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Biomedical subjects

G Pelosi

Publications and source records attributed to G Pelosi.

At least 19 recordsLinked to original sources
PubMed2001

Synthesis, characterisation, X-ray structure and biological activity of three new 5-formyluracil thiosemicarbazone complexes.

Three new complexes of transition metals as copper, nickel and cobalt with 5-formyluracil thiosemicarbazone (H3ut) have been synthesised and characterised by single-crystal X-ray diffraction. In all compounds the ligand behaves as SNO terdentate. In the copper complex the coordination geometry is square pyramidal with the ligand lying on the basal plane and two water molecules that complete the metal environment, the nickel compound is surrounded by six donor atoms (three of the ligand, two water oxygen atoms and a chlorine atom) in an octahedral fashion, and cobalt also shows an octahedral geometry but determined only by two terdentate ligand molecules. These three compounds have been tested on human leukemic cell lines K562 and CEM. The nickel and cobalt complexes have demonstrated low activity in cell growth, while the copper complex that is more active has been tested also on a third leukemic human cell line (U937), but it was not able to induce apoptosis on all cell lines.

Apoptosis↗
PubMed2001

Pulmonary epithelial-myoepithelial tumor of unproven malignant potential: report of a case and review of the literature.

Epithelial-myoepithelial tumors of the lung are rare neoplasms whose biological behavior and clinical course still remain to be defined. A case of epithelial-myoepithelial tumor of the lung arising from bronchial mucosa-submucosa and occurring as a polypoid lesion of the upper left bronchus in a 47-year-old man is reported. The tumor did not infiltrate the cartilaginous wall of the bronchus and showed a biphasic histological appearance with a double layering of epithelial and myoepithelial cells. Myoepithelial spindle cells with eosinophilic cytoplasm were also observed. Mitotic figures were very rare and necrosis absent. Immunohistochemical study for epithelial and muscular markers confirmed the presence of a double-cell component in the tumor, namely epithelial and myoepithelial. The patient is alive and well, with no evidence of recurrent or metastatic disease 6 months after surgery. On the basis of the present case and the six previously reported cases, we suggest using the noncommittal term pulmonary epithelial-myoepithelial tumor of unproven malignant potential (PEMTUMP) for this type of neoplasm. In addition, we first introduce p63 as a novel marker for highlighting the myoepithelial cells of the respiratory tract and speculate on the role of these cells in the development of this unusual tumor.

Adenoma, Pleomorphic↗
PubMed2001

Efficient otoacoustic emission protocols employed in a hospital-based neonatal screening program.

Within the context of a hospital-based newborn hearing screening program, we have studied the application of two OAE protocols (TEOAE and DPOAE) on a group of 250 well babies. The main goal of this study was to evaluate the performance of DPOAE protocol in a relatively large population sample. using a preset number of five tested frequencies, in comparison with a default TEOAE screening protocol. The data were collected on the second day of life and during spontaneous sleep. The TEOAE recordings were acquired with linear protocols using click stimuli of 70-75 dB SPL and were used as indicators of normal cochlear function. The cubic distortion product DPOAE responses were evoked by an asymmetrical 75-65 dB SPL protocol, with a frequency ratio of 1.22. Five frequencies (referring to F2) were tested at 1.5, 2.0, 3.0, 4.0 and 5.0 kHz. The data from the DPOAE responses show a similar pass rate (similarity = 0.98) to the linear TEOAE protocol. The data presented suggest that a DPOAE cochlear evaluation, at 5 pre-selected frequencies, has clinical potential.

Deafness↗
PubMed2001

Immunoreactivity for thyroid transcription factor-1 in stage I non-small cell carcinomas of the lung.

Thyroid transcription factor-1 (TTF-1) is a nuclear protein regulating the transcriptional activity of lung-specific genes in the normal and neoplastic bronchioloalveolar cells. It has been implicated in the normal growth and development of the lung, and the disruption of the TTF-1 locus leads to neonatal death with pulmonary hypoplasia. We evaluated retrospectively the prevalence and clinical significance of TTF-1 immunoreactivity in 222 patients with stage I non-small cell lung carcinoma (NSCLC) with a follow-up time of at least 5 years, and we investigated its relationship with other markers of tumor growth, namely cell proliferation and angiogenesis. TTF-1 immunoreactivity was documented by using the commercially available monoclonal antibody 8G7G3/1 in 72% of 97 adenocarcinomas, 5% of 119 squamous cell carcinomas, and in the glandular component of two adenosquamous carcinomas. Four large cell carcinomas were completely unreactive. In adenocarcinomas, but not squamous cell carcinomas, TTF-1 immunoreactivity correlated significantly with microvessel density (p = 0.04) and inversely with the tumor proliferation fraction assessed by Ki-67 immunostaining (p = 0.03). Also, TTF-1-immunoreactive adenocarcinomas showed a trend for a size less than 3 cm (p = 0.08). TTF-1 expression was not related to specific growth patterns, tumor grade, or tumor cell typing. TTF-1 immunoreactivity did not significantly affect patient survival, although patients with more than 75% immunoreactive neoplastic cells showed a trend for longer overall and disease-free survival. Our findings suggest that TTF-1 could be involved in the development of small pulmonary adenocarcinomas, but it has not prognostic implications in patients with stage I NSCLC.

Adenocarcinoma↗
PubMed2001

111In platelet scintigraphy for the noninvasive detection of carotid plaque thrombosis.

BACKGROUND AND PURPOSE: Thrombosis on atherosclerotic lesions in the large extracranial arteries is the main cause of embolization in the distal cerebral circulation and thus is involved in the pathogenesis of ischemic stroke. The assessment of biological characteristics of lesions that are predictive of thrombotic complications might help in stratification of the risk for stroke but is currently imperfect. METHODS: We compared the performance of (111)In-platelet scintigraphy with blood pool subtraction, ultrasound-based tissue texture analyses, and transcranial Doppler techniques in their ability to predict the occurrence of superficial thrombosis or the presence of a lipid pool in carotid artery plaque specimens removed at the time of carotid endarterectomy in 22 patients with unilateral carotid artery stenosis of >70%. RESULTS: Positivity at (111)In-platelet scintigraphy was present in 8 patients and correctly identified the presence of thrombosis superimposed on a complicated plaque. Neither tissue texture analysis nor emboli detection by transcranial Doppler, performed in 12 patients, significantly identified plaque thrombosis. None of the techniques used were able to detect the presence of a significant lipid pool inside the plaque. CONCLUSIONS: Indium-platelet scintigraphy is an accurate noninvasive diagnostic tool to detect thrombotic complications in carotid plaques. Prospective studies should assess its ultimate value in risk stratification, possibly to guide the decision of whether to perform endarterectomy in selected patient categories.

Aged↗
PubMed2000

Synthesis, structural characterization and biological activity of p-fluorobenzaldehyde thiosemicarbazones and of a nickel complex.

New thiosemicarbazones (1-7), derived from p-fluorobenzaldehyde and differently substituted thiosemicarbazides, were synthetized and characterized by means of NMR and IR techniques. The p-fluorobenzaldehyde thiosemicarbazone Hfbt (1), the p-fluorobenzaldehyde 4-phenylthiosemicarbazone Ph-Hfbt (4) and complex [Ni(fbt)2] (8) were also characterized by X-ray diffractometry. Molecules 1 and 4 consist of two units: the p-fluorobenzaldehyde residue and the thiosemicarbazonic chain. In the reaction of 1 with NiAc2.4H2O, complex 8 was afforded. The molecular structure of 8 consists of the neutral molecules [Ni(fbt)2] with the metal placed on a symmetry centre. The coordination results in a square planar configuration and involves the sulphur atom and the hydrazine nitrogen atom of the two ligands in a trans configuration. Moreover, for compounds 1, 2, 4, and 8, assays of proliferation inhibition and apoptosis tests in vitro on human leukemia cell line U937 were carried out.

Apoptosis↗
PubMed2000

CD99 immunoreactivity in gastrointestinal and pulmonary neuroendocrine tumours.

Although considered a specific marker for Ewing's sarcoma/peripheral neuroectodermal tumour, the MIC2 gene product (CD99) has been immunolocalised in a variety of human tumours. The present study evaluated immunohistochemically the prevalence of CD99 expression in a series of 68 neuroendocrine tumours of different gastrointestinal and pulmonary sites. We now report on membrane and/or granular cytoplasmic immunoreactivity in 25% of these tumours, independent of their anatomical sites. In lung neuroendocrine tumours, CD99 was preferentially confined to typical carcinoids (P=0.009). A statistically significant relationship was observed between the number of CD99 positive cells but not the immunostaining patterns and the presence of local invasion and/or distant metastases (P<0.001). Moreover, there was a tendency for CD99-reactive tumours to show a reduced proliferative activity expressed by a Ki67 index of 2% (P=0.119). The number of CD99 immunoreactive cells or patterns of immunoreactivity did not correlate with the presence of associated clinical syndrome or particular hormonal immunostaining. Although the molecular basis underlying CD99 expression in neuroendocrine tumours is still poorly understood, our data suggest that CD99 may be involved in cell-to-cell adhesion of neuroendocrine tumour cells and in downregulation of their proliferative activity.

12E7 Antigen↗
PubMed2000

Early hilar lung cancer--clinical aspects and long term survival. Identification of a subgroup of stage IA patients with more favorable prognosis.

Twenty-nine patients out of 2018 operated on for a non-small-cell lung cancer from 1987 to February 1998 met the criteria proposed by the Japan Lung Cancer Society (JLCS) for the definition of early hilar lung cancer (EHLC). Twenty-six patients were symptomatic and 20 had a radiologically visible lesion. All cancers were located and diagnosed by bronchoscopy and all patients were resected. At histology, all tumors were squamous in nature. The five-year cumulative survival rate was 96%--a second primary lung cancer (2nd Pr.) developed in 4 patients (13.8%). The definition of EHLC proposed by the JLCS allows the selection of a subgroup of stage I patients with a very good prognosis. Nevertheless, a close follow-up is mandatory because more than 10% of these patients develop a 2nd Pr.

Adult↗
PubMed2000

Synthesis, spectroscopic characterization and biological properties of new natural aldehydes thiosemicarbazones.

As part of a research programme aimed at the synthesis of compounds with antiviral, antibacterial and antitumor properties and their spectroscopic characterization, new thiosemicarbazones deriving from natural aldehydes have been investigated. These substances contain in the same molecule both a chain with nucleophilic centres N, S with tubercolostatic activity, and a glycosidic or alkyl moiety (modified glycosides and nucleosides have recently received a great deal of attention in the fields of neoplastic diseases and viral infections). In this paper the synthesis and the characterization of these compounds by means of 1H NMR, IR, and MS techniques is reported. Biological studies have involved both inhibition of cell proliferation and apoptosis tests on human leukemia cell line U937.

Apoptosis↗
PubMed2000

[Distortion product otoacoustic emission (DPOAEs) and newborn hearing screening: a feasibility and performance study].

In view of the great psychological effect deafness has on one's social life, the scientific community has long sought the best way to define the hearing function. The development of new technologies in this field has set "early intervention" as the primary target for screening. For this reason, within the contest of a program of audiological newborn hearing screening, the Authors have used data from a selected group of 1250 newborns to (a) compare the clinical feasibility and performance of three different DPOAE protocols and (b) establish the scoring criteria defining "pass" or "fail" responses. All subjects participating in this study were randomly selected and their normal hearing was verified by linear TEOAE recordings. The test was carried out, using an Otodynamics ILO92 Analyser version 5.60, on the second day of life or later (in case of extended recovery), during natural sleep and after feeding. The DPOAE recordings were elicited using asymmetric stimuli with L1 > L2 and a frequency-ratio of 1.22 following three different SPL protocols: 60-50 dB (PR1), 65-55 dB (PR2) and 75-65 dB (PR3). Five frequencies of the cubic distortion product (referring to f2) were tested with an ILO macro at 1.5 KHz, 2.0 KHz, 3.0 KHz, 4.0 KHz and 5.0 KHz. The statistical evaluation of differences in the signal-to-noise ratio (S/N) between the PR1 and PR2 protocols showed no significant differences. On the other hand significant differences were found between the PR3 and the PR2 S/N ratios, the former providing the best performance (higher values). The scoring criteria were defined by minimum free distribution tolerance intervals of the S/N ratios at the five tested frequencies. In conclusion this study confirms the feasibility of DPOAE recordings in a un iversal newborn hearing screening program and shows the appropriate pass-fail parameters to be used for this purpose. It should be noted that this approach enables acquisition of frequency-specific information which might further improve audiological diagnosis.

Cochlea↗
PubMed1999

TIPS allowing for an endoscopic mucosal resection of early gastric cancer in a cirrhotic patient with severe hypertensive gastropathy: report of a case.

This report describes the use of a transjugular intrahepatic portosystemic shunt (TIPS) in a cirrhotic patient with early gastric cancer, presenting with gastroesophageal varices and severe hypertensive gastropathy, in order to perform an endoscopic mucosal resection. The patient first underwent a TIPS to reduce the hypertensive gastropathy and thereafter was successfully treated by an endoscopic mucosal resection. Owing to the high operative risk, the treatment of gastric cancer in cirrhotic patients needs to be individualized. New procedures such as TIPS and an endoscopic mucosal resection may be useful in selected high-risk patients.

Endoscopy↗
PubMed1999

Classification of lymph node metastases from carcinoma of the stomach: comparison of the old (1987) and new (1997) TNM systems.

The pN classification of gastric cancer is currently based on the distance of metastatic nodes from the primary tumor (TNM-1987). The UICC (Union Internationale Contre le Cancer) has recently proposed a new classification system based on the number of the involved nodes (TNM-1997). The present prospective study is aimed at verifying whether the two classifications (1) assign approximately a similar rank to individual patients and (2) give comparable prognostic information. The Cox regression model was used to evaluate the prognostic significance of either the distance or the number of positive nodes, controlling for sex, age, site, histology and depth of tumor invasion, in a group of 175 patients who underwent curative surgery for gastric cancer from March 1988 to October 1997. Among the patients classified as N1 and N2 according to TNM-1987, 81.8% (36/44) and 35.8% (19/53), respectively, were coded as N1 and N2 by the new classification. The survival probabilities of N1 and N2 categories were similar in both classifications. The N2 category of TNM-1987 comprised also 10 cases with >15 positive nodes (N3 category of TNM-1997), who presented a large excess mortality (RR = 35.14 with respect to N0). When the site and number of positive nodes are combined in a new variable, both appear to be important from a prognostic point of view. Both anatomic location and number of nodes with metastasis are important predictors of survival in gastric cancer patients. Caution should be used when replacing the old classification with the new one, as they group patients in a different way.

Age Factors↗
PubMed1999

High density of endothelin binding sites in the hearts of infants and children.

Endothelin (ET)-1 peripheral levels are high in children with respect to values of adults, but its pathophysiological significance remains to be established. In these conditions the interaction of ET-1 with its receptors may constitute a clue to the understanding of ET-1 function. Because a direct determination of ET binding sites in the heart of children is lacking, in this study we have attempted an assessment of the ET receptor status in cardiac tissue of infants (<1 year; 0.39 +/- 0.26 (SD) years, n=6) and children (1-14 years; 6.3 +/- 4.9 years, n=7) as well as an evaluation of the receptor modulation as a function of age, associated to the observed decrease of plasma ET levels between infants and children. ET-1 binding sites have also been evaluated in atrium and ventricle membranes of adult subjects recipient of cardiac transplantation (CHF) and of post-mortem cardiac specimens (autopsy) of non cardiac patients. Considering all the pediatric patients (infants +/- children) studied, an affinity constant (Kd) value of 38.2 +/- 6.1 (SEM) pM and a density (Bmax) value of 166.2 +/- 11.6 fmol/mg protein has been obtained for atrium. Similar values have been found in the ventricle. These values are significantly higher with respect to those obtained in adults: for atrial membranes, Kd = 22.2 +/- 9.7 and 11.6 +/- 1.8 pM; Bmax = 58.4 +/- 22.8 and 42.1 +/- 8.9 fmol/mg protein, respectively in explanted hearts and in post mortem specimens. No significant differences have been found in the binding parameters between infants and children, while, considering our results as a whole, a significant inverse correlation between Bmax and subject age (p<0.001) is suggested. The ET-A/ET-B ratio, evaluated by competition experiments with the specific ET-A antagonist BQ-123, was about 70:30 in pediatric patients, in both atrium and ventricle, without any difference between infants and children. Similar values for ET-A/ET-B ratio in adult CHF patients, in contrast to a reduction (significant only in ventricle) of the percent of ET-A subtype in autopsy, has been found. This is the first study concerning a direct evaluation of ET receptor status in children's hearts; the higher density of binding sites, associated to the elevation of plasma levels, could suggest a enhanced biological function of ET in children.

Adolescent↗
PubMed1999

Bone marrow micrometastases in breast cancer patients.

The presence of epithelial cells in bone marrow may be a prognostic factor in breast cancer, and so we evaluated their evolution in treated and untreated patients. A first bone marrow aspirate was obtained from 125 stage I/II breast cancer patients at diagnosis and repeated every 6-8 months; the samples were processed for leukocyte separation, used to prepare cytospin slides, stained with a pool of monoclonal antibodies (MoAb) recognising epithelial antigens, and immunocytochemically processed. The median follow-up was 48 months (range 15-82); 23 patients relapsed, and 14 died. MoAb positive cells were observed in 31.2% of first, 24.3% of second, and 27.8% of third aspirates. In 68/100 pairs of successive aspirates, bone marrow status remained unchanged; in 20 it became negative, and in 12 positive (not statistically significant even after adjusting for adjuvant therapy). An analysis based on Mantel and Byar's approach to time-dependent covariates using all 225 aspirates found no statistically significant prognostic difference between the patients with negative and positive bone marrow. Bone marrow status changed over time in about 1/3 of the patients; adjuvant therapy did not affect the probability of its becoming negative or positive. No significant association was found between bone marrow evolution and relapse or death, but the relatively high probability of a change in status over time cannot exclude the possibility that a positive aspirate during the course of breast cancer may be a negative prognostic factor.

Antibodies, Monoclonal↗
PubMed1999

Immunocytochemical assessment of bone marrow aspirates for monitoring response to chemotherapy in small-cell lung cancer patients.

Recent reports have suggested that tumour cell immunodetection in bone marrow of small-cell lung cancer patients is by far more frequent than found cytohistologically and may have clinical relevance. This study evaluates primarily the efficacy of chemotherapy as method of in vivo purging, but also the relationship of marrow involvement with survival. A total of 112 bone marrow aspirates from 30 chemo-naïve patients were stained twice using anti-NCAM antibodies, first at diagnosis and then after chemotherapy (24 patients) or at disease progression (six patients). Marrow contamination was associated with lower survival (P = 0.002), and was also detected in 7/17 patients conventionally staged as having limited disease. At multivariate analysis, marrow involvement was an independent factor of unfavourable prognosis (P = 0.033). The amount of tumour contamination, before and after chemotherapy, remained unchanged also in responders and even in the subset of patients with apparent limited disease. Following chemotherapy, bone marrow became tumour negative only in 25% of initially positive responders and in none of non-responders. Our results indicate that (i) chemotherapy is not effective in purging bone marrow even in chemo-responsive patients and (ii) a subset of patients with limited disease and negative bone marrow aspirates might have a more favourable prognosis.

Aged↗
PubMed1999

A TEOAE screening protocol based on linear click stimuli: performance and scoring criteria.

In order to improve the quality of current TEOAE recording methodologies, we have conducted a comparison of TEOAE neonatal recordings acquired with linear protocols using click stimuli of 68 dB SPL and non-linear protocols using the ILO default stimulus values. From a theoretical standpoint it was expected that the linear recordings would generate responses characterized by higher S/N ratios due to the fact that the stimulus sequence contains four clicks of the same intensity and polarity. The project included recordings from 1,416 neonatal ears (age 48 h). The TEOAE data were compared in terms of correlation, response amplitude, noise, corrected response and S/N ratio in the 1.0-, 2.0-, 3.0-, 4.0- and 5.0-kHz bands, using a paired t-test criterion. We found that windowed (4-14 ms) responses evoked by a linear TEOAE protocol generated superior S/N estimates in the 2.0-, 3.0-, 4.0- and 5.0-kHz TEOAE bands, in addition to superior correlation estimates, and demonstrated lower levels of noise. Clear-cut scoring criteria were established for the S/N ratios at 2.0, 3.0 and 4.0 kHz, by constructing one-sided distribution-free tolerance boundaries.

Acoustic Stimulation↗
PubMed1999

Effects of different immunolabeling techniques on the detection of small-cell lung cancer cells in bone marrow.

Recent reports have suggested that the immunodetection of tumor cells in bone marrow of small-cell lung cancer (SCLC) patients is by far more effective than traditional cytohistological methods and that this may be clinically relevant. This study aimed to evaluate whether the level of detection of tumor cells in bone marrow is affected by different immunostaining methods. Using two anti-NCAM monoclonal antibodies (MAbs), we compared four different "sandwich" methods on cytospin preparations of the N592 human SCLC cell line and of bone marrow aspirates from 37 SCLC patients. Our data indicate that the combination of the alkaline phosphatase-anti-alkaline phosphatase and streptavidin-biotin-alkaline phosphatase complex methods provides the best results in terms of sensitivity and specificity, and of intensity of immunoreaction and absence of staining background. Moreover, bone marrow micrometastases detected by this method were prognostically relevant and identified, among patients with apparently limited disease according to conventional staging procedures, a subgroup with shorter survival. We suggest that the choice of a sensitive immunostaining technique may significantly increase the detection rate of SCLC cells in bone marrow, mirroring the biological aggressiveness of the disease.

Bone Marrow Neoplasms↗