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Biomedical subjects

E Castellano

Publications and source records attributed to E Castellano.

At least 19 recordsLinked to original sources

Transcriptional networks of knockout cell lines identify functional specificities of H-Ras and N-Ras: significant involvement of N-Ras in biotic and defense responses.

We characterized differential gene expression profiles of fibroblast cell lines harboring single or double-homozygous null mutations in H-ras and N-ras. Whereas the expression level of the individual H-, N- and K-ras genes appeared unaffected by the presence or absence of the other ras loci, significant differences were observed between the expression profiles of cells missing N-ras and/or H-ras. Absence of N-ras produced much stronger effects than absence of H-ras over the profile of the cellular transcriptome. N-ras(-/-) and H-ras(-/-) fibroblasts displayed rather antagonistic expression profiles and the transcriptome of H-ras(-/-) cells was significantly closer to that of wild-type fibroblasts than to that of N-ras(-/-) cells. Classifying all differentially expressed genes into functional categories suggested specific roles for H-Ras and N-Ras. It was particularly striking in N-ras(-/-) cells the upregulation of a remarkable number of immunity-related genes, as well as of several loci involved in apoptosis. Reverse-phase protein array assays demonstrated in the same N-ras(-/-) cells the overexpression and nuclear migration of tyrosine phosphorylated signal transducer and activator of transcription 1 (Stat1) which was concomitant with transcriptional activation mediated by interferon-stimulated response elements. Significantly enhanced numbers of apoptotic cells were also detected in cultures of N-ras(-/-) cells. Our data support the notion that different Ras isoforms play functionally distinct cellular roles and indicate that N-Ras is significantly involved in immune modulation/host defense and apoptotic responses.

Animals↗

Southern Ocean sea-ice extent, productivity and iron flux over the past eight glacial cycles.

Sea ice and dust flux increased greatly in the Southern Ocean during the last glacial period. Palaeorecords provide contradictory evidence about marine productivity in this region, but beyond one glacial cycle, data were sparse. Here we present continuous chemical proxy data spanning the last eight glacial cycles (740,000 years) from the Dome C Antarctic ice core. These data constrain winter sea-ice extent in the Indian Ocean, Southern Ocean biogenic productivity and Patagonian climatic conditions. We found that maximum sea-ice extent is closely tied to Antarctic temperature on multi-millennial timescales, but less so on shorter timescales. Biological dimethylsulphide emissions south of the polar front seem to have changed little with climate, suggesting that sulphur compounds were not active in climate regulation. We observe large glacial-interglacial contrasts in iron deposition, which we infer reflects strongly changing Patagonian conditions. During glacial terminations, changes in Patagonia apparently preceded sea-ice reduction, indicating that multiple mechanisms may be responsible for different phases of CO2 increase during glacial terminations. We observe no changes in internal climatic feedbacks that could have caused the change in amplitude of Antarctic temperature variations observed 440,000 years ago.

Calcium↗

Chemical composition and physical features of summer aerosol at Terra Nova Bay and Dome C, Antarctica.

During the 2002-2003 austral summer field season, aerosol samples were collected at a coastal (Terra Nova Bay--Northern Victoria Land) and an inland site (Dome C--East Antarctic Plateau). The sampling was carried out by stacked filter units made up of two filters at different porosity (5.0 and 0.4 microm at Terra Nova Bay and 3.0 and 0.4 microm at Dome C), able to roughly separate a coarse from a fine fraction. At Dome C, a further investigation on aerosol size distribution was performed by an inertial impactor able to collect aerosol particles on 8 size classes (from 10 to 0.4 microm). Atomic Force Microscopy was applied to the filter collecting the finer fraction in both sites in order to assess the real cut-off value of the filter sandwich apparatus and to reconstruct the volume size distribution. At the employed flow conditions, the real cut-off value was revealed to be about one third with respect to the filter nominal porosity in both stations. The size distribution plots showed a bimodal distribution with a mode centered around 0.22 microm in both the sites and a second broader mode which is centered between 0.3 microm and 1.2 microm diameter at Terra Nova Bay and shifted toward higher values (centred around 1.0 microm diameter) at Dome C. Each filter was analysed for the main and trace ionic components allowing evaluation of the contributions of primary and secondary aerosol sources at the two sites as a function of the particle size class. The coastal site is mainly affected by primary and secondary marine inputs: the sea spray contribution (Na+, Mg2+, Cl- and ssSO4(2-)) is dominant (77% w/w) in the coarse fraction whereas the biogenic source (methanesulfonate and nssSO4(2-)) prevails (67.5% w/w) in the fine fraction. In this fraction a significant contribution (15.5% w/w) is provided by ammonium likely to be related to surrounding penguin colonies. Dome C atmosphere is characterised by fine particles arising from secondary sources and long-range transport processes. The main component in the fine and coarse fractions at Dome C is sulfate whose nssSO4(2-) represents the 99.5% and the 92.3%(w/w) in fine and coarse fraction, respectively. The observed agreement between nssSO4(2-) and methanesulfonate temporal profiles in the fine fraction demonstrates that biogenic emissions dominate the inland background aerosol. Results from the sampling by the 8-stage impactor at Dome C are presented here: chloride and nitrate are mainly deposited on the 10-2.1 microm stages while the highest sulfate concentration was found in the submicrometric fraction which turned out to be the most acidic. Such a distribution is able to prevent nitrate and chloride re-emission as gaseous HCl and HNO3 in the 10-2.1 microm stages, arising from the exchange reaction between chloride and nitrate salts and sulfuric acid. Moreover, the concentration peak observed for nitrate in coarser fractions is probably related also to the formation of hygroscopic NH4NO3 particles and nitrate adsorption on sea salt particles.

Aerosols↗

Sensitization to food or inhalant allergens in pediatric patients. Clinical usefulness of first-level panel tests for specific IgE.

First-level in vitro diagnostic tests for specific IgE against common inhalant or food allergens have been used to identify allergic patients. We evaluated the performance of Phadiatop and Fx5 (mixed food allergens) serological tests (Pharmacia Diagnostics AB, Uppsala, Sweden) in different groups of pediatric patients. We studied two groups of pediatric patients: 61 children recruited from an Allergy and Clinical Immunology Unit (Group 1); 136 children from a Pediatric Unit not specifically devoted to allergic diseases (Group 2); the two groups comprised patients with (A) or without (B) clinical suspicion of allergic disease. Sera were collected from routine blood analysis. Frequencies of positivities for Phadiatop and/or Fx5 were very high (68.8%) in Group 1, however, as many as 35.5% of Group 2 children were positive, as well. All the patients of Group 1 with clinical suspicion of allergic disease (1A), confirmed by allergologic diagnostic tests, had a positive first-level test; 42.8% only of the patients in Group 2 with suspicion of allergic disease (2A) had a positive first-level test. None of the Phadiatop/Fx5-negative children of Group 2A had specific-IgE with conventional tests. In 30% of children not suspected for allergic diseases (1B and 2B), positive first-level tests were observed. Such unexpected positivities were confirmed by single specific-IgE assays in 94.7% (for inhalants) or 71% (for foods) of cases. In conclusion, altogether the sensitivity and overall performance of first-level tests in pediatric populations (especially for inhalant allergens) may suggest their use, under appropriate circumstances, both as a first diagnostic approach (to rule out negative patients) and for screening purposes.

Administration, Inhalation↗

Severe attack of ulcerative colitis in children: retrospective clinical survey.

AIM: To obtain clinical data concerning severe attacks of ulcerative colitis in children. PATIENTS AND METHODS: A retrospective chart review of 37 children with ulcerative colitis was carried out in order to assess the prevalence, risk factors, timing of presentation, and outcome of severe attacks of ulcerative colitis. RESULTS: A total of 20 severe attacks occurred in 15 out of the 37 patients. No difference in the occurrence of severe attacks was detected in relation to age or disease extent at diagnosis. The mean interval between disease diagnosis and a severe attack was 9.1 months (range 0-30). Of the 20 severe attacks, 11 were resolved with medical treatment in a mean time of 1 1 +/- 4.6 days while 9 out of 20 needed urgent surgery in a mean time of 7.4 +/- 4.8 days. Of 10 out of the 15 patients who recovered from the first attack 4 required colectomy after a mean time of 6.7 months, another 4 are still in remission at a mean period of 40.7 months, one needed elective surgery after 25 months and one was lost to follow-up. CONCLUSIONS: Severe attacks of ulcerative colitis had a high prevalence rate [40%); age and disease extent at presentation were not predictors of their occurrence. Approximately half the attacks resolved with medical treatment alone, while the other half required emergency surgery. After successful medical treatment of the first attack, 40% of children maintained long-term remission, while 40% required early colectomy

Adolescent↗

Acute pancreatitis in children. An Italian multicentre study.

AIM: To evaluate the clinical, morphological and aetiological aspects of acute pancreatitis in children in Italy. PATIENTS: The hospital records of 50 consecutive patients with acute pancreatitis observed in 5 Italian Pediatric Departments were reviewed. RESULTS: A total of 25 males and 25 females (median age 10.5 years, range 2-17) were studied. Of these patients, 48 (96%) had abdominal pain. The pancreatitis was associated with biliary disease in 10 patients (20%); it was due to viral infection in 6 patients (12%), pancreatic duct abnormalities in 4 (8%, familial chronic pancreatitis in 3 (6%), trauma in 5 (10%) and other causes in 5 (10%); the pancreatitis was of unknown origin in 17 patients (34%). Previous attacks of the disease had occurred in 14 patients. A diagnosis of mild pancreatitis was made in 41 patients (82%) and of severe disease in 9 (18%). One patient with severe pancreatitis died from multiorgan failure. Patients with severe pancreatitis had significantly higher serum concentrations of C-reactive protein than patients with mild pancreatitis. Hospital stay was similar for patients with the mild form and those with the severe form of the disease. CONCLUSIONS: In Italian children, acute pancreatitis is of unknown origin in about one-third of the children and is recurrent in 28% of the cases. The disease is severe in 18% of the cases.

Acute Disease↗

Pregnancy and tyrosinaemia type II.

A female patient with tyrosinaemia type II is reported having undergone two untreated pregnancies. During pregnancies, plasma tyrosine was raised. The outcomes of both offspring show that maternal tyrosinaemia may have an adverse effect on the developing fetus.

Adult↗

The use of ciclosporin in paediatric inflammatory bowel disease: an Italian experience.

AIM: To asses the efficacy and safety of ciclosporin in a paediatric population with inflammatory bowel disease. PATIENTS AND METHODS: Twenty-three Italian children treated with ciclosporin were studied retrospectively. The indications for treatment were severe unresponsive colitis, chronic active colitis or severe fistulizing Crohn's disease. The treatment duration, follow-up and causes of drug discontinuation were assessed. RESULTS: Sixteen patients were treated intravenously for a mean time of 10 +/- 7 days (1-24 days) and 19 orally for a mean time of 133 days (17-660 days). The mean follow-up of all patients was 13.2 months. Ciclosporin was totally ineffective, being discontinued for surgery, in nine of 23 patients (39%); it was discontinued for partial response in three patients (13%). During treatment, clinical remission was achieved in eight children (35%) and maintained after drug withdrawal in four (17%). In severe unresponsive colitis, urgent colectomy was avoided in 12 (85%) of 14 patients who tolerated the drug. Side-effects appeared in six of 23 patients (26%), and three (13%) required ciclosporin to be discontinued due to neurotoxicity. CONCLUSIONS: Ciclosporin shows disappointing long-term results in the treatment of refractory inflammatory bowel disease, but can play an important role in preventing urgent surgery in unresponsive severe colitis. Severe side-effects can occur.

Adolescent↗

Hepatitis A vaccine in pediatric patients affected by metabolic liver diseases.

Twenty children with a variety of metabolic liver diseases were given two doses of hepatitis A vaccine. Adverse reactions were mild. All subjects responded to vaccine with seroconversion to hepatitis A virus antibodies after the first dose, regardless of transaminase values, and had a booster effect from the second doses.

Adolescent↗

A girl with severe fistulizing Crohn's disease.

We report the case of a girl with a severe perianal fistulizing Crohn's disease who during intravenous infusion of cyclosporine developed headache, general seizures and cortical blindness. Head magnetic resonance imaging showed spread, cortical-subcortical nonenhancing signal changes. Full neurological recovery was achieved in 24 hours. Cyclosporine was stopped and a single dose of infliximab was infused with rapid improvement of the fistula that at 7 months' follow-up is still closed.

Brain Diseases↗

True hermaphroditism in a horned goat with 60XX/60XY chimerism.

Anatomical, behavioral, histological, endocrinological, and cytogenetic characteristics were determined in a horned intersex goat. Histology of the gonads confirmed that the goat was a true hermaphrodite. Cytogenetic analysis showed that it was a chimera (60XX/60XY). Use of laparoscopy allowed determination of characteristics of the internal gonads.

Animals↗

IgA antiendomysium antibodies in human umbilical cord sections as a screening test in relatives of patients with celiac disease.

We performed the serum IgA antiendomysium antibody (EmA) assay by indirect immunofluorescence on human umbilical cord sections in 86 subjects with celiac disease, in 187 first-degree relatives of such patients, and in a control group of 68 unrelated subjects, to investigate the suitability of the method in the screening of populations at risk of gluten sensitivity. Conventional EmA assay using monkey esophagus sections was performed in parallel experiments. The results obtained showed a perfect correlation between the two methods. All the celiac patients and none of the controls were positive for EmA. EmA positivity was also observed in 11 apparently healthy relatives: intestinal biopsy performed in five of them invariably showed villous atrophy and increase of mucosal lymphocytes. Taking into account the low cost of EmA assay on human umbilical cord, especially when compared to monkey esophagus sections, the method is probably suitable and effective in identifying latent, asymptomatic gluten sensitivity in at-risk populations.

Adolescent↗

Survival and antigenic profile of irradiated malarial sporozoites in infected liver cells.

Exoerythrocytic (EE) stages of Plasmodium berghei derived from irradiated sporozoites were cultured in vitro in HepG2 cells. They synthesized several antigens, predominantly but not exclusively those expressed by normal early erythrocytic schizonts. After invasion, over half the intracellular sporozoites, both normal and irradiated, appeared to die. After 24 h, in marked contrast to the normal parasites, EE parasites derived from irradiated sporozoites continued to break open, shedding their antigens into the cytoplasm of the infected host cells. Increasing radiation dosage, which has previously been shown to reduce the ability of irradiated sporozoites to protect animals, correlated with reduced de novo antigen synthesis by EE parasites derived from irradiated sporozoites.

Animals↗

[Ovarian and adrenal influence on the ontogenesis of uterine cytosol and nuclear receptors of estrogens].

Adrenal and ovarian relative influence over rat uterus estrogenic receptor, both cytosolic (RcE) and nuclear (RnE) ontogenesis, has been studied. Ovarian influence has been studied by practising bilateral ovariectomy the first day of life and examining estrogenic receptor content evolution from, birth to puberty in these ovariectomized animals (OVX1) by comparison with the normal ones. This influence seems to be of scarce importance until the 20th day of life, since estrogenic receptors content is practically coincident in the OVX1 animals and in the control ones. From the 20th day, ovarian secretion influence increases and estrogenic receptor evolution starts evolving in a different way in the two types of animals. Adrenal influence has been studied by practising bilateral adrenalectomy on the 10th or 30th day of life to OVX1 animals or else OVX and ADX on the 10th or 30th day. Adrenal influence in the upkeep of high estrogen receptor levels on the 10th day, seems to be important, since in the absence of these glands it decreases in a considerable way. The situation is different on the 30th day. At this age ovarian secretion seems to be the most important in maintaining estrogen receptor levels, while adrenal secretion effects tend to inhibit them, especially RnE.

Adrenal Glands↗