Histology and histopathology Vol.18, nº 4 (2003)
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PublicationMetadata onlya-synuclein: between synaptic function and dysfunction(2003) Di Rosa, G.; Puzzo, D.; Sant'Angelo, A.; Trinchese, F.; Arancio, O.Alpha-synuclein belongs to a family of vertebrate proteins, encoded by three different genes: a, ß, and g. The protein has become of interest to the neuroscience community in the last few years after the discovery that a mutation in the a-synuclein gene is associated with familial autosomal-dominant early-onset forms of Parkinson Disease. However, it is not yet clear how the protein is involved in the disease. Several studies have suggested that a-synuclein plays a role in neurotransmitter release and synaptic plasticity. This hypothesis might help elucidate how a-synuclein malfunctioning contributes to the development of a series of disorders known as synucleinopathies.- PublicationOpen AccessTherapeutic trials for a rabbit model of EBV-associated Hemophagocytic Syndrome (HPS): Effects of vidarabine or CHOP, and development of Herpesvirus papio (HVP)-negative lymphomas surrounded by HVP-infected lymphoproliferative disease(Murcia : F. Hernández, 2003) Hayashi, K.; Joko, H.; Koirala, T.R.; Onoda, S.; Jin, Z.S.; Munemasa, M.; Ohara, N.; Oda, W.; Tanaka, T.; Oka, T.; Kondo, E.; Yoshino, T.; Takahashi, K.; Yamada, M.; Akagi, T.Epstein-Barr virus-associated hemophagocytic syndrome (EBV-AHS), which is often associated with fatal infectious mononucleosis or T-cell lymphoproliferative diseases (LPD), is a distinct disease characterized by high mortality. Treatment of patients with EBV-AHS has proved challenging. To develop some therapeutic interventions for EBV-AHS, we examined the effectiveness of an antiviral agent (vidarabine) or chemotherapy (CHOP), using a rabbit model for EBV-AHS. Fourteen untreated rabbits were inoculated intravenously with cell-free virions of the EBV-like virus Herpesvirus papio (HVP). All of the rabbits died of HVP-associated (LPD) and hemophagocytic syndrome (HPS) between 21 and 31 days after inoculation. Furthermore, three HVP-infected rabbits treated with vidarabine died between days 23 and 28 after inoculation, and their clinicopathological features were no different from those of untreated rabbits, indicating that this drug is not effective at all to treat HVP-induced rabbit LPD and HPS. Three of the infected rabbits that were treated with one course, with an incomplete set of three courses, or with three full courses of CHOP treatment died of HVPinduced LPD and HPS with a bleeding tendency and/or with opportunistic infections. They died on the 26th, 62nd and 105th day after virus inoculation, respectively. CHOP treatment transiently suppressed the HVPinduced LPD and contributed to the prolonged survival time of two infected rabbits. However, it did not remove all of the HVP-infected cells from the infected rabbits, and residual HVP-infected lymphocytes caused recurrences of rabbit LPD and HPS. The most interesting finding of this experiment was observed in the infected rabbit with the longest survival time of 105 days: HVP-negative lymphomas surrounded by HVPinduced LPD developed in the larynx and ileum of this rabbit, causing an obstruction of the lumen. We concluded that these were not secondary lymphomas caused by CHOP treatment, because no suspicious lesions were detected in three uninfected rabbits that were treated with three courses of CHOP for 120 days. It is therefore necessary to clarify the mechanism by which HVP-negative lymphomas associated with HVP-induced LPD can develop. Our data from therapeutic trials using EBV-AHS animal models indicate that vidarabine is not effective as an agent to treat HVP-infected rabbits, and even the cytotoxic chemotherapy of CHOP is not sufficient to cure the HVP-infected rabbits or to prolong the survival time of infected rabbits. Further studies will therefore be required to develop better therapies to treat EBV-AHS.
- PublicationOpen AccessIGSF4: a new intercellular adhesion molecule that is called by three names, TSLC1, SgIGSF and SynCAM, by virtue of its diverse function(Murcia : F. Hernández, 2003) Watanabe, K.; Ito, A.; Koma, Y.; Kitamura, Y.Members of the immunoglobulin superfamily often play key roles in intercellular adhesion. IGSF4 is a novel immunoglobulin (Ig)-like intercellular adhesion molecule. Three Ig-like domains are included in the extracellular domain of IGSF4 and mediate homophilic or heterophilic interactions independently of Ca2+. The cytoplasmic domain of IGSF4 contains the binding motifs that connect to actin fibers. Since IGSF4 has been characterized by several independent research groups, this molecule is called by three names, TSLC1, SgIGSF and SynCAM. IGSF4 was first characterized as a tumor suppressor of non-small cell lung cancer and termed TSLC1, although how IGSF4 suppresses tumor growth remains unknown. Silencing of the IGSF4 gene was primarily achieved by allelic loss and promoter methylation in this type of cancers. Soon after this discovery, IGSF4 was found to have roles in adhesion of spermatogenic cells to Sertoli cells and mast cells to fibroblasts and termed SgIGSF. Other researchers revealed that IGSF4 drives synaptic formation of neural cells and termed it SynCAM.
- PublicationOpen AccessMuscle injuries and repair: The role of prostaglandins and inflammation(Murcia : F. Hernández, 2003) Prisk, V.; Huard, J.Skeletal muscle injuries are a common problem in trauma and orthopaedic surgery. Muscle injuries undergo the healing phases of degeneration, inflammation, regeneration, and fibrosis. Current and experimental therapies to improve muscle regeneration and limit muscle fibrosis include conservative and surgical principles with the adjuvant use of non-steroidal anti-inflammatory drugs (NSAIDs) and growth factor manipulation. NSAIDs appear to have a paradoxical effect on the healing of muscle injuries with early signs of improvement and subsequent late impairment in functional capacity and histology. In vitro and in vivo studies have explored the role of the cyclooxygenases and prostaglandins in the biological processes of healing muscle, including precursor cell activation, myoblast proliferation, myoblast fusion, and muscle protein synthesis. Through use of more specific cyclooxygenase inhibitors, we may be able to better understand the role of inflammation in muscle healing.
- PublicationOpen AccessAssessment of cumulated genetic alterations in colorectal cancer(Murcia : F. Hernández, 2003) Risques, R.A.; Ribas, M.; Peinado, M.A.Widespread genetic alterations are a common feature of most colorectal cancers. While specific recurrent alterations may reveal the involvement of a gene or set of genes in the biology of the disease, the cumulated genomic damage is likely to reflect the biological history of the neoplastic cells. Furthermore, the functional implications behind many of these genetic changes may show the evolutionary potential of the neoplastic cells. Different approaches, ranging from the gross determination of total nuclear DNA content to cytogenetic and molecular approaches, reveal different types of chromosomal and subchromosomal alterations and have been applied to measure generalized genomic damage in colorectal carcinomas. High levels of genomic damage usually appear associated with increased aggressiveness in colorectal cancer, and the use of different assessments of genomic damage as independent prognostic factors has been proposed. Therefore, appropriate definition of the extent of cumulated alterations and their functional consequences may be of interest in the understanding and management of cancer. The different methodologies and clues to the interpretation and integration of the results obtained with each technique are discussed in this review.