Discovery of powerful gamma-ray flares from the Crab Nebula.

The well-known Crab Nebula is at the center of the SN1054 supernova remnant. It consists of a rotationally powered pulsar interacting with a surrounding nebula through a relativistic particle wind. The emissions originating from the pulsar and nebula have been considered to be essentially stable. Here, we report the detection of strong gamma-ray (100 mega-electron volts to 10 giga-electron volts) flares observed by the AGILE satellite in September 2010 and October 2007. In both cases, the total gamma-ray flux increased by a factor of three compared with the non-flaring flux. The flare luminosity and short time scale favor an origin near the pulsar, and we discuss Chandra Observatory x-ray and Hubble Space Telescope optical follow-up observations of the nebula. Our observations challenge standard models of nebular emission and require power-law acceleration by shock-driven plasma wave turbulence within an approximately 1-day time scale.

Terrestrial gamma-ray flashes as powerful particle accelerators.

Strong electric discharges associated with thunderstorms can produce terrestrial gamma-ray flashes (TGFs), i.e., intense bursts of x rays and γ rays lasting a few milliseconds or less. We present in this Letter new TGF timing and spectral data based on the observations of the Italian Space Agency AGILE satellite. We determine that the TGF emission above 10 MeV has a significant power-law spectral component reaching energies up to 100 MeV. These results challenge TGF theoretical models based on runaway electron acceleration. The TGF discharge electric field accelerates particles over the large distances for which maximal voltages of hundreds of megavolts can be established. The combination of huge potentials and large electric fields in TGFs can efficiently accelerate particles in large numbers, and we reconsider here the photon spectrum and the neutron production by photonuclear reactions in the atmosphere.

Extreme particle acceleration in the microquasar Cygnus X-3.

Super-massive black holes in active galaxies can accelerate particles to relativistic energies, producing jets with associated gamma-ray emission. Galactic 'microquasars', which are binary systems consisting of a neutron star or stellar-mass black hole accreting gas from a companion star, also produce relativistic jets, generally together with radio flares. Apart from an isolated event detected in Cygnus X-1, there has hitherto been no systematic evidence for the acceleration of particles to gigaelectronvolt or higher energies in a microquasar, with the consequence that we are as yet unsure about the mechanism of jet energization. Here we report four gamma-ray flares with energies above 100 MeV from the microquasar Cygnus X-3 (an exceptional X-ray binary that sporadically produces radio jets). There is a clear pattern of temporal correlations between the gamma-ray flares and transitional spectral states of the radio-frequency and X-ray emission. Particle acceleration occurred a few days before radio-jet ejections for two of the four flares, meaning that the process of jet formation implies the production of very energetic particles. In Cygnus X-3, particle energies during the flares can be thousands of times higher than during quiescent states.

[Ectopic pancreas in Meckel's diverticulitis: a description of a new clinical case]. / Pancreas ectopico nel diverticolo di Meckel: descrizione di un caso clinico.

Ectopic pancreas is a rare congenital abnormality probably due to a derangement of embryologic development of digestive tract. Its frequency is reported in the literature between 0.5-14% predominantly distributed in the stomach, duodenum, jejunum. Such condition is extremely difficult to be diagnosed, in fact most of the case of ectopic pancreas are an accidental finding. We describe a case of ectopic pancreas located in the Meckel's diverticulum, resected at laparotomy performed for colonic disease. Although in retrospective review symptoms from ectopic pancreas are reported in up to 50% of the cases our patient was free of symptoms. In addition the finding of ectopic pancreas in Meckel's diverticulum has been described only seldom in the previous literature. Treatment however should always be resection in order to prevent complications that may occur, although rarely.

Systemic administration of recombinant interferon alfa in carcinoma patients upregulates the expression of the carcinoma-associated antigens tumor-associated glycoprotein-72 and carcinoembryonic antigen.

PURPOSE: The ability of interferons (IFNs) to enhance tumor-associated antigen expression may be an important approach to enhance the efficacy of some monoclonal antibody (MAb)-based protocols for tumor diagnosis and/or therapy. The present study was designed to determine whether systemic IFN alpha-2a administration (via the intramuscular [IM] route) could upregulate the expression of tumor-associated glycoprotein-72 (TAG-72) and/or carcinoembryonic antigen (CEA) at histologically confirmed sites of carcinoma. PATIENTS AND METHODS: Eighteen patients diagnosed with gastrointestinal (GI) carcinoma received systemic IFN alpha-2a according to four dose schedules. In cohorts I and II, patients received two injections of 3 or 6 x 10(6) U IFN alpha-2a per injection, respectively. Patients in cohorts III and IV received the same doses of IFN alpha-2a, 3 and 6 x 10(6) U, respectively, but three injections were given. Tumor and normal colonic mucosa biopsies were obtained from each patient by endoscopy before IFN alpha-2a and after IFN alpha-2a at surgery. The levels of TAG-72 and CEA expression were measured by (1) immunohistochemistry and reported as percent antigen-positive tumor cells, as well as the relative staining intensity, and (2) a quantitative radioimmunoassay. RESULTS: TAG-72 and CEA levels were consistently increased in tumor biopsies taken from patients in cohorts III and IV. For example, of 10 patients treated in cohorts III and IV, eight had enhanced TAG-72 expression when measured either as percentage TAG-72-positive tumor cells or as an increased MAb staining intensity following IFN alpha-2a. CEA expression in tumor biopsies from seven of 10 patients in cohorts III and IV was also elevated following IFN alpha-2a treatment. Quantitative analysis of TAG-72 and CEA levels in tumor biopsies confirmed higher tumor antigen levels following IFN alpha-2a administration. No such increases in TAG-72 or CEA levels were observed in tumor samples taken from patients in cohorts I and II. CEA or TAG-72 expression in samples of histologically confirmed normal colonic mucosa showed little or no change after IFN alpha-2a treatment. CONCLUSION: Systemic IFN alpha-2a administration can upregulate TAG-72 and CEA expression at distal tumor sites, which may play an important role in immunodiagnosis and therapy.

Intraoperative radioimmunolocalization of an anti-CEA MAb F(Ab')2 (FO23C5) in CEA serum-negative colorectal cancer patients.

Serum positivity to an antigen recognized by the monoclonal antibody (MAb) which will be administered is frequently being used as a predictive criterion for positive MAb tumor localization. In the present study, which is based on our previous data that clearly showed no correlation between quantitative levels of CEA in sera and in carcinoma tissues, we selected a population of 12 primary colorectal carcinoma patients which were serum CEA-negative. The main purpose was to assess the potential diagnostic use of Radioimmunoguided Surgery (RIGS) with an anti-CEA FO23C5 F(Ab')2 MAb and its clinical value in this series of patients. In all RIGS patients, the MAb localized to histologically confirmed tumor; this included 96% of primary tumor tissues, 29% of lymph nodes and one occult liver metastasis. Thus, serum CEA positivity should not be a criterion for the use of anti-CEA MAbs for the diagnosis of colon cancer, since the serum CEA level is not indicative of CEA expression in tumors.

Clinical value of radiolabeled monoclonal antibodies in the management of carcinoma patients.

A significant number of monoclonal antibodies, suitable for in vivo management of carcinoma patients, have been recently developed and evaluated in clinical trials. They can be used successfully either for imaging or for radioimmunotherapy, although their clinical application shows advantages and limitations. With the advent of genetic engineering, it has become feasible to design molecules (i.e. chimeric and humanized antibodies, single-chain) to circumvent drawbacks or enhance a certain property. Several radionuclides can actually be used to be linked to monoclonal antibodies, including radiometallic isotopes which need bifunctional chelators. Coupling these radiometals to proteins will greatly increase diagnostic and therapeutic possibilities. The ability of radiolabeled monoclonal antibodies to localize tumors, markedly contributed to the development of a new intraoperative approach termed "Radioimmunoguided Surgery". This system, being used to better define tumor margin resection as well as occult tumor sites, is of importance in postoperative decision-making. Optimization of this technique is actually under evaluation at our Institution, especially in combination with Biological Response Modifiers.

Monoclonal antibodies in the management of carcinoma patients.

The use of monoclonal antibodies (MAbs) in the clinical management of carcinoma patients is reported in the present review. Among the various MAbs generated, MAb B72.3 (LTIB, National Cancer Institute, U.S.A.) has been extensively used in clinical trials either for antigen identification (TAG-72) in sera, or for tumor localization in carcinoma patients. Serum assay results, in colorectal cancer patients, showed the usefulness of the MAb B72.3 in monitoring the clinical course of the malignant disease. Its specific tumor localization (70% of the biopsy specimens) and the immunoscintigraphy studies, after in vivo administration, have also been discussed. The positive results obtained, markedly contributed in the development of a new intraoperative methodology termed "radioimmunoguided surgery".