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Biomedical subjects

S Giordano

Publications and source records attributed to S Giordano.

At least 19 recordsLinked to original sources

Crimes and misdemeanours: the case of child abandonment.

In 2002, a child was abandoned in a Burger King restaurant in Amsterdam by a Chinese woman, who hoped that the baby would be picked up by someone able to give the child a better life. She was convicted for child abandonment and imprisoned. Whereas some forms of child abandonment are criminalised, others are socially accepted and not even on the ethics agenda. This paper is an invitation to reflect on the inconsistency in the ways in which we prosecute, punish or try to correct some forms of child abandonment and yet make allowances for others.

Abortion, Legal↗

Lichen and moss bags as monitoring devices in urban areas. Part I: influence of exposure on sample vitality.

Samples of the lichen Pseudevernia furfuracea (L.) Zopf and the moss Hypnum cupressiforme Hedw. were exposed for 6 weeks in nylon bags in two air pollution monitoring stations in Trieste and Naples (Italy) with different climates and pollution loads to evaluate influence of environmental conditions on sample vitality. This was assessed before and after exposure by transmission electron microscopy observations, K cellular location, and measurements of C, N, S and photosynthetic pigments content, CO2 gas exchange, and chlorophyll fluorescence. Almost all data sets indicate that exposures caused some damage to the species, considerably heavier in the moss, especially in Naples. The two cryptogams differed significantly in accumulation and retention of C, N, and S, the lichen clearly reflecting NO2 availability. The difference in vitality loss was related to the different ecophysiology of the species, because concentrations of phytotoxic pollutants were low during exposure. Critical notes on the analytical techniques are also given.

Air Pollutants↗

Lichen and moss bags as monitoring devices in urban areas. Part II: trace element content in living and dead biomonitors and comparison with synthetic materials.

Lobes of the lichen Pseudevernia furfuracea (L.) Zopf and shoots of the moss Hypnum cupressiforme Hedw. were subjected to different treatments (water washing, oven drying, HNO3 washing, NH4-oxalate extraction) to assess the influence of vitality on accumulation efficiency, during a 6-week exposure in bags in two Italian cities, Trieste and Naples. No trend emerged between treatments, in terms of accumulation ability, for major and trace elements. Only water-washed lichens showed an increased C and N content after exposure in both cities. Element concentrations generally reached higher values in mosses than in lichens, especially for Al, Fe, and Zn (both cities), and for Cu, Mg and Na (Naples). Surface development strongly influenced accumulation capacity of the biomonitors. Quartzose and cation exchange filters revealed, on a weight basis, a poor performance. In urban environments, surface interception of atmospheric particulate seems to play a major role in accumulation, irrespective of organism vitality.

Air Pollutants↗

Biphasic metaplastic sarcomatoid carcinoma of the breast.

BACKGROUND: Breast biphasic metaplastic sarcomatoid carcinoma (MSC) is rare and aggressive. We analyzed 100 patients treated at M. D. Anderson Cancer Center (MDACC) with 213 MSC and 98 carcinosarcoma patients identified through the Surveillance, Epidemiology and End-Results (SEER) database to describe clinical and pathologic characteristics. PATIENTS AND METHODS: We searched the MDACC (1985-2001) and SEER databases (1988-2001) for breast MSC and carcinosarcoma patients. RESULTS: We identified 100 MDACC MSC patients: 66% had node-negative disease and 6% distant metastases at presentation. Median recurrence-free survival (RFS) of 94 patients with stages I-III disease was 74 months (range 3-74), with 52% 5-year RFS [95% confidence interval (CI) 0.42-0.63]. Median overall survival in these patients was not reached, with 64% 5-year survival (95% CI 0.54-0.75). The initial stage of the tumor, but not use of adjuvant chemo- or radiotherapy, had a strong association with outcome. The pathologic complete response rate to neoadjuvant chemotherapy was 10%. Median survival from the time of recurrent disease was 14 months (range 1-55). Tumors were usually hormone receptor- and HER2/neu-negative. SEER data were consistent with MDACC findings. CONCLUSIONS: Breast MSC and carcinosarcoma are aggressive, treatment-refractory tumors with shared clinical features and outcome similar to poorly differentiated receptor-negative adenocarcinomas. New therapeutic agents are needed.

Adult↗

Pro-metastatic signaling by c-Met through RAC-1 and reactive oxygen species (ROS).

Overexpression of the c-Met/hepatocyte growth factor receptor(HGF-R) proto-oncogene and abnormal generation of intracellular oxygen species (reactive oxygen species (ROS)) have been linked, by independent lines of evidence, to cell transformation and to malignant growth. By comparing two subpopulations of the B16 mouse melanoma (B16-F0 and B16-F10) endowed with different lung metastasis capacities (low and high, respectively) we found that both the expression/phosphorylation of c-Met and the steady-state levels of ROS positively correlated with metastatic growth. shRNA-mediated downregulation of c-Met in F10 cells led to a parallel decrease in the generation of oxygen species and in metastatic capacity, suggesting that oxidants may mediate the pro-metastatic activity of the HGF receptor. c-Met activation by a ligand elicits the formation of oxidant species through the oxidase-coupled small GTPase Rac-1, a relevant downstream target of the HGF-R. Moreover, cell treatment with the catalytic ROS scavengers EUK-134 and EUK-189 attenuates Met signaling to ERKs and inhibits the anchorage-independent growth of F10 cells, consistent with a critical role for oxygen species in HGF signaling and in aggressive cell behavior. Finally, genetic manipulation of the Rac-ROS cascade at different levels demonstrated its crucial role in the pro-metastatic activity of c-Met in vivo. Thus, we have outlined a novel cascade triggered by c-Met and mediated by ROS, linked to metastasis and potentially targetable by new antimetastatic, redox-based therapies.

Animals↗

Induction of apoptosis of human primary osteoclasts treated with a transcription factor decoy mimicking a promoter region of estrogen receptor alpha.

In this paper we investigated how the increase of human estrogen receptor alfa (ERalpha) gene expression may affect breast, osteoblast and osteoclast cells. Increase of ERalpha expression was obtained by interfering with the activity of a negative transcription factor and by removing it with a short and powerful decoy oligonucleotide (RA4-3') mimicking a region of distal promoter C of ERalpha gene. We provide evidence that this decoy was able to induce apoptosis in osteoclasts, but not in osteoblasts and in breast cancer cells, in an estrogen dependent manner. This effect was associated with increase of the levels of Caspase 3 and Fas receptor. Since ERalpha is important in the transcription of different genes and is involved in several pathological processes, including neoplastic and osteopenic diseases, our findings may be of relevance for a possible new therapeutical approach of such diseases.

Apoptosis↗

Atmospheric trace metal pollution in the Naples urban area based on results from moss and lichen bags.

The results of trace element content analysed in Sphagnum capillifolium and Pseudevernia furfuracea exposed in bags in 1999 are reconsidered to evaluate the reliability of moss and lichen transplants to detect urban trace element atmospheric pollution, using Naples as a case example. After 4 months' exposure, trace element concentrations were at least twice as high as the pre-exposure values and in general higher in Sphagnum than in Pseudevernia. Moss samples were enriched in the following order: As=Cu>Mo>Pb>V>Co>Cr>Zn; lichen samples in the order: Mo>Cu>As=Co=Ni>V>Pb. Based on the calculation of a cumulative load factor, all sites located along the coast had higher trace element loads compared to sites in the hilly inland area. Complementary SEM, TEM and EDS observations showed, despite significant damage to tissue and cell integrity, the recurrent presence of particulate matter in moss and lichen, indicating the considerable presence of dust in the urban atmosphere which, according to chemical composition, may be due both to anthropogenic and natural sources such as volcanic rock and soil and sea salts.

Air Pollutants↗

Risk and supervised exercise: the example of anorexia to illustrate a new ethical issue in the traditional debates of medical ethics.

Sport and physical activity is an area that remains relatively unexplored by contemporary bioethics. It is, however, an area in which important ethical issues arise. This paper explores the case of the participation of people with anorexia nervosa in exercise. Exercise is one of the central features of anorexia. The presence of anorexics in exercise classes is becoming an increasingly sensitive issue for instructors and fitness professionals. The ethics of teaching exercise to anorexics has, however, seldom, if ever, been addressed. Codes of ethics and legislation do not offer guidelines pertinent to the case and it is left unclear whether anorexics should be allowed to participate in exercise classes. It is shown by this paper that there are strong ethical reasons to let anorexics participate in exercise classes. However, the paper also explains why, despite these apparently cogent ethical reasons, there is no moral obligation to allow a person with anorexia to take part in exercise/sports activities.

Anorexia↗

[Urinary schistosomiasis: remarks on a case].

Urinary tract schistosomiasis is a parasitic disease caused by S. haematobium with a wide range of clinical manifestations related to the mucosal and submucosal granulomatous lesions of the bladder. It affects about 80 million people in Africa, Middle-East and India, while in Italy it is rarely seen among immigrants from endemic areas and returning travellers. The authors describe a case occurred in a 26 years old man, recently emigrated from a rural area of Ghana. He had the symptoms of a haemorrhagic cystitis. Cystoscopy and biopsy showed granulomatous lesions of bladder with calcified eggs. Microscopic examination of urine was positive for Schistosoma haematobium eggs. The therapy with Praziquantel (40 mg/Kg una tantum) was effective. The authors emphasized the risk of introduction of schistosomiasis in some regions of our country, in consideration of the presence of the intermediate host as well as of an appropriate climate.

Adult↗

[Pulmonary infection caused by Blastoschizomices capitatus].

Geotrichum capitatum, now known as Blastoschizomyces capitatus, can be responsible for several opportunistic infections (systemic infection or localized at lungs, liver, kidney, encephalitis or meningitis) in an immunocompromised host, especially in those patients affected by leukaemia or under immunosuppressive therapies. A 66-year-old woman with polimyosite under steroid and immunosuppressant therapy was hospitalized in ICU for an acute respiratory distress with moderate hypoxaemia and normocapnia. Pulmonary X-ray revealed a bilateral pneumonia. Hypoxaemia became severe 48 hours later and the patient underwent mechanical ventilation and empirical antibiotic therapy. Blood cultures, urine cultures and serological tests were negative, while yeast was identified by Gram's stain of bronchoaspirate. Before identifying the yeasts Fluconazole was added to therapy. At day 5 the clinical conditions remained severe and Candida spp were excluded: so Fluconazole was switched to liposomal Amphotericin B. At day 8 B. capitatus was identified. At day 26 the patient died of refractory respiratory insufficiency. B. capitatus infection is infrequent and its prognosis is severe, with a high mortality rate (>50%). Microbiological diagnosis requires time to characterize the yeast. At present no standard therapy is available although some authors report a good susceptibility to Amphotericin B and Voriconazole (100%), according to NCCLS guidelines.

Aged↗

Plexin signaling hampers integrin-based adhesion, leading to Rho-kinase independent cell rounding, and inhibiting lamellipodia extension and cell motility.

Plexins encode receptors for semaphorins, molecular signals guiding cell migration, and axon pathfinding. The mechanisms mediating plexin function are poorly understood. Plexin activation in adhering cells rapidly leads to retraction of cellular processes and cell rounding "cell collapse"). Here we show that, unexpectedly, this response does not require the activity of Rho-dependent kinase (ROCK) nor the contraction of F-actin cables. Interestingly, integrin-based focal adhesive structures are disassembled within minutes upon plexin activation; this is followed by actin depolymerization and, eventually, by cellular collapse. We also show that plexin activation hinders cell attachment to adhesive substrates, blocks the extension of lamellipodia, and thereby inhibits cell migration. We conclude that plexin signaling uncouples cell substrate-adhesion from cytoskeletal dynamics required for cell migration and axon extension.

Actins↗

Sulphur, nitrogen and carbon content of Sphagnum capillifolium and Pseudevernia furfuracea exposed in bags in the Naples urban area.

The accumulation ability of the major elements sulphur, nitrogen and carbon by the moss Sphagnum capillifolium (Ehrh.) Hedw. and the lichen Pseudevernia furfuracea (L.) Zopf exposed in bags in Naples urban area,was investigated. Bags were exposed at the beginning of July 1999 and gathered in two subsequent moments: at the end of the dry season (after 10 weeks of exposure) and during the wet season (after 17 weeks of exposure), to include the effects of rainy conditions. Sulphur and N content of the lichen increased all over the exposure period, while the level of C did not change significantly either after 10 or 17 weeks of exposition. For the moss the S accumulation was limited to the dry period of exposure, whereas N and C content decreased with exposure. Results, in contrast with those obtained in a previous study on trace elements bioaccumulation [Adamo et al., Environmental Pollution, (2003) 122, 91-103], suggest that accumulation of gaseous pollutants is strongly influenced by biomonitor vitality and that lichen bags are a more reliable and effective tool for monitoring S, N and C atmospheric depositions in urban areas compared to moss bags, because of greater lichen resistance to dry and stressing conditions of urban environment.

Air Pollutants↗

[Human hydatidosis: advances and report of four paediatric cases with unusual presentation].

Human hydatid disease due to Echinococcus granulosus is frequently observed in Italy, especially in the central and southern areas and on the islands. In the last twenty years some major advances in the field of epidemiology as well as diagnostic and therapeutical approaches have changed our knowledge of this disease. In Italy, localization in the liver, kidney or peritoneum accounts for about 95% of cases. The authors describe four paediatric cases with unusual localization (kidney and muscle), highlighting difficulties in the diagnosis.

Adolescent↗

ErbB2 and bone sialoprotein as markers for metastatic osteosarcoma cells.

Osteosarcoma is the most common malignant bone neoplasia occurring in young patients in the first two decades of life, and represents 20% of all primitive malignant bone tumours. At present, treatment of metastatic osteosarcoma is unsatisfactory. High-dose chemotherapy followed by CD34+ leukapheresis rescue may improve these poor results. Neoplastic cells contaminating the apheresis may, however, contribute to relapse. To identify markers suitable for detecting osteosarcoma cells in aphereses we analysed the expression of bone-specific genes (Bone Sialoprotein (BSP) and Osteocalcin) and oncogenes (Met and ErbB2) in 22 patients with metastatic osteosarcoma and six healthy stem cell donors. The expression of these genes in aphereses of patients affected by metastatic osteosarcoma was assessed by RT-PCR and Southern blot analysis. Met and Osteocalcin proved to be not useful markers since they are positive in aphereses of both patients with metastatic osteosarcoma and healthy stem cell donors. On the contrary, BSP was expressed at significant levels in 85% of patients. Moreover, 18% of patients showed a strong and significantly positive (seven to 16 times higher than healthy stem cell donors) ErbB2 expression. In all positive cases, neoplastic tissue also expressed ErbB2. Our data show that ErbB2 can be a useful marker for tumour contamination in aphereses of patients affected by ErbB2-expressing osteosarcomas and that analysis of Bone Sialoprotein expression can be an alternative useful marker.

Adolescent↗

Trace element accumulation by moss and lichen exposed in bags in the city of Naples (Italy).

This paper presents the results of a bioaccumulation study of trace elements in the Naples urban area based on the use of the moss Sphagnum capillifolium (Ehrh.) Hedw. and the lichen Pseudevernia furfuracea (L.) Zopf exposed in bags in 23 sites. Moss and lichen bags were exposed for 4 months starting from the beginning of July 1999. Bags gathering was carried out after 10 weeks of exposure, at the end of the dry season, and after 17 weeks, during the wet season. The elements Al, As, Ca, Cd, Cr, Co, Cu, Fe, K, Mg, Mn, Mo, Ni, Pb, Ti, V and Zn were analysed by inductively coupled plasma-mass spectrometry ICP-MS in both biomonitors. For the majority of the elements the total amounts found in S. capillifolium were higher than in P. furfuracea whether considering the whole period of exposure or the weekly uptake. It was observed that there was a much greater difference in metal accumulation by P. furfuracea between the dry and wet seasons compared with S. capillifolium. In the wet period, the lichen seems to accumulate a larger quantity of metals. With the exception of Mn, trace element concentrations did not appear to be significantly affected by the washing away of rainfall. K loss during exposure suggested cell membrane damage in both organisms. For P. furfuracea the K leakage was limited to the dry period of exposure. A clear distinction between "lithophilic" and "anthropogenic" elements was achieved by cluster analysis. Significant correlations were found among Fe-Cu-Cr-Ni, Pb-Cd-Co, V-Cr-Ni, Zn-Ni-Pb, suggesting a common source for each group of elements.

Bryopsida↗

Treatment of human brucellosis with rifampin plus minocycline.

In order to evaluate the efficacy and tolerability of a high intravenous dose of rifampin plus oral minocycline (administered daily for 3 weeks) for the treatment of acute brucellosis, we retrospectively reviewed the outcome of 239 consecutive patients (135 adults and 104 children) diagnosed and treated over a 17-year period in Italy. The combination used resulted in 100% response and a relapse rate lower than 2%. Fifty-two (30 adults and 22 children) (29.8%) complained of mild adverse effects including an increase in aspartate aminotransferase (>250 IU) observed in 12 cases and considered related to rifampin and in 11 cases a reversible hyperpigmentation of the tongue attributed to minocycline. A randomized prospective comparative study should be performed to confirm our encouraging results.

Adolescent↗

Differential requirement of the last C-terminal tail of Met receptor for cell transformation and invasiveness.

Biological responses to Hepatocyte Growth Factor are mediated by the tyrosine kinase receptor encoded by the Met oncogene. Under physiological conditions, Met triggers a multi-step genetic program called 'invasive growth' including cell-dissociation, invasion of extracellular matrices and growth. When constitutively activated, Met can induce cell transformation and metastasis. Phosphorylation of two docking tyrosines in the receptor tail is essential for all biological responses. To investigate the role of the C-terminal part of Met, we have generated mutants lacking either the last 26 or 47 amino acids. As expected, mutants lacking the docking sites fail to mediate cell transformation and invasion. Interestingly, while Met Delta26 can mediate invasion, its transforming ability is severely impaired. Moreover, the lack of the last 26 amino acids strongly reduces Met ability to phosphorylate substrates in vitro and in vivo. These data indicate that the last 26 amino acids are required to confer the kinase its full enzymatic activity, which is critical for cell transformation but dispensable for invasive properties. Finally, we also show that up-regulation of Met enzymatic activity by insertion of a point mutation in the kinase domain (M1250T) overcomes the regulatory role played by the last 26 amino acids of the tail. It is concluded that the C-terminal domain of Met is crucial not only for recruitment of transducers but also for regulation of receptor enzymatic activity.

3T3 Cells↗

Hepatocyte growth factor is a regulator of monocyte-macrophage function.

Hepatocyte growth factor (HGF) is a potent paracrine mediator of stromal/epithelial interactions, which is secreted as a matrix-associated inactive precursor (pro-HGF) and locally activated by tightly controlled urokinase cleavage. It induces proliferation and motility in epithelial and endothelial cells, and plays a role in physiological and pathological processes involving invasive cell growth, such as angiogenesis and parenchymal regeneration. We now report that HGF induces directional migration and cytokine secretion in human monocytes. Monocyte activation by endotoxin and IL-1beta results in the up-regulation of the HGF receptor expression and in the induction of cell-associated pro-HGF convertase activity, thus enhancing cell responsiveness to the factor. Furthermore, we provide evidence for the secretion of biologically active HGF by activated monocytes, implying an autocrine stimulation. Altogether, these data indicate that monocyte function is modulated by HGF in a paracrine/autocrine manner, and provide a new link between stromal environment and mononuclear phagocytes.

Cell Adhesion↗