Objective. The purpose of this study was to correlate the presence and patterns of distribution of B‐flow imaging (BFI) twinkling signs within thyroid nodules with the histologic evidence of ...microcalcifications and the results of the sonographically guided fine‐needle aspiration to establish their role in predicting the risk of malignancy. Methods. Between September 2006 and December 2007, 343 consecutive patients with 479 suspected nodules (maximum diameter >9 mm) were enrolled in this prospective study. Sonographic and BFI examinations were performed with a commercially available real‐time sonography system, and all patients also underwent a cytologic evaluation. Written informed consent was obtained from all patients. Patients with suspicious or malignant cytologic features underwent surgery. Results. On histologic examination, 66 of 479 nodules were malignant (59 papillary thyroid carcinoma, 1 Hürthle cell carcinoma, and 6 follicular carcinoma). All sonographic characteristics, which were potential predictors of thyroid malignancy (microcalcifications, hypoechogenicity, absence of a halo, and a predominantly solid composition), were found in different percentages in both histologically verified malignant and benign nodules. For BFI, pattern 3 (≥ 4 signs and distance >2 mm) was the most predictive factor for malignancy (specificity, 99.6%; sensitivity, 65.2%), whereas pattern 2 (≥ 4 signs and distance <2 mm) was a positive factor because it was detected only in benign lesions, with a positive predictive of 0. Conclusions. Our results indicate that BFI can overcome the limits of the traditional B‐mode and color Doppler sonographic features in the diagnosis of thyroid nodules. This technique provides maximum specificity levels both in the case of benign nodules with pattern 2 and in the case of malignant nodules with pattern 3.
BACKGROUND: Reactivation of latent CMV in immunocompromised recipients of allogeneic stem cell transplantation remains a major cause of morbidity and mortality. Reconstitution of immunity by CMV ...specific immunotherapy is an attractive alternative to drugs currently used, which show high toxicity and are sometimes ineffective. It has been demonstrated that CD4 helper T-cell function is crucial for the persistence of in vivo transferred CD8 CMV-specific CTL. Based on this finding, we have explored the feasibility of generating both anti-CMV CD4 and anti-CMV CD8 T-cell lines.
METHODS: Dendritic Cells (DC) were generated from donor peripheral blood (PB) monocytes after a 7-day culture in the presence of GM-CSF plus IL-4 and matured with TNF-α, IFN-α, IFN-γ, IL1-β, POLI I:C. Matured-DC were then pulsed with a pool of 50 peptides spanning pp65 and IE1 proteins which are recognised by both CD4 and CD8 T lymphocytes. Donor T cells were stimulated three times at a T cell/DC ratio of 1:6 on day 0, +7 and +14 with mature peptide pulsed-DC. At the end of the culture the specificity of generated T cells was determined as percentage of pentamer-positive cells and intracellular IFN-γ production after incubation with peptide pulsed-DC. Cultured T cells were also analysed for their ability to proliferate in response to peptide pulsed-target cells, to kill them in a standard citotoxicity assay and to migrate in response to inflammatory (CXCL9, CCL3 and CCL5) and constitutive (CXCL12) chemokines.
RESULTS: CMV-specific T cell lines were generated from five CMV seropositive donors. In four cases CD4 and CD8 CMV-specific T cell lines were expanded successfully. Cultured T cells expressed CD8 (mean= 70%, range 60–81%) and CD4 (mean= 20%, range 15–28%) and showed a CD45RA- CCR7- Effector Memory phenothype (mean=26%, range 19–30%) or a CD45RA+ CCR7- T Effector Memory RA-Positive phenothype (mean=67%, range 59–77%). An enriched CMV-specific T cell population was observed after staining with pentamers (7–45% pentamer-positive T cells). Furthermore, 90% of CD8+ and 40% of CD4+ T cells expressed high levels of intracytoplasmatic perforin and granzyme. In 4/5 cases tested, cutured T cells showed a cytolitic activity against CD8-peptide pulsed target cells (average lysis=50%, range 40–55%) and to a lesser extent against CD4-peptide pulsed target cells (average lysis=35%, range 30–40%). In addition, cultured T lymphocytes were able to proliferate and to produce intracytoplasmic IFN-γ (average production=50%, range 35–60%) after exposure to peptide-pulsed DC. Finally, Cultured T cells strongly migrated in response to chemokines (CXCL9, CCL3 and CCL5) involved in the recruitment of effector cells during viral infection.
DISCUSSION: In conclusion, a great advantage of this method is represented by the possibility to generate anti-CMV CD4+ T cells, which could support in vivo the persistence of re-infused CMV-specific CTL. Moreover, the possibility of generating peptides under GMP conditions would facilitate the translation of this approach into clinical intervention.
To test the feasibility of altering polyamine levels by influencing their catabolic pathway, we obtained transgenic tobacco (Nicotiana tabacum) plants constitutively expressing either maize (Zea ...mays) polyamine oxidase (MPAO) or pea (Pisum sativum) copper amine oxidase (PCuAO), two extracellular and H(2)O(2)-producing enzymes. Despite the high expression levels of the transgenes in the extracellular space, the amount of free polyamines in the homozygous transgenic plants was similar to that in the wild-type ones, suggesting either a tight regulation of polyamine levels or a different compartmentalization of the two recombinant proteins and the bulk amount of endogenous polyamines. Furthermore, no change in lignification levels and plant morphology was observed in the transgenic plants compared to untransformed plants, while a small but significant change in reactive oxygen species-scavenging capacity was verified. Both the MPAO and the PCuAO tobacco transgenic plants produced high amounts of H(2)O(2) only in the presence of exogenously added enzyme substrates. These observations provided evidence for the limiting amount of freely available polyamines in the extracellular space in tobacco plants under physiological conditions, which was further confirmed for untransformed maize and pea plants. The amount of H(2)O(2) produced by exogenously added polyamines in cell suspensions from the MPAO transgenic plants was sufficient to induce programmed cell death, which was sensitive to catalase treatment and required gene expression and caspase-like activity. The MPAO and PCuAO transgenic plants represent excellent tools to study polyamine secretion and conjugation in the extracellular space, as well as to determine when and how polyamine catabolism actually intervenes both in cell wall development and in response to stress.
Italian Poison Centers answer to approximately 100,000 calls per year. Potentially, this activity is a huge source of data for toxicovigilance and for syndromic surveillance. During the last decade, ...surveillance systems for early detection of outbreaks have drawn the attention of public health institutions due to the threat of terrorism and high-profile disease outbreaks. Poisoning surveillance needs the ongoing, systematic collection, analysis, interpretation, and dissemination of harmonised data about poisonings from all Poison Centers for use in public health action to reduce morbidity and mortality and to improve health. The entity-relationship model for a Poison Center relational database is extremely complex and not studied in detail. For this reason, not harmonised data collection happens among Italian Poison Centers. Entities are recognizable concepts, either concrete or abstract, such as patients and poisons, or events which have relevance to the database, such as calls. Connectivity and cardinality of relationships are complex as well. A one-to-many relationship exist between calls and patients: for one instance of entity calls, there are zero, one, or many instances of entity patients. At the same time, a one-to-many relationship exist between patients and poisons: for one instance of entity patients, there are zero, one, or many instances of entity poisons. This paper shows a relational model for a poison center database which allows the harmonised data collection of poison centers calls.
CYP1A1 Variability In Human Populations Martínez-Labarga, Cristina; Scano, Giuseppina; Lelli, Roberta ...
Collegium antropologicum,
10/2019, Volume:
43, Issue:
3
Paper
Open access
The human cytochrome P4501A1 (CYP1A1) enzyme plays an important role in the metabolism of xenobiotics and endogenous substrates. Because polymorphisms within the CYP1A1 gene have been shown to be ...associated with various cancer risks and with the predicting clinical efficacy of some chemotherapies in different populations, most studies focus on their clinical significance. We, however, were interested in evaluating whether the polymorphisms could be used to distinguish human populations. Four single nucleotide CYP1A1 polymorphisms (rs4646903/ g.75011641; rs1048943/g.75012985; g.75012235; and rs1799814/ g.75012987) were analysed via PCR-RFLP assay in 1,195 individuals of various human groups from all over the world. In order to gain a more complete view of the genetic variability of the CYP1A1 gene, different statistical analyses were performed upon the populations of the present study and upon the limited data gleaned from previously studied populations. The allele and haplotype frequencies vary among populations: the rs4646903 (C) and rs1048943 (G) have been found to be nearly always linked and were found at the highest frequencies in Native Americans, while the variant associated to the position g.75012235 was only detected in certain African populations. Our work clearly indicates that the CYP1A1 polymorphisms differ among populations and that the prediction of genotypes constitutes an important aspect of precision medicine since some variants were associated with certain cancers and rs1048943 show strong association with optimized chemotherapy. Moreover, the CYP1A1 gene plays an important role in the metabolism of xenobiotics and it is likely that its frequencies could be strongly influenced by environmental factors.
Some taxonomical, biological and ecological notes for Arrhenocoela lineata are reported, and the systematic position of the genus Arrhenocoela is discussed. The complete descriptions of the egg and ...the first-instar larva are also given. Line drawings and scanning electron micrographs of particular morphological aspects for both the adult and the larva are also provided.
The first-instar larva of Derocrepis sodalis based on central Apennine specimens associated with Vicia sp. (Fabaceae), is described for the first time. In addition, brief information about the ...distribution, taxonomy and ecology of the genus Derocrepis is also reported. Finally the systematic position of the genus Derocrepis is clarified, on the basis of the first-instar larval morphology.
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