HCV and C282Y: a sinister synergism?
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Hemochromatosis↗
Biomedical subjects
M Russo
Publications and source records attributed to M Russo.
C3 molecules internalize and enhance the growth of Lewis lung carcinoma cells.
C3 molecules from normal murine serum are mainly bound to Lewis lung carcinoma cells (3LL) that do not express CRs, mainly through covalent binding as determined by the appearance of bands stained with anti-C3 and larger than 190 kD in immunoblots of proteins in whole cell extracts. Methylamine-treated, or zymosan-treated normal mouse serum, heat inactivated, or EDTA-treated murine serum resulted in low C3 deposition on 3LL cells, as indicated by fluorescence tests and immunoblotting. Cytofluorimetric studies showed that C3 molecules bound to 3LL cells were internalized in a time- and temperature-dependent process. This was confirmed by electronmicroscopic studies. The conditions allowing C3 fixation to acceptor sites and subsequent internalization increased cell proliferation. This was also true, when serum from mice genetically deficient in C5 was used which stresses the role of C3 in contrast to effects of membrane attack complex formation.
Animals↗
Bacterium-dependent induction of cytokines in mononuclear cells and their pathologic consequences in vivo.
Viridans streptococci are a heterogeneous group of gram-positive bacteria that are normal inhabitants of the mouth. These organisms are thought to contribute significantly to the etiology of infective endocarditis, although recently they have been implicated in serious infections in other settings. Another group of oral bacteria, gram-negative anaerobes, is associated with chronic dental infections, such as periodontal diseases or endodontic lesion formation. We evaluated the ability of the oral pathogens Streptococcus mutans and Porphyromonas endodontalis to induce a pathogenic response in vivo, with the goal of quantifying the inflammatory response in soft tissue by measuring leukocyte recruitment and hard tissues by measuring osteoclastogenesis. S. mutans induced a strong inflammatory response and was a potent inducer of osteoclast formation, while P. endodontalis was not. To further study the mechanisms by which P. endodontalis and S. mutans elicit significantly different levels of inflammatory responses in vivo, we tested the capacity of each to induce production of cytokines by mononuclear cells in vitro. S. mutans stimulated high levels of interleukin-12 (IL-12), gamma interferon (IFN-gamma), and tumor necrosis factor alpha (TNF-alpha), all of which are associated with inflammation, enhanced monocyte function, and generation of a Th1 response. In contrast, P. endodontalis stimulated production of IL-10 but not of TNF-alpha, IL-12, or IFN-gamma. These results demonstrate that oral pathogens differ dramatically in their abilities to induce inflammatory and immunoregulatory cytokines. Moreover, there is a high degree of correlation between the cytokine profile induced by these bacteria in vitro and their pathogenic capacity in vivo.
Animals↗
Membrane targeting sequences in tombusvirus infections.
Infection of Nicotiana benthamiana cells with cymbidium ringspot (CymRSV) and carnation Italian ringspot (CIRV) viruses results in the formation of conspicuous membranous bodies [multivesicular bodies (MVBs)], which develop from modified peroxisomes or mitochondria, respectively. The organelle targeting signal is located in the proteins of 33 kDa (CymRSV) or 36 kDa (CIRV) encoded by ORF 1, which contain an N-terminal hydrophilic portion followed by two predicted hydrophobic transmembrane segments. Biochemical analysis showed that the 33- and 36-kDa proteins are integral membrane proteins. By exchanging small portions of the ORF 1 sequence between the infectious full-length clones of the two viruses, hybrid constructs were obtained of which the in vitro synthesized RNA was inoculated to N. benthamiana plants and protoplasts. The structure of infectious clones suggested that both the N-terminal hydrophilic region and the transmembrane segments of the ORF 1-encoded proteins specify which organelle is involved in the synthesis of MVBs. Mutational analysis of the CIRV 36-kDa protein also suggested the presence of an internal mitochondrial targeting sequence similar to that found in several normal host proteins that are synthesized in the cytoplasm and transported to mitochondria. The CymRSV 33-kDa protein did not contain the obvious consensus signals thought to be characteristic of proteins targeted to peroxisomes, and an mitochondrial targeting sequence motif was not evident.
Amino Acid Sequence↗
Lipid mediators, tumor necrosis factor and nitric oxide and their interactions in immune-complex-induced lung injury.
We investigated the contribution of eicosanoids, platelet-activating factor, tumor necrosis factor and nitric oxide to the neutrophil influx and development of pulmonary haemorrhagic lesions following immune-complex-induced pneumonitis in rats and possible interactions between these mediators. Increased levels of leukotriene B4 and tumor necrosis factor, measured by enzyme immunoassay and L-929 cytotoxicity assay, were found in the bronchoalveolar lavage 1 and 4 h after induction of the reaction, respectively, and their release was dependent on the previous generation of platelet activating factor. Antagonism of leukotriene B4 receptors by RO-0254094 (2-[(5-carboxypentyl])oxy]-6-[6-[3,4-dihydro-4-oxo-8-propyl-2H-1-benzopy ran-7-yl)oxy]hexyl] benzenepropanoic acid), inhibition of nitric oxide synthesis by L-NAME (Nw-nitro-L-arginine methyl ester) and antagonism of PAF-receptors by WEB-2170 (5-(2-chlorphenyl)-3-4-dihydro-10-methyl-3-((4-morpholinyl)carbony l)-2 H,7H-cyclopenta (4,5)thieno(3,2-f)(1,2,4)-triazolo-4,3,a)91,4)diazepine), significantly inhibited the intensity of haemorrhage, evaluated by the increased levels of extravascular hemoglobin in homogenates of lung tissues. Little evidence support the role of tumor necrosis factor in these lesions. The infiltration of neutrophils, evaluated by measuring myeloperoxidase in homogenates of lungs, was reduced by compounds L-663,536 (3-[1-(4 chlorobenzyl)-3-t-butyl thio-5-isopropylindol-2-yl]-2-2-dimethylpropanoic acid), WEB-2170 and L-NAME. These results indicate that neutrophil infiltration and haemorrhagic lesions in immune-complex-induced lung inflammation are mediated by platelet activating factor, leukotriene B4 and nitric oxide and point out to interesting interactions between these mediators.
Animals↗
Dose variation at bone/titanium interfaces using titanium hollow screw osseointegrating reconstruction plates.
PURPOSE: To evaluate dose variations at bone/titanium interfaces in an experimental model designed to simulate postoperative radiotherapy in patients with mandibular reconstructions using a titanium hollow-screw osseointegrating reconstruction plate (THORP) system. MATERIALS AND METHODS: The model consisted of a 25 x 25 x 10 mm3 block of fresh bovine femoral diaphysis, to the surface of which a segment of THORP system reconstruction plate was fixed by means of a solid titanium screw 4 mm in diameter and 10 mm in length. Using specially designed thermoluminescent dosimeters (TLD) 2 mm in diameter and 0.13 mm in thickness, dose measurements were carried out at four distances from the screw axis (0.1, 0.3, 0.6, and 1 mm). 60Co and 6-MV photon beams were used at incidences both perpendicular and parallel ("axial") to the screw axis. RESULTS: For 6-MV X-ray beams incident perpendicular to the screw axis, the maximum dose enhancement (due to backscatter) and the maximum dose reduction (due to attenuation) at the bone/titanium interface were 5% (+/- 2%) and 6% (+/- 2%), respectively. The corresponding values for 60Co beams were 6% (+/- 5%) and 10% (+/- 5%). For the axial incidences, a maximum dose enhancement of 5-7% was noted for both 6-MV X-rays and 60Co for beams incident on the surface containing the THORP plate segment, whereas beams incident on the opposite surface induced only a very small dose enhancement (2-3%). CONCLUSION: Using a new experimental model, TLD measurements showed only marginally significant dose variations at bone/titanium interfaces around THORP screws, all measured values being very close to the uncertainty limits (+/- 5%) associated with the method. For both 60Co and 6-MV beams, dose variations appeared smaller for axial than for perpendicular incidences. Because photon beams used in head and neck cancer treatment are most often directed parallel to the screw axes, these results suggest that failures of prosthetic osseointegration are unlikely to be explained by an overdosage at the bone/titanium interface.
Animals↗
Molecular cloning and complete nucleotide sequence of galinsoga mosaic virus genomic RNA.
The complete genomic sequence of galinsoga mosaic virus (GaMV) was determined. The genome consists of 3,803 nucleotides and has five open reading frames (ORFs). The 5' ORF (ORF 1) encodes a protein with predicted molecular mass of 23 kDa and readthrough of its amber stop codon probably yields a 82 kDa protein (ORF 2). ORFs 3 and 4 encode two polypeptides with molecular masses of 8 and 7 kDa, respectively. ORF 5 encodes the 36 kDa capsid protein. Amino acid sequence comparisons revealed that the nonstructural proteins encoded by ORFs 1, 3, and 4 were more similar to the corresponding gene products of tobacco necrosis virus, strain A, than to those of carmoviruses. Conversely, the coat protein was more similar to that of tombusviruses. The readthrough region of the viral replicase (ORF 2) had high sequence homology with that of carmo-, tombus-, and necroviruses. Computer analysis of the protein encoded by ORF 1 as well as of the corresponding product of turnip crinkle (TCV) and melon necrotic spot (MNSV) carmoviruses revealed the presence of a sequence with local hydrophobicity and hydrophobic moment characteristic of mitochondrial targeting sequence which may explain the origin of the carmovirus-induced multivesicular bodies from mitochondria.
Amino Acid Sequence↗
Aureusvirus, a novel genus in the family Tombusviridae.
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Tombusviridae↗
Washing the clothes of cat owners is a simple method to prevent cat allergen dispersal.
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Allergens↗
Prevention of lung eosinophilic inflammation by oral tolerance.
Airway inflammation plays a major role in human asthma. Increasing evidence points to a close correlation between eosinophil infiltration and allergic lung disease. A new murine model of eosinophilic lung inflammation has recently been developed; it consists of immunizing mice with small fragments of solidified hen egg white implanted (EWI) into the subcutaneous tissue. In this model, which is further characterized here, mice challenged with ovalbumin (OVA) present an intense and persistent lung eosinophilia, as well as histopathological findings that resemble human asthma. In the present work, the effect of oral tolerance on the development of allergic lung inflammation in B6 mice immunized with antigen plus adjuvant or with EWI is investigated. It was found that in mice rendered orally tolerant by previous exposure to antigen in the drinking water, the T-helper type 2 cell (Th2)-associated allergic responses in both protocols of immunization were almost completely abolished. The allergic responses were assessed by pulmonary and bone marrow eosinophilia, lung histopathology and antigen-specific IgE and IgG1 production. These findings provide the first indication that Th2-associated lung pathology can be prevented by oral tolerance.
Administration, Oral↗
Prenatal diagnosis of aortic insufficiency.
The prenatal diagnosis of various forms of left ventricular outflow tract obstruction has been reported in detail. However, the appearance and the characteristics of fetal aortic insufficiency have been described only in association with complete absence of the value. We report here a case of aortic insufficiency associated with severe aortic stenosis. Features characteristic of insufficiency were severe cardiomegaly due to left ventricle dilatation and the hypocontractility of the myocardium. The aortic root was enormously dilated and the semilunar valve showed thick and dysplastic cusps. On color Doppler, the retrograde high-velocity regurgitant jet was clearly visible.
Adult↗
Personality characteristics of temporomandibular disorder patients using M.M.P.I.
It is generally recognized that psychological factors play an important role in chronic orofacial pain patients. This study analysed psychological profiles of chronic pain patients affected with temporomandibular disorders (TMD), by means of the Minnesota Multiphasic Personality Inventory (MMPI) test. Fifty consecutive TMD patients were examined and were then divided into two subgroups: 1. myofascial pain and 2. temporomandibular joint articular disorders. Sixty-two percent of the whole sample presented pathological MMPI scores. Both subgroups presented similar profiles with alteration of the neurotic triad (hypochondriasis, depression, hysteria), and pathological values of hypochondriasis and hysteria ("V" configuration). Since the personality profile did not differ between the two subgroups investigated, it was not dependent on the dysfunctional origin of the pathology (myalgia or primary TMJ pathology). Chronic TMD patients presented personality characteristics similar to those of other chronic pain patients according to the MMPI.
Adolescent↗
Pollen-related allergy in Europe.
The increasing mobility of Europeans for business and leisure has led to a need for reliable information about exposure to seasonal airborne allergens during travel abroad. Over the last 10 years or so, aeropalynologic and allergologic studies have progressed to meet this need, and extensive international networks now provide regular pollen and hay-fever forecasts. Europe is a geographically complex continent with a widely diverse climate and a wide spectrum of vegetation. Consequently, pollen calendars differ from one area to another; however, on the whole, pollination starts in spring and ends in autumn. Grass pollen is by far the most frequent cause of pollinosis in Europe. In northern Europe, pollen from species of the family Betulaceae is a major cause of the disorder. In contrast, the mild winters and dry summers of Mediterranean areas favor the production of pollen types that are rarely found in central and northern areas of the continent (e.g., the genera Parietaria, Olea, and Cupressus). Clinical and aerobiologic studies show that the pollen map of Europe is changing also as a result of cultural factors (e.g., importation of plants for urban parklands) and greater international travel (e.g., the expansion of the ragweed genus Ambrosia in France, northern Italy, Austria, and Hungary). Studies on allergen-carrying paucimicronic or submicronic airborne particles, which penetrate deep into the lung, are having a relevant impact on our understanding of pollinosis and its distribution throughout Europe.
Allergens↗
Tombusvirus isolation and RNA extraction.
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Genetic Techniques↗
Thioglycollate-elicited murine macrophages are cytotoxic to Mycoplasma arginini-infected YAC-1 tumor cells.
Macrophages are important components of natural immunity involved in inhibition of tumor growth and destruction of tumor cells. It is known that these cells can be activated for tumoricidal activity by lymphokines and bacterial products. We investigated whether YAC-1 tumor cells infected with Mycoplasma arginini stimulate nitric oxide (NO) release and macrophage cytotoxic activity. Thioglycollate-elicited macrophages from male BALB/c mice were co-cultured for 20 h with YAC-1 tumor cells infected or not with Mycoplasma arginini. The cytotoxic activity was evaluated by MTT assay and nitrite levels were determined with the Griess reagent. Thioglycollate-elicited macrophages co-cultured with noninfected YAC-1 cells showed low cytotoxic activity (34.7 +/- 8.6%) and low production of NO (4.7 +/- 3.1 microM NO2-). These macrophages co-cultured with mycoplasma-infected YAC-1 cells showed significantly higher cytotoxic activity (61.4 +/- 9.1%; P < 0.05) and higher NO production (48.5 +/- 13 microM NO2-; P < 0.05). Addition of L-NAME (10 mM), an inhibitor of NO synthesis, to these co-cultures reduced the cytotoxic activity to 37.4 +/- 2% (P < 0.05) and NO production to 3 +/- 4 microM NO2- (P < 0.05). The present data show that Mycoplasma arginini is able to induce macrophage cytotoxic activity and that this activity is partially mediated by NO.
Animals↗
Cytotoxic activity of BCG-activated macrophages against L929 tumor cells is nitric oxide-dependent.
The tumoricidal activity of activated macrophages has been attributed largely to the release of tumor necrosis factor (TNF), or to the production of reactive oxygen or nitrogen intermediates. The L929 tumor cell line (a murine fibroblast-like cell) when treated with actinomycin D (ActD) has been used to measure TNF alpha cytotoxicity. In the present study, we determined the cytotoxic activity of BCG-activated peritoneal macrophages against ActD-untreated L929 tumor cells. Furthermore, we measured the production of hydrogen peroxide (H2O2), nitric oxide (NO) and TNF by macrophages cultured in the presence or absence of L929 cells. As expected, BCG-activated macrophages produced significant amounts of H2O2 (16.0 +/- 3.0 microM), TNF (512 U/ml) and NO (71.5 +/- 3.2 microM). TNF (256 U/ml) and NO (78.9 +/- 9.7 microM) production was unchanged in co-cultures of L929 cells with BCG-activated macrophages but H2O2 production was totally inhibited. The cytotoxic activity was dependent on NO release since L-NAME (2.5, 5.0 and 10 mM), which blocks NO synthase, inhibited the killing of L929 cells. Addition of anti-TNF (20 micrograms/ml) antibodies to the cultures did not affect the tumoricidal activity of macrophages. Our results indicate that macrophage-mediated killing of L929 cells is largely dependent on NO production but independent of H2O2 or TNF release.
Animals↗
Potential role of proton therapy in the treatment of pediatric medulloblastoma/primitive neuro-ectodermal tumors: spinal theca irradiation.
PURPOSE: Conventional postoperative photon-beam radiotherapy to the spine in children with medulloblastoma/PNET is associated with severe late effects. This morbidity (growth and developmental) is related to the exit dose of the beams and is particularly severe in young children. With the purpose of reducing this toxicity, a dosimetric study was undertaken in which proton therapy was compared to standard megavoltage photon treatment. METHODS AND MATERIALS: The results of a comparative dosimetric study are presented in such a way that the dose distribution achievable with a posterior modulated 100 MeV proton beam (spot scanning method) is compared with that of a standard set of posterior 6 MV x-ray fields. The potential improvements with protons are evaluated, using dose-volume histograms to examine the coverage of the target as well as the dose to the vertebral bodies (growth plates), lungs, heart, and liver. RESULTS: The target (i.e., the spinal dural sac) received the full prescribed dose in both treatment plans. However, the proportions of the vertebral body volume receiving > or = 50% of the prescribed dose were 100 and 20% for 6 MV x-rays and protons, respectively. For 6 MV x-rays > 60% of the dose prescribed to the target was delivered to 44% of the heart volume, while the proton beam was able to completely avoid the heart, the liver, and in all likelihood the thyroid and gonads as well. CONCLUSION: The present study demonstrates a potential role of proton therapy in decreasing the dose (and toxicity) to the critical structures in the irradiation of the spinal neuraxis in medulloblastoma/PNET. The potential bone marrow and growth arrest sparing effects make this approach specially attractive for intensive chemotherapy protocols and for very young children. Sparing the thyroid gland, the posterior heart wall, and the gonads may be additional advantages in assuring a long-term posttreatment morbidity-free survival.
Brain Neoplasms↗
Influence of modifications in breast irradiation technique on dose outside the treatment volume.
PURPOSE: There is increasing interest in potential long-term effects of radiotherapy (RT) in patients treated for breast cancer, particularly those in whom long-term survival can be expected. The purpose of the present study was to determine the effects of treatment techniques, including patient positioning (supine vs. prone) on the absorbed dose in organs at a distance from the treatment volume in breast RT. METHODS AND MATERIALS: Dose distribution was studied in a Rando-Alderson phantom, modified with a simulated left breast of tissue-equivalent material. RT delivery was studied using 60Co and 6 MV x-ray beams, as well as electrons and a 192Ir source for tumor bed boost RT. Doses were measured in several organs and tissues of interest using LiF thermoluminescent dosimeters. Tangential breast RT was simulated using both supine and prone positioning. RESULTS: Peripheral doses generally decreased approximately exponentially with distance from the edge of the treatment field. Peripheral doses in various target organs were significantly higher for supine than for prone tangential breast RT (for 50 Gy prescribed dose): 0.50 Gy vs. 0.25 Gy for the upper abdomen, 0.05 Gy vs. 0.02 Gy for pelvic organs, 0.17 Gy vs. 0.08 Gy for active bone marrow, and 0.47 Gy vs. 0.12 Gy for ipsilateral lung (discounting lung in primary beam). CONCLUSIONS: The present study suggests that peripheral doses in several organs and tissues of interest can be reduced by 40 to 75% by prone tangential breast RT. These results may have implications for future strategies in the treatment of screen-detected breast cancer.
Abdomen↗