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C Giannini

Publications and source records attributed to C Giannini.

At least 37 records · Page 2Linked to original sources
PubMed2001

Oligodendrogliomas: reproducibility and prognostic value of histologic diagnosis and grading.

Prognostic value of histological grading of oligodendroglial tumors is controversial and interobserver reproducibility in grading of these tumors is unknown. Seven neuropathologists and 6 surgical pathologists experienced in brain tumor-diagnosis assessed 124 oligodendroglial tumors operated at the Mayo Clinic (1960-1990). Among histologic parameters upon which current oligodendroglioma grading systems are based, only high cellularity, presence of mitoses, microcalcifications, endothelial hypertrophy, endothelial proliferation, and necrosis appeared to be reproducible. Reproducible histologic features, based on consensus ratings among neuropathologists (defined as > 60%), were evaluated for the association with cause-specific survival by fitting Cox regression models. By univariate analysis, a significant association with survival was found for age, high cellularity, presence of mitoses, endothelial hypertrophy and proliferation and necrosis. On multivariable analysis with a stepwise variable selection method, only age and presence of endothelial proliferation were found to be independently associated with survival with a discriminatory index of the model of 0.68. Mitotic index was significantly associated with survival based on the grading from each separate neuropathologist, but it was not based on consensus, most likely because this was classified as indeterminate in 54% of cases. Alternatively, "models fit" considering the assessment of single neuropathologists, identified a model based on age and on mitotic index with similar discriminatory indices of 0.69-0.7. Our study found few factors independently associated with cause specific-survival among morphological parameters. These findings are consistent with the present WHO stratification of oligodendrogliomas into low- and high-grade variants.

Adult↗
PubMed2000

Variable expression of familial Alzheimer disease associated with presenilin 2 mutation M239I.

In a family with autopsy-confirmed Alzheimer disease, the authors found a mutation in the presenilin 2 (PS2) gene (PSEN2) that predicts a methionine-to-isoleucine change at PS2 residue 239 (M239I), at which a change to valine was known in another family. Phenotypic expression of M239I was highly variable, with disease onset between age 44 and 58 years, and two nonaffected mutation carriers at age 58 and 68 years. The data showed no influence of APOE but were compatible with other possible genetic modifiers of the phenotype or penetrance of M239I.

Adult↗
PubMed2000

Non-destructive determination of local strain with 100-nanometre spatial resolution

Structure sizes of approximately 180 nm are now standard in microelectronics, and state-of-the-art fabrication techniques can reduce these to just a few tens of nanometres. But at these length scales, the strain induced at interfaces can locally distort the crystal lattice, which may in turn affect device performance in an unpredictable way. A means of non-destructively characterizing such strain fields with high spatial resolution and sensitivity is therefore highly desirable. One approach is to use Raman spectroscopy, but this is limited by the intrinsic approximately 0.5-microm resolution limit of visible light probes. Techniques based on electron-beam diffraction can achieve the desired nanometre-scale resolution. But either they require complex sample preparation procedures (which may alter the original strain field) or they are sensitive to distortional (but not dilational) strain within only the top few tens of nanometres of the sample surface. X-rays, on the other hand, have a much greater penetration depth, but have not hitherto achieved strain analysis with sub-micrometre resolution. Here we describe a magnifying diffraction imaging procedure for X-rays which achieves a spatial resolution of 100nm in one dimension and a sensitivity of 10(-4) for relative lattice variations. We demonstrate the suitability of this procedure for strain analysis by measuring the strain depth profiles beneath oxidized lines on silicon crystals.

Journal Article↗
PubMed2000

T(14;18) translocation in chronic hepatitis C virus infection.

Pathogenic mechanisms of B-cell lymphoproliferative disorders in chronic hepatitis C virus (HCV) infection are unclear. We studied t(14;18) translocation by polymerase chain reaction in peripheral blood mononuclear cells from 50 patients with HCV-related liver disease (group A), 7 with mixed cryoglobulinemia syndrome (group B), 55 with HCV-negative liver disease (group C), and 30 with HCV-negative chronic rheumatic disorders or chronic infection by nonhepatotropic agents (group D). T(14;18) was significantly more frequent in group A (13/50 patients = 26 %) and group B (5/7 = 71.4%) patients than in group C (1/55 = 3.6%) and group D (1/30 = 3.3%) ones. Immunoblot analysis showed bcl-2 over-expression in all t(14;18)-positive samples. In group A, 10/13 (77%) patients with t(14;18) and 13/37 (35%) without t(14;18) had serum cryoglobulins in the absence of mixed cryoglobulinemia symptoms (P <.05). These data indicate that t(14;18) and bcl-2 over-expression in lymphoid cells are frequent in chronic HCV infection and suggest that this event may contribute to the pathogenesis of HCV-related lymphoproliferative disorders.

Aged↗
PubMed2000

The immunophenotype of ependymomas.

The morphologic distinction of ependymomas with epithelial cytology from metastatic carcinoma may pose a significant problem in differential diagnosis. The known presence of keratin in glioma cells further complicates the issue. Using the labeled streptavidin-biotin method with automated staining, we studied epithelial and glial marker expression in 52 ependymomas of varying type and grade, including 20 epithelial-appearing, 14 glial-appearing, eight mixed pattern, and 10 myxopapillary tumors; 38 were low grade and 14 anaplastic. All tumors were immunoreactive for glial fibrillary acidic protein (GFAP), and S-100 protein. Diffuse staining for GFAP was noted in glial-appearing ependymomas featuring perivascular pseudorosettes. Diffuse immunostaining for S-100 protein was seen in cellular lesions exhibiting epithelial-like features. Staining was more diffuse for GFAP than S-100 protein in anaplastic ependymomas. Keratin (AE1/AE3) reactivity was seen in 98% of cases, the pattern being similar to that of GFAP. The frequency of staining for other keratins varied: wide-spectrum keratin (35%), cytokeratin (CK)7 (20%), CAM 5.2 (19%), CK903 (14%), and CK20 (8%); as a rule, it was scant and limited to occasional cells and processes. epithelial membrane antigen (EMA) staining was seen in 36% of all cases and in 67% of epithelial-appearing tumors wherein it often high-lighted microlumina. Aside from AE1/AE3 staining and very infrequent wide-spectrum keratin and EMA reactivity, expression of epithelial markers was not seen in anaplastic ependymomas. No carcinoembryonic antigen (CEA) positivity was noted in any case. Collagen IV reactivity was limited to tumor cell-stroma interfaces. Although variable, S-100 protein and GFAP staining is seen in all ependymomas, particularly in true and perivascular pseudorosettes. Widespread reactivity for keratin AE1/AE3 corresponds closely to the pattern of GFAP staining. Significant staining for other keratins or for CEA is inconsistent with a diagnosis of ependymoma. EMA reactivity is largely limited to luminal staining of rosettes and tubules.

Biomarkers, Tumor↗
PubMed1999

Hepatitis B virus X mutants, present in hepatocellular carcinoma tissue abrogate both the antiproliferative and transactivation effects of HBx.

Chronic infection by HBV is the leading cause of hepatocellular carcinoma in man. Several lines of evidence suggest that the viral transactivator HBx plays a critical role in the molecular pathogenesis of HBV-related HCC. To study the actual impact of HBx and the mechanism of its action, we have recently cloned and characterized a set of X-sequences from HCC in patients with chronic infection by HBV. In the present study, we have compared the effects of HBx and its naturally arising mutants on cell growth and viability. We report that HBx inhibits clonal outgrowth of cells and induces apoptosis by a p53-independent pathway. Furthermore, HBx expression induced a late G1 cell cycle block prior to their counterselection by apoptosis. Importantly, mutations in the HBx-gene evolving in hepatocellular carcinoma abolished both HBx-induced growth arrest and apoptosis. Using a panel of engineered mutants we have mapped the growth suppressive effect of HBx to domains shown to be required for its transactivating function. Based on these results, we propose that abrogation of the anti-proliferative and apoptotic effects of HBx by naturally occurring mutations might render the hepatocytes susceptible to uncontrolled growth and contribute to multistep hepatocarcinogenesis associated with HBV-infection.

Amino Acid Sequence↗
PubMed1999

Pleomorphic xanthoastrocytoma: what do we really know about it?

BACKGROUND: Pleomorphic xanthoastrocytomas (PXA) may recur and demonstrate aggressive clinical behavior with a mortality rate between 15% and 20%. To the authors' knowledge, no histopathologic features currently are known to reliably predict recurrence or tumor progression. METHODS: The study was based on 71 cases with available information regarding clinical and therapeutic data and follow-up. Diagnostic features included cellular pleomorphism, giant and/or xanthic cells, eosinophilic granular bodies, desmoplasia, and leptomeningeal involvement. The mitotic index (MI), the presence of necrosis, and endothelial proliferation were recorded in all primary resection specimens. RESULTS: The study included 35 females and 36 males, age 26+/-16 years (mean +/- standard deviation). Approximately 98% of tumors were supratentorial, with 49% in the temporal lobe. Seizures were the presenting symptoms in 71% of patients. Extent of tumor removal was macroscopic total resection in 68% of cases and subtotal resection (STR) in 32% of cases. Postoperative radiotherapy, alone or with chemotherapy, was administered in 29% and 12.5% of cases, respectively. The recurrence free survival rates (RFS) were 72% at 5 years and 61% at 10 years, whereas overall survivals rates (OS) were 81% at 5 years and 70% at 10 years. In univariate analysis, the extent of resection was the single factor associated most strongly with RFS (P=0.003), followed by MI (P=0.007) and atypical mitoses (P=0.04). Necrosis was not found to be significant. The extent of resection and MI were confirmed as independent predictors of RFS by multivariate analysis. MI (P=0.001), atypical mitoses (P=0.02), and necrosis (P=0.04) were associated with OS by univariate analysis. In multivariate analysis, only MI was an independent predictor of survival. Information regarding MIB-1 labeling index and the use of adjuvant therapy was too limited to explore their prognostic significance confidently. CONCLUSIONS: The study confirms that PXA is an astrocytic tumor with a relatively favorable prognosis. MI and extent of resection appear to be the main predictors of RFS and OS. Given the slow growth of the tumor, more studied cases and longer periods of follow-up will be essential to confirm our findings regarding prognostic factors affecting this unusual tumor.

Adolescent↗
PubMed1999

Monocyte chemotactic protein-1 as a chemoattractant for human hepatic stellate cells.

Following liver injury, hepatic stellate cells (HSC) undergo proliferation and migrate into damaged areas in response to chemotactic factors. HSC have been shown to regulate leukocyte trafficking by secreting monocyte chemotactic protein-1 (MCP-1), a chemokine that recruits monocytes and lymphocytes. In this study, we explored whether MCP-1 exerts biological actions on HSC. HSC were isolated from normal human livers, cultured on plastic, and studied in their myofibroblast-like phenotype, and three different cells lines were used. Chemotaxis was measured in modified Boyden chambers. Phosphatidylinositol 3-kinase (PI 3-K) was assayed on phosphotyrosine immunoprecipitates. Exposure of HSC to MCP-1 stimulated migration of HSC in a dose-dependent fashion. Maximal stimulation was obtained with 250 ng/mL MCP-1, which resulted in a 3- to 4-fold stimulation of cell migration. Checkerboard analysis showed that the increase in cell migration was almost completely a result of chemotaxis rather than chemokinesis. In contrast, in quiescent HSC, MCP-1 did not exert any effect on cell migration. In leukocytes, MCP-1 activates the pertussis toxin-sensitive CCR2 receptor. However, transcripts for CCR2 could not be shown in HSC, and pertussis toxin only modestly inhibited MCP-1-induced migration. Exposure of HSC to MCP-1 was associated with an increase in cytosolic calcium concentration, PI 3-K activity, protein tyrosine phosphorylation. Blocking calcium influx or pretreatment of HSC with the PI 3-K inhibitor wortmannin markedly reduced cell migration. This study shows, for the first time, a potential direct profibrogenic action of MCP-1 via HSC chemotaxis. MCP-1-dependent signals in these cells are not transduced by CCR2 and may be mediated by alternative chemokine receptors. (HEPATOLOGY 1999;29:140-148.)

Blotting, Western↗
PubMed1999

Prevalence of mixed infection by different hepatitis C virus genotypes in patients with hepatitis C virus-related chronic liver disease.

Multiple infection by different hepatitis C virus (HCV) genotypes may be of great clinico-pathologic interest. In this study we determined the effective prevalence of coinfections by two or more HCV genotypes in 213 subjects with HCV-positive chronic hepatitis by using genotype-specific polymerase chain reaction (PCR), genotype-specific probe hybridization, and direct sequencing. The most prevalent genotype was HCV-1b (54%). HCV-2 (a/c) was also prevalent (27%), and types 1a and 3a were found in 5% and 3% of patients, respectively. A mixed infection was detected in 23 patients (10.8%): 4 out of 23 were coinfected by types 1a + 1b, while the remaining 19 patients had a b + 2 (a/c) mixed infection. Further analysis based on restriction fragment length polymorphism (RFLP) on type-specific PCR products was used to verify genotyping results. Only four coinfections (1a + 1b in 2 patients and 1b + 2 (a/c) in the remaining 2 patients, respectively) were confirmed by enzyme cleavage. All patients with true coinfection had long-lasting infection and liver cirrhosis. Both true and false mixed infections resulting from RFLP analysis were confirmed by direct sequencing of type-specific amplification products. We also determined a recurrent C/T transversion at position 618 in all sequenced samples. In 4 cases another point mutation (G/A at position 626) was found, reducing the number of mismatches between HCV-2 and HCV-1b from 4 to 3 (or 2). Interestingly, all HCV-2 isolates sequenced showed the highest degree of nucleotide homology with HCV-2 subtype c, confirming the relatively high prevalence of this subtype in Italy. In conclusion, we showed the possibility of multiple infection by different HCV types in the general population of chronically infected patients without particular risk factors, even if in a low percentage of cases. Further studies are needed to assess the clinical relevance of chronic HCV infection with multiple genotypes.

Adult↗
PubMed1999

New jaspamide derivatives from the marine sponge Jaspis splendans collected in Vanuatu.

Two new jaspamide derivatives (1 and 2) along with jaspamide have been isolated from the marine sponge Jaspis splendans collected in Vanuatu. Their chemical structures were determined from 1D and 2D NMR studies and MS data. These two compounds inhibited the in vitro growth of the NSCLC-N6 human tumor cell lines with IC50 values in the microg/mL range.

Animals↗
PubMed1999

Primary melanocytic neoplasms of the central nervous systems.

Primary melanocytic neoplasms of the central nervous system (CNS) consist of a spectrum ranging from well-differentiated melanocytoma to its overtly malignant counterpart, melanoma. Diagnostically difficult intermediate lesions lie between these extremes. Clinicopathologic features of 33 cases were studied to define histologic appearances, diagnostic criteria, and the clinical behavior of lesions along this spectrum. Seventeen cases were well-differentiated, solitary leptomeningeal tumors classified as melanocytomas. They contained variably pigmented melanocytic cells arranged in tight nests, sheets, or fascicles. Mitotic rates ranged from zero to one per 10 high-power fields (HPFs), with most having zero per 10 HPFs. All tumors were immunoreactive for HMB-45 and S-100 protein and negative for epithelial membrane antigen. MIB-1 staining was low (<1-2%). Nuclei were regular, often with small, eosinophilic nucleoli. These lesions arose predominantly in the spinal canal (65%) in patients ranging in age from 17 to 73 years. None recurred after surgical resection. In contrast to these benign lesions, there were 13 cases with histologic and cytologic features consistent with those of malignant melanoma. These cases contained larger, cytologically atypical, pigmented tumor cells growing in loose nests or sheets, often with CNS invasion or necrosis. Some contained bizarre, pleomorphic nuclei; others were densely cellular and mitotically active, but less pleomorphic. Mitotic rates (mean, 5.7 per 10 HPFs) and MIB-1 labeling indices (mean, 8.1%) were higher than those of melanocytomas. Melanomas occurred at spinal (38%), posterior fossa (38%), and supratentorial (23%) levels in patients ranging in age from 15 to 71 years. After resection, 8 of 13 lesions recurred, with four being fatal (mean survival, 14 months). Of five totally resected melanomas, four did not recur (mean follow-up, 26 months). Three intermediate-grade melanocytic tumors could not be classified as melanocytoma or melanoma. All showed sheetlike growth patterns, microscopic CNS invasion, and occasional mitoses. MIB-1 staining ranged from 1% to 4%. One tumor recurred after 17 months; one patient was lost to follow-up after 5 months; and the third died after surgery. Although melanocytic tumors represent a spectrum of lesions, certain histopathologic features are helpful in predicting biologic behavior.

Adolescent↗
PubMed1999

Cellular proliferation in pilocytic and diffuse astrocytomas.

Using quantitative image analysis, we evaluated the MIB-1 labeling index (LI) in a large population of pilocytic (n = 131) and diffuse astrocytomas (n = 140), explored its significance as a prognostic predictor of survival, and compared it to other commonly accepted predictors, including grade and its histologic determinants, atypia, mitoses, endothelial proliferation, and necrosis. Diffuse astrocytomas were graded according to the St Anne-Mayo scheme and included 45 grade 2, 50 grade 3, and 45 grade 4 astrocytomas. In pilocytic astrocytomas, mean, median, and range of MIB-1 LIs were 1.1, 0.9, and 0-3.9%, respectively. In diffuse astrocytomas, these values were 2.3, 2, and 0-7.6% in grade 2; 6, 4.4, and 0.1-25.7% in grade 3; 9.1, 6, and 0.3-36% in grade 4. There was a significant difference in the distribution of MIB-1 LIs between pilocytic and diffuse grade 2 astrocytomas (p < 0.001), between grade 2 and grade 3 (p < 0.001), and between tumors of grade 3 and 4 (p = 0.014). Among pilocytic astrocytomas there was no association between survival and MIB-1 LI or any histologic parameter. In diffuse astrocytomas, MIB-1 LI was significantly correlated with grade as well as with mitotic activity (<0.001) and survival. While in diffuse astrocytomas of all grades, necrosis was the strongest factor associated with survival, in tumors of grades 2 and 3 the MIB-1 LI preceded other histologic parameters and, on multivariate analysis, remained the only feature predictive of survival. Grade 3 astrocytomas with a single "solitary" mitosis had a significantly lower MIB-I LI than did grade 3 tumors with >1 mitosis and, compared to the latter, had a significantly longer survival (p = 0.013), one not significantly different from patients with grade 2 astrocytomas. These findings suggest that the cutoff point between grade 2 and 3 in the St. Anne-Mayo scheme may not be optimal and may need to be revised.

Adolescent↗
PubMed1999

Direct association and nuclear import of the hepatitis B virus X protein with the NF-kappaB inhibitor IkappaBalpha.

The X protein of hepatitis B virus (HBV) is a transcriptional activator which is required for infection and may play an important role in HBV-associated hepatocarcinogenesis. It has been suggested that X acts as a nuclear coactivator or stimulates several signal transduction pathways by acting in the cytoplasm. One of these pathways leads to the nuclear translocation of NF-kappaB. A recent report indicates that X activates NF-kappaB by acting on two cytoplasmic inhibitors of this family of transcription factors: IkappaBalpha and the precursor/inhibitor p105. We demonstrate here that X directly interacts with IkappaBalpha, which is able to transport it to the nucleus by a piggyback mechanism. This transport requires a region of IkappaBalpha (the second ankyrin repeat) which has been demonstrated to be involved in its nuclear import following NF-kappaB activation. Using deletion mutants, we showed that amino acids 249 to 253 of IkappaBalpha (located in the C-terminal part of the sixth ankyrin repeat) play a critical role in the interaction with X. This small region overlaps one of the domains of IkappaBalpha mediating the interaction with the p50 and p65 subunits of NF-kappaB and is also close to the nuclear export sequence of IkappaBalpha, therefore providing a potential explanation for the nuclear accumulation of IkappaBalpha with X. This association can also be observed upon the induction of endogenous IkappaBalpha by tumor necrosis factor alpha (TNF-alpha) treatment of Chang cells expressing X. In accordance with this observation, band shift analysis indicates that X induces a sustained NF-kappaB activation following TNF-alpha treatment, probably by preventing the reassociation of newly synthesized nuclear IkappaBalpha with DNA-bound NF-kappaB complexes.

Animals↗
PubMed1999

[Cytogenetics of tumors of the central nervous system: a case study and review of the literature].

The introduction of cytogenetic techniques, especially chromosome banding techniques, has facilitated a more detailed study of the chromosomal basis of hematological malignancies and solid tumours. With the advent of molecular cell biology many new insights have been gained into the pathogenetic mechanisms of cancer. With G banding technique we have studied chromosomal aberrations of 174 tumours of the Central Nervous System in adults and the results obtained have been compared with the literature data.

Adult↗
PubMed1998

Prevalence of monoclonal gammopathies in patients with hepatitis C virus infection.

BACKGROUND: An association between monoclonal gammopathies and chronic liver diseases has been reported. OBJECTIVE: To determine the prevalence of monoclonal gammopathies in patients with chronic hepatitis C virus (HCV) infection and the possible association of monoclonal gammopathies with HCV genotypes. DESIGN: Prospective study. SETTING: Departments of internal medicine and hematology at two university hospitals in Italy. PATIENTS: 239 HCV-positive and 98 HCV-negative patients with chronic liver diseases were recruited consecutively. MEASUREMENTS: Clinical data were gathered, liver histologic examination was done, serum immunoglobulin and cryoglobulin levels were measured, and immunoelectrophoresis was done for monoclonal component detection. Patients with monoclonal gammopathy had serum HCV RNA measured and HCV genotype determined by polymerase chain reaction and had histologic examination of bone marrow. RESULTS: Monoclonal band was detected in 11% of HCV-positive patients and in 1% of HCV-negative patients (P = 0.004). The prevalence of HCV genotype 2a/c was higher in patients with monoclonal gammopathies than in those without (50% compared with 18%; P = 0.009). CONCLUSION: The prevalence of monoclonal gammopathies in patients with HCV-related chronic liver disease is striking and is often associated with genotype 2a/c infection.

Adolescent↗
PubMed1998

Erdheim-Chester disease with extensive intraaxial brain stem lesions presenting as a progressive cerebellar syndrome.

We report a rare case of Erdheim-Chester disease (ECD) presenting as a progressive cerebellar syndrome and diabetes insipidus. On magnetic resonance imaging, a 7-mm extraaxial, enhancing mass was seen enveloping the right vertebral artery and was confirmed at autopsy to represent an adventitial xanthoma with lipid-laden, foamy histiocytes. The cerebellar syndrome most likely resulted from extensive histiocytic infiltration of the pons, particularly the basis pontis and middle cerebellar peduncles.

Aged↗
PubMed1998

Immature teratoma of the pineal gland with isochromosome 12p.

An immature teratoma arising in the pineal gland in a 27-year-old male was shown to present an isochromosome 12p as evidenced by cytogenetic and fluorescence in situ hybridization analysis. As i(12p) is characteristic of gonadal germ cell tumors, this case indicates that similar genetic pathways may operate in gonadal and intracranial teratomas.

Adult↗