-1 (TIMP-1) can inhibit MMP-9 activity. We observed reduced airway tissue elastin volume density in six subjects with nocturnal asthma (NA) as compared with seven subjects with nonnocturnal asthma (NNA) and seven normal controls (NL) when endobronchial biopsies were evaluated morphometrically at 4:00 PM and 4:00 AM. OBJECTIVE: We hypothesized that increased metalloproteinases and decreased tissue inhibitors of metalloproteinases in the airways of subjects with NA may be responsible for reduced elastin volume density. METHODS: Ten additional subjects with NA, 10 subjects with NNA, and 7 normal control subjects underwent bronchoscopy with bronchoalveolar lavage at 4:00 PM and 4:00 AM. Levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 were determined in bronchoalveolar lavage by enzyme-linked immunosorbent assay. RESULTS: There was a fourfold circadian increase in bronchoalveolar lavage levels of MMP-9, and there was a twofold increase in MMP-9:TIMP-1 ratio in NA subjects from 4:00 PM to 4:00 AM. There were no circadian changes in the NNA and NL subjects. At 4:00 AM, MMP-9 levels and the MMP-9:TIMP-1 ratio were highest in NA subjects. At 4:00 PM, no significant group differences were observed. The MMP-9 levels positively correlated with the overnight fall in forced expiratory volume in 1 second and the MMP-9/TIMP-1 ratio negatively correlated with the 4:00 AM % predicted forced expiratory volume in 1 second. CONCLUSIONS: Our results from these two pilot studies suggest that increased MMP-9 and decreased TIMP-1 at night in NA may lead to reduced elastin density.     

A rapid hemi-nested PCR for HTLV-I detection.

A hemi-nested PCR approach was adopted to detect HTLV-1 infection in clinical samples of peripheral blood mononuclear cells (PBMCs) from subjects with positive or indeterminate serological results. Our results showed that the hemi-nested PCR quickly solved the diagnostic query, detecting the presence of proviral HTLV-1 DNA in two of the 252 patients with inconclusive serological results. The main advantage of this method are the typology of DNA extraction, allowing a consistent DNA recovery without amplification problems, the rapidity (4-5 hours), the performance of the assay and its comparable or better sensitivity than other HTLV-1 PCR formats.     

Domains of macaque DC-SIGN essential for capture and transfer of simian immunodeficiency virus

The C-type lectin DC-SIGN mediates the capture and transfer of simian immunodeficiency virus (SIV) from macaque dendritic cells (DCs) to permissive T-cells. To further identify the determinants in macaque DC-SIGN required for capture and transfer of virus, we created mutants containing deletions or point mutations in the extracellular domains, and tested their ability to capture and transmit SIV. We found that SIV bound to the carbohydrate recognition domain (CRD) of macaque DC-SIGN via the envelope protein. In addition, deleting the C-terminal half of the CRD, or mutating amino acids within this region that contact Ca(2+) or mannose, disrupted virion capture activity. However, an N-terminal CRD deletion mutant was capable of binding SIV, indicating that this region was not necessary for binding. Finally, deletion of the neck domain also reduced the capacity for macaque DC-SIGN to capture SIV. Interestingly, ICAM-3, the cellular ligand for DC-SIGN, did not bind to any of the DC-SIGN mutants, including mutants with amino acid changes in the N-terminal region of the CRD. These data suggest that the binding sites for SIV and ICAM-3 may be distinct but overlapping. Together, the data demonstrate the importance of both the neck and the CRD of macaque DC-SIGN for efficient capture of SIV and binding to ICAM-3.     

Correlation of human decidual and cord blood mononuclear cell cytokine production

Human decidua has been shown to produce a number of cytokines. We hypothesized that decidual cytokine production influences cord blood mononuclear cell (CBMC) cytokine production and that cytokine profiles of decidua from allergic women differ from those of decidua from nonallergic women. Using enzyme-linked immunosorbent assay, we measured unstimulated and concanavalin A/phorbol myristate acetate-stimulated production of interleukin-4 (IL-4), IL-5, IL-10, IL-13 and interferon- gamma (IFN-gamma) by decidual explants from 59 healthy women delivered by unlabored cesarean section and from corresponding CBMCs in 39 of the 59. Except for IL-10, there was little or no unstimulated cytokine production. There was a strong correlation between stimulated decidual and stimulated CBMC IFN-gamma production (p = 0.01). In allergic women the ratio of IL-13 to IL-4 production was increased in stimulated explants (p = 0.03). Stimulated CBMCs from infants of allergic mothers were more likely to produce detectable levels of IL-5 than those from infants of nonallergic mothers (p = 0.04) and had a tendency toward higher IL-13 levels as well (p = 0.07). These results suggest that maternal and fetal IFN-gamma production is closely linked and that maternal allergy appears to influence cytokine production in the neonate for IL-5 and possibly IL-13.     

Endophytic bacteria in Coffea arabica L

Eighty-seven culturable endophytic bacterial isolates in 19 genera were obtained from coffee plants collected in Colombia (n = 67), Hawaii (n = 17), and Mexico (n = 3). Both Gram positive and Gram negative bacteria were isolated, with a greater percentage (68%) being Gram negative. Tissues yielding bacterial endophytes included adult plant leaves, various parts of the berry (e.g., crown, pulp, peduncle and seed), and leaves, stems, and roots of seedlings. Some of the bacteria also occurred as epiphytes. The highest number of bacteria among the berry tissues sampled was isolated from the seed, and includes Bacillus , Burkholderia , Clavibacter , Curtobacterium , Escherichia , Micrococcus , Pantoea , Pseudomonas , Serratia , and Stenotrophomonas . This is the first survey of the endophytic bacteria diversity in various coffee tissues, and the first study reporting endophytic bacteria in coffee seeds. The possible role for these bacteria in the biology of the coffee plant remains unknown.