The ascidian pigmented sensory organs: structures and developmental programs.

The recent advances on ascidian pigment sensory organ development and function represent a fascinating platform to get insight on the basic programs of chordate eye formation. This review aims to summarize current knowledge, at the structural and molecular levels, on the two main building blocks of ascidian light sensory organ, i.e. pigment cells and photoreceptor cells. The unique features of these structures (e.g., simplicity and well characterized cell lineage) are indeed making it possible to dissect the developmental programs at single cell resolution and will soon provide a panel of molecular tools to be exploited for a deep developmental and comparative-evolutionary analysis.

[Pregnancy in lupus patients: our experience]. / La gravidanza nelle pazienti con lupus: nostra esperienza.

AIM: Systematic lupus erythematosus (SLE) is the most common autoimmune disease associated with pregnancy. The aim of this study was to evaluate management and outcome of pregnancy complicated by SLE. METHODS: Twenty pregnant women affected by SLE were admitted to Prenatal Diagnosis Centre of University "Sapienza" from January 2007 to July 2009. Pregnancy was monitored from diagnosis to delivery by at least a monthly consultation. At each visit general blood laboratory assessment were registered. An ultrasound examination was performed to evaluate fetal growth. From 26 weeks of gestation an estimation of fetal weight was calculated according to the standard of Lubchenco. At birth newborns weight was registered. RESULTS: Patient mean age was 32.9 years. There were 18 live births (90%), and 2 spontaneous abortions; 50% of pregnancy ended with a preterm delivery. 20% of the patient had signs of disease activity during pregnancy. Fifteen percent of women presented gestational hypertension. An high rate of small for gestational age was registered and 2 cases of intrauterine growth retardation (IUGR). Ultrasound evaluation at 28-30 weeks of gestation showed a normal weight (≥ 50th percentile) in 83% fetuses. Only 45% of the newborns presented ≥ 50th percentile. The mean weight of the newborns was 2700 grams. CONCLUSION: Pregnancy outcome could be improved by close obstetrical and ultrasound monitoring in a multidisciplinary setting.

Vascular endothelial growth factor receptor tyrosine kinase inhibitors for the treatment of advanced non-small cell lung cancer.

Introduction: Angiogenesis is the process by which the tumor develops its potential for growth and distant metastasis. The main proangiogenic switch is vascular endothelial growth factor (VEGF), which, along with its receptor VEGFR, is a target for biological drugs such as multi-targeted tyrosine kinase inhibitors used for many neoplasms, including non-small cell lung cancer (NSCLC).Areas covered: The fact that angiokinase inhibitors act on several signaling molecules simultaneously means that the use of alternative transmission pathways, which nullifies the effect of drugs directed against a single target, is avoided. Nevertheless, most of these drugs have failed to improve any outcome in NSCLC patients. The authors discuss these points and provide their expert perspectives.Expert opinion: Multikinase inhibitors are the fruit of research which regards cancer as a complex system of interacting processes. However, the lack of predictive biomarkers of response has limited the development of this class of drugs in NSCLC. Combination trials with chemotherapy, immunotherapy or other targeted drugs are ongoing, and while some have already confirmed the role of antiangiogenic small molecules in integrated regimes, others are still evaluating the efficacy of these drugs and raising questions about their cost and tolerability.

Cititf1 and endoderm differentiation in Ciona intestinalis.

Studies on the initial formation of the endoderm have lead to the identification, mostly in Xenopus, of numerous genes relevant for the formation of this tissue during early embryogenesis (reviewed by Date, Curr. Biol. 9 (1999) R812-R815 and by Yasuo and Lemaire, Curr. Biol. 9 (1999) 869-879). In ascidians, the most primitive chordates, endoderm differentiation is an autonomous process which is almost complete at 64 cells stage. Cititf1, a gene homologous to mammalian Titf1, is the first specific endodermal marker isolated from the ascidian Ciona intestinalis (Ristatore et al., Development 126 (1999) 5149-5159). Here we study the in vivo role of Cititf1 by using two different approaches: interference and ectopic expression. The results presented here show that interference with Cititf1 function seems to affect gastrulation movements, while ectopic expression of Cititf1 mRNA into the notochord alters differentiation of this tissue probably by recruiting notochord blastomeres to an endodermal fate. These data together with studies, still in progress in our laboratory, on the transcriptional regulation of Cititf1, strongly indicate that Cititf1 plays an important role in the process of endoderm formation in Ciona embryogenesis.

Isolation and characterization of two genes encoding calitoxins, neurotoxic peptides from Calliactis parasitica (Cnidaria).

Among sea anemone neurotoxins, calitoxin, recently isolated from Calliactis parasitica, is a highly toxic peptide of 46 amino acids (aa), whose sequence differs greatly from that of all sea anemone toxins isolated so far. In this study, two genes (clx-1 and clx-2) coding for two highly homologous calitoxins were isolated and characterized from a C. parasitica genomic library. The clx-1 gene encodes the already known calitoxin sequence, named CLX-I, whereas a single bp substitution in the coding region of clx-2 is responsible for a single Glu6-->Lys replacement in a new peptide named CLX-II. The structural organization of the two genes is very similar: two introns and three exons, whose sequences are highly homologous for clx-1 and clx-2 (95% identity). The open reading frame (ORF) of both clx-1 and clx-2 codes for a precursor peptide of 79 aa, whose N-terminus has the feature of a single peptide, while the C-terminus corresponds to the sequences of mature CLX-I and CLX-II. The finding that a pair of basic aa is located upstream from the sequence of both mature toxins strongly suggests that proteolytic events, at specific cleavage sites, are responsible for the release of neurotoxins from their respective precursor molecules.

Cloning of ascidian homeobox genes provides evidence for a primordial chordate cluster.

In order to isolate genes important in controlling embryonic development in Tunicates, a genomic library from the ascidian Ciona intestinalis was screened with a degenerate oligodeoxyribonucleotide encoding the third helix of Antennapedia-type homeoboxes. Fourteen C. intestinalis homeobox genes, corresponding to several classes of homeodomains, have been identified. Five of the isolated homeoboxes show their highest homology to members of the Vertebrate HOX clusters. mRNAs for two of the isolated homeoboxes are present in unfertilized C. intestinalis eggs.

Gonadotropin-releasing hormone in elasmobranch (electric ray, Torpedo marmorata) brain and plasma: chromatographic and immunological evidence for chicken GnRH II and novel molecular forms.

Gonadotropin-releasing hormone (GnRH) peptides in the brain, testis and plasma of an electric ray (Torpedo marmorata) were investigated by gel filtration chromatography, reverse phase high performance liquid chromatography and radioimmunoassay with region-specific antisera. In the brain, two major forms of GnRH were demonstrated. One form had identical chromatographic and immunological properties to chicken GnRH II, and the second, novel, molecular form had structural features in common with mammalian, chicken II and salmon GnRHs. A minor, early-eluting immunoreactive peak, possibly also a novel GnRH, was also evident. Immunoreactive GnRH was not detected in the testis. In the plasma, a single major early-eluting immunoreactive peak was demonstrated. This peak, identical to the minor peak observed in the brain, is likely to represent a novel form of GnRH which has immunological properties in common with mammalian, chicken II and salmon GnRHs. Immunoreactive GnRH was not detected in the plasma of species from other vertebrate classes, including rabbit, chicken, monitor lizard, clawed toad, frog, cichlid fish and lamprey. The finding of chicken GnRH II in a species of Chondrichthyes adds further support to our hypothesis that this widespread structural variant may represent an early-evolved and conserved form of GnRH. The presence of a GnRH molecular form in the plasma of the electric ray suggests that GnRH may reach target organs (pituitary and gonads) via the general circulation in some species of Chondrichthyes.

Isolation and partial characterization of rhizolysin, a high molecular weight protein with hemolytic activity, from the jellyfish Rhizostoma pulmo.

A new cytolysin has been isolated from the nematocysts of the jellyfish, Rhizostoma pulmo, and named rhizolysin. The hemolysin has a mol. wt of approximately 260,000, a sedimentation coefficient of 10.3 S and is rod-shaped with a calculated axial ratio of about 1:5. It appears to be composed of three subunits with a pI value near 7.8. Rhizolysin shows no phospholipase A activity, nor an induction period for its hemolytic activity and is completely inhibited by sucrose. The optimum pH was 6.75. The mu value calculated from the Arrhenius plot is 5940 cal/mole. Rhizolysin was inhibited by cholesterol and less by sphingomyelin.

HLA antigens and infantile psoriasis.

The frequency distribution of HLA-A, -B, -C and -DR antigens in a group of 52 unrelated psoriatic patients, aged from 0 to 12 years, selected according the following four clinical subsets: guttate, inverted, follicular and minimal, was evaluated. A statistical analysis on 85 infantile psoriatic patients, randomly selected, and divided into two groups according to the age of onset of the disease, was also performed. The results show an increase of HLA-B27 antigen in the minimal psoriasis, A2 in the guttate form and of B41 allele in the inverted psoriasis. A significantly prevalence of CW6 antigen either in follicular subset or in total psoriatic patients or in both groups of age was observed, showing a strict association with the disease. An increase of HLA-B17, CW6 and DR6 in the total psoriatic patients was also noticed. The authors underline the prognostic value of this analysis.

Reduced deformability of erythrocytes as feature of congenital dyserythropoietic anaemia type II (HEMPAS).

In this study we report results regarding erythrocytes deformability in congenital dyserythropoietic anemia type II (HEMPAS) by the use of LORCA (Laser-assisted Optical Rotational Cell Analyzer). The reduced erythrocytes deformability observed in seven case of CDA II is caused by changes in the structure of glycoproteins due to the incomplete glycosylation of erythrocytic and erythroblastic membrane. Erythrocytes deformability (EI) was shown to be inversely related with mean corpuscular volume (MCV) and mean haemoglobin concentration (MCH).

Erythrocytes stored in CPD SAG-mannitol: evaluation of their deformability.

The erythrocytes deformability of three blood samples coming from healthy donors has been evaluated by Laser-assisted Optical Rotational Cell Analyzer (LORCA). Blood samples were stored in CPD SAG-mannitol. The study of progressive reduction in the Elongation Index (EI) during the preservation may be used as way of evaluation of erythrocyte vitality in stored blood samples.

Efficacy of three different antithrombotic regimens on pregnancy outcome in pregnant women affected by recurrent pregnancy loss.

INTRODUCTION: Recurrent pregnancy loss (RPL) is a common health problem affecting 1-5% of women at reproductive age. AIM OF THE STUDY: Evaluation of three different antithrombotic treatments in women with antecedent of RPL, comparing the results in negative and positive to thrombophilic screening pregnant women. MATERIALS AND METHODS: We recruited 361 women with an antecedent of two or more pregnancy losses. From this group, 167 women became pregnant and considered for the study. The evaluated pregnant women were divided as negative/positive to thrombofilic screening: (a) 80 (48%) with negative thrombophilic screening, (b) 87 (52%) positive to thrombophilic screening. Pregnant women included in the study and considered negative or positive for thrombophilic screening, were randomized into three different therapy groups: (a) group 1: Acetil salicylic acid (ASA) 100 mg daily until third month of pregnancy, (b) group 2: low molecular-weight heparin (LMWH) - enoxaparine 40 mg daily until third month of pregnancy, (c) group 3: ASA 100 mg plus LMWH 40 mg daily until third month of pregnancy. RESULTS: In 80 negative to thrombophilic screening pregnant women, the comparison of efficacy of the three treatments, shows that all three treatment regimens were significantly effective comparing live births against fetal losses. In 87 positive to thrombophilic screening pregnant women, the comparison of efficacy for the three regimens, shows that the therapy with LMWH or LMWH plus ASA are significantly protective against fetal losses with respect to ASA, which showed a high number of fetal losses (11 live births, 18 fetal losses). COMMENT: We suggest that thromboprophylaxis is indicated in women with RPL independently from positiveness to thrombophilic markers.

CT colonography with reduced bowel preparation after incomplete colonoscopy in the elderly.

We prospectively assessed the feasibility and acceptance of computerized tomographic colonography (CTC) without bowel cathartic preparation in elderly patients after incomplete colonoscopy. A total of 136 patients underwent CTC without cathartic preparation. The time delay between conventional colonoscopy and CTC ranged between 3 and 20 days, depending on the clinical situation. Before CTC, fecal tagging was achieved by adding diatrizoate meglumine and diatrizoate sodium to regular meals. CTCs were interpreted using a primary two-dimensional (2D) approach and 3D images for further characterization. Patients were interviewed before and 2 weeks after CTC to assess preparation acceptance. CTC was feasible and technically successful in all the 136 patients. Fecal tagging was judged as excellent in 113 (83%) patients and sufficient in 23 (17%). Average CT image interpretation time was 14.8 min. Six (4.4%) cases of colorectal cancer and nine (6.6%) large polyps were detected, as well as 23 (11.3%) extracolonic findings of high clinical importance. No major side effect occurred, although 25% patients reported minor side effects, especially diarrhea. Overall, 76/98 patients replied that they would be willing to repeat the test if necessary. CTC without cathartic preparation is a technically feasible and safe procedure to complete a colonic study in the elderly, prompting its use in clinical practice.

[Clinical experience in surgical-orthodontic treatment of patients with anterior skeletal open-bite]. / Esperienze cliniche nel trattamento ortodontico-chirurgico dei pazienti con open-bite dentoscheletrico anteriore.

After a short clinical classification of the various open-bite types, the Authors describe from the clinical and cephalometric point of view the main structural alterations responsible for the skeletal open-bite. Then they consider the orthodontic problems in the orthodontic surgical treatment of the skeletal open-bite. Finally they describe the combined orthodontic surgical treatment in two anterior skeletal open-bite clinical cases.

[Tooth extraction in surgical orthodontic treatment of malformations of the facial mass]. / Le estrazioni dentali nel trattamento ortodontico chrirugico delle malformazioni del massiccio facciale.

In the present article the Authors take under consideration the most important role of the presurgical orthodontic treatment from the point of view of the orthodontic techniques which aim to improve the occlusion. The authors, therefore describe the different faces, and they focalize the fact that the therapy may frequently require extractions to resolve serious crowdings of the teeth. They take also care of the maxillo facial skeleton alterations, to decide on extracting and about the ratio between the space available and required in the different cases.

Assessment of erythrocyte deformability with the laser-assisted optical rotational cell analyzer (LORCA).

The erythrocyte deformability of 28 patients with anemia was evaluated with the laser-assisted optical rotational cell analyzer (LORCA), an image analyzer that converts into numerical form the degree of refraction of a laser beam induced by red cells subjected to a range of torsional stresses. The patients were 10 thalassemics, including three with intermediate forms (1 HbC/beta degree, 1 homozygote beta for Orkin's haplotype VI, 1 beta degree/beta delta Sicilian type) and seven heteroygotes for beta Th; six with hereditary spherocytosis (including 2 with structural alteration of the spectrin beta chain); three with type II congenital dyserythropoietic anemia (HEMPAS), two hemizygotes and one heterozygote for G-6PD deficiency, and six with severe hypochromic hyposideremic anemia. Red cell deformability was reduced in intermediate thalassemia, hereditary spherocytosis and HEMPAS, normal in heterozygous beta thalassemia and G-6PD deficiency, and increased in hypochromic hyposideremic anemia. These results show that erythrocyte deformability can be impaired by an Hb chain imbalance, membrane and cyto skeleton structure anomalies and changes in the red cell area/volume ratio.

[Use of the Frankel functional regulator in Class II, div. 1]. / Esperienze cliniche sull'uso del regolatore di funzione di Frankel nelle II Classi, div. 1.

Frankel's Fr is an activator particularly suitable in malocclusions of II/1 Class in the age of growth. Such device can be also utilized in combination with the fixed multibands therapy in such a way as to connect the effects of the morphofunctional modifications, gettable with activator during the growth of the (effects) maxillary-mandibolar set, to orthodontic ones, of the fixed equipment employed in a successive stage for the perfecting of occlusive connection. For this reason the AA. analyze the applications of Frankel's FR in the treatment of the II/1 Classe in the age of growth. The Authors present three clinical cases, the first is resolved through functional therapy with Frankel's FR, while in the second and third cases at first is made use of functional therapy with FR and afterwards is made use of multi-bands therapy according to Edgewise's technique.

[Clinical picture and orthodontic-surgical therapeutic problems in treatment of Class II division 1 dento-skeletal malformations]. / Inquadramento clinico e problematiche terapeutiche ortodontico-chirurgiche nel trattamento delle malformazioni dento-scheletriche di II Classe 1 divisione.

In the present study different types of Class II, Division 1 malocclusions have been taken under consideration. First of all, have been analysed the main etiopathogenetic factors which are the causes of an anomalous development of the Maxillo-Facial complex. It has been pointed out the clinical characteristics of these malformations, necessaries for a careful therapeutical program. The Authors, therefore, in the first face describe the principal orthodontic problematics to tackle, in the second face they describe the surgical techniques mostly used to correct the Class II malocclusions; finally it has been pointed out the role of the orthodontic post-operative treatment, to improve the occlusion and the rehabilitation of the neuromuscular system after correcting maxillo facial skeleton alterations. Three cases are presented for this kind of malformation, treated with the various surgical techniques on the ground of the different kinds of clinical variants.

The roles of maternal alpha-catenin and plakoglobin in the early Xenopus embryo.

Catenins (alpha-, beta- and gamma- or plakoglobin) are cytoplasmic cadherin-associated proteins. Studies on cultured cells have suggested that both alpha-catenin and plakoglobin are important for the adhesive function of cadherins. alpha-catenin binds to both beta-catenin and plakoglobin and may link the cadherin/catenin complex to actin filaments. Separate domains of plakoglobin bind to cadherin and alpha-catenin, suggesting it may act as a bridge between these molecules. However, plakoglobin may have other activities: it is expressed in both desmosomal junctions in association with desmogleins and the cytoplasm in conjunction with APC, and previous work suggests it may act in a dorsal signalling pathway when overexpressed in Xenopus embryos. Here, we have studied the roles of alpha-catenin and plakoglobin directly, by depleting the maternal mRNAs coding for each of them in developing Xenopus embryos. We find that depletion of maternal alpha-catenin causes the loss of intercellular adhesion at the blastula stage, similar to that reported previously for EP cadherin. Depletion of plakoglobin results in a partial loss of adhesion, and a loss of embryonic shape, but does not affect dorsal signalling.