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We study transitionless quantum driving in an infinite-range many-body system described by the Lipkin-Meshkov-Glick model. Despite the correlation length being always infinite the closing of the gap at the critical point makes the driving Hamiltonian of increasing complexity also in this case. To this aim we develop a hybrid strategy combining a shortcut to adiabaticity and optimal control that allows us to achieve remarkably good performance in suppressing the defect production across the phase transition.

We report the experimental reconstruction of the nonequilibrium work probability distribution in a closed quantum system, and the study of the corresponding quantum fluctuation relations. The experiment uses a liquid-state nuclear magnetic resonance platform that offers full control on the preparation and dynamics of the system. Our endeavors enable the characterization of the out-of-equilibrium dynamics of a quantum spin from a finite-time thermodynamics viewpoint.

Among the multiple factors concurring to Alzheimer's disease (AD) pathogenesis, greater attention should be devoted to the role played by infectious agents. Growing epidemiological and experimental evidence suggests that recurrent herpes simplex virus type-1 (HSV-1) infection is a risk factor for AD although the underlying molecular and functional mechanisms have not been fully elucidated yet. Here, we review literature suggesting the involvement of HSV-1 infection in AD also briefly mentioning possible pharmacological implications of these findings.

A growing body of epidemiologic and experimental data point to chronic bacterial and viral infections as possible risk factors for neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis. Infections of the central nervous system, especially those characterized by a chronic progressive course, may produce multiple damage in infected and neighbouring cells. The activation of inflammatory processes and host immune responses cause chronic damage resulting in alterations of neuronal function and viability, but different pathogens can also directly trigger neurotoxic pathways. Indeed, viral and microbial agents have been reported to produce molecular hallmarks of neurodegeneration, such as the production and deposit of misfolded protein aggregates, oxidative stress, deficient autophagic processes, synaptopathies and neuronal death. These effects may act in synergy with other recognized risk factors, such as aging, concomitant metabolic diseases and the host's specific genetic signature. This review will focus on the contribution given to neurodegeneration by herpes simplex type-1, human immunodeficiency and influenza viruses, and by Chlamydia pneumoniae.

Accumulation of DNA damage and deficiency in DNA repair potentially contribute to the progressive neuronal loss in neurodegenerative disorders, including Alzheimer disease (AD). In multicellular eukaryotes, double strand breaks (DSBs), the most lethal form of DNA damage, are mainly repaired by the nonhomologous end joining pathway, which relies on DNA-PK complex activity. Both the presence of DSBs and a decreased end joining activity have been reported in AD brains, but the molecular player causing DNA repair dysfunction is still undetermined. β-Amyloid (Aβ), a potential proximate effector of neurotoxicity in AD, might exert cytotoxic effects by reactive oxygen species generation and oxidative stress induction, which may then cause DNA damage. Here, we show that in PC12 cells sublethal concentrations of aggregated Aβ(25-35) inhibit DNA-PK kinase activity, compromising DSB repair and sensitizing cells to nonlethal oxidative injury. The inhibition of DNA-PK activity is associated with down-regulation of the catalytic subunit DNA-PK (DNA-PKcs) protein levels, caused by oxidative stress and reversed by antioxidant treatment. Moreover, we show that sublethal doses of Aβ(1-42) oligomers enter the nucleus of PC12 cells, accumulate as insoluble oligomeric species, and reduce DNA-PK kinase activity, although in the absence of oxidative stress. Overall, these findings suggest that Aβ mediates inhibition of the DNA-PK-dependent nonhomologous end joining pathway contributing to the accumulation of DSBs that, if not efficiently repaired, may lead to the neuronal loss observed in AD.

Epidemiological and experimental findings suggest that chronic infection with Herpes simplex virus type 1 (HSV-1) may be a risk factor for Alzheimer's disease (AD), but the molecular mechanisms underlying this association have not been fully identified. We investigated the effects of HSV-1 on excitability and intracellular calcium signaling in rat cortical neurons and the impact of these effects on amyloid precursor protein (APP) processing and the production of amyloid-β peptide (Aβ). Membrane depolarization triggering firing rate increases was observed shortly after neurons were challenged with HSV-1 and was still evident 12 hours postinfection. These effects depended on persistent sodium current activation and potassium current inhibition. The virally induced hyperexcitability triggered intracellular Ca(2+) signals that significantly increased intraneuronal Ca(2+) levels. It also enhanced activity- and Ca(2+)-dependent APP phosphorylation and intracellular accumulation of Aβ42. These findings indicate that HSV-1 causes functional changes in cortical neurons that promote APP processing and Aβ production, and they are compatible with the co-factorial role for HSV-1 in the pathogenesis of AD suggested by previous findings., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Niemann-Pick Type C Disease (NPCD) is a progressive neurodegenerative disorder characterized by accumulation of free cholesterol, sphingomyelin, glycosphingolipids (GSLs) and sphingosine in lysosomes, mainly due to a mutation in the NPC1 gene. One of the main symptoms in NPCD patients is hyperexcitability leading to epileptic activity, however, the pathophysiological basis of this neural disorder is not yet well understood. Here we studied the excitatory neurotransmission in the hippocampus of BALB/c NPC1NIH (NPC1-/-) mice, a well-described animal model of the disease. We report that hippocampal field potential population spike (fPS), as well as paired pulse ratio, is enhanced in NPC1-/- with respect to Wild Type (WT). To evaluate the contribution of glutamate receptor activity in the enhanced fPS observed in mutant mice, we recorded slices treated with glutamate receptor agonists alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) and Kainate (KA). We found that a prolonged application of KA and AMPA in NPC1-/- mice do not induce the dramatic decrease of synaptic transmission observed in WT hippocampal slices suggesting a functional impairment of presynaptic KA receptors and an imbalance of AMPA receptor exo/endocytosis. In line with electrophysiological data, we also found notable differences in calcium influx during KA and AMPA bath application in NPC1-/- hippocampal culture as compared with WT. Nevertheless in synaptosomal membranes, Western Blot analysis didn't reveal any modification in protein expression levels of KA and AMPA receptor subunits. All together these data indicate that in mutant mice the hyperexcitability, that is at the basis of the insurgence of seizures, might be due to the enhanced glutamatergic neurotransmission caused by an altered KA and AMPA receptor functioning., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Background and Aim: We aimed to validate the non-invasive criteria for the characterization of portal vein thrombosis (PVT) in patients with cirrhosis and hepatocellular carcinoma (HCC). In a prospective study, we examined the impact of arterial hypervascularity, as established by the European Association for the Study of the Liver and the American Association for the Study of Liver Diseases recommendations for the non-invasive diagnosis of HCC, as a criterion for characterizing macroscopic PVT (EASL/AASLD extension criteria)., Methods: A total of 96 cases of PVT detected using ultrasonography in patients with cirrhosis and HCC were included in the study. When coincidental arterial hypervascularity was detected by contrast perfusional ultrasonography and helical computed tomography, the thrombus was considered malignant according to our EASL/AASLD extension criteria. In all cases, an ultrasound-guided biopsy examination of the thrombus was performed., Results: Coincidental hypervascularity was found in 54 of 96 nodules (56.2%), and all were malignant upon biopsy (100% positive predictive value). Twenty-four (25%) had negative results with both techniques (non-vascular thrombus). Biopsies showed HCC in five non-vascular thrombi (5.3% of all thrombi) and in 13 of 18 thrombi with a hypervascularity result from only one technique., Conclusions: The EASL/AASLD extension criteria for non-invasive diagnosis of malignant thrombosis were satisfied in 75.2% of malignant thrombi; thus, a biopsy is frequently required in this setting. However, in the presence of coincidental hypervascularity of a thrombus with both techniques, a biopsy is not required (absolute positive predictive value for malignancy). Relying on imaging techniques in thrombi could miss the diagnosis of malignant portal invasion in up to 24.9% of cases., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Lifelong latent infections of the trigeminal ganglion by the neurotropic herpes simplex virus type 1 (HSV-1) are characterized by periodic reactivation. During these episodes, newly produced virions may also reach the central nervous system (CNS), causing productive but generally asymptomatic infections. Epidemiological and experimental findings suggest that HSV-1 might contribute to the pathogenesis of Alzheimer's disease (AD). This multifactorial neurodegenerative disorder is related to an overproduction of amyloid beta (Aβ) and other neurotoxic peptides, which occurs during amyloidogenic endoproteolytic processing of the transmembrane amyloid precursor protein (APP). The aim of our study was to identify the effects of productive HSV-1 infection on APP processing in neuronal cells. We found that infection of SH-SY5Y human neuroblastoma cells and rat cortical neurons is followed by multiple cleavages of APP, which result in the intra- and/or extra-cellular accumulation of various neurotoxic species. These include: i) APP fragments (APP-Fs) of 35 and 45 kDa (APP-F35 and APP-F45) that comprise portions of Aβ; ii) N-terminal APP-Fs that are secreted; iii) intracellular C-terminal APP-Fs; and iv) Aβ(1-40) and Aβ(1-42). Western blot analysis of infected-cell lysates treated with formic acid suggests that APP-F35 may be an Aβ oligomer. The multiple cleavages of APP that occur in infected cells are produced in part by known components of the amyloidogenic APP processing pathway, i.e., host-cell β-secretase, γ-secretase, and caspase-3-like enzymes. These findings demonstrate that HSV-1 infection of neuronal cells can generate multiple APP fragments with well-documented neurotoxic potentials. It is tempting to speculate that intra- and extracellular accumulation of these species in the CNS resulting from repeated HSV-1 reactivation could, in the presence of other risk factors, play a co-factorial role in the development of AD.

Background: Factors responsible for the progression of primary biliary cirrhosis (PBC) are still poorly understood. In the present study, we investigated the associations between the stage of PBC and the immune reaction triggered by oxidative stress; the presence of obesity, steatosis,steatohepatitis; and other toxic, metabolic, or steatogenic factors., Methods: We studied clinical, laboratory, and histological data for 274 untreated patients with serum antimitochondrial antibody (AMA)-positive PBC. Circulating IgG against human serum albumin adducted with malondialdeyde, the major product of lipid peroxidation, was measured in these patients and in a group of 98 sex-, age and body mass index (BMI)-matched controls., Results: Steatosis was present in 40.5% of all patients. Steatohepatitis was present in 14.9% of all patients. There was a significant association between the frequencies of steatosis and steatohepatitis and the worsening of PBC. Circulating IgG against lipid peroxidation products was significantly higher in the PBC patients than in the controls. Titers of lipid peroxidation-related antibodies were significantly increased in patients with steatosis and inpatients at more advanced stages. Bivariate analysis revealed a significant association between indirect evidence of oxidative stress, steatosis, steatohepatitis, age, BMI, frequency of diabetes, alcohol intake, iron grade after Perl's stain, and PBC stage. Logistic regression analysis confirmed that the titers of antibodies against lipid peroxidation products (odds ratio 4.5, p< .001, 95% confidence interval 3.9–14.4), the presence of steatosis (odds ratio 4.1, 95% confidence interval 2.5–15.4, p< .001), higher BMI (odds ratio 3.9, p< .021, 95%confidence interval 1.4–9.5), and alcohol intake (males ≥ 30 g/day, females ≥ 20 g/day, odds ratio 4.5,95% confidence interval 1.3–19.8, p< .029) were independently associated with more advanced stages of the disease., Conclusions: The immune reactions triggered by oxidative stress, steatosis, obesity, and alcohol intake are independent predictors of PBC stage progression.

Protein phosphorylation is the main signaling system known to trigger synaptic changes underlying long-term potentiation (LTP). The timing of these phosphorylations plays an essential role to maintain the potentiated state of synapses. However, in mice a simultaneous analysis of phosphorylated proteins during early-LTP (E-LTP) has not been thoroughly carried out. Here we described phosphorylation changes of alphaCaMKII, ERK1/2, PKB/Akt and CREB at different times after E-LTP induced at Schaffer collateral/commissural fiber-CA1 synapses by 1 s 100 Hz tetanic stimulation in mouse hippocampal slices. We found that phosphorylation levels of all the molecules examined rapidly increased after tetanisation and remained above the basal level up to 30 min. Notably, we observed a sustained increment in the phosphorylation level of Akt at Ser473, whereas the phosphorylation level of Akt at Thr308 was unchanged. Unexpectedly, we also detected a marked increase of CREB target genes expression levels, c-fos, Egr-1 and exon-III containing BDNF transcripts. Our findings, besides providing a detailed timing of phosphorylation of the major kinases involved in E-LTP in mice, revealed that a modest LTP induction paradigm specifically triggers CREB-mediated gene expression.

Previous reports have shown that various steps in the influenza A virus life cycle are impaired in cells expressing the antiapoptotic protein Bcl-2 (Bcl-2(+) cells). We demonstrated a direct link between Bcl-2 and the reduced nuclear export of viral ribonucleoprotein (vRNP) complexes in these cells. However, despite its negative impact on viral replication, Bcl-2 did not prevent host cells from undergoing virally triggered apoptosis. The protein's reduced antiapoptotic capacity was related to phosphorylation of its threonine 56 and serine 87 residues by virally activated p38MAPK. In infected Bcl-2(+) cells, activated p38MAPK was found predominantly in the cytoplasm, colocalized with Bcl-2, and both Bcl-2 phosphorylation and virally induced apoptosis were diminished by specific inhibition of p38MAPK activity. In contrast, in Bcl-2-negative (Bcl-2(-)) cells, which are fully permissive to viral infection, p38MAPK activity was predominantly nuclear, and its inhibition decreased vRNP traffic, phosphorylation of viral nucleoprotein, and virus titers in cell supernatants, suggesting that this kinase also contributes to the regulation of vRNP export and viral replication. This could explain why in Bcl-2(+) cells, where p38MAPK is active in the cytoplasm, phosphorylating Bcl-2, influenza viral replication is substantially reduced, whereas apoptosis proceeds at rates similar to those observed in Bcl-2(-) cells. Our findings suggest that the impact of p38MAPK on the influenza virus life cycle and the apoptotic response of host cells to infection depends on whether or not the cells express Bcl-2, highlighting the possibility that the pathological effects of the virus are partly determined by the cell type it targets.

Myxoma is the most common type of cardiac tumour in all age groups. It may simulate infective endocarditis but is rarely infected. We describe one case of infected left atrial myxoma caused by Enterococcus faecalis. Combined therapy, consisting of surgical management and antimicrobial therapy, was used. Histological examination of the excised tumour revealed a typical myxoma with infiltrates of neutrophils. Few cases of infected atrial myxomas have been reported in the literature.

Several viruses, including influenza, induce an imbalance of intracellular redox state toward pro-oxidant conditions. Through different mechanisms these alterations contribute both to influenza virus replication and to the pathogenesis of virus-induced disease. At the same time, influenza virus activates several intracellular signaling pathways involved in important physiological functions of the cell. Interestingly, many of these pathways are finely regulated by small changes in intracellular redox state, and the virus-induced redox imbalance might also control viral replication through this mechanism. Here we review the main intracellular redox-sensitive pathways activated upon influenza infection and involved in regulating viral replication.

Objective: Interstitial laser photocoagulation (ILP) is a recently proposed therapeutic procedure for the ablation of benign thyroid nodules, which has already proven to be safe and effective. However, results supporting the routine use of ILP are still limited., Design: The aim of the study was to evaluate the efficacy and safety of ILP treatment in benign nonfunctioning thyroid nodules and to establish whether the therapeutic outcome may be predicted by any clinical parameter at baseline. Twenty-three patients with either a solitary nodule or a dominant nodule within a multinodular goiter underwent ILP and were evaluated 1 and 3 months later. In order to assess the efficacy of low-energy ILP, the procedure was performed with an output power of 3 W, delivering a mean energy of 33.4 +/- 12.7 Joule/mL of nodule volume, which is much lower than previously reported., Main Outcome: Nodule volume significantly decreased after ILP as assessed after 1 and 3 months (analysis of variance; F = 5.37; p = 0.007). Patients with multinodular goiter showed a greater reduction at 3 months compared with patients bearing a solitary thyroid nodule (38.6 +/- 5.3 vs. 30.9 +/- 6.5%; p < 0.01). Age, sex, ultrasound pattern (isoechogenous/hypoechogenous), pretreatment volume, number of ILP treatments, and total energy delivered did not show any significant correlation with treatment outcome., Conclusions: Our results demonstrate that ILP can produce a significant reduction of thyroid nodule volume even when a much lower energy than previously reported is delivered. ILP constitutes a minimally invasive technique, which can be carried out on an outpatient basis and could represent a valid nonsurgical alternative for thyroid nodule management. Dominant nodules within a multinodular goiter appear to be more responsive to ILP compared with solitary thyroid nodules.

Spinor Bose condensates loaded in optical lattices have a rich phase diagram characterized by different magnetic order. Here we apply the density matrix renormalization group to accurately determine the phase diagram for spin-1 bosons loaded on a one-dimensional lattice. The Mott lobes present an even or odd asymmetry associated to the boson filling. We show that for odd fillings the insulating phase is always in a dimerized state. The results obtained in this work are also relevant for the determination of the ground state phase diagram of the S = 1 Heisenberg model with biquadratic interaction.

We have previously shown that the life cycles of several viruses are influenced by host-cell redox states. Reports of the antioxidant activities of the plant polyphenol resveratrol (RV) prompted us to investigate its effects on influenza virus replication in vitro and in vivo. We found that RV strongly inhibited the replication of influenza virus in MDCK cells but that this activity was not directly related to glutathione-mediated antioxidant activity. Rather, it involved the blockade of the nuclear-cytoplasmic translocation of viral ribonucleoproteins and reduced expression of late viral proteins seemingly related to the inhibition of protein kinase C activity and its dependent pathways. RV also significantly improved survival and decreased pulmonary viral titers in influenza virus-infected mice. No toxic effects were observed in vitro or in vivo. That RV acts by inhibiting a cellular, rather than a viral, function suggests that it could be a particularly valuable anti-influenza drug.

The sIgG(+) lymphoblastoid B cell line CESS spontaneously produces a high amount of nerve growth factor (NGF) and expresses both high affinity (p140(Trk-A)) and low affinity (p75(NTR)) NGF receptors. Autocrine production of NGF maintains the survival of CESS cells through the continuous deactivation of p38 MAPK, an enzyme able to induce Bcl-2 phosphorylation and subsequent cytochrome c release and caspase activation. In this paper, we show that NGF induces transcriptional activation and synthesis of MAPK phosphatase 1 (MKP-1), a dual specificity phosphatase that dephosphorylates p38 MAPK, thus preventing Bcl-2 phosphorylation. Furthermore, NGF increases MKP-1 protein stability by preventing its degradation through the proteasome pathway. Following NGF stimulation, MKP-1 protein mainly localizes on mitochondria, suggesting an interaction with p38 MAPK in this compartment. Incubation of CESS cells with MKP-1-specific antisense oligonucleotides induces cell death, which was not prevented by exogenous NGF. By contrast, overexpression of native MKP-1, but not of its catalytically impaired form, inhibits apoptosis induced by NGF neutralization in CESS cells. Thus, the molecular mechanisms underlying the survival function of NGF in CESS B cell line predominantly consist in maintaining elevated levels of MKP-1 protein, which controls p38 MAPK activation.

Overexpression of HER-2/neu in breast cancer has been associated with more aggressive disease and poor overall survival. Trastuzumab, a recombinant humanized monoclonal antibody with high affinity for the HER-2 protein, inhibits the growth of breast cancer cells overexpressing HER-2. Trastuzumab showed, as second-line treatment, 15% of objective response in metastatic breast cancer. Bone marrow metastases are detectable in 23% of the patients with advanced breast cancer at first relapse and this rate increases in patients with metastatic disease. We report a case of a complete response of bone marrow metastases from breast cancer using a 3-weekly trastuzumab schedule, in a heavily pretreated patient with severe symptomatic pancytopenia.

The effect of fluctuations in the classical control parameters on the Berry phase of a spin 1/2 interacting with an adiabatically cyclically varying magnetic field is analyzed. It is explicitly shown that in the adiabatic limit dephasing is due to fluctuations of the dynamical phase.

Background: The renal biopsy is usually performed as an in-patient procedure, with patients admitted to hospital for at least 24 hours. We have carried out renal biopsies on two groups of patients. In the first group, patients rest in the hospital for 8 hours following the procedure. They are discharged after undergoing ultrasonography and a TC scan. These patients return to the hospital after 24 hours to verify possible post-biopsy complications. In the comparison group, patients remain in hospital for 24 hours., Results: In both groups, the only observed complication was asymptomatic postbiopsy hematoma. No major complications were present in either group., Conclusions: In selected cases, renal biopsy performed by an expert practitioner as an outpatient procedure is safe and does not require 24-hour observation.

Background: Alterations in fibroblast growth factors (FGFs) production and/or FGF receptors expression have been described to play key roles in prostate tumor progression, particularly in androgen-independent tumors. However, the role of androgen receptor (AR) in altering FGF-mediated growth and survival of prostatic neoplastic cells has not been completely defined. In this study, we investigated the alterations in FGF2 production and utilization by the PC3 cell line, after transfection with a full-length AR., Methods: FGF1,2,7, FGF-binding protein (FGF-BP) production and FGF receptor (FGFR) 1-4 expression were investigated by polymerase chain reaction (PCR) and Western blot analysis., Results: De novo AR expression by PC3 cells restores FGFR2 IIIb isoform expression and sensitivity to FGF7 and FGF2. Androgen stimulation induces AR+ PC3 clones to secrete FGF-BP, likely responsible for activation and mobilization from the extracellular matrix of the high amounts of FGF2 produced by the same cells. In addition to the effects on cell proliferation, FGF2 maintains the survival of AR+ PC3 clones through a positive modulation of the Bcl-2 protein and down-modulates AR protein expression, allowing the escape of selected clones from androgen regulation., Conclusion: In the presence of an active AR, the combined production of FGF2 and FGF-BP may play an important role in the progression of prostate cancer through the selection of AR- clones expressing high levels of Bcl-2., (Copyright 2002 Wiley-Liss, Inc.)

Survival of memory B lymphocytes is tightly linked to the integrity of the Bcl-2 protein and is regulated by a nerve growth factor (NGF) autocrine circuit. In factor-starved memory B cells, the addition of exogenous NGF promptly induced p38 mitogen-activated protein kinase (MAPK), but not c-Jun N-terminal kinase (JNK), dephosphorylation. Conversely, withdrawal of endogenous NGF was followed by p38 MAPK activation and translocation onto mitochondria, whereby it combined with and phosphorylated Bcl-2, as assessed by co-immunoprecipitation and kinase assays in vivo and in vitro. Mitochondria isolated from human memory B cells, then exposed to recombinant p38 MAPK, released cytochrome c, as did mitochondria from Bcl-2-negative MDCK cells loaded with recombinant Bcl-2. Apoptosis induced by NGF neutralization could be blocked by the specific p38 MAPK inhibitor SB203580 or by Bcl-2 mutations in Ser-87 or Thr-56. These data demonstrate that the molecular mechanisms underlying the survival factor function of NGF critically rely upon the continuous inactivation of p38 MAPK, a Bcl-2-modifying enzyme.

The sIgG(+) lymphoblastoid B cell line CESS spontaneously produces a high amount of NGF and expresses both high affinity (p140(Trk-A)) and low affinity (p75(NTR)) NGF receptors. Blocking NGF signals with neutralizing antibodies or specific Trk-A inhibitors induces a rapid phosphorylation of antiapoptotic Bcl-2 protein, followed by caspase activation, and apoptotic death of CESS cells. Bcl-2 phosphorylation in several sites within a approximately 60 aa "loop" domain of protein is known to regulate its antiapoptotic function. Accordingly, CESS cells expressing the loop deletional mutant cDNA constructs Bcl-2 Delta40-91 were completely resistant to apoptosis induced by NGF withdrawal, indicating that Bcl-2 phosphorylation is a critical event. NGF withdrawal induces p38 MAPK, but not JNK, activation in CESS cells, and SB203580, a specific inhibitor of p38 MAPK, is able to prevent both Bcl-2 phosphorylation and apoptosis, indicating that p38 MAPK is the enzyme responsible for these events., (Copyright 2000 Academic Press.)

The molecular mechanisms underlying the growth inhibition induced by interferon-alpha (IFN-alpha) in B16 murine melanoma cells were investigated. IFN-alpha did not induce cell apoptosis, but strongly interfered with the synthesis of basic fibroblast growth factor (bFGF), which acts as an autocrine growth factor in this system. Inhibition of bFGF synthesis was observed at the same concentrations (50-500 pM, 10-100 U/ml) of IFN-alpha able to induce growth arrest of B16 melanoma cells. Although the synthesis of acidic (a)FGF was only slightly affected by IFN-alpha, the cytokine induced release of an aFGF-related low-molecular-weight peptide, which was able to interfere with bFGF binding to surface receptors. Thus, the molecular mechanisms of IFN-alpha activity on melanoma cells include a specific modulation of the bFGF autocrine circuit., (Copyright 1999 Academic Press.)

We report a case of an extramedullary plasmocytoma of the breast in a 71 years old woman who suffered from six years of an osseous plasmocytoma. This lesion is rare and is associated with a serum monoclonal lambda gammopathy. A correct diagnosis of metastasis to the breast is important since the treatment of primary and secondary malignancies of the breast is different.

A panel of monoclonal antibodies to human IL-1 beta has been used to probe its conformational and functional characteristics. Real time antibody-protein interaction was assessed by surface plasmon resonance with a BIAcore apparatus, in order to determine the kinetic and thermodynamic parameters of the interaction and to map the recognition sites of the antibodies on the IL-1 beta surface. Topological analysis was thus compared to the inhibitory capacity of antibodies for IL-1 beta bioactivity and binding to the activating receptor IL-1RI. This functional mapping analysis allows the following hypothesis. At least two discrete areas of IL-1 beta, located within the sequences 133-147 and 177-186 (as defined by mAbs MhC1 and BRhD2, respectively), are apparently involved in IL-1RI-independent agonist activity, and thus possibly take part in the interaction with the receptor accessory protein IL-1RAcP. Another area in the 133-147 sequence (defined by mAb BRhC3) is involved in agonist binding to its receptor CDw121a (IL-1RI), whereas a site recognized by mAb BRhG5 within the sequence 218-243 is selectively responsible for non-agonist binding to the activating receptor. The loop between the 4th and the 5th beta-strand, at the open end of the IL-1 beta-barrel structure, may possibly take part in both non-agonist binding to IL-1RI and in the interaction with IL-1RAcP.

Intranasal desmopressin represents the treatment of choice in Central Diabetes Insipidus. Nevertheless, this route of administration bears some practical disadvantage, linked to either difficult delivering technique, or the status of nasal mucose. The antidiuretic effectiveness of oral desmopressin has been recently demonstrated, both in experimental animals and in man. In our study we compared oral vs. intranasal desmopressin efficacy in 13 patients affected by Central Diabetes Insipidus. The results show that the peroral administration of Desmopressin at a mean dose of 500-600 micrograms/die determines an antidiuretic effect comparable to that of intranasal route, without affecting body weight, arterial pressure and chemical analysis. Side effects, generally limited to the first week of treatment, were described (nausea, vomiting, headache, dizziness [corrected], bitter taste, epygastralgia, asthenia, epystassis), inducing 4/13 patients to withdrawal the trial.

The present study aimed at evaluating the anterior pituitary hormone levels in the inferior petrosal sinuses and in the peripheral blood of 55 patients affected by various pituitary disorders and undergoing perihypophysial phlebography on neurosurgical indication or for diagnostic purposes. The results indicated that in 6 patients with Cushing's disease and in 4 with hyperprolactinemia the secreting adenoma could be localized by inferior petrosal sinus sampling. Furthermore, the concentrations of all the pituitary hormones were found to be higher in the right and/or in the left inferior petrosal sinus than in peripheral blood, showing a clear gradient between central and peripheral samples. Moreover, the evaluation of hormone central/peripheral concentration ratios revealed noteworthy differences, namely, that central/peripheral concentration ratios of GH, ACTH, and PRL were significantly higher than those of TSH, FSH, and LH (p less than 0.01). On the contrary, no significant differences were found when the concentration ratios of GH, ACTH and PRL or TSH, FSH and LH were compared among themselves. This finding may be attributed to at least two factors: the increased pulsatility and the relatively short biological halftime of polypeptic hormones (GH, ACTH, and PRL) compared with glycoprotein hormones (TSH, FSH, and LH).