Immunohistochemistry differentiates papillary thyroid carcinoma arising in ectopic thyroid tissue from secondary lymph node metastases.

OBJECTIVE: To verify whether immunohistochemistry might be useful in the distinction between a true laterocervical metastasis of an undetected thyroid carcinoma and a primary tumor outside the gland. DESIGN: Galectin-3, cytokeratin 19, and HBME-1 were assessed in six cases (group A) of laterocervical masses harboring papillary thyroid carcinoma (PTC) but without a thyroid tumor, and in eight cases (group B) showing PTC both in the thyroid and in the laterocervical masses. In both groups, normal-looking follicles adjacent to the laterocervical neoplasia were present. MAIN OUTCOME: We found that the apparently normal follicles in group A were negative for all the antibodies, while group B showed strong and diffuse positive immunostaining. The neoplastic areas were always positive for all the antibodies in both groups. CONCLUSION: Even if immunohistochemical patterns of residual follicles of group B are very well differentiated that they resemble normal thyroid parenchyma, they may well be metastatic carcinomas. On the contrary, the presence of morphologically and immunohistochemically normal-looking follicles in group A, with no intrathyroid tumor, suggests that the primary PTC might possibly develop in the ectopic thyroid tissue. In cases showing morphologically and immunohistochemically normal-looking follicles in laterocervical masses, these findings might lead to a reduction of the overdiagnosis of metastatic disease of an undetected carcinoma.     

Long-term Doppler echocardiographic evaluation of the right heart after major lung resections.

OBJECTIVE: The effects of major lung resections on cardiac function in the medium and long term have not been thoroughly evaluated. We have studied right heart function with serial Doppler echocardiography in patients undergoing lobectomy and pneumonectomy during 4 years of follow-up after surgery. METHODS: Thirty-six patients undergoing lobectomy and 15 receiving pneumonectomy were evaluated with one- and two-dimensional Doppler standard transthoracic echocardiography before surgery and 1 week, 3 months, 6 months, 1 year, and 4 years postoperatively. We have studied the right midventricular diastolic diameter (RVDD), the right ventricle free wall thickness, the tricuspid valve insufficiency (TVI) and regurgitation jet (TRJ), and the pulmonary artery systolic pressure (PASP). RESULTS: None of the patients died within the first postoperative year. After lobectomy there were no significant modifications of any variable at any time. RVDD progressively increased after pneumonectomy (26.5+/-2.2mm preoperatively vs 34.3+/-7.6 at 4 years; p<0.001). Four years after surgery all patients undergoing pneumonectomy had moderate TVI while only 55% of patients receiving lobectomy showed it (low grade in 50% and moderate in 5%). In this group of patients PASP increased from 26.1+/-2.6 mmHg preoperatively to 34.3+/-7.6 mmHg at 4 years (p<0.00001). CONCLUSIONS: Right ventricle modifications are clearly evident after pneumonectomy and even if they do not show a clear clinical impact they should not be neglected.     

Super-reactivity to amphetamine toxicity induced by schedule of reinforcement

The chronic exposure of rats to a schedule of operant water reinforcement coupled with chronically restricted access to water sensitized the animals to intermittentd-amphetamine injections (0.31–2.5 mg/kg with intervals of 12–23 days between any two injections) in such a way that this drug came to produce catastrophic losses of body weight (32.4% of control levels). In the sessions whend-amphetamine was administered, the rats were also given a total of 12 brief electric shocks. Loss of body weight was unaccompanied by parallel changes in operant behavior performance, or in food or water intake. Remarkably, in other studies with the same interventions (sham schedule sessions, water deprivation, and foot shocks), with the exception that reinforcers were never delivered,d-amphetamine did not produce catastrophic falls in body weight. This super-reactivity tod-amphetamine toxicity may be mediated by a possible stressor action of the schedule of reinforcement. Its mechanism might be analogous to the known sensitization produced by classical experimental stressor stimuli to the repeated administration ofd-amphetamine.     

Percutaneous Alcohol Sclerotherapy of Simple Hepatic Cysts. Results From a Multicentre Survey in Italy

The increased use of Ultrasonography (US) has led to increased detection of simple hepatic cysts. For symptomatic cysts treatment is necessary. Until some years ago surgery was the only therapy. We have treated a large number of patients with Percutaneous Alcohol Sclerotherapy (PAS) and evaluated retrospectively the efficacy of this approach.Data on 21 patients with symptomatic simple hepatic cysts were reviewed retrospectively. Cysts had a mean diameter of 9 cm (range: 7–15 cm). PAS was always performed under local anesthesia and US guidance. 25% of the volume was replaced with 95% ethanol and then completely aspirated after 20–30 minutes.No complications or deaths occurred. In all patients symptoms disappeared after treatment. In 15 out of 21 cases there was no evidence of residual cyst on US, computed tomography (CT) or magnetic resonance (MRI). In 6 patients with shorter follow-up, cysts showed a mean reduction in diameter of 50%. The mean follow-up was 18 months (range 6–60 months).We conclude that PAS is easy with low risk for the patients and with good long-term results; it should therefore become the procedure of choice for simple hepatic cysts.     

Stress signaling through Ca2+/calmodulin-dependent protein phosphatase calcineurin mediates salt adaptation in plants

Calcineurin (CaN) is a Ca²⁺- and calmodulin-dependent protein phosphatase (PP2B) that, in yeast, is an integral intermediate of a salt-stress signal transduction pathway that effects NaCl tolerance through the regulation of Na⁺ influx and efflux. A truncated form of the catalytic subunit and the regulatory subunit of yeast CaN were coexpressed in transgenic tobacco plants to reconstitute a constitutively activated phosphatase in vivo. Several different transgenic lines that expressed activated CaN also exhibited substantial NaCl tolerance, and this trait was linked to the genetic inheritance of the CaN transgenes. Enhanced capacity of plants expressing CaN to survive NaCl shock was similar when evaluation was conducted on seedlings in tissue culture raft vessels or plants in hydroponic culture that were transpiring actively. Root growth was less perturbed than shoot growth by NaCl in plants expressing CaN. Also, NaCl stress survival of control shoots was enhanced substantially when grafted onto roots of plants expressing CaN, further implicating a significant function of the phosphatase in the preservation of root integrity during salt shock. Together, these results indicate that in plants, like in yeast, a Ca²⁺- and calmodulin-dependent CaN signal pathway regulates determinants of salt tolerance required for stress adaptation. Furthermore, modulation of this pathway by expression of an activated regulatory intermediate substantially enhanced salt tolerance.     

Conservation of epitopes recognized by monoclonal antibodies against the separated subunits of influenza hemagglutinin among type A viruses of the same and different subtypes

Summary Monoclonal antibodies raised against the separated hemagglutinin subunits (HA1 and HA2) of influenza A/Vic/3/75 (H3N2) virus were tested against a large panel of human and avian strains. The epitopes recognized by most antibodies were conserved among subtype H3 viruses, but reactivity of some antibodies with members of other subtypes was also observed. Particularly, the H4 virus reacted with most antibodies directed against the HA2 subunit. These results are discussed in terms of sequence similarities between subtypes and application of these antibodies as subtyping reagents.     

Two cases of misinterpretation of molecular results in incontinentia pigmenti,and a PCR-based method to discriminate NEMO/IKKgamma dene deletion

Familial incontinentia pigmenti (IP) is a rare X-linked dominant disorder that affects ectodermal tissues. Over 90% of IP carrier females have a recurrent genomic deletion of exons 4-10 of the NEMO (IKBKG-IKKgamma) gene, which encodes a regulatory component of the IkB kinase complex, required to activate the NF-kB pathway. In IP, mutations in NEMOlead to the complete loss of NF-kB activation creating a susceptibility to cellular apoptosis in response to TNF-alpha. This condition is lethal for males during embryogenesis while females, who are mosaic as a result of X-inactivation, can survive. Recently, a second nonfunctional copy of the gene, DeltaNEMO, was identified, opposite in direction to NEMO in a 35.5-kb duplicated sequence tract. PCR-based detection of the NEMO deletion is diagnostic for IP disease. However, we present instances in which ex 4-10 DeltaNEMO pseudogene deletion occurs in unaffected parents of two females with clinically characteristic IP. These were missed by the currently standard PCR-based method, but can be easily discriminated by a new PCR-based test reported here that permits unambiguous molecular diagnosis and proper familial genetic counseling for IP.     

Role of Apoptosis in Autoimmunity

Autoimmune diseases are characterized by the activity of autoreactive lymphocytes that produce antibodies targeting self tissue or organ for destruction. Although the pathogenesis of these diseases is poorly understood, during the past two decades basic research has indicated apoptosis as the pivotal molecular mechanism leading to autoimmunity. Recently cytokines have been invoked in the regulation of the apoptosis-related factors and death receptors in autoimmune target destruction. These research advances have contributed to the identification of mechanisms controlling autoimmunity for defining novel therapeutic strategies.     

Dendritic spines in the posterodorsal medial amygdala after restraint stress and ageing in rats

Several evidences suggest that the posterodorsal medial amygdala (MePD) can be a relevant part of the rat neural circuitry for the regulation of hypothalamic neuroendocrine secretion and for ontogenetically different behavioral displays. The dendritic spine density of Golgi-impregnated neurons from the MePD was evaluated in young rats following acute or chronic restraint stress and in aged animals (24 months old). Compared to the control group, a single 1 h restraint stress session promoted a decreased spine density (p < 0.01) whereas a single 6 h restraint stress session or daily 6-h restraint sessions for 28 consecutive days did not lead to the same effect (p > 0.05). Aged rats showed no difference in this dendritic spine parameter when compared to young adults (p > 0.05). These results indicate that short-term stress (1 h) can affect MePD dendritic spines and that neural plasticity is involved with adaptive responses onwards in restrained rats. On the other hand, brain structural modifications related with ageing appear not to influence the number of certain postsynaptic sites in the MePD of rats.     

Induction of interleukin 2 (IL2) and interferon-γ and enhancement of IL2 receptor expression by a CD26 monoclonal antibody

The ability of the 134-2C2 monoclonal antibody (mAb; CD26) to transmit an activation signal and to affect T cell proliferation has been studied. The 134-2C2 mAb, although not being mitogenic by itself, is able to increase the proliferation of purified T cells in the presence of exogenous interleukin 2 (IL2) or phorbol 12-myristate 13-acetate (PMA). No effect of our mAb was observed on the proliferation of T cells induced by other stimuli such as Sepharose-bound CD3 mAb, phytohemagglutinin or calcium ionophore. Since the co-stimulatory effect of 134-2C2 mAb on PMA-induced T cell proliferation was strongly inhibited by an anti-Tac antibody, its involvement on the IL2/IL2 receptor pathway was investigated. An increased IL2 secretion in T cells cultured with PMA plus 134-2C2 mAb was observed and Northern blot analysis showed that the mAb 134-2C2 acts synergistically with PMA favoring the induction of both IL2 and interferon-γ mRNA synthesis, as well as the enhancement of IL2 receptor and transferrin receptor mRNA expression. Studies on mechanisms implicated in signal transduction showed that 134-2C2 mAb modifies neither intracellular calcium levels nor phosphoinositide breakdown. Additionally, no effect was exerted on protein kinase C translocation. These data suggest that the CD26 antigen is involved in T cell activation in an IL2/IL2 receptor-dependent pathway.