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L Grazioli

Publications and source records attributed to L Grazioli.

At least 37 records · Page 2Linked to original sources
PubMed1999

Fibrolamellar hepatocellular carcinoma: imaging and pathologic findings in 31 recent cases.

PURPOSE: To review characteristic findings of fibrolamellar hepatocellular carcinoma (HCC) at computed tomography (CT) and magnetic resonance (MR) imaging. MATERIALS AND METHODS: The authors retrospectively reviewed the clinical, pathologic, and preoperative imaging findings in 31 patients with histologically proved fibrolamellar HCC. Dynamic contrast material-enhanced CT of the liver was performed in 31 patients, helical multiphase CT in 21, and MR imaging in 11. Complete resection was performed in 17 patients, and imaging-pathologic correlation was performed. RESULTS: Large tumors (mean diameter, 13 cm) were depicted at CT and MR in all cases. At CT, the margins of the tumors were well defined in 24 (77%) of 31 cases calcifications were depicted in 21 (68%), a central scar in 22 (71%), and abdominal lymphadenopathy in 20 (65%). In 20 (80%) of 25 cases with hepatic arterial phase CT images, all tumors were heterogeneous and depicted areas of hypervascularity. At MR imaging, tumors were hypointense to liver on T1-weighted images (n = 11) and hyperintense to liver on T2-weighted images (n = 10). Calcification was not depicted on MR images, but a central scar was depicted as hypointense to surrounding tumor in nine cases. CONCLUSION: CT and MR images demonstrate characteristic features that may allow confident diagnosis of fibrolamellar HCC.

Adolescent↗
PubMed1998

Anti-peptide antibodies detect conformational changes of the inter-SH2 domain of ZAP-70 due to binding to the zeta chain and to intramolecular interactions.

T cell receptor (TCR) triggering induces association of the protein tyrosine kinase ZAP-70, via its two src-homology 2 (SH2) domains, to di-phosphorylated Immunoreceptor Tyrosine-based Activation Motifs (2pY-ITAMs) present in the intracellular tail of the TCR-zeta chain. The crystal structure of the SH2 domains complexed with a 2pY-ITAM peptide suggests that the 60-amino acid-long inter-SH2 spacer helps the SH2 domains to interact with each other to create the binding site for the 2pY-ITAM. To investigate whether the inter-SH2 spacer has additional roles in the whole ZAP-70, we raised antibodies against two peptides of this region and probed ZAP-70 structure under various conditions. We show that the reactivity of antibodies directed at both sequences was dramatically augmented toward the tandem SH2 domains alone compared with that of the entire ZAP-70. This indicates that the conformation of the inter-SH2 spacer is not maintained autonomously but is controlled by sequences C-terminal to the SH2 domains, namely, the linker region and/or the kinase domain. Moreover, antibody binding to the same two determinants was also inhibited when ZAP-70 or the SH2 domains bound to the zeta chain or to a 2pY-ITAM. Together, these two observations suggest a model in which intramolecular contacts keep ZAP-70 in a closed configuration with the two SH2 domains near to each other.

Amino Acid Sequence↗
PubMed1996

[Peripheral intrahepatic cholangiocarcinoma. The role of imaging diagnosis and fine-needle biopsy].

Peripheral intrahepatic cholangiocarcinoma (ICC) is a fairly uncommon type of cancer in Italy which may be misdiagnosed as a metastasis from extrahepatic adenocarcinoma. In all, 22 cases of intrahepatic cholangiocarcinoma were diagnosed at the Radiology Department of the University of Brescia, Italy, from 1989 to 1994. The patients were 15 men and 7 women and their age ranged 30-77 years. Most of them underwent US examinations because of abdominal pain, weight loss or a general malaise and, less frequently, for signs of cholestasis. Hepatic cirrhosis was found in 8 patients. US showed a single nodular lesion with irregular margins in 6 cases and a large nodule with adjacent smaller satellite nodules in 12 cases. In the other 4 subjects, an infiltrative and diffuse lesion with no apparent nodules was observed. US showed hypoechoic lesions in 17 cases and both hypo- and hyperechoic areas in the other patients. The main nodular lesion was 1-3 cm in diameter in 2 cases, 3-10 cm in 15 and over 10 cm in 6 cases. Both hepatic lobes were involved in 14 patients. Twenty-one of 22 patients were submitted to CT and 3 to MR examinations. Both techniques confirmed US findings of an intrahepatic tumor but they did not help locating its origin in the intrahepatic biliary tract. Therefore, every patient was submitted to US-guided fine needle biopsy which allowed the correct diagnosis to be made in 12 cases. The remaining 10 patients had an initial diagnosis of adenocarcinoma metastases and only further studies of the histologic specimens, performed after a series of useless and negative exams (e.g., barium enema and endoscopy), allowed ICC to be correctly diagnosed. Since no typical pattern of this type of cancer can be observed with US, CT or MR examinations, we suggest that US-guided fine needle biopsy be used as the method of choice, which however needs a fruitful cooperation between the radiologist and the pathologist.

Adult↗
PubMed1995

Characterization of parotid gland tissue: a description of an MRI protocol set-up and results of in-vivo applications.

A reliable protocol for proton T2 mapping of the parotid region was set up for future characterization of parotid gland disease. A Carr-Purcell-Meiboom-Gill sequence, phase compensated, available on our 1.5 T imager, was selected and acquisition parameters were chosen on the basis of tests performed on phantoms (agarose-doped gels with T2 in the physiological range). Some experiments were carried out to evaluate the accuracy of T2 calculations for selective and nonselective refocussing pulses, for image uniformity corrections, and for different situations of slice shift and repetition times. The chosen protocol was then applied to in vivo evaluations to check the long-term precision by means of repeated measurements performed on the same subject over a 2-month period. Two or more reference gels were positioned both in the phantom and volunteer at the edge of the field-of-view (FOV). Image postprocessing consisted of an automatic procedure, written by the authors in Fortran 77, that selected the best fit for each pixel between mono- and biexponential decay models, and prepared four parametric images (T2 and Rho slow and fast contribution, Rho being a function of proton density and of T1) that may be used for future elaborations. The phantom experiment results showed an accuracy of 2.5% if a linear correction was performed using the reference gels at the edge of the FOV. No significant differences in accuracy were found between selective and nonselective refocussing pulse, and a homogeneity correction was not demonstrated necessary. The measurements performed on four volunteers showed that the best decaying model for healthy parotid tissue was monoexponential. Evaluated T2 resulted 80.18 +/- 6.11 ms (72.96 +/- 4.97 ms for uncorrected results). Long-term reproducibility of the group of measurements from one volunteer, summarizing all the measurement errors, ranged from 0.9 to 8.5%. The two-way ANOVA that was carried out considering the two classes of volunteers and of parotid positions (right or left) showed that differences found between the two parotids were not significant, while T2 differences among individuals are significant if a probability level higher than 1.1% is accepted. As in this case, the main source of error can be attributed to the biological variations among individuals. Future statistics collected on patients for the T2 evaluations of the pathologic tissue will clarify whether the T2 relaxation is a sufficient parameter for T2 discrimination of healthy and pathologic tissue.

Humans↗
PubMed1994

Tumor necrosis factor-driven formation of disulfide-linked receptor aggregates.

We have characterized, by ligand blotting, solubilized tumor necrosis factor receptors (TNFR) from K562 cells. Preparations that had been partially purified by gel filtration chromatography yielded two prominent bands of M(r) 60,000 and 75,000 corresponding to the two known TNFR (types I and II, respectively). In addition to these, types I and II TNFR-related species of M(r) > 100,000 were detected after purification by tumor necrosis factor (TNF)-affinity chromatography, suggesting that TNF had driven receptor aggregation during this step. To test this hypothesis ligand blots were performed on receptor preparations that had been partially purified by gel filtration chromatography and incubated with TNF before electrophoretic separation. Indeed, type II TNFR aggregates, but not type I TNFR aggregates, were generated at optimal TNF concentrations. Formation of type II TNFR aggregates in this last experimental setting and of both type I and type II TNFR aggregates during affinity purification could be prevented if an alkylating agent (N-ethylmaleimide) was added during the TNFR-TNF incubation step. Similar results were obtained when intact K562 cells were incubated with TNF and then analyzed for receptor aggregation; type II TNF receptor aggregates were generated at TNF concentrations ranging from 10(-9) to 10(-10) M and their formation was prevented in the presence of N-ethylmaleimide.

Blotting, Western↗
PubMed1994

[Morphologic imaging of thyroid carcinoma].

Ultrasonography (US) is the choice morphological imaging modality in the study of thyroid carcinomas. The present technological evolution (high frequency probes, development of Colour-Doppler) allows the detection of small non-palpable nodules, being able to define, in a high percentage of cases, features pointing to the malignant character of a thyroid mass, although the definite assessment of malignancy (invasion of adjacent structures, metastatic cervical nodes) is quite rare. From a diagnostic viewpoint US is required to identify nodules with suspect features, to be submitted to fine needle aspiration biopsy. Moreover, US plays a basic role in the staging--at the cervical level--of carcinomas as well as in the post-operative follow-up. The other imaging modalities (Computed Tomography, Magnetic Resonance Imaging) play a limited role in both staging and post-operative follow-up.

Follow-Up Studies↗
PubMed1993

Suramin induces deoligomerization of human tumor necrosis factor alpha.

Suramin inhibits the biological activity of human tumor necrosis factor alpha (TNF) through a direct action on the ligand rather than on its receptors (Grazioli, L., Alzani, R., Ciomei, M., Mariani, M., Restivo, A., Cozzi, E., and Marcucci, F. (1992) Int. J. Immunopharmacol. 14, 637-642). In order to clarify the mechanism whereby suramin leads to inhibition of TNF, we investigated the possibility that suramin might modify the quaternary structure of TNF which is biologically active as a trimer. For this purpose we used a new assay (double streptavidin sandwich assay) designed for the rapid detection of oligomer-monomer conversion of proteins. Taking advantage of this assay we observed, upon incubation with suramin, dissociation of TNF. Suramin-induced dissociation of TNF was confirmed by gel filtration chromatography. Under conditions of partial dissociation, two molecular species were separated. One of higher molecular weight, corresponding to trimeric TNF, was biologically active, whereas the other, corresponding to monomeric TNF, was inactive. These results are at variance with others recently reported, where suramin has been shown to induce microaggregation of several polypeptides (Middaugh, C. R., Mach, H., Burke, C. J., Volkin, D. B., Dabora, J. M., Tsai, P. K., Bruner, M. W., Ryan, J. A., and Marfia, K. E. (1992) Biochemistry 31, 9016-9024). This suggests that suramin inhibits the bioactivity of different protein molecules through opposite effects on their quaternary structure. The present results are, to our knowledge, the first demonstration of a drug inhibiting a target molecule through dissociation of its quaternary structure.

Animals↗
PubMed1993

Expression, in Escherichia coli, of a soluble human tumor necrosis factor receptor.

We have expressed in Escherichia coli a soluble, truncated form of the human 55 kDa Tumor Necrosis Factor (TNF) receptor. For this purpose a plasmid was constructed which contains the extracellular domain of the 55 kDa TNF receptor fused to the coding sequence of the IgG binding domains of protein A from Staphylococcus aureus. The fusion product (TNFR-PA) obtained in E. coli is a soluble protein which bound human TNF alpha (huTNF alpha) with high affinity. In ligand-blotting experiments huTNF alpha bound to a single 52 kDa protein, a molecular mass corresponding to that expected for the monomeric fusion product. In gel filtration experiments binding activity was recovered from fractions that eluted at a volume corresponding to 140-150 kDa. TNFR-PA neutralized huTNF alpha in an in vitro cytotoxicity assay.

Chromatography, Gel↗
PubMed1993

[Comparison of ultrasonography, computerized tomography, and magnetic resonance in the study of parotid masses].

One hundred and seven patients were examined to compare advantages and pitfalls of the imaging methods currently used to stage parotid masses. Thirty patients underwent US and CT, 44 were investigated with US and MRI and 33 with US, CT and MRI. The accuracy of the three techniques was analyzed in detecting and assessing the intra-/extraglandular location of the parotid lesions and their benign/malignant nature. The intraglandular lesion spread to superficial/deep lobes was also investigated, together with its relationship to the surrounding structures. The findings were correlated with the cytohistological data from US-guided biopsy or from surgical resection. US was less accurate than CT and MRI, the latter being not statistically superior to the former. Because of the low incidence of pitfalls, US with fine-needle aspiration cytology should be the technique of choice; CT and MRI must be used for lesions > 3 cm or for masses in the deep gland lobes. In conclusion, CT accurately assesses parotid lesions but MRI demonstrates the relationship to adjacent structures better.

Adolescent↗
PubMed1993

[Anatomo-radiologic definition of minimal interstitial silicosis and diagnostic contribution of high-resolution computerized tomography].

Minimal interstitial silicosis (MIS) is a histologic entity characterized by questionable radiologic findings--i.e., the p/p 0/1 and 1/0 classes of the International Labour Office (ILO) 1980 classification. Thus, the condition may be responsible for borderline radiologic findings ("suspect" phase of pneumoconiosis). In order to test an alternative method to conventional radiology (CR), HRCT was performed on 35 workers exposed to silica and with histologic diagnosis of MIS: HRCT scans were compared with posteroanterior chest radiographs by using the ILO classification. Histology was the gold standard. HRCT identified many more MIS lesions. Moreover, the superiority of HRCT over CR was also proved by its better correlation with pathologic findings. HRCT provided pieces of information which could not always be obtained by means of conventional chest films. Thus, HRCT can be considered the method of choice in MIS before transbronchial lung biopsy.

Adult↗
PubMed1992

Inhibitory effect of suramin on receptor binding and cytotoxic activity of tumor necrosis factor alpha.

The effect of suramin on the binding of human Tumor Necrosis Factor alpha (huTNF alpha) to specific cell-surface receptors as well as on its cytotoxic activity in vitro was investigated. Suramin inhibited both activities in a dose-dependent manner. Experiments designed to discriminate if suramin exerted its inhibitory activity on the ligand or on the receptor showed that the ligand (huTNF alpha) was the most likely target for suramin in this system. These results may explain, in part, the immunosuppressive activities of suramin that have been observed in vivo and suggest that suramin could be useful in those disease states in which hyperproduction of huTNF alpha has been shown to play a pathogenic role.

Cell Survival↗
PubMed1992

[The dynamic magnetic resonance study of focal liver lesions by FLASH sequences with bolus intravenous gadolinium-DTPA].

Thirty-five patients with hepatic hemangioma (n = 12), metastasis (n = 10), hepatocellular carcinoma (HCC) (n = 10) and focal nodular hyperplasia (n = 3) were examined with the fast low-angle shot (FLASH) technique and an intravenous bolus injection of Gd-DTPA. In order to differentiate the lesions, the following criteria were used: a) pre Gd-DTPA intensity of lesions; b) post Gd-DTPA patterns of contrast enhancement. On the basis of these criteria, an unquestionable differential diagnosis could be made. Hemangiomas were characterized by an hypointense mass before Gd-DTPA, by peripheral contrast enhancement and by subsequent continuous hyperintense fill-in; thus, hemangiomas were visualized as hyperintense lesion during the late phase. Before contrast administration hypovascular metastases appeared as hypointense; they were characterized by delayed uptake of contrast agent. HCCs were hyperintense lesions before contrast administrations; then, quick contrast enhancement and rapid decrease in signal intensity were observed with visualization of a hyperintense ring due to the capsule. Finally, focal nodular hyperplasia appeared isointense or hypointense relative to normal liver on precontrast scans; the lesions were enhanced transiently with subsequent quick dismission of contrast agent. This initial experience suggests dynamic contrast-enhanced MR imaging as an effective method to improve the differential diagnosis among hepatic tumors when precontrast T2-weighted images are equivocal.

Adult↗
PubMed1991

[Magnetic resonance in the study of the temporo-mandibular joint. I. Anatomo-functional findings].

Thirty-four temporomandibular joints (TMJ) were examined in 17 normal subjects with two superconductive MR units at 1T and 1.5T. TMJ evaluation was performed with both SE sequences in occlusal position and with "fast" sequences (flash) during the gradual opening of the mouth. Therefore, both the anatomic features of the TMJs and their dynamic behavior during mouth opening were analyzed. The information acquired allowed the complete and non-invasive evaluation of TMJ function. The knowledge of the normal anatomic and functional patterns is of paramount importance for the diagnostic approach to TMJ pathologic conditions.

Adult↗