Bone marrow ectopic expression of a non-coding RNA in childhood T-cell acute lymphoblastic leukemia with a novel t(2;11)(q11.2;p15.1) translocation

Background

The implementation of gene therapy for the treatment of pituitary tumors emerges as a promising complement to surgery and may have distinct advantages over radiotherapy for this type of tumors. Up to now, suicide gene therapy has been the main experimental approach explored to treat experimental pituitary tumors. In the present study we assessed the effectiveness of insulin-like growth factor I (IGF-I) gene therapy for the treatment of estrogen-induced prolactinomas in rats.

Results

Female Sprague Dawley rats were subcutaneously implanted with silastic capsules filled with 17-β estradiol (E₂) in order to induce pituitary prolactinomas. Blood samples were taken at regular intervals in order to measure serum prolactin (PRL). As expected, serum PRL increased progressively and 23 days after implanting the E₂ capsules (Experimental day 0), circulating PRL had undergone a 3–4 fold increase. On Experimental day 0 part of the E₂-implanted animals received a bilateral intrapituitary injection of either an adenoviral vector expressing the gene for rat IGF-I (RAd-IGFI), or a vector (RAd-GFP) expressing the gene for green fluorescent protein (GFP). Seven days post vector injection all animals were sacrificed and their pituitaries morphometrically analyzed to evaluate changes in the lactotroph population. RAd-IGFI but not RAd-GFP, induced a significant fall in serum PRL. Furthermore, RAd-IGFI but not RAd-GFP significantly reversed the increase in lactotroph size (CS) and volume density (VD) induced by E₂ treatment.

Conclusion

We conclude that IGF-I gene therapy constitutes a potentially useful intervention for the treatment of prolactinomas and that bioactive peptide gene delivery may open novel therapeutic avenues for the treatment of pituitary tumors.     

Prognostic role of slow vital capacity in amyotrophic lateral sclerosis

Journal of Neurology - To compare the prognostic role of FVC and SVC at diagnosis in amyotrophic lateral sclerosis (ALS) patients. We included all patients from the Piemonte and Valle D’Aosta...     

SECOND CASE OF HEPATOBLASTOMA IN A YOUNG PATIENT WITH SIMPSON-GOLABI-BEHMEL SYNDROME

Simpson-Golabi-Behmel syndrome (SGBS) is an X-linked overgrowth syndrome associated with multiple congenital anomalies caused by a mutant X-linked recessive trait. The authors report on a 14-month-old male patient affected by hepatoblastoma. As far as is known, this is the second patient reported with SGBS and hepatoblastoma. The observations emphasize that an increased risk of neoplasia in SGBS must be kept in mind, especially in young patients.     

Sarcopenia and its relationship with osteoarthritis: risk factor or direct consequence?

Purpose

The aim of this review is to evaluate the clinical role of sarcopenia in patients affected by osteoarthritis (OA) of major joints.

Methods

An online database research was performed, in order to retrieve all articles investigating the relationship between sarcopenia and OA. No peer-reviewed journal was excluded. Papers in English, French, Spanish and Italian language were considered. After consulting the full-text article, five studies have been included in the review.

Results

Of the five studies included, four are prospective studies and only one is a cross-sectional study which retrieved data retrospectively. A total of 4,231 patients, presenting a mean age of 62.0 years, were studied. Three studies evaluated only female subjects. Weight, height and body mass index were reported in all the articles. Knee OA has been assessed using the Kellgren–Lawrence grading system and the American college of rheumatology criteria. Alterations of the lean body mass on body weight ratio have been reported to be as a significant predictive parameter in two studies. Relationship between radiographic OA and an increase in the leg lean mass has been observed in one study.

Conclusions

We cannot support neither the thesis of a direct effect of sarcopenia on OA development nor the opposite relation, because the up-to-date literature lacks basic science studies concerning these topics. The absence of clinical studies regarding measurements and tools to compare sarcopenia and OA do not allow to definitely clarify this relationship.     

Abnormal cardiac enzymes in systemic sclerosis: a report of four patients and review of the literature

Cardiac involvement in systemic sclerosis (SSc) is heterogeneous and can include primary involvement of the myocardium, pericardium and coronary arteries or be secondary to cardiac complications of pulmonary and renal disease. Primary cardiac involvement in SSc is uncommon but can result in ventricular dysfunction, organ failure, arrhythmias and death. It can remain clinically silent and the prevalence is likely to be under-reported. We report four cases of SSc associated with a raised serum troponin T (TnT), in a proportion of whom cardiac MRI myocardial abnormalities were detected. These cases highlight the heterogeneity of cardiac involvement in SSc, the role of cardiac MRI and promising biochemical responses to immunosuppression. Cardiac biomarkers such as TnT may be useful screening tools to identify subclinical cardiac disease and assess response to therapeutic intervention.     

Evidence that insulin and isoprenaline activate the cGMP-inhibited low-Km cAMP phosphodiesterase in rat fat cells by phosphorylation.

Incubation of intact rat fat cells with maximally effective concentrations of insulin (1 nM, 12 min) or isoprenaline (300 nM, 3 min) increased particulate cGMP- and cilostamide-inhibited, low-Km cAMP phosphodiesterase (cAMP-PDE) activity by about 50% and 100%, respectively. In 32P-labeled cells, these agents induced serine 32P-phosphorylation of a 135-kDa particulate protein and, to a variable and lesser extent, a 44-kDa protein, which were selectively immunoprecipitated by anti-cAMP-PDE, as analyzed by SDS/PAGE and autoradiography. In the absence of hormonal stimulation, little phosphorylation was detected (less than 10% of that with the hormones). The two phosphoproteins were identified as cAMP-PDE or a closely related molecule (in the case of the 44-kDa species, perhaps a proteolytic fragment) since (i) amounts of 32P in the immunoprecipitated 135-kDa protein paralleled enzyme inactivation, (ii) prior incubation of the anti-cAMP-PDE with the pure rat or bovine enzyme selectively blocked the immunoprecipitation of the phosphoproteins, (iii) 135- and 44-kDa proteins reacted with the anti-cAMP-PDE on Western immunoblots, and (iv) the two phosphoproteins copurified with cAMP-PDE activity through DEAE-Sephacel chromatography and were isolated by highly selective affinity chromatography on cilostamide-agarose. Thus, in fat cells, catecholamine- and insulin-induced activation of the cAMP-PDE may be mediated via phosphorylation by cAMP-dependent protein kinase and an insulin-activated serine protein kinase, respectively.     

EVIDENCE FOR THE EXISTENCE OF A DIVERSE FAMILY OF IMMUNOGLOBULIN-RELATED RECOGNITION MOLECULES

All classes of molecule postulated to play a role in recognition or to have some structural homology to immunoglobulins were compared by the SΔQ index of differences in amino acid composition. The results suggest that there is a wide family of immunoglobulin-related molecules that includes vertebrate immunoglobulins, T cell receptors, MHC products, C-reactive proteins, and (some) invertebrate lectins.     

Structure of S-lectin, a developmentally regulated vertebrate beta-galactoside-binding protein.

The crystal structure of a 14-kDa bovine spleenS-lectin complexed with the disaccharide N-acetyllactosamine at 1.9-A resolutionreveals a surprising structural relationship to legume lectins, despite the lackof sequence homology. Two monomers associate to form an extended beta-sandwich,each with the same jelly roll topology typical of legume lectins but withdramatically trimmed loops and with different dimer association. Each monomerbinds one N-acetyllactosamine molecule in a topologically and spatiallydifferent site than that of legume lectins. The carbohydrate-binding siteprovides an unprecedented paradigm for carbohydrate binding, with a uniquenetwork of salt bridges. The specificity for beta-galactose arises fromintricate interactions that constrain the position of the O4atom.