High Prevalence of Vertebral Fractures Associated With Preoperative GH Levels in Patients With Recent Diagnosis of Acromegaly.

CONTEXT: Osteopathy and morphometric vertebral fractures (VFs) are emerging complications in acromegaly. However, the prediction of VFs in this clinical setting is still a matter of uncertainty, and it is debated whether they are an early event in the natural history of the disease. OBJECTIVE: We aimed to evaluate the prevalence and determinants of morphometric VFs in patients with recently diagnosed acromegaly. METHODS: We enrolled 92 patients (43 men/49 women) on admission to the neurosurgery unit before transsphenoidal surgery, and compared them with control individuals without secondary forms of osteoporosis and pituitary disorders. We performed a VF assessment on preoperative chest x-ray images and collected biochemical, demographic, and clinical data. RESULTS: We detected a significantly higher prevalence of VFs (33.7%) in patients with acromegaly than in controls (P = .001). Among the patients with acromegaly and VFs, 12 (38.7%) showed multiple VFs, and 5 (16.1%) showed moderate/severe VFs. Patients with VFs had higher random serum growth hormone (GH) levels than those with no VFs (P = .03), but there was no difference in insulin-like growth factor-1 (IGF-1) (P = .07) and IGF-1/Upper Normal Limit ratio (P = .08). Free 3,5,3'-triiodothyronine was slightly lower in patients with acromegaly and VFs than in those without VFs (P = .05). In multiple logistic analysis, GH was independently associated with risk for VFs (P = .003). The preoperative serum GH cutoff value that predicted VFs was 12 ng/mL. CONCLUSION: For the first time, high prevalence of radiological VFs is reported in patients with recent diagnosis of acromegaly. Therefore, we can hypothesize that VFs are an early phenomenon of acromegaly and related to GH levels. VF assessment should be included in the workup at the diagnosis of acromegaly.

Integrative diagnosis, biological observations, and histopathology of the fig cyst nematode Heteroderafici Kirjanova (1954) associated with Ficuscarica L. in southern Italy.

Morpho-biological notes and histopathology, based on LM and SEM observations, of the fig cyst nematode Heteroderafici isolated from Ficuscarica roots, collected in home and public gardens of Apulia region, southern Italy, are described and illustrated. Seventy-five localities throughout the Apulia region were sampled and one-quarter of the sampled localities had fig roots infested with H.fici, with population densities ranging from 44 to 180 cysts/100 ml of soil. All attempts to detect H.fici on ornamental Ficus spp. as well as on imported bonsai in Italy were unsuccessful. Morphometric characters of the Italian population conform to those of the type and re-description populations reported for H.fici. Molecular analysis using ITS, D2-D3 expansion domains of the 28S rRNA, and the partial 18S rRNA sequences of H.fici newly obtained in this study matched well with the corresponding sequences of H.fici present in the GenBank database. Phylogenetic trees confirmed and supported the grouping of H.fici in the Humuli group. Heteroderafici completes its embryogenic development in 14-16 days at 25 °C. Post-invasion development and maturity in the roots of F.carica seedlings is completed in 64-68 days at 25-28 °C with juveniles and adults showing different parasitic habits, being endoparasitic and semi-endoparasitic respectively. The establishment of permanent feeding sites that consist of the formation of large syncytia causes anatomical modification of vascular elements and general disorder in the root stelar structures. Syncytia structures associated with mature females showed different degrees of vacuolisation, numbers of syncytial cells, and contained nuclei and nucleoli which were constantly hypertrophied.

Motor imagery in stroke patients: a descriptive review on a multidimensional ability.

Purpose/aim: Motor imagery (MI) is the mental representation of a movement without engaging its actual execution. MI shares neuroanatomical correlates with brain motor networks. Neurologic disorders affecting motor skills, such as stroke, have been related to impairments in MI. A descriptive review was conducted to explore the effects of stroke on MI ability and its background mechanisms. Materials and Methods: We searched on PubMed and Web of Science databases and screening references of included studies and review articles for additional citations. Results: On a total of 885 studies, only 15 articles met inclusion criteria. Results suggested that MI is impaired after stroke, in implicit and explicit abilities. Impairments in mental chronometry as well as in accuracy and reaction times were observed. Conclusions: Neuroimaging findings confirmed a brain reorganization after a stroke and a compensatory over-usage of contralesional hemisphere was highlighted.

Human haemato-endothelial precursors: cord blood CD34+ cells produce haemogenic endothelium.

Embryologic and genetic evidence suggest a common origin of haematopoietic and endothelial lineages. In the murine embryo, recent studies indicate the presence of haemogenic endothelium and of a common haemato-endothelial precursor, the haemangioblast. Conversely, so far, little evidence supports the presence of haemogenic endothelium and haemangioblasts in later stages of development. Our studies indicate that human cord blood haematopoietic progenitors (CD34+45+144-), triggered by murine hepatocyte conditioned medium, differentiate into adherent proliferating endothelial precursors (CD144+CD105+CD146+CD31+CD45-) capable of functioning as haemogenic endothelium. These cells, proven to give rise to functional vasculature in vivo, if further instructed by haematopoietic growth factors, first switch to transitional CD144+45+ cells and then to haematopoietic cells. These results highlight the plasticity of haemato-endhothelial precursors in human post-natal life. Furthermore, these studies may provide highly enriched populations of human post-fetal haemogenic endothelium, paving the way for innovative projects at a basic and possibly clinical level.

CDDO-Im is a stimulator of megakaryocytic differentiation.

Although the triterpene CDDO and its potent derivatives, CDDO-Im and CDDO-Me, are now in phase I/II studies in the treatment of some pathological conditions, their effects on normal hematopoiesis are not known. In the present study we provide evidence that CDDO-Im exerts in vitro a potent inhibitory effect on erythroid cell proliferation and survival and a stimulatory action on megakaryocytic differentiation. The effect of CDDO-Im on erythroid and megakaryocytic differentiation was evaluated both on normal hemopoietic progenitor cells (HPCs) induced to selective erythroid (E) or megakaryocytic (Mk) differentiation and on erythroleukemic cell lines HEL and TF1. The inhibitory effect of CDDO-Im on erythroid cell survival and proliferation is mainly related to a reduced GATA-1 expression. This conclusion is supported by the observation that GATA-1 overexpressing TF1 cells are partially protected from the inhibitory effect of CDDO-Im on cell proliferation and survival. The stimulatory effect of CDDO-Im on normal megakaryopoiesis is seemingly related to upmodulation of GATA2 expression and induction of mitogen-activated protein kinases ERK1/2.

NFI-A directs the fate of hematopoietic progenitors to the erythroid or granulocytic lineage and controls beta-globin and G-CSF receptor expression.

It is generally conceded that selective combinations of transcription factors determine hematopoietic lineage commitment and differentiation. Here we show that in normal human hematopoiesis the transcription factor nuclear factor I-A (NFI-A) exhibits a marked lineage-specific expression pattern: it is upmodulated in the erythroid (E) lineage while fully suppressed in the granulopoietic (G) series. In unilineage E culture of hematopoietic progenitor cells (HPCs), NFI-A overexpression or knockdown accelerates or blocks erythropoiesis, respectively: notably, NFI-A overexpression restores E differentiation in the presence of low or minimal erythropoietin stimulus. Conversely, NFI-A ectopic expression in unilineage G culture induces a sharp inhibition of granulopoiesis. Finally, in bilineage E + G culture, NFI-A overexpression or suppression drives HPCs into the E or G differentiation pathways, respectively. These NFI-A actions are mediated, at least in part, by a dual and opposite transcriptional action: direct binding and activation or repression of the promoters of the beta-globin and G-CSF receptor gene, respectively. Altogether, these results indicate that, in early hematopoiesis, the NFI-A expression level acts as a novel factor channeling HPCs into either the E or G lineage.

Prunus avium: nuclear DNA study in wild populations and sweet cherry cultivars.

The PCR-SSR technique was used to detect nuclear DNA diversity in five wild populations of Prunus avium from deciduous forests in Italy, Slovenia, and Croatia and 87 sweet cherry accessions from different geographical areas that have been maintained in the sweet cherry collection in Italy. This sweet cherry collection includes local accessions from the Campania Region as well as accessions from different countries. Twenty-eight microsatellites, previously developed in this species, generated polymorphic amplification products. Between 2 and 14 alleles were revealed for the polymorphic loci studied, with the expected heterozygosity ranging from 0.045 to 0.831. The total probability of identity was 56.94 x 10-18. A model-based Bayesian clustering analysis identified nine distinct gene pools in cultivated P. avium. The probability that wild populations were assigned to cultivated gene pools indicated that three gene pools accounted for the genomic origin of 53% of P. avium sampled. A dendrogram was generated using UPGMA (unweighted pair group method with arithmetic averages) based on Nei genetic distance analysis. This dendrogram classified most of the genotypes into one major group with an additional group of five accessions. The results indicate that this set of SSRs is highly informative, and they are discussed in terms of the implications for sweet cherry characterization.

MicroRNA 223-dependent expression of LMO2 regulates normal erythropoiesis.

BACKGROUND: MicroRNAs are small non-coding RNAs that regulate gene expression through mRNA degradation or translational inhibition. MicroRNAs are emerging as key regulators of normal hematopoiesis and hematologic malignancies. Several miRNAs are differentially expressed during hematopoiesis and their specific expression regulates key functional proteins involved in hematopoietic lineage differentiation. This study focused on the functional role of microRNA-223 (miR-223) on erythroid differentiation. DESIGN AND METHODS: Purified cord blood CD34+ hematopoietic progenitor cells were grown in strictly controlled conditions in the presence of saturating dosage of erythropoietin to selectively induce erythroid differentiation. The effects of enforced expression of miR-223 in unilin-eage erythroid cultures were evaluated in liquid phase culture experiments and clonogenic studies. RESULTS: In unilineage erythroid culture of cord blood CD34+ hematopoietic progenitor cells miR-223 is down-regulated, whereas LMO2, an essential protein for erythroid differentiation, is up-regulated. Functional studies showed that enforced expression of miR-223 reduces the mRNA and protein levels of LMO2, by binding to LMO2 3' UTR, and impairs differentiation of erythroid cells. Accordingly, knockdown of LMO2 by short interfering RNA mimics the action of miR-223. Furthermore, hematopoietic progenitor cells transduced with miR-223 showed a significant reduction of their erythroid clonogenic capacity, suggesting that downmodulation of this miRNA is required for erythroid progenitor recruitment and commitment. CONCLUSIONS: These results show that the decline of miR-223 is an important event for erythroid differentiation that leads to the expansion of erythroblast cells at least partially mediated by unblocking LMO2 protein expression.

Proteomic analysis of the major soluble components in Annurca apple flesh.

Apple is one of the most worldwide-consumed fruits and a number of cultivars, differing in organoleptic and nutritional characteristics, are available for the market. Annurca apple is a regional variety from Southern Italy, which is known for crispness, excellent taste and long shelf life of fruits. These features have renewed the interest in the investigation of their genetic potential and different studies have lead to their partial genetic and metabolic characterisation. In this study, we present the analysis of the protein repertoire of the pseudocarp tissues of three accessions of Malus x domestica Borkh. cv. Annurca, as first example of the systematic annotation of the apple proteome. Proteins were extracted from fruit tissues and resolved on 2-DE gels; commonly expressed proteins were in-gel digested and analysed by MALDI-TOF-MS and muLC-ESI-IT-MS/MS approaches. Peptide MS and MS/MS data were searched against publicly available protein and EST databases, and 44 spots were identified and associated to 28 different species. They were related to important physiological processes such as energy production, ripening and stress response. The occurrence of allergens causative of widespread food allergy syndromes was also detected. Integration of genomic, metabolomic and proteomic data will be indispensable for future molecular characterisation and hence full exploitation of the peculiar organoleptic, nutritional and agronomic traits of local cultivars of fruits.

MicroRNAs 221 and 222 inhibit normal erythropoiesis and erythroleukemic cell growth via kit receptor down-modulation.

MicroRNAs (miRs) are small noncoding RNAs that regulate gene expression primarily through translational repression. In erythropoietic (E) culture of cord blood CD34+ progenitor cells, the level of miR 221 and 222 is gradually and sharply down-modulated. Hypothetically, this decline could promote erythropoiesis by unblocking expression of key functional proteins. Indeed, (i) bioinformatic analysis suggested that miR 221 and 222 target the 3' UTR of kit mRNA; (ii) the luciferase assay confirmed that both miRs directly interact with the kit mRNA target site; and (iii) in E culture undergoing exponential cell growth, miR down-modulation is inversely related to increasing kit protein expression, whereas the kit mRNA level is relatively stable. Functional studies show that treatment of CD34+ progenitors with miR 221 and 222, via oligonucleotide transfection or lentiviral vector infection, causes impaired proliferation and accelerated differentiation of E cells, coupled with down-modulation of kit protein: this phenomenon, observed in E culture releasing endogenous kit ligand, is magnified in E culture supplemented with kit ligand. Furthermore, transplantation experiments in NOD-SCID mice reveal that miR 221 and 222 treatment of CD34+ cells impairs their engraftment capacity and stem cell activity. Finally, miR 221 and 222 gene transfer impairs proliferation of the kit+ TF-1 erythroleukemic cell line. Altogether, our studies indicate that the decline of miR 221 and 222 during exponential E growth unblocks kit protein production at mRNA level, thus leading to expansion of early erythroblasts. Furthermore, the results on kit+ erythroleukemic cells suggest a potential role of these miRs in cancer therapy.