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A Scarpa

Publications and source records attributed to A Scarpa.

At least 55 records · Page 3Linked to original sources
PubMed2000

Analysis of CIITA encoding AIR-1 gene promoters in insulin-dependent diabetes mellitus and rheumatoid arthritis patients from the northeast of Italy: absence of sequence variability.

Qualitative and/or quantitative alterations in the expression of the MHC class II molecules affect the onset and maintenance of the immune response and may be the basis of a wide variety of disease states, such as autoimmunity and immunodeficiency.CIITA is a major physiological regulator of the expression of MHC class II genes. The availability of CIITA ap- pears generally essential for MHC class II gene expression, and hence its own transcriptional regulatory mechanisms result of fundamental importance for a correct homeostasis of the immune response. Therefore, it is possible to hypothesize that variability at the CIITA-encoding locus, AIR-1, could constitute an additional source of susceptible traits to autoimmune diseases. Mutations at AIR-1/CIITA promoters could modulate expression of CIITA. Variations in CIITA expression could influence the qualitative and quantitative expression of MHC class II molecules at cell surface. We have analyzed sequence variation at AIR-1/CIITA promoters by PCR-SSCP in 23 IDDM and 30 RA patients compared to a sample of 19 unaffected normal controls and 16 unaffected IDDM family members, for a total of 88 Caucasian subjects from the Northeast of Italy. No sequence difference was found at the four AIR-1/CIITA promoters between autoimmune patients and normal controls. Moreover, the promoters resulted invariant within the entire group of 88 subjects analyzed, comprising patients and controls. This finding suggests a possible selective advantage in maintaining CIITA upstream regulatory sequences invariant.

Arthritis, Rheumatoid↗
PubMed2000

Renal angiomyolipoma with epithelioid sarcomatous transformation and metastases: demonstration of the same genetic defects in the primary and metastatic lesions.

Angiomyolipoma (AML) is a benign neoplasm that occurs either sporadically or in patients with tuberous sclerosis complex (TSC) and shows frequent allelic losses at chromosome arm 16p. It has been suggested recently that the melanogenesis marker-positive perivascular epithelioid cell (PEC) has been found consistently in AML. The authors report a 50-year-old woman without evidence of TSC affected by classic renal AML containing an area composed of atypical epithelioid cells with the same morphoimmunophenotypic characters of PEC. After 7 years from surgical removal of the lesion, the patient developed a local recurrence and successive lung and abdominal metastases that showed morphologic and immunohistochemical features overlapping those of the epithelioid area of the previously removed AML. Genetic analysis showed that the classic AML and its epithelioid area as well as the pulmonary and abdominal metastases shared the same allelic loss on chromosome arm 16p. Based on these findings, the authors view this case as evidence of a malignant transformation of a classic AML with morphologic, immunophenotypic, and genetic demonstration of its clonal origin.

Abdominal Neoplasms↗
PubMed2000

Cancer of the ampulla of Vater: chromosome 17p allelic loss is associated with poor prognosis.

BACKGROUND: Cancer of the ampulla of Vater kills 60% of affected patients. Local spread of the tumour (T stage) is the only reliable prognostic factor. Nevertheless, any cancer stage includes long term survivors and patients dying from the disease. The molecular anomalies involved in this process have the potential to serve as additional prognostic markers. AIM: To evaluate if allelic losses (LOH) of chromosomes 17p and 18q may be of prognostic value in multivariate survival analysis. METHODS: We examined 53 ampullary cancers for chromosome 17p and 18q LOH using microsatellite markers and DNA from paraffin embedded tumours. All patients were treated by surgery alone (pancreaticoduodenectomy). Multivariate survival analysis included age, sex, tumour size, macroscopic appearance, grade of differentiation, T stage, lymph node metastasis, and chromosome 17p and 18q status. RESULTS: Chromosome 17p and 18q LOH were detected in 28 (53%) and 18 (34%) cancers, respectively. Multivariate survival analysis indicated chromosome 17p status as an independent prognostic factor together with T stage. The five year survival for chromosome 17p retention and 17p loss was 80% and 7%, respectively. The risk of death from cancer within the five year follow up period for patients with cancers harbouring chromosome 17p LOH was 11 times higher than that of patients with cancers retaining chromosome 17p (p<0.0001), regardless of the tumour stage at diagnosis. CONCLUSIONS: Chromosome 17p status is an independent prognostic factor among ampullary cancers at the same stage. The combined use of T stage and chromosome 17p status may help in deciding whether ampullary cancer patients require additional therapy other than surgery alone.

Adult↗
PubMed2000

Inventory of Interpersonal Problems Personality Disorder scales: operating characteristics and confirmatory factor analysis in nonclinical samples.

Research involving clinical samples has demonstrated the utility of a 28-item personality disorder (PD) screening measure (Inventory of Interpersonal Problems--Personality Disorder scale [IIP-PD]) culled from the IIP in the prediction of the presence or absence of a PD (Pilkonis, Kim, Proietti, & Barkham, 1996). This article extends these diagnostic efficiency findings to nonclinical samples and presents additional data regarding the factor structure of the 28 IIP-PD items. Diagnostic efficiency statistics for the IIP-PD scale, calculated using both interview and self-report methods, support the utility of the IIP-PD scale as a screening tool for the presence or absence of a PD. High specificity estimates indicate that individuals who do not exceed Diagnostic and Statistical Manual of Mental Disorders (4th ed.; American Psychiatric Association, 1994) symptom thresholds rarely exceed the IIP-PD cutoff. Furthermore, a high negative predictive power (NPP) estimate derived using an interview-based diagnostic standard suggests that the IIP-PD scale accurately screens out individuals who do not have a PD. Finally, cross-validated confirmatory factor-analytic results involving items composing the 5 IIP PD subscales identified in previous research (Kim, Pilkonis, & Barkham, 1997) suggest that a measurement model with a single second-order factor (general PD) and 5 first-order factors (one representing each PD subscale) provided the best fit to the observed data compared to 2 other competing models.

Adult↗
PubMed2000

Intraductal papillary mucinous tumors of the pancreas. Verona University Pancreatic Team.

METHODS: Literature is thoroughly reviewed and compared to our own experience. RESULTS: Clinical history data do not appear to be useful in differentiating between benign and malignant cases. Usually IPMT patients are older than individuals suffering from chronic obstructive pancreatitis and tend to drink and smoke less. Malignant forms of IPMT are more frequently associated with diabetes, and pain seems to be more frequent in benign cases, although these findings are not confirmed in all reports. Also, laboratory tests are of little use, whereas imaging findings currently enable us to reach a correct diagnosis in about 70% of cases without differentiating in a reliable and definitive way the benign or malignant nature of the neoplasm. The WHO classification appears to be related to the different prognosis. Surgery, whenever possible, is the gold standard treatment. CONCLUSION: IPMT are a recent established clinical entity embracing a spectrum of lesions ranging from benign to malignant infiltrating cases. The only recognized radical treatment is surgery. Despite diagnostic capacity based on clinical presentation and imaging techniques has becoming increasingly refined we are still incapable of identifying the different degree of malignancy preoperatively, if any. The lengthy mean survival after resection confirm the high potential cure rate of IPMT of the pancreas.

Adenocarcinoma, Mucinous↗
PubMed2000

Detection of bladder cancer by semi-automated microsatellite analysis of urine sediment.

Patients with transitional-cell carcinoma (TCC) require careful follow-up due to the high risk of recurrence. Cystoscopy and biopsy are reliable but invasive, while urine cytology is plagued by low sensitivity. It has recently been shown that allelic abnormalities detected by microsatellite analysis of DNA extracted from urine can be used to diagnose TCC with high reliability. As this analysis by classic techniques is unfeasible in a clinical setting, we performed a pilot study to determine the possibility of applying quick DNA extraction methods with laser detection and computer-based analysis of 15 fluorescently labeled PCR amplified microsatellites to detect molecular anomalies in urine sediment in 25 TCC follow-up patients. Of the eighteen cases with recurrent TCC, 14 (78%) were positive by the molecular test whereas only eight (44%) were detected by cytology. Of the seven patients with negative cystoscopy, one resulted positive by the molecular test and had recurrent TCC six-months later. Thus, this microsatellite analysis correctly predicted the clinical diagnosis in 84% (21/25) of cases, compared to 60% by cytology. The application of these semi-automated procedures allows the analysis of 18 samples with 15 markers in one day, encouraging a more expedient introduction into routine clinical use.

Aged↗
PubMed1999

Genomic anomalies in pancreatic tumors other than common adenocarcinoma.

In recent years enormous advances have been made in the understanding of the molecular mechanisms governing pancreatic ductal adenocarcinoma. However, little is known about other pancreatic neoplasms, which include intraductal papillary mucinous (IPMT), serous cystic (SCT), mucinous cystic (MCT), solid pseudopapillary (SPT), acinar and islet cell tumors. In addition, the study of tumors grouped under the unfortunate term of periampullary cancers will help distinguish the pathogenetic features of these neoplasms, often confused with pancreatic head neoplasms. The available data suggest that the less common pancreatic tumor types do not generally follow the same molecular pathway as the more common ductal carcinoma. IPMT seems to contain chromosomal anomalies similar to those found in ductal cancers, whereas papilla of Vater and duodenal cancers show genetic anomalies resembling those of gastrointestinal malignancies. The application of genome-wide screening techniques to these less common pancreatic tumors will undoubtedly play a central role in unraveling the complexity behind their pathology.

Adenocarcinoma↗
PubMed1999

The FHIT gene is expressed in pancreatic ductular cells and is altered in pancreatic cancers.

We examined 2 normal pancreata, 21 primary pancreatic ductal cancers, and 19 pancreatic cancer cell lines for Fhit expression and FHIT gene status. The normal pancreas expressed Fhit protein in the cytoplasm of ductular cells, whereas interlobular and larger ducts, acini, and insulae of Langerhans were negative. Fhit protein was detected by immunoblot assay in 11 pancreatic cancer cell lines; of the 8 cell lines lacking Fhit protein, 7 lacked FHIT mRNA and 1 showed an abnormally sized transcript. DNA from five of these eight cell lines showed homozygous loss of FHIT exon 5. In 8 of the 21 primary cancers, Fhit expression was detected by immunohistochemistry. Reverse transcription-PCR analysis of 6 of the 13 cases lacking Fhit showed normal-sized FHIT product in 3 cases and a mixture of normal and abnormal products in the other 3. Sequencing showed that abnormal bands were missing variable numbers of exons. Loss of microsatellite DNA markers internal to the FHIT gene was observed in 10 of 13 primary cancers lacking Fhit protein (homozygous in two cases) and in only 1 of the 8 cancers expressing Fhit protein. In nine primary cancers, four expressing and five lacking Fhit protein, it was possible to obtain pure cancer DNA by microdissection. Three of the five microdissected cases lacking Fhit protein exhibited homozygous deletion of FHIT exon 5. In conclusion, the lack of Fhit protein in pancreatic cancers correlated with absence or alteration of FHIT mRNA and was often associated with FHIT gene anomalies.

Acid Anhydride Hydrolases↗
PubMed1999

Correlation of poly(ADP-ribose)polymerase and p53 expression levels in high-grade lymphomas.

The steady-state levels of mRNA for the poly(ADP-ribose)polymerase (PARP), c-myc, p53, and histone H3 genes were investigated in 31 high-grade B-cell lymphomas by northern blot analysis. The panel included 15 nodal large B-cell lymphomas, nine mediastinal large B-cell lymphomas, and seven sporadic Burkitt's lymphomas. The PARP mRNA level was significantly higher in lymphomas than in control tissues and corresponded with the amount of PARP protein, as assessed by immunoblot analysis in six samples. The level of PARP mRNA was positively correlated with that of p53 mRNA. No correlation was found between the mRNA expression levels of PARP and histone H3, suggesting that PARP expression levels are independent of the proliferation rate of neoplastic cells. In this setting, the strong correlation between PARP and p53 suggests that the high expression of PARP may be associated with ongoing DNA damage in high-grade lymphomas.

Adolescent↗
PubMed1999

Hepatitis C virus infection of peripheral nerves in type II cryoglobulinaemia.

Peripheral neuropathy is a frequent complication in patients suffering from type II mixed cryoglobulinaemia (mCGII), a sort of vasculitis that is strongly associated with hepatitis C virus (HCV) infection and characterised by high concentrations of anti-HCV antibodies and HCV RNA in the cryoprecipitates. We report the finding of HCV RNA in homogenates of nerve biopsies from five such patients, by reverse transcription-polymerase chain reaction (RT-PCR) amplification of different regions of the viral genome. HCV RNA was localized in epineurial cells by in situ RT-PCR. Our data suggest that HCV infection of nerves plays a major role in mCGII-associated neuropathy.

Cryoglobulinemia↗
PubMed1999

Intermediate results of extended pancreaticoduodenectomy. Verona experience.

BACKGROUND: Extended pancreaticoduodenectomy (EPD) with retroperitoneal lymphatic, neural, and connective clearance has been proposed to improve survival in patients with carcinomas of the head of the pancreas. The open questions are: does EPD allow better staging of the tumor? Does it reduce local recurrences? And does it improve survival? METHOD: We treated 26 patients by EPD between January 1994 and September 1996. Eighteen patients had pancreatic ductal carcinoma, 7, periampullary carcinoma; and 1, intraductal papillary mucinous carcinoma. RESULTS: The pancreatic cancers were International Union against Cancer (UICC) stage I in 3 patients, stage III in 14, and stage IV in 1. Two patients with stage III disease would have been considered as having stage I without EPD. Pancreatic cancer and periampullary carcinoma patients had a 3-year actuarial survival of 32% and 86%, respectively. At a mean follow-up time of 22.5 months (range, 6-39 months), 3 pancreatic cancer patients (16.6%) had loco-regional recurrences, 6 patients (33%) had distant metastases, and 1 (5.5%) had distant and loco-regional recurrences. Only 1 of 7 patients with periampullary carcinoma had distant metastasis 20 months after resection. CONCLUSION: EPD seems to decrease the rate of local recurrences and allows more correct staging. The intermediate survival results are encouraging but a definitive conclusion awaits longer follow-up.

Adenocarcinoma↗
PubMed1999

Molecular features of primary mediastinal B-cell lymphoma: involvement of p16INK4A, p53 and c-myc.

Primary mediastinal B-cell lymphoma (PMBL) shows chromosome 9p anomalies in 50% of cases. Based on reports that p16INK4A gene, located on this chromosomal arm, is frequently altered in aggressive lymphomas, we analysed for alterations of this gene in 27 cases of PMBL, which were part of a series of 32 PMBL cases that have been characterized for alterations in c-myc, p53, N-ras, bcl-1, bcl-2, bcl-6 and for Epstein-Barr virus (EBV) infection. Four cases showed p16INK4A gene anomalies, including three with promoter methylation and one homozygous deletion. Eight PMBLs showed c-myc rearrangements. Three additional cases showed sequence variations in the c-myc P2 promoter, two of which consisted of the same germline variation involving a novel polymorphic XhoI site. Four tumours contained p53 gene mutations and three had clonal EBV infection. One case had a bcl-6 rearrangement. In conclusion, our study shows that p16INK4, c-myc and p53 alterations occur in 15%, 25% and 13% of PMBLs, respectively. EBV monoclonality was found in 9% of cases, whereas no abnormality was detected in bcl-1, bcl-2 and N-ras. Thus, none of the common genetic aberrations seen in other types of non-Hodgkin's lymphomas appears to be stringently involved in the pathogenesis of this unique lymphoma type.

Adult↗
PubMed1999

High-copy suppressor analysis reveals a physical interaction between Sec34p and Sec35p, a protein implicated in vesicle docking.

A temperature-sensitive mutant, sec34-2, is defective in the late stages of endoplasmic reticulum (ER)-to-Golgi transport. A high-copy suppressor screen that uses the sec34-2 mutant has resulted in the identification of the SEC34 structural gene and a novel gene called GRP1. GRP1 encodes a previously unidentified hydrophilic yeast protein related to the mammalian Golgi protein golgin-160. Although GRP1 is not essential for growth, the grp1Delta mutation displays synthetic lethal interactions with several mutations that result in ER accumulation and a block in the late stages of ER-to-Golgi transport, but not with those that block the budding of vesicles from the ER. Our findings suggest that Grp1p may facilitate membrane traffic indirectly, possibly by maintaining Golgi function. In an effort to identify genes whose products physically interact with Sec34p, we also tested the ability of overexpressed SEC34 to suppress known secretory mutations that block vesicular traffic between the ER and the Golgi. This screen revealed that SEC34 specifically suppresses sec35-1. SEC34 encodes a hydrophilic protein of approximately 100 kDa. Like Sec35p, which has been implicated in the tethering of ER-derived vesicles to the Golgi, Sec34p is predominantly soluble. Sec34p and Sec35p stably associate with each other to form a multiprotein complex of approximately 480 kDa. These data indicate that Sec34p acts in conjunction with Sec35p to mediate a common step in vesicular traffic.

Amino Acid Sequence↗
PubMed1999

Mucinous cystic tumors of the pancreas: clinicopathological features, prognosis, and relationship to other mucinous cystic tumors.

The clinicopathological features of 56 patients with mucinous cystic tumors (MCTs) of the pancreas were studied. Particular attention was paid to the prognosis of MCTs and the relationship to their ovarian, hepatic, and retroperitoneal counterparts. To distinguish MCTs from pancreatic intraductal papillary-mucinous tumors, MCTs were defined as tumors lacking communication with the duct system and containing mucin-producing epithelium, usually supported by ovarian-like stroma. All 56 tumors occurred in women (mean age 48.2 years) and were preferentially (93%) located in the body and tail of the pancreas. In accordance with the WHO classification, MCTs were divided into adenomas (n = 22), borderline tumors (n= 12), and noninvasive and invasive carcinomas (n = 22). Survival analysis revealed the extent of invasion to be the most significant prognostic factor (p<0.0001). Malignancy correlated with multilocularity and presence of papillary projections or mural nodules, loss of ovarian-like stroma, and p53 immunoreactivity. Stromal luteinization with expression of tyrosine hydroxylase, calretinin, or alpha inhibin was found in 66% of the cases. We conclude that the biologic behavior of MCTs is predictable on the basis of the extent of invasion. The similarities (i.e. gender, morphology, stromal luteinization) between pancreatic MCT and its ovarian, hepatobiliary, and retroperitoneal counterparts suggest a common pathway for their development.

Adenocarcinoma, Mucinous↗
PubMed1999

Screening for personality disorders in a nonclinical population.

Based on the Inventory of Interpersonal Problems (IIP), the IIP-PD and the IIP-C screening scales were developed to distinguish personality disorder (PD) from non-PD and Cluster C from other PD, respectively, in a clinic population. Two studies were conducted to determine (a) validity and reliability of these IIP scales for PD screening in a nonclinical population, (b) specificity of IIP-C for identifying Cluster C, and (c) usefulness of the IIP scales for screening Cluster A. College students were screened using the IIP scales (Study 1, N = 454, Study 2, N = 87). High and low scorers completed PD-related questionnaires in Study 1 and a clinical interview for PD symptomatology in Study 2. Results indicated strong test-retest reliability, internal consistency, and factorial, convergent, and external validity. The scales tapped a common deficit in interpersonal relatedness, with some distinction between externalizing and internalizing dimensions, respectively, and both scales were positively and significantly associated with schizotypal traits. In conclusion, the IIP-PD and IIP-C are useful and valid screening instruments for identifying any versus no PD in nonclinical populations.

Adolescent↗
PubMed1999

Nonrandom chromosomal imbalances in primary mediastinal B-cell lymphoma detected by arbitrarily primed PCR fingerprinting.

We used arbitrarily primed polymerase chain reaction (AP-PCR) fingerprinting to identify chromosomal imbalances in six primary mediastinal B-cell lymphomas (PMBLs). Seventy-four chromosomal imbalances were detected, consisting of 49 sequence gains and 25 losses. Amplifications on chromosome X were seen in five cases, four of which involved the same chromosomal locus. Nonrandom gains at the same locus were also identified on chromosomes 2 and 7 in four cases and on chromosomes 5, 9, and 12 in three cases. Five PMBLs were also analyzed by comparative genomic hybridization (CGH), which found chromosome arm 9p amplification as the only nonrandom imbalance. Our data demonstrate that chromosomal amplifications outnumber losses in PMBL. These mainly involve chromosomes 9 and X and may reflect more complex phenomena, such as translocations or other chromosomal rearrangements, as AP-PCR found coexistent gains and losses on these chromosomes. Comparison between AP-PCR and CGH suggests that anomalies affecting the same chromosomal regions may occur at much higher frequencies than expected by CGH, suggesting that genomic amplifications are usually confined to DNA segments smaller than the megabase long segments required for detection in CGH. Modest increases in genetic material may be as effective as higher-level amplifications when affecting sites where a proto-oncogene resides.

Chromosome Aberrations↗
PubMed1998

TRAPP, a highly conserved novel complex on the cis-Golgi that mediates vesicle docking and fusion.

We previously identified BET3 by its genetic interactions with BET1, a gene whose SNARE-like product acts in endoplasmic reticulum (ER)-to-Golgi transport. To gain insight into the function of Bet3p, we added three c-myc tags to its C-terminus and immunopurified this protein from a clarified detergent extract. Here we report that Bet3p is a member of a large complex ( approximately 800 kDa) that we call TRAPP (transport protein particle). We propose that TRAPP plays a key role in the targeting and/or fusion of ER-to-Golgi transport vesicles with their acceptor compartment. The localization of Bet3p to the cis-Golgi complex, as well as biochemical studies showing that Bet3p functions on this compartment, support this hypothesis. TRAPP contains at least nine other constituents, five of which have been identified and shown to be highly conserved novel proteins.

Amino Acid Sequence↗