Paranoid Thoughts in Adolescents with Social Anxiety Disorder.

Recently, social anxiety disorder (SAD) and paranoia have been demonstrated to be closely related. However, data were primarily drawn from adult community samples or patients with schizophrenia. The present study used a cross-sectional design to evaluate a sample of adolescents with SAD (n = 30, mean age 15.3 ± 0.9 years) compared with an age- and sex-matched group of healthy controls (n = 26, mean age 15.9 ± 1.6 years). The SAD group displayed more frequent and intense paranoid thoughts than the control group (t = 4.16, p < 0.001). The level of paranoid thoughts was significantly predicted by the degree of social phobia, even after adjusting for sex and other anxiety disorders, although adjusting for depression slightly reduced the extent and significance of the prediction. A lack of awareness about the association between SAD and paranoia may lead to incorrect diagnoses (e.g. misdiagnosis of psychotic disorders), or it may negatively influence the (psycho)therapeutic process and patient outcomes.

Rat protein tyrosine phosphatase eta suppresses the neoplastic phenotype of retrovirally transformed thyroid cells through the stabilization of p27(Kip1).

The r-PTPeta gene encodes a rat receptor-type protein tyrosine phosphatase whose expression is negatively regulated by neoplastic cell transformation. Here we first demonstrate a dramatic reduction in DEP-1/HPTPeta (the human homolog of r-PTPeta) expression in a panel of human thyroid carcinomas. Subsequently, we show that the reexpression of the r-PTPeta gene in highly malignant rat thyroid cells transformed by retroviruses carrying the v-mos and v-ras-Ki oncogenes suppresses their malignant phenotype. Cell cycle analysis demonstrated that r-PTPeta caused G(1) growth arrest and increased the cyclin-dependent kinase inhibitor p27(Kip1) protein level by reducing the proteasome-dependent degradation rate. We propose that the r-PTPeta tumor suppressor activity is mediated by p27(Kip1) protein stabilization, because suppression of p27(Kip1) protein synthesis using p27-specific antisense oligonucleotides blocked the growth-inhibitory effect induced by r-PTPeta. Furthermore, we provide evidence that in v-mos- or v-ras-Ki-transformed thyroid cells, the p27(Kip1) protein level was regulated by the mitogen-activated protein (MAP) kinase pathway and that r-PTPeta regulated p27(Kip1) stability by preventing v-mos- or v-ras-Ki-induced MAP kinase activation.

The activation of the phosphotyrosine phosphatase eta (r-PTP eta) is responsible for the somatostatin inhibition of PC Cl3 thyroid cell proliferation.

The aim of this study was the characterization of the intracellular effectors of the antiproliferative activity of somatostatin in PC Cl3 thyroid cells. Somatostatin inhibited PC Cl3 cell proliferation through the activation of a membrane phosphotyrosine phosphatase. Conversely, PC Cl3 cells stably expressing the v-mos oncogene (PC mos) were completely insensitive to the somatostatin antiproliferative effects since somatostatin was unable to stimulate a phosphotyrosine phosphatase activity. In PC mos cells basal phosphotyrosine phosphatase activity was also reduced, suggesting that the expression of a specific phosphotyrosine phosphatase was impaired in these transformed cells. We suggested that this phosphotyrosine phosphatase could be r-PTP eta whose expression was abolished in the PC mos cells. To directly prove the involvement of r-PTP eta in somatostatin's effect, we stably transfected this phosphatase in PC mos cells. This new cell line (PC mos/PTP eta) recovered somatostatin's ability to inhibit cell proliferation, showing dose-dependence and time course similar to those observed in PC Cl3 cells. Conversely, the transfection of a catalytically inactive mutant of r-PTP eta did not restore the antiproliferative effects of somatostatin. PC mos/PTP eta cells showed a high basal phosphotyrosine phosphatase activity which, similarly to PC Cl3 cells, was further increased after somatostatin treatment. The specificity of the role of r-PTP eta in somatostatin receptor signal transduction was demonstrated by measuring its specific activity after somatostatin treatment in an immunocomplex assay. Somatostatin highly increased r-PTP eta activity in PCCl3 and PC mos/PTP eta (+300%, P < 0.01) but not in PCmos cells. Conversely, no differences in somatostatin-stimulated SHP-2 activity, (approximately +50%, P < 0.05), were observed among all the cell lines. The activation of r-PTP eta by somatostatin caused, acting downstream of MAPK kinase, an inhibition of insulin-induced ERK1/2 activation with the subsequent blockade of the phosphorylation, ubiquitination, and proteasome degradation of the cyclin-dependent kinase inhibitor p27(kip1). Ultimately, high levels of p27(kip1) lead to cell proliferation arrest. In conclusion, somatostatin inhibition of PC Cl3 cell proliferation requires the activation of r-PTP eta which, through the inhibition of MAPK activity, causes the stabilization of the cell cycle inhibitor p27(kip1).

Rat protein tyrosine phosphatase eta physically interacts with the PDZ domains of syntenin.

The tyrosine phosphatase r-PTPeta is able to suppress the malignant phenotype of rat thyroid tumorigenic cell lines. To identify r-PTPeta interacting proteins, a yeast two-hybrid screening was performed and an insert corresponding to the full-length syntenin cDNA was isolated. It encodes a protein containing two PDZ domains that mediates the binding of syntenin to proteins such as syndecan, proTGF-alpha, beta-ephrins and neurofascin. We show that r-PTPeta is able to interact with syntenin also in mammalian cells, and although syntenin is a tyrosine-phosphorylated protein it is not a substrate of r-PTPeta. The integrity of both PDZ domains of syntenin and the carboxy-terminal region of r-PTPeta are required for the interaction between syntenin and r-PTPeta.

Iodide symporter gene expression in normal and transformed rat thyroid cells.

OBJECTIVE: Decrease or loss of the Na+/I- symporter (NIS) activity profoundly affects the suitability of the use of radioiodine to detect or treat metastatic thyroid tissues. The aim of our study was to verify whether specific oncogene abnormalities were responsible for the alteration in NIS activity in thyroid cells. DESIGN AND METHODS: Expression of the NIS gene was investigated by Northern blot analysis in normal and in some oncogene-transformed cell lines with different degrees of malignancy which had lost the iodide uptake ability. RESULTS: NIS gene expression was up-regulated by TSH in a dose-dependent and time-dependent way in normal PC Cl 3 cells. The same effect was observed by activating the cAMP-dependent pathway by forskolin. Conversely, insulin and 12-O-tetradecanoylphorbol-13-acetate (TPA) showed a partial inhibitory effect on NIS gene expression. The oncogene-transformed cell lines PC v-erbA, PC HaMSV, PC v-raf, and PC E1A cells showed reduced NIS mRNA levels compared with the normal PC Cl 3 cells. Conversely, an almost complete absence of NIS gene expression was found in PC RET/PTC, PC KiMSV, PC p53(143ala), and PC PyMLV cell lines. CONCLUSIONS: Our data show that oncogene activation could play a role in affecting the iodide uptake ability in thyroid tumoral cells; different mechanisms are involved in the oncogene-dependent loss of NIS activity in transformed thyroid cells.

The highly malignant phenotype of anaplastic thyroid carcinoma cell lines is recessive.

OBJECTIVE: The aim of our studies was to determine whether the phenotype of the anaplastic thyroid carcinomas is dominant or recessive. In fact, it is hypothesized, on the basis of epidemiological and pathological data, that undifferentiated thyroid carcinomas are derived from differentiated tumours through a mechanism of tumour progression. DESIGN: Cell hybrids have been generated by cell fusion of anaplastic thyroid carcinoma cell lines, which show a highly malignant phenotype, to cell lines deriving from differentiated thyroid carcinoma, which show a non-tumorigenic or a poorly tumorigenic phenotype. All of the parental cell lines showed impaired p53 gene function. RESULTS: The cell hybrids contained alleles from the parental cell lines. All of the cell hybrids showed a lower growth rate compared with the parental undifferentiated carcinoma cell lines and were unable to grow in soft agar and to induce tumours after injection into athymic mice. CONCLUSION: Taken together, these findings suggest that the highly malignant phenotype of the anaplastic thyroid carcinoma is achieved by the impairment of gene functions that negatively regulate cell growth, rather than by the activation of dominant oncogenes.

[The activation of the phosphotyrosine phosphatase eta is responsible for the somatostatin inhibition of PCCl3 thyroid cell proliferation]. / L'attivazione della fosfotirosino fosfatasi eta è responsabile dell'inibizione della proliferazione delle cellule tiroidee PCC13 ad opera della somatostatin.

BACKGROUND: This study was aimed to identify possible intracellular effectors of the somatostatin (SST) antiproliferative activity, in PCCl3 thyroid cells. METHODS: To prove the involvement of r-PTPeta in SST's effect, we studied th proliferative activity of subclones of PCCl3 cells that do or do not express this PTP. RESULTS: SST inhibited PCCl3 TSH+insulin-dependent cell proliferation through the induction of a phosphotyrosine phosphatase (PTP) activity, detected using the synthetic substrate pNPP (+150%, p<0.01). Conversely, PCCl3 cells stably expressing the v-mos oncogene (PCmos) were completely insensitive to SST antiproliferative effects due to the incapability of SST to increase PTP activity, that correlated with the abolishment of the expression of the receptor-like PTP, r-PTPeta. In the cells in which r-PTPeta was transfected (PCmos/ PTPeta) SST inhibited cell proliferation showing a dose-dependence similar to that observed in PCCl3 cells. Conversely, the transfection of a catalytically inactive mutant of r-PTPeta did not restore the responsivity to SST. Also in PCmos/PTPeta cells SST, treatment increased membrane PTP activity. CONCLUSIONS: SST inhibition of PCC13 cell proliferation requires the activation of r-PTPeta.

HIV-plasma viral load detection by branched DNA signal amplification.

To detect HIV-1 plasma viral load in seropositive patients, we applied a new molecular quantitation technique: branched DNA signal amplification (bDNA). We performed bDNA with 99 sera from HIV-1 seropositive patients undergoing antiretroviral therapy. We compared the results obtained with p24 antigenemia and CD4+ cell count. The bDNA proved quite sensitive and available for routine use in laboratories.

[Lactoferrin]. / La lattoferrina.

Lactoferrin is a protein present in many fluids of the human organism and in the secondary granules of polymorphonuclear cells (PMN). In the blood stream lactoferrin favours the segregation of PMN by mediating and amplifying the immune response, and realizes a negative feedback control on the Colony Forming Unit Granulocyte/Macrophage (CFU-GM) proliferation. At intestinal level it promotes iron absorption and prevents bacterial overgrowth. The antibacterial effect of lactoferrin is used clinically to prevent bacterial infections in neutropenic patients submitted to chemotherapy for leukemic diseases type M1, M2, M4 and M5, according to FAB criteria. In patients affected by chronic pancreatitis the lactoferrin concentration, in duodenal juice, is found to be significantly higher than in normal subjects. This finding suggests a pathogenetic role of the protein in chronic pancreatitis.

[Early gastric cancer. Survival and prognostic factors in 95 consecutive cases]. / Early gastric cancer. Sopravvivenza e fattori prognostici in 95 casi consecutivi.

In order to characterize prognostic factors and therapeutic strategies for EGC, we have studied 95 patients operated on from 1980 to 1988. EGC was limited to the mucosa in 36% and extended to the submucosa in 64% of the cases. Lymph nodes involvement was observed in 13 patients; in 12 of them EGC extended to the submucosa. Gastric resection was performed in 73 and total gastrectomy in 22 patients with a postoperative mortality of 6% and 16% respectively. During the follow-up 8 patients died for causes related to EGC, 8 for unrelated causes. The 5 years survival rate was 79, without differences according to site, type, size and histology of EGC, lymph nodes involvement, type of gastrectomy; only EGC limited to the mucosa was associated with a better survival experience (96% vs 70% of tumors extended to the submucosa p less than 0.05). The prognosis of EGC is good and a curative surgery may be accomplished, especially if the lesion is limited to the mucosa. In EGC extended to the submucosa an accurate lymphadenectomy may further improve the prognosis, while total gastrectomy--de principe--carries a higher postoperative mortality, without significant improvement of the long term prognosis.

[Borderline ovarian tumors. Retrospective analysis of 20 cases]. / Tumori ovarici borderline. Analisi retrospettiva di 20 casi.

BACKGROUND: To evaluate the clinical features, the surgical management and outcome of 20 patients with stage-I borderline ovarian tumors. METHODS: Twenty cases of FIGO stage-I ovarian tumors, aged from 31 to 58 years (mean 37 years) have been reviewed. All informations of clinical stage, surgical intervention and prognosis were achieved by reviewing hospital records. Minimal requirements for conservative management were adequate staging and complete information about the therapeutic options. Factors important in the choice of the treatment were, age, wish to preserve fertility, histologic type and grade, and the stage of the tumour. RESULTS: Eleven of the 20 patients (55%) were at stage IA, 6 cases (30%) were at stage IB, 3 cases (15%) were at stage IC. Thirteen (65%) were with mucinous cystadenoma of borderline malignancy, 7 cases (35%) were of serous type. Thirteen patients underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy (TAH and BSO). Seven patients were treated with unilateral oophorectomy or unilateral salpingo-oophorectomy (USO). One patient underwent enucleation of ovarian tumor and biopsy of contralateral ovary. Any patient were treated with chemotherapy after operation. With a median follow up of two years, we observed no recurrence of carcinoma in women treated conservatively or in those treated more radically. CONCLUSIONS: Conservative surgery remains a therapeutic option in selected patients with borderline ovarian tumors. Prolonged intensive follow-up is required for women treated conservatively for borderline malignant ovarian tumours.

[Ovarian cysts in adolescence: epidemiologic, clinical and management assessment]. / Cisti ovariche in età adolescenziale: valutazione epidemiologica, clinica e strumentale.

BACKGROUND: To evaluate the frequency of ovarian cyst formation in the adolescents and to report on the clinical implications of these cysts. METHODS: A prospective analysis of data on 94 girls (aged 10-19) with diagnosed ovarian cysts was performed at the Gynecology Department of Aversa and Naples hospitals between 1995-2000. Operations were performed because of pains or ultrasound suspected features. The patients who were not operated on were kept under observation and had ultrasound tests monthly, receiving gestogen to facilitate resolution of the cyst and as treatment of menstrual disorders. The site, number, size and type of the cysts were examined. RESULTS: The ovarian cysts were unilateral, unilocular, and simple, with the size varying between 3 cm and 5 cm in 83 cases, more than 5 cm in 8 cases and less than 3 cm in 3 cases. Among 94 patients 6 (6.4%) were initially qualified for the operation because of the strong pains or ultrasound equivocal aspect. Hormonal treatment was given in 74 cases, whereas in 14 cases only follow up sonography was performed. Cysts resolved spontaneously in 2 months on average, or in 1 month after hormonal treatment. No malignant tumors were found in the observed group. CONCLUSIONS: Clinical observation periodically repeated ultrasound tests seems to be the most appropriate procedure employed at adolescent girls with asymptomatic ovarian cysts. Hormonal treatment shortened the duration of the cysts somewhat, even if in a not significant manner, and thus was useful mainly in the treatment of concomitant menstrual disorders.

Detection of lymphotropic herpesvirus DNA by polymerase chain reaction in cerebrospinal fluid of AIDS patients with neurological disease.

Cerebrospinal fluid (CSF) samples from 49 acquired immunodefficiency disease syndrome (AIDS) patients with a central nervous system (CNS) disease were examined by polymerase chain reaction (PCR) to evaluate the association between the positivity for cytomegalovirus (CMV) and Epstein-Barr virus (EBV), and clinical diagnosis of a CNS disease. Frequency and clinical relevance of detection of DNA of human herpesviruses 6 (HHV-6), 7 (HHV-7) and 8 (HHV-8) were also determined. DNA of one or more of the following viruses was found in 26 of 49 patients (53%): CMV in 16 (33%), EBV in 13 (27%), human herpesvirus 6 (HHV-6) in 2 (4%), human herpesvirus 7 (HHV-7) in 1 (2%), and human herpesvirus 8 (HHV-8) in 1 (2%). The CMV detection was significantly associated with encephalitis and peripheral neuropathy (7/16 vs. 2/33, p = 0.003), while EBV with primary CNS lymphoma (P-CNSL) (8/13 vs. 0/36, p < 0.0001). HHV-6 DNA was found in CSF of two patients with neuroradiological features suggestive of cerebral lesions. HHV-8 or HHV-7 DNA was detected in the CSF of patients with unexplained neurological symptoms. This study confirms that the PCR analysis of CSF is a valid tool for the diagnosis of neurological diseases associated with CMV and EBV. On the other hand, HHV-6, HHV-7 and HHV-8, instead, were rarely detected in CSF of AIDS patients and have certainly no correlation with the CNS disease found.

Sgk1 enhances RANBP1 transcript levels and decreases taxol sensitivity in RKO colon carcinoma cells.

The serum- and glucocorticoid-regulated kinase (Sgk1) is essential for hormonal regulation of epithelial sodium channel-mediated sodium transport and is involved in the transduction of growth factor-dependent cell survival and proliferation signals. Growing evidence now points to Sgk1 as a key element in the development and/or progression of human cancer. To gain insight into the mechanisms through which Sgk1 regulates cell proliferation, we adopted a proteomic approach to identify up- or downregulated proteins after Sgk1-specific RNA silencing. Among several proteins, the abundance of which was found to be up- or downregulated upon Sgk1 silencing, we focused our attention of RAN-binding protein 1 (RANBP1), a major effector of the GTPase RAN. We report that Sgk1-dependent regulation of RANBP1 has functional consequences on both mitotic microtubule activity and taxol sensitivity of cancer cells.

Correlation between plasma HIV-1 RNA levels and the rate of immunologic decline.

To determine the influence of HIV-1 replication on immunologic decline and clinical outcome, we quantified the HIV-1 plasma viral load in 20 patients at different times over a mean period of 10.8 months. Quantitation was performed by branched DNA signal amplification (bDNA) and p24 antigenemia. Immunologic status was assessed through beta 2-microglobulin and CD4+ cell count determinations. CD4+ cell decline was expressed as a slope of the regression line constructed by the logarithms of CD4+ cell count observations. Mean values of plasma viral load were correlated with CD4+ cell decline and mean beta 2-microglobulin levels. Significant correlation was observed between plasma viral load quantified by the bDNA technique and CD4+ cell decline. No significant correlation was observed between plasma viral load quantified by p24 antigenemia and CD4+ cell decline. A significant correlation was observed between plasma viral load and beta 2-microglobulin levels. Immunologic decline was better predicted from HIV-1 RNA levels than from the CD4+ cell count. Significantly higher plasma viral load was observed in patients who had clinical progression of HIV-1 infection. Thus, HIV-1 plasma viral load quantified by a highly reliable technique such as bDNA showed that the immunologic decline is closely related to HIV-1 RNA replication.

Antitissue antibodies in chronic pancreatitis.

Organ- and nonorgan-specific autoantibodies (AA) have been investigated in 49 patients affected by alcoholic or idiopathic chronic pancreatitis (CP) to evaluate their prevalence and correlation with the clinical features of the disease. AA have been found in about 50% of CP and their recurrence rate was similar to that of alcoholic or cryptogenic liver cirrhosis (LC); age- and sex-matched healthy subjects (C) showed only about 8% positive sera (C vs. CP, p less than 0.001). Quite different IFL patterns between CP and LC have been detected. Antibrush border, antireticulin and antigastric parietal cell antibodies alone or combined prevailed in CP, while antinuclear and antismooth muscle AA prevailed in LC. No correlation with sex, age, etiology, presence of pancreatic stones, diabetes, symptoms and years of CP was found for one or more AA. In conclusion, the detection of AA in CP is a quite common finding of still unclear clinical significance.

Duodenal lactoferrin in patients with chronic pancreatitis and gastrointestinal diseases.

Lactoferrin (LF), chymotrypsin and lipase activity were measured in duodenal juice during pancreatic stimulation. Secretin (0.5 CU/kg/h) plus cerulein (75 ng/kg/h) were infused intravenously in 98 subjects: 33 patients without organic diseases (C), 40 patients affected by chronic pancreatitis (CP), and 25 patients with different gastrointestinal diseases (GID). LF was determined by means of a new noncompetitive immunoenzymatic assay with a sensitivity in the duodenal juice of 5 ng/ml. Duodenal LF concentrations were significantly higher in CP than in C or GID (p less than 0.001). LF was in a normal range in acute relapsing pancreatitis due to biliary stones or pancreas divisum. In the diagnosis of the chronic pancreatitis, LF/lipase ratios showed a specificity of 93% and a sensitivity of 95%. Our results show that LF immunoassay in duodenal juice is a sensitive and accurate assay to apply in pancreatic function tests involving duodenal content analysis.

Increased incidence of cancer in chronic pancreatitis.

Patients affected by chronic pancreatitis were followed between 1970 and 1984 in a study set up to evaluate the natural history of the disease. The study population included 172 consecutive patients diagnosed as having chronic pancreatitis in the Gastroenterology Unit of the S. Giovanni Battista Hospital in Torino, Italy. Of them, 23 were found to be affected by cancer during the 14-year follow-up period. The incidence calculated using the person-year method was compared with data from the General Population Cancer Registry of Piemonte Region. The age-specific relative risks of cancer were increased manifold. Sex- and age-specific relative risks were markedly increased for liver, tongue, lip, and rectum tumors in males, and for liver, bone, and breast tumors in females. Selection bias did not seem to be an adequate explanation of this association. Survival curves were plotted by the estimation methods of Cutler-Ederer with year intervals for the complete study population and for the different type of cancer. Known risk factors and indicators for the expected tumors were evaluated by the Cox Proportional Hazard Regression Model. The incidence of cancer increases significantly with age but not with smoking, alcohol use, and diabetes. Our epidemiological study suggests an increased risk of pancreatic as well as extrapancreatic cancer in patients with chronic pancreatitis compared with the general population. Cancer seems to be a main determinant in the natural history of the disease.

Minute and small early gastric cancers in a Western population: a clinicopathologic study.

Early endoscopic diagnosis improves the prognosis of patients with gastric cancer, as shown by the finding that 5-year survival rates exceeding 90% are observed in Japanese patients with early gastric cancer. It has been hypothesized that tumor size may have prognostic significance; therefore, a distinction between minute, small, and large early gastric cancers has been proposed. The aim of this study was to determine the prevalence of minute and small early gastric cancers in Western countries and to compare their clinicopathologic features with those of large early gastric cancers. Of 465 Italian patients with gastric cancer who were studied, 20.5% had an early gastric cancer, and 34.7% of these were minute or small. Tumor size is correlated with intramural spreading and metastasis to perigastric lymph nodes. Nodal involvement occurs more frequently in the diffuse than in the intestinal type of early gastric cancer. Long-term survival rate is not correlated with tumor size, intramural spreading, or nodal metastasis. The minute and small early gastric cancers of Italian patients are indistinguishable from those occurring in Japanese patients. These lesions are more common than previously thought and should be carefully searched for by endoscopists. The correlation of tumor size with intramural invasion and perigastric lymph node metastasis suggests that minute and small early gastric cancers are precursors of large early gastric cancers. Although the distinction between minute, small, and large early gastric cancers is of low prognostic value, the distinction might be useful for selecting different therapeutic approaches.