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Biomedical subjects

G D'Angelo

Publications and source records attributed to G D'Angelo.

At least 19 recordsLinked to original sources

Performance of a neutron spectrometer based on a PIN diode.

The neutron spectrometer discussed in this work consists of a PIN diode coupled with a polyethylene converter. Neutrons are detected through the energy deposited by recoil-protons in silicon. The maximum detectable energy is -6 MeV and is imposed by the thickness of the fully depleted layer (300 microm for the present device). The minimum detectable energy which can be assessed with pulse-shape discrimination (PSD) is -0.9 MeV. PSD is performed with a crossover method and setting the diode in the 'reverse-injection' configuration (i.e. with the N+ layer adjacent to the converter). This configuration provides longer collection times for the electron-hole pairs generated by the recoil-protons. The limited interval of detectable energies restricts the application of this spectrometer to low-energy neutron fields, such as the ones which can be produced at facilities hosting low-energy ion accelerators. The capacity to reproduce continuous neutron spectra was investigated by optimising the electronic chain for pulse-shape discrimination. In particular, the spectrometer was irradiated with neutrons that were generated by striking a thick beryllium target with protons of several energies and the measured spectra were compared with data taken from the literature.

Equipment Design↗

A recoil-proton spectrometer based on a p-i-n diode implementing pulse-shape discrimination.

A recoil-proton spectrometer was created by coupling a p-i-n diode with a polyethylene converter. The maximum detectable energy, imposed by the thickness of the totally depleted layer, is approximately 6 MeV. The minimum detectable energy is limited by the contribution of secondary electrons generated by photons in the detector assembly. This limit is approximately 1.5 MeV at full-depletion voltage and was decreased using pulse-shape discrimination. The diode was set up in the 'reverse-injection' configuration (i.e. with the N+ layer adjacent to the converter). This configuration provides longer collection times for the electron-hole pairs generated by the recoil-protons. The pulse-shape discrimination was based on the zero-crossing time of bipolar signals from a (CR)2-(RC)2 filter. The detector was characterised using monoenergetic neutrons generated in the Van De Graaff CN accelerator at the INFN-Laboratori Nazionali di Legnaro. The energy limit for discrimination proved to be approximately 900 keV.

Body Burden↗

Identification of genetic alterations related to chemoresistance in epithelial ovarian cancer.

OBJECTIVE: After the completion of primary chemotherapy, the majority of advanced ovarian cancer patients have persistent, chemoresistant disease. Comparative genomic hybridization (CGH) has been used to study genetic alterations that may be responsible for chemoresistance in ovarian cancer. CGH is a useful, genomewide screen but resolution is limited to 5-10 Mb. Recently, quantitative microsatellite analysis (QuMA), a TaqMan-based quantitative PCR technology, has been used for higher resolution of DNA copy number abnormalities. Our goal is to identify specific chromosomal aberrations correlated with platinum resistance. METHODS: Snap-frozen ovarian tissue samples taken from 22 patients with ovarian cancer between 1994 and 1998 were analyzed. Patients whose ovarian cancer actually demonstrated growth during platinum-combination treatment or no objective evidence of regression following four to six cycles of therapy were considered to have clinically defined platinum-resistant disease. QuMA was carried out at the following loci using the ABI Prism 7700 (TaqMan) instrument with a microsatellite repeat probe: D3S1553, D3S1617, D5S464, D5S630, D6S1581, D6S446, D8S557, D19S208, D20S196, DXS1068. Fisher's exact test, exact logistic regression, and the Cochran-Armitage trend test were used. Because of multiple hypothesis testing, the P values were adjusted with the Bonferroni procedure to limit the familywise error rate to at most 5%. RESULTS: Of the 22 patients, 12 (54.5%) were platinum-sensitive and 10 (45.5%) were platinum-resistant. When comparing sensitive and resistant patients, no statistically significant difference was noted among stage, grade, histology, and age (P = 0.1292, P = 1.0000, P = 1.0000, P = 1.0000, respectively). In the QuMA analysis, 10 of the 14 (71.4%) patients who had a low copy number of D6S1581 were platinum-resistant, while none of the patients with a normal or high copy number of D6S1581 were platinum-resistant. This was statistically significant when the marker data were treated as either a continuous or a categorical variable (P = 0.0410 and P = 0.0170, respectively). No other loci correlated significantly with platinum resistance. CONCLUSIONS: D6S1581 was the only genetic marker, of those examined, significantly related to chemoresistance. Patients with a loss of D6S1581 are more likely to be platinum-resistant. Identification of genetic alterations associated with platinum resistance detected by QuMA may contribute to a better understanding of clinical behavior and chemotherapy treatment options for patients.

Adenocarcinoma↗

[Treatment of childhood obesity. Long-term outcome and predictive factors of success in a group of 130 subjects].

BACKGROUND: In the last years the prevalence of childhood obesity has notably increased. The treatment of this condition is very difficult, because of the frequent relapses. The aim of our study was to examine the long-term outcomes of different dietary treatments (1200 or 1400 calories or chetogenic diet, derived from the protein sparing modified fast) in children and adolescents with primary obesity, in order to show factors predictive of the long-term success. METHODS: A group of 130 obese children previously undergoing a dietary treatment have been re-evaluated after a 3, 5 and 7 years period from the beginning of the diet. RESULTS: Ninety-seven out of 130 contacted patients (52 males and 45 females; mean age: 16+/-3 years) participated in this study. An overall improvement of the weight indexes has been observed (relative DBMI mean value: -10.5%). About 1/5 of the whole study-group is not overweight anymore. The statistical analysis (ANOVA and multiple regression analysis) showed that the factors positively affecting the long-term outcome were the following: use of chetogenic diet, initial success of the treatment, older age and strong motivation at the beginning of the diet, gender (male) and lack of familiarity for obesity. CONCLUSIONS: It is important, in the clinical practice, to consider the above factors that can predict the long-term success of the dietary treatment, in order to individualize the therapy.

Body Mass Index↗

A feasibility study of a single event spectrometer based on semiconductor devices.

The electronics employed around particle accelerators can be disturbed or damaged because of single event effects (SEE). The most likely effect is the single event upset (SEU) which may affect all memory devices. In the case of high energy accelerators, SEUs are mostly produced by secondary charged particles generated by neutron interactions. The measurement of the energy and the lineal energy distribution of these neutron-induced charged particles was proposed. As a first approach, a commercial p-i-n photodiode was employed. This device was irradiated with thermal and monoenergetic fast neutrons. Some effects limiting the use of such a detector as a SEE spectrometer were observed, giving guidelines for the design of an application specific integrated circuit (ASIC). The possibility of creating a solid state microdosemeter by coupling the ASIC with a tissue-equivalent radiator is discussed. Moreover, the p-i-n photodiode covered with a hydrogenated plastic radiator may be employed as a proton-recoil spectrometer.

Dose-Response Relationship, Radiation↗

A phase I/II study of hypofractionated whole abdominal radiation therapy in patients with chemoresistant ovarian carcinoma: Karnofsky score determines treatment outcome.

PURPOSE: Radiation therapy can provide useful palliation in chemorefractory ovarian cancer patients. The purpose of this study was to prospectively study the palliative effect of a hypofractionated radiation treatment regimen. Change in quality-of-life scores (Functional Assessment of Cancer Therapy [FACT], Karnofsky scale), pain score, and tolerance to therapy were also assessed. METHODS AND MATERIALS: A single-institution Phase I/II trial was initiated in patients with chemoresistant recurrent or progressive ovarian cancer. All patients had symptomatic and measurable intra-abdominal disease. Patients were treated with a single radiation fraction (700 cGy) or two fractions (300 cGy twice a day) to the whole abdomen over 1 day. Quality-of-life scale (FACT G version 2) was assessed at baseline and 1 and 3 months following treatment. Karnofsky scale and pain score were also evaluated in the same time frame. RESULTS: Sixteen patients were prospectively entered into this protocol between February 1996 and September 1998. Twelve patients received a single 700 cGy fraction and four 300 cGy twice a day. All were heavily pretreated and 9 (56%) had a poor performance status prior to treatment. Symptoms needing palliation included pain (14), ascites (10), and bleeding (2). Symptomatic improvement occurred in all patients with pain (5 complete response [CR] and 7 partial response [PR], all patients with bleeding (CR 2), and two (20%) with ascites. Five patients (31%) had a reduction in lesion size documented radiologically in three. The mean duration of response was 22 weeks in patients with a Karnofsky score >70. Thirteen patients developed transient nausea and vomiting which resolved in 48 hours in all. All patients developed a transient lymphopenia. Thirteen patients completed a follow-up quality-of-life scale. There was an improvement in the physical and functional components of the scale in patients with Karnofsky score of 90-100. There was no improvement in quality of life in patients with Karnofsky score <90 despite symptomatic response. Median survival was 3 months from the date of treatment. CONCLUSION: Hypofractionated radiation therapy is an effective palliative treatment for end-stage ovarian cancer patients. Karnofsky score can help determine the duration of response and survival for this high-risk population.

Adult↗

Hypoxia-induced transcriptional activation of vascular endothelial growth factor is inhibited by serum.

Expression of vascular endothelial growth factor (VEGF) by cultured vascular smooth muscle cells was analyzed. Serum and hypoxia had nearly additive actions on VEGF mRNA expression. The function of the VEGF promoter in smooth muscle cells was analyzed using transient luciferase reporter assays. Serum and hypoxia stimulated expression of luciferase. The presence of hypoxia response element (HRE) was necessary for the hypoxic induction. AP-1 sequences located upstream of HRE and AP-2/Sp-1 sequences located downstream of HRE are not necessary. Hypoxic responses were best observed in serum-deprived cells. They were largely absent in serum-stimulated cells. Serum did not suppress the hypoxic response by interfering with the hypoxia sensor mechanism or with the signaling cascade that leads to the activation of HIF-1. It is concluded that growth-promoting cytokines regulate hypoxic gene induction in smooth muscle cells.

Animals↗

[Meniscal injuries of the knee. Diagnostic imaging].

Nowadays, treatment of meniscal tears is conservative with removal only of the broken part of meniscus. For this reason, before arthroscopy, the orthopaedic surgeon needs for an accurate preoperative diagnosis that could be obtained with computed tomography (CT) and magnetic resonance (MR). Our purpose is to value the actual role of CT and MR in diagnosis of meniscal tears. We retrospectively evaluated CT and MR images of 128 patients (average age 32 years) who then underwent arthroscopy. On the basis of our findings CT and MR have been shown to be very accurate to detect meniscal tears, even if with both methodics false positives and false negatives are possible. Nevertheless, MR is able to give high resolution multiplanar images without using ionising radiations and is preferable because of its high accuracy in recognising associated lesions of ligaments or articular cartilage.

Adolescent↗

Mammal-specific, ERK-dependent, caldesmon phosphorylation in smooth muscle. Quantitation using novel anti-phosphopeptide antibodies.

Extracellular signal-regulated kinases (ERKs) phosphorylate the high molecular mass isoform of the actin-binding protein caldesmon (h-CaD) at two sites (Ser(759) and Ser(789)) during smooth muscle stimulation. To investigate the role of phosphorylation at these sites, antibodies were generated against phosphopeptides analogous to the sequences around Ser(759) and Ser(789). Affinity-purified antibodies were phosho- and sequence-specific. The major site of phosphorylation in h-CaD in porcine carotid arterial muscle strips was at Ser(789); however, the amount of phosphate did not vary appreciably with either KCl or phorbol ester stimulation. Phosphorylation at Ser(759) of h-CaD was almost undetectable (<0.005 mol of phosphate/mol of protein). Moreover, phosphorylation of the low molecular mass isoform of the protein (l-CaD) at the site analogous to Ser(789) was greater in serum-stimulated cultured smooth muscle cells than in serum-starved cells. Serum-stimulated l-CaD phosphorylation was attenuated by the protein kinase inhibitor PD98059. These data 1) identify Ser(789) of h-CaD as the major site of ERK-dependent phosphorylation in carotid arteries; 2) show that the level of phosphorylation at Ser(789) is relatively constant following carotid arterial muscle stimulation, despite an increase in total protein phosphate content; and 3) suggest a functional role for ERK-dependent l-CaD phosphorylation in cell division.

Amino Acid Sequence↗

Opposing actions of intact and N-terminal fragments of the human prolactin/growth hormone family members on angiogenesis: an efficient mechanism for the regulation of angiogenesis.

Angiogenesis, the process of development of a new microvasculature, is regulated by a balance of positive and negative factors. We show both in vivo and in vitro that the members of the human prolactin/growth hormone family, i.e., human prolactin, human growth hormone, human placental lactogen, and human growth hormone variant are angiogenic whereas their respective 16-kDa N-terminal fragments are antiangiogenic. The opposite actions are regulated in part via activation or inhibition of mitogen-activated protein kinase signaling pathway. In addition, the N-terminal fragments stimulate expression of type 1 plasminogen activator inhibitor whereas the intact molecules have no effect, an observation consistent with the fragments acting via separate receptors. The concept that a single molecule encodes both angiogenic and antiangiogenic peptides represents an efficient model for regulating the balance of positive and negative factors controlling angiogenesis. This hypothesis has potential physiological importance for the control of the vascular connection between the fetal and maternal circulations in the placenta, where human prolactin, human placental lactogen, and human growth hormone variant are expressed.

Allantois↗

16K human prolactin inhibits vascular endothelial growth factor-induced activation of Ras in capillary endothelial cells.

Signaling pathways mediating the antiangiogenic action of 16K human (h)PRL include inhibition of vascular endothelial growth factor (VEGF)-induced activation of the mitogen-activated protein kinases (MAPK). To determine at which step 16K hPRL acts to inhibit VEGF-induced MAPK activation, we assessed more proximal events in the signaling cascade. 16K hPRL treatment blocked VEGF-induced Raf-1 activation as well as its translocation to the plasma membrane. 16K hPRL indirectly increased cAMP levels; however, the blockade of Raf-1 activation was not dependent on the stimulation of cAMP-dependent protein kinase (PKA), but rather on the inhibition of the GTP-bound Ras. The VEGF-induced tyrosine phosphorylation of the VEGF receptor, Flk-1, and its association with the Shc/Grb2/Ras-GAP (guanosine triphosphatase-activating protein) complex were unaffected by 16K hPRL treatment. In contrast, 16K hPRL prevented the VEGF-induced phosphorylation and dissociation of Sos from Grb2 at 5 min, consistent with inhibition by 16K hPRL of the MEK/MAPK feedback on Sos. The inhibition of Ras activation was paralleled by the increased phosphorylation of 120 kDa proteins comigrating with Ras-GAP. Taken together, these findings show that 16K hPRL inhibits the VEGF-induced Ras activation; this antagonism represents a novel and potentially important mechanism for the control of angiogenesis.

Biological Transport↗

Regulation of vascular endothelial growth factor expression by cAMP in rat aortic smooth muscle cells.

Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen which stimulates angiogenesis. VEGF is regulated by multiple factors such as hypoxia, phorbol esters, and growth factors. However, data concerning the expression of VEGF in the different vascular cell types and its regulation by cAMP are not available. In the present study, we have investigated the effect of adenylate cyclase activation on VEGF mRNA expression in rat vascular cells in primary culture. Basal VEGF expression is greater in smooth muscle cells than in endothelial cells and fibroblasts. A 4-h treatment with forskolin (10(-5) M) induced a 2-fold stimulation of VEGF mRNA expression in smooth muscle cells and fibroblasts, but, in contrast, did not affect VEGF expression in endothelial cells. In smooth muscle cells, a pharmacologically induced increase in intracellular cAMP levels using iloprost or isoprenaline led to a rise in VEGF mRNA expression comparable to that induced by forskolin. Adenosine, which increases cAMP levels in smooth muscle cells, also increases VEGF expression. Moreover, the 2.2-fold stimulation of VEGF expression by adenosine was enhanced following a cotreatment with cobalt chloride (a hypoxia miming agent). The observed additive effect (4.3-fold increase) suggests that these two factors, hypoxia and adenosine, regulate VEGF mRNA expression in smooth muscle cells by independent mechanisms.

1-Methyl-3-isobutylxanthine↗

Hyde's prurigo nodularis and chronic HCV hepatitis.

The authors describe a woman with chronic active hepatitis, Hyde's prurigo nodularis and hepatitis C virus infection. The association of these three pathologies and their parallel evolution during treatment suggest a possible pathogenic link between the chronic hepatitis C virus infection and the skin disease.

Female↗

[Probiotics in childhood].

The Probiotics (Lactic acid bacteria) represent a nutritional live microbial supplement that positively affects host by enhancing the microbial balance. A survey is made of the most relevant studies concerning the use of probiotics in the prevention and treatment of infantile acute diarrhoea (by rotavirus or other agents), pseudomembranous colitis, hospital-acquired and antibiotic-associated diarrhoeas. Although the probiotics mechanism of action is not yet completely understood, it has been hypothesized that they exert an inhibitory effect on the intestinal inflammation by immune response modulation. Due to this property, the use of probiotics has therefore been suggested in other severe diseases such as chronic inflammatory bowel diseases, rheumatoid arthritis, food allergy, atopic dermatitis and as immunoadjuvant for oral vaccines.

Child↗

[Hemophagocytic syndrome in a patient with anemia and liver pathology].

A case of 62-year old female with history of alcohol abuse, anemia and hepatopathy is reported. The bone marrow aspiration showed the increase of the histiocytes without morphological alteration but with increased hemophagocytic activity compatible with hemophagocytic syndrome. The case is reported because, beyond of the diagnostic guideline, the hemophagocytic syndrome can be considered still a morphological diagnosis.

Anemia↗

cAMP-dependent protein kinase inhibits the mitogenic action of vascular endothelial growth factor and fibroblast growth factor in capillary endothelial cells by blocking Raf activation.

Proliferation of endothelial cells is regulated by angiogenic and antiangiogenic factors whose actions are mediated by complex interactions of multiple signaling pathways. Both vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) stimulate cell proliferation and activate the mitogen-activated protein kinase (MAPK) cascade in bovine brain capillary endothelial (BBE) cells. We have extended these findings to show that both mitogens activate MAPK via stimulation of Raf-3. Activation of Raf/MAPK is inhibited by increasing intracellular cAMP levels pharmacologically or via stimulation of endogenously expressed beta-adrenergic receptors. Both VEGF- and bFGF-induced Raf-1 activity are blocked in the presence of forskolin or 8-bromo-cAMP by 80%. The actions of increased cAMP appear to be mediated by cAMP-dependent protein kinase (PKA), since treatment with H-89, a the specific inhibitor of PKA, reversed the inhibitory effect of elevated cAMP levels on mitogen-induced cell proliferation and Raf/MAPK activation. Moreover, elevations in cAMP/PKA activity inhibit mitogen-induced cell proliferation. These findings demonstrate, in cultured endothelial cells, that the cAMP/PKA signaling pathway is potentially an important physiological inhibitor of mitogen activation of the MAPK cascade and cell proliferation.

1-Methyl-3-isobutylxanthine↗

Integrin-mediated reduction in vascular smooth muscle [Ca2+]i induced by RGD-containing peptide.

It has previously been shown that synthetic peptides containing the sequence arginine-glycine-aspartic acid (RGD) cause vasodilation by activation of alpha(v)beta3-integrin present on vascular smooth muscle (VSM) cells. The purpose of this study was to determine whether this dilatory effect is mediated by a reduction in VSM cytosolic Ca2+ concentration ([Ca2+]i). First-order arterioles from the rat cremaster were isolated, cannulated, and pressurized. [Ca2+]i was quantitated from the ratio of emitted fluorescence intensity during alternate excitation of fura 2-loaded vessels at 340 and 380 nm. Cyclo(-Arg-Gly-Asp-D-Phe-Val) (cycloRGD; 0.21-210 microM) produced a concentration-dependent dilation of arterioles that had developed basal myogenic tone. Over the entire concentration range tested, [Ca2+]i decreased from 91 +/- 6 to 27 +/- 4 nM (69.7 +/- 5.0% reduction). In association with the decrease in [Ca2+]i, arteriolar lumen diameter increased from 89 +/- 8 to 184 +/- 8 pm (89.8 +/- 1.8% dilation). At intermediate concentrations, cycloRGD induced rhythmic spiking of Ca2+ superimposed on the concentration-dependent lowering of basal [Ca2+]i. These data directly link integrin activation with alterations in Ca2+ regulation, the net effect of which is a reduction in [Ca2+]i. These data further suggest that integrins, through their role in mediating cellular attachment to the extracellular matrix and in cellular signaling involving Ca2+, could provide a logical link to mechanotransduction and myogenic phenomena.

Acetylcholine↗