Altered biodistribution of [68Ga]Ga-DOTA-TOC during somatostatin analogue treatment.

PURPOSE: The need for an interval between the administration of long-acting Somatostatin Receptor Analogues (SSA) and the [68Ga]Ga-DOTA-TATE PET has been questioned based on recent literature in the new EANM guidelines. Here an earlier studies showed that SSA injection immediately before SSTR PET had minimal effect on normal organ and tumor uptake (1). However, data are scarce and there are (small) differences between [68Ga]Ga-DOTA-TATE and [68Ga]Ga-DOTA-TOC binding affinity, and it remains unknown whether these findings can be directly translated to scans with [68Ga]Ga-DOTA-TOC as well. The purpose of this study was to assess the effect of SSA use on the biodistribution in a subsequent [68Ga]Ga-DOTA-TOC PET/CT and compare this intra-individually across several cycles of SSA treatments. METHODS: Retrospectively, 35 patients with NENs were included. [68Ga]Ga-DOTA-TOC PET at staging and after the 1st and 2nd cycle of SSA were included. SUVmean and SUVmax of blood, visceral organs, primary tumor and two metastases were determined. Also, the interval between SSA therapy and the PET scan was registered. RESULTS: Treatment with SSA resulted in a significantly higher bloodpool activity and lower visceral tracer uptake. This effect was maintained after a 2nd cycle of SSA therapy. Furthermore, there was an inverse relationship between bloodpool tracer availability and visceral tracer binding and a positive correlation between bloodpool tracer availability and primary tumor tracer uptake. With an interval of up to 5 days, there was a significantly higher bloodpool activity than at longer intervals. CONCLUSION: Absolute comparison of the SUV on [68Ga]Ga-DOTA-TOC PET should be done with caution as the altered biodistribution of the tracer after SSA treatment should be taken into account. We recommend not to perform a scan within the first 5 days after the injection of lanreotide.

Does treatment strategy influence the ability to achieve and sustain DMARD-free remission in patients with RA? Results of an observational study comparing an intensified DAS-steered treatment strategy with treat to target in routine care.

OBJECTIVES: To study the impact of treatment strategy on achieving and sustaining disease-modifying antirheumatic drug (DMARD)-free remission in patients with rheumatoid arthritis (RA). METHODS: Two hundred seventy-nine RA patients (median follow-up 7.8 years) were studied. Of these, 155 patients participated in a disease activity score (DAS) < 1.6 steered trial aimed at DMARD-free remission. Initial treatment comprised methotrexate with high-dose prednisone (60 mg/day) and a possibility to start biologicals after 4 months. In the same period and hospital, 124 patients were treated according to routine care, comprising DAS < 2.4 steered treatment. Percentages of DMARD-free remission (absence of synovitis for ≥ 1 year after DMARD cessation), late flares (recurrence of clinical synovitis ≥ 1 year after DMARD cessation), and DMARD-free sustained remission (DMARD-free remission sustained during complete follow-up) were compared between both treatment strategies. RESULTS: Patients receiving intensive treatment were younger and more often ACPA-positive. On a group level, there was no significant association between intensive treatment and DMARD-free remission (35% vs 29%, corrected hazard ratio (HR) 1.4, 95%CI 0.9-2.2), nor in ACPA-negative RA (49% versus 44%). In ACPA-positive RA intensive treatment resulted in more DMARD-free remission (25% vs 6%, corrected HR 4.9, 95%CI 1.4-17). Intensive treatment was associated with more late flares (20% versus 8%, HR 2.3, 95%CI 0.6-8.3). Subsequently, there was no difference in DMARD-free sustained remission on a group level (28% versus 27%), nor in the ACPA-negative (43% versus 42%) or ACPA-positive stratum (17% versus 6%, corrected HR 3.1, 95%CI 0.9-11). CONCLUSIONS: Intensive treatment did not result in more DMARD-free sustained remission, compared to routine up-to-date care. The data showed a tendency towards an effect of intensive treatment in ACPA-positive RA; this needs further investigation.

A Novel Marker for Purkinje Cells, Ribosomal Protein MPS1/S27: Expression of MPS1 in Human Cerebellum.

BACKGROUND: The ribosomal protein metallopanstimulin-1 (MPS1/S27) serves critical survival purposes in cell division, in normal and cancerous cells; for this reason, selective pressures of evolution have conserved the DNA sequences encoding MPS1/S27 in Archaea and Eukariotic cells. The expression of MPS1/S27 protein in human adult cerebellum has not been established. MATERIAL AND METHODS: The presence of MPS1/S27, was screened in paraffin-embedded human adult brain specimens processed for tissue inmunohistochemistry. Affinity-purified specific antibodies were directed against the N-terminus of MPS1. RESULTS: The antibodies to MPS1 detected Purkinje cells (PC) and their dendrites. In PC, MPS1 antigen-positive staining was found in: the nucleolus, which was strongly stained; ribosomes attached to the external nuclear membrane; cytoplasm of PC, with strong staining in a punctuate fashion; the soma-attached large dendrite trunks of PC, which were MPS1 antigen-positive; and the granular cell layer, where cellular staining in a few cells that appeared to resemble smaller PC was observed. CONCLUSION: Since MPS1 is involved in cell division, DNA repair, and ribosomal biogenesis, it may be a useful antigen for studying processes such as protein synthesis, oncogenesis, regeneration, aging, and perhaps diseases of the human cerebellum.

Inter- and intra-rater reproducibility of automated and integrated pressure-flow analysis of esophageal pressure-impedance recordings.

BACKGROUND: Automated impedance manometry pressure-flow analysis (AIM analysis) determines pressure measurements relative to bolus flow and has to date shown subtle variations in esophageal motility in relation to dysphagia. In this study, we assessed intra- and inter-rater reproducibility of AIM metrics derived using purpose designed software. METHODS: Fifty patients referred for evaluation of gastro-esophageal reflux symptoms (33 men, age 52 ± 1.9 years) underwent combined high-resolution impedance manometry and completed a dysphagia questionnaire. From 10 liquid and 10 viscous swallows, a subset of four swallows (two saline and two viscous) was systematically selected from each patient for manual and AIMplot analysis, which was performed twice by five observers (two experts, three non-experts). Intra- and inter-rater agreement were determined using intraclass correlation coefficients. KEY RESULTS: AIMplot-based analysis showed high intra-rater and inter-rater reproducibility for all metrics (mean ICCs of 0.95 and 0.94, respectively). Reproducibility of metrics derived for liquid and viscous did not differ (ICCs of 0.96 and 0.91 for liquid and viscous, respectively). In addition, metrics derived by experts had an equivalent level of reproducibility compared to non-experts (ICCs of 0.96 and 0.94, respectively). Variables that could be derived with commercial software (ManoView™) correlated highly with variables from AIMplot-based analysis, such as 4-s integrated relaxation pressure (r = 0.85) and the 20-mmHg isobaric contour defect (r = 0.92). CONCLUSIONS & INFERENCES: Esophageal AIM analysis is highly reproducible, independent of an observer's level of experience in esophageal motility. Therefore, AIM analysis produces data that are reliable for clinical and research purposes.

The maintenance of pulp health 17 years after root fracture in a maxillary incisor illustrating the diagnostic benefits of cone bean computed tomography.

AIM: To demonstrate the maintenance of pulp health in a tooth with a fractured root without any complications or endodontic treatment and the advantage of cone bean computed tomography (CBCT) compared with traditional radiographs in the diagnosis of root fractures. SUMMARY: The horizontal fracture of a maxillary central incisor is described that was an incidental finding on a routine radiographic examination 17 years after trauma. The tooth was asymptomatic. Intra-oral radiography revealed a complicated multiple root fracture with separation of the root fragments, which was not confirmed by CBCT. This case report illustrates spontaneous healing of root fracture and the reparative potential in the area of root fracture including preservation of pulp health and also demonstrates that CBCT is a more reliable imaging technique than conventional radiographs regarding root fracture diagnosis. KEY LEARNING POINTS: The dental pulp is characterized by the ability to heal spontaneously in cases of root fracture. CBCT has advantages in diagnosing root fractures over intra-oral radiographs. CBCT should be employed with caution due to its increased radiation dose compared with periapical radiography.

Polyomavirus BK in the pathogenesis of bladder cancer.

Polyomaviruses are able to drive malignant transformation in rodent models, and have been implicated in the aetiology of a variety of human malignancies. However, the reports on this association in humans are strongly conflicting. Here we describe a renal transplant (RT) recipient with ureteral stenosis against the background of polyomavirus BK (BKV) activity. Six and a half years after transplantation, this patient developed metastasised bladder cancer. Prior to the diagnosis of cancer, atypical cells were detected in the urine that were denoted as 'decoy cells': virally infected epithelial cells that are frequently seen in the urine of RT recipients with BKV (re)activation, which may morphologically resemble malignant cells. Intriguingly, the primary urothelial carcinoma, as well as the mesenterial and two intestinal metastases, stained positive with antibodies against polyomavirus virus large T antigen protein, whereas the adjacent healthy tissue did not. This case suggests a role for BKV in the pathogenesis of bladder cancer, at least in the context of immunodeficiency.

Increased serum level of RPMPS-1/S27 protein in patients with various types of cancer is useful for the early detection, prevention and therapy.

BACKGROUND: When a protein has a useful and unique function, the selective pressures of evolution conserve the DNA sequences encoding such proteins; the conservation of these domains may have pragmatic use in better understanding viral and spontaneous carcinogenesis in eukaryotic cells. The unique functions of ribosomal protein (RP) Metallopanstimulin-1 (MPS-1/RPS27), and a few other RPs, in growth regulation and carcinogenesis (chemical, viral, radiation and chemotherapy-induced) could be used for the early detection of cancer using serum, or in follow-up therapy. MATERIALS AND METHODS: The MPS-1 serum test was performed in the serum of patients by radioimmunoassay using specific antibodies directed against the N-terminus (amino acids 2 to 17; synthetic peptide) of MPS-1 according to previously described procedures (Fernandez-Pol, JA, 1994). RESULTS: The data presented here indicate that antibodies to MPS-1 detect a zinc finger protein of Mr 9.8 kDa identified by MS and sequencing as MPS-1 in patients having various types of cancer. MPS-1 increases with aggressivity of cancer, irrespective of the cancer types studied in this work. In healthy individuals of the same age range, the levels of MPS-1 increase slowly and progressively at less than 1% per year as the patients age. CONCLUSION: The MPS-1 test may be useful as an aid in: i) early detection of a wide variety of cancer types; and ii) the prognosis and management of cancer patients by following the changes in the concentrations of MPS-1 in serum. Moreover, the results suggest that the combined use of MPS-1 with physical methods of cancer detection such as positron emission tomography, computer assisted tomography, or magnetic resonance imaging techniques may significantly improve the chances of identifying an active tumor in early stages by serodiagnosis of MPS-1. In patients having other diseases (such as rheumatoid arthritis, which manifests as a proliferative disease) or in healthy individuals having no evidence of disease, the identification of as yet unrecognized active oncogenesis, may be significantly improved by using MPS-1. The data on genome context analysis indicates that the presence of MPS-1 in the blood is an indicator of oncogenesis. Thus, the test may be used to help prolong the life of the patients, if the cancer is detected early.

Residual infrarenal aortic neck following endovascular and open aneurysm repair.

BACKGROUND: The effectiveness of open and endovascular aneurysm repair of aortic abdominal aneurysms (AAAs) can be jeopardised by deterioration of the residual infrarenal neck of the aneurysm. OBJECTIVE: The study aims to determine the length of the residual infrarenal aortic segment after endovascular and open aneurysm repair. METHODS: In a multicentre randomised controlled trial comparing open and endovascular AAA repair, 165 patients were discharged after open AAA repair (OR) and 169 after endovascular repair (EVAR). Immediately after the operation, surgeons were asked to enter in the case record form whether the level of their anastomosis after open repair was within or beyond 10 mm of the caudal renal artery. Postoperative computed tomography (CT) scans that were obtained within 6 months after surgery were used for comparative analysis. The distance between the caudal renal artery and the proximal anastomosis of the (endo-) graft was measured using axial CT slices and a standardised protocol. CT images were available and suitable for analysis in 156 (95%) of 165 OR patients and in 160 (95%) of 169 EVAR patients. Data are presented as median (range). Differences were analysed using the Mann-Whitney test. RESULTS: The distance from the caudal renal artery to the proximal anastomosis was 24 mm (16-30 mm) in the OR group versus 0 mm (0-6 mm) in the EVAR group (p < 0.0001, Mann-Whitney). In 140 of 156 (90%) patients, at least 1 cm of untreated infrarenal neck persisted after OR and in 17 of 160 (10%) after EVAR. In 84 of the 156 open repair patients (54%), the surgeon had indicated that the proximal anastomosis was within 10 mm of the caudal renal artery. Only five surgeons (6%) were accurate in this respect. CONCLUSION: After open repair, a longer segment of the infrarenal aortic neck is left untreated compared with endovascular repair and this length is underestimated by most surgeons. Long-term studies are required to determine the consequences of this difference.

Value of PCR in surgically treated patients with staphylococcal infective endocarditis: a 4-year retrospective study.

The aim of the study was to establish a diagnostic value for broad-range polymerase chain reaction (br-PCR) and staphylococci-specific multiplex PCR (ssm-PCR) performed on surgical material from patients with staphylococcal infective endocarditis (IE). Data were analysed retrospectively from 60 patients with suspected staphylococcal IE and 59 controls who were surgically treated at three cardiosurgery centres over 4 years. Both PCR tests showed high agreement and could be aggregated. In patients with definite and rejected IE, the clinical sensitivity and specificity of PCR reached 89 and 95%, respectively. Tissue culture (TC) and PCR agreed with blood culture (BC) in 29% and 67% of IE cases. TC helped to determine aetiology in five BC negative cases while PCR aided in nine cases. Out of 52 patients with conclusive staphylococcal IE, 40 were diagnosed with S. aureus and 12 with coagulase-negative staphylococci. PCR was shown to be highly superior to TC in confirming preoperative diagnosis of IE. In addition to aid in culture negative patients, PCR helped to establish or refine aetiology in inconclusive cases. We suggest that simultaneous br-PCR and ssm-PCR performed on surgical material together with histopathology could significantly increase the performance of current Duke criteria.

Conservation of multifunctional ribosomal protein metallopanstimulin-1 (RPS27) through complex evolution demonstrates its key role in growth regulation in Archaea, eukaryotic cells, DNA repair, translation and viral replication.

BACKGROUND: When the functions of a protein serve a useful survival and unique purpose, the selective pressures of evolutionary laws of nature conserve the DNA sequences encoding such proteins. In many instances, the conservation of these sequences has occurred since the inception of life on earth to the present in phylogenetically related species. The unique function(s) of metallopanstimulin (MPS-1/RPS27) ribosomal protein (RP) and a limited number of other RPs, in growth regulation, and viral infection is further documented here. Based on the correlation of information concerning Genome Context Analysis, and new information presented here, the author proposes that neutralization or elimination of ribosomal MPS-1/S27 DNA, mRNA or translated protein in eukaryote cells, initiated in the process of chemical, viral or radiation carcinogenesis can result in control of most carcinogenic processes by selective elimination of transformed cells which display overexpression of RPMPS-1/S27, and/or non-lethal pathogenic mutations of RPMPS-1/S27 gene. Recently, critical interactions were reported between RPMPS-1/S27 and p53 induced by DNA damage such as ionizing radiation, or chemotherapy drugs, that result in the activation of p53 which in turn represses RPMPS-1/S27 actions. Thus, p53, RPS27L, and RPS27/MPS-1) regulate growth and survival. MATERIALS AND METHODS: Antivirals were tested in virus-infected cells using: cell culture, cytotoxicity assays, apoptosis, defined virus strains, cloned cells, and RT-PCR. Purity of antivirals was validated by mass spectroscopy (MS). Disruption of zinc finger peptides (ZFPs), by these agents was determined by NMR. RESULTS: The data presented here indicates that anti-ZFP agents can potentially be used to prevent and control viral infections by disrupting viral ZFP motifs. Different DNA/RNA virus-infected cells exposed to the antivirals resulted in distruption of both RPMPS-1/S27 and essential viral ZFPs. Picolinic acid (PA) and fusaric acid (FU) were tested and have been shown to have both antiviral and preventive antiviral activities which have been consistently shown to be mediated, at least in part, via interacting with RPMPS-1/S27. The same antiviral agents simultaneously disrupt essential viral ZFPs. Both antiviral events on ZFPs render the pathogenic virus inactive. CONCLUSION: It is demonstrated here that PA and FU exhibit antiviral activity towards several DNA and RNA viruses of human and animal importance. Illustrative evidence of the mechanism of action was obtained via MS, NMR, and molecular modeling that PA and, more potently, FU, bind to a particular site of the viral ZFPs. Similarly, it was previously shown by MS, NMR and molecular modeling with RPMPS-1/S27 that PA and FU disrupts the function of this RP protein, preventing viral replication by formation of ternary complexes. This work is consistent with a critical role of RPMPS-1/S27 in the life cycle of various viruses and shows that disruption of viral ZFPs is potentially important to control and prevent deathly viral diseases.

Kinetics of carotenoid distribution in human skin in vivo after exogenous stress: disinfectant and wIRA-induced carotenoid depletion recovers from outside to inside.

The human organism has developed a protection system against the destructive effect of free radicals. The aim of the present study was to investigate the extent of exogenous stress factors such as disinfectant and IR-A radiation on the skin, and their influence on the kinetics of carotenoids distribution during the recovery process. Ten healthy volunteers were assessed with resonance spectroscopy using an Argon-laser at 488 nm to excite the carotenoids in vivo. Additionally, Raman-confocal-micro-spectroscopy measurements were performed using a model 3510 Skin Composition Analyzer with spatially resolved measurements down to 30 µm. The measurements were performed at a baseline of 20, 40, 60, and 120 min after an external stressor consisting either of water-filtered infrared A (wIRA) with 150 mW∕cm(2) or 1 ml∕cm(2) of an alcoholic disinfectant. Both Raman methods were capable to detect the infrared-induced depletion of carotenoids. Only Raman-microspectroscopy could reveal the carotenoids decrease after topical disinfectant application. The carotenoid-depletion started at the surface. After 60 min, recovery starts at the surface while deeper parts were still depleted. The disinfectant- and wIRA-induced carotenoid depletion in the epidermis recovers from outside to inside and probably delivered by sweat and sebaceous glands. We could show that the Raman microscopic spectroscopy is suited to analyze the carotenoid kinetic of stress effects and recovery.

Seroprevalence of IgG antibodies against 13 vaccine Streptococcus pneumoniae serotypes in the Netherlands.

In this study the seroprevalence of IgG antibodies against 13 vaccine serotypes of the pneumococcus was assessed in the Netherlands. Sera from 7904 persons obtained in a cross-sectional population-based study were analysed. The 13 serotype specific IgG concentrations were assessed simultaneously using a fluorescent bead-based multiplex immuno assay (MIA). Overall, the geometric mean IgG concentrations (GMCs) against the 13 serotypes in unvaccinated individuals increased with age up to 5 years and remained at a plateau thereafter. The data also show that individuals develop antibodies against an increasing number of different serotypes with increasing age. The highest GMCs were found for antibodies directed against serotype 14 and 19F, whereas antibodies against serotypes 4 and 5 had the lowest GMCs. There was no uniform relationship between the occurrence of serotypes causing invasive pneumococcal disease (IPD) and the GMCs against these serotypes. Increased IPD incidence in the elderly did not seem to be the result of a decline in the concentration of IgG antibodies.

[Surgical treatment of pulmonary embolism]. / Chirurgická lécba plicní embolie.

BACKGROUND: Surgical embolectomy is established method of treatment of pulmonary embolism. The aim of the study is to evaluate the experience with this procedure. PATIENTS AND METHODS: Twenty two patients, aged 22-77 years, were operated on in Centre of cardiovascular surgery and transplantation in Brno from 1999 to 2009. Nine patients suffered from massive pulmonary embolism with hemodynamic instability, 13 were stable. All the operations were performed in cardiopulmonary bypass with cross clampimg time 50.4 minutes on average. In six patients the retrograde perfusion via pulmonary veins were used. Emboli in the main trunk and/or in both pulmonary branches were found in 16 patients (72.7%). No macroscopic emboli were found in three patients, but they were flushed from the pulmonary vessels during the retrograde perfusion in two of them. Emboli or thrombi in cardiac atria or ventricles were detected in 8 patients simultaneously. RESULTS: Five patients died early after operation (mortality 22.7%). The mortality was different in the group of patients with massive pulmonary embolism and cardiogenic shock (44.4%) and with submassive embolism and hemodynamic stability (7.7%). CONCLUSION: Developments in surgical technique with retrograde perfusion offer removing of emboli not only from the pulmonary trunk and main branches, but also from the peripheral branches. It improves results and facilitates extension of indications for surgical treatment.

Wall stress analysis in small asymptomatic, symptomatic and ruptured abdominal aortic aneurysms.

OBJECTIVES: To evaluate the potential of wall stress analysis for the identification of abdominal aortic aneurysm (AAA) at elevated risk of rupture in spite of small diameter. MATERIALS AND METHODS: Thirty patients with small AAA, 10 asymptomatic, 10 symptomatic and 10 ruptured, were included. Demographic data and results from physical examinations were recorded in a retrospective fashion. After CT-evaluation and the creation of a patient specific 3D model, wall stress was calculated using the finite element method. RESULTS: No differences were observed in diameter between asymptomatic, symptomatic or ruptured aneurysms (5.1+/-0.2 cm vs. 5.1+/-0.2 cm vs. 5.3+/-0.2 cm respectively; p=0.57). Peak aortic wall stress at maximal systolic blood pressure is significantly higher in ruptured than asymptomatic aneurysms (51.7+/-2.4 N/cm(2) vs. 39.7+/-3.3 N/cm(2) respectively; p=0.04). Wall stress analysis at uniform blood pressure, performed to correct for higher blood pressure in the symptomatic and rupture group did not result in significant differences in peak wall stress (asymptomatic 31.7+/-2.3 N/cm(2); symptomatic 30.5+/-1.3 N/cm(2); rupture 36.7+/-4.0 N/cm(2); p=0.26). CONCLUSIONS: Wall stress analysis at maximal systolic blood pressure is a promising technique to detect aneurysms at elevated aneurysm rupture risk. Since no significant differences were found at uniform blood pressure, the need for adequate blood pressure control in aneurysm patients is reiterated.

Linear hoof defects in sheep infected with foot-and-mouth disease.

During the epidemic of foot-and-mouth disease (FMD) in The Netherlands in 2001, a sheep farm was identified that had been subclinically infected with the disease. The FMD virus genome was detected in 12 of 16 probang samples collected from the sheep and the virus was isolated from four of these samples. Linear defects were observed, 1 to 3 cm from the coronary band, in the hooves of several of the sheep. The defects were thought to have been caused by the FMD infection. It was thought that the distance of the defects from the coronary band might be an indication of the time since the animals had been infected. To determine the growth rate of the claws of sheep, the growth of the hoof horn of uninfected lambs and ewes was measured; in the lambs the growth rate was 0.44 mm per day and in the ewes it was 0.29 mm per day.

Genomics, Proteomics and Cancer: Specific Ribosomal, Mitochondrial, and Tumor Reactive Proteins Can Be Used as Biomarkers for Early Detection of Breast Cancer in Serum.

We have used genomics and proteomics based technologies to study tissue and serum protein profiles in patients with breast cancer (BC) in comparison to control healthy subjects. One critical objective of this study was to identify and characterize new tissue and serum biomarkers of BC using differential screening of a recombinant cDNA human BC expression library. A second major objective of this study was to evaluate the clinical utility of Metallolpanstimulin (MPS-1/S27 ribosomal) protein as a biomarker for the early detection and monitoring of BC by immunoassay measurements of serum MPS-1 protein levels and to identify MPS-1 protein in sera of BC patients. A third objective was to present data on cloned BC genes denoted protein subgroup-30 (PS-30), consisting of mitochondria, nuclear, and ribosomal proteins which are increased after growth factor stimulation of BC cells in tissue culture. To study in detail MPS-1 protein expression in BC, the MPS-1 concentrations were determined in the blood of 117 females free of any disease, and in 203 female patients diagnosed with primary BC. The results indicate that increased serum MPS-1 levels can be used for the early detection of BC. Normal subjects have low concentrations of MPS-1 protein in sera. Moreover, changes in MPS-1 protein serum levels can be used for the study of BC progression or regression after various types of therapy. In both the low and high value range, MPS-1 is 10-fold more effective than CA-15-3 in modifying the probability of the target condition -breast cancer. The use of HPLC, Western blot, Immuno-Mass Spectrometry, and protein sequencing confirmed the presence of authentic MPS-1 in sera of patients with BC. Negligible levels of MPS-1 protein were detected in sera from normal subjects. We conclude that (1) the increase in serum MPS-1 can be used for the early detection of BC; and (2) MPS-1 proved to be reliable in the follow-up of patients with advanced BC as demonstrated by the close correlation between MPS-1 protein levels and BC progression or regression after various types of therapy. Furthermore, all proteins denoted group -30 (Mr <30,000), consisting of ribosomal, nuclear and mitochondria proteins, were found to be significantly increased in BC tissues in comparison to control tissues, suggesting that these proteins may be useful markers for detection of BC. Finally, several serum reactive proteins such as haptoglobin and C3 complement components provided valuable information on oncogenic activity in BC patients.

Metallopanstimulin / S27 Ribosomal Antigen Expression in Stages I and II Breast Cancer: its Relationship with Clinicopathologic Factors.

Metallopanstimulin (MPS-1)/S27 ribosomal protein is involved in cellular proliferation and oncogenesis. In this study, we have examined the expression of the MPS-1 protein in 120 stages I and II breast carcinomas to study its relationship with breast cancer prognosis. We also determined if there was any relationship of MPS-1 with other biological markers commonly used in breast cancer prognosis. The expression of MPS-1 protein was analyzed by immunohistochemistry using specific anti-MPS-1 antibodies. We found that there was greater expression of MPS-1 in tumors of greater size and in higher histological grades. Thus, in tumors with more histological aggressiveness there is more MPS-1. Both were frequently associated with a greater proliferative activity. There was also a significant association between the expression of MPS-1 with the expression of receptors for progesterone (p=0.004), estrogens (p=0.03), bcl-2 (p=0.002), and MIB-1 (p=0.03). After univariate logistic regression analysis, we found that overexpression of MPS-1 correlated with Disease Free Survival (DFS) (p=0.039), showing that MPS-1 positivity is associated with a greater incidence of recurrence and/or metastasis. There was no association between overexpression of MPS-1 and poor Overall Survival (OS) (p=0.146). The results presented here indicate a significant correlation between overexpression of MPS-1/S27 ribosomal protein and more aggressive breast cancer growth. These results suggest that the MPS-1 antigen may be a useful marker to understand better the biological behavior of breast cancer.

Oral transmission of porcine reproductive and respiratory syndrome virus by muscle of experimentally infected pigs.

The current study was performed to determine if porcine reproductive and respiratory syndrome virus (PRRSV) could be transmitted to pigs by feeding muscle tissue obtained from recently infected pigs. Muscle obtained from pigs infected with either a European strain (EU donor pigs) or American strain (US donor pigs) of PRRSV was fed to PRRSV-free receiver pigs. The donor pigs were slaughtered 11 days post-infection (dpi). PRRSV was detected by conventional virus isolation in muscle at 11 dpi from 7 of 12 EU donor pigs and 5 of 12 US donor pigs. In contrast to conventional virus isolation, all muscle samples from infected pigs were positive for viral nucleic acid by PCR, except for muscle from one animal infected with the American strain of PRRSV. Five hundred grams of raw semimembranosus muscle from each of the donor pigs was fed over a 2 days period (250 g per day) to each of two receiver pigs (48 receiver pigs). The receiver pigs were housed separately in five groups. One of the five groups was fed muscle obtained from US donor pigs that was also spiked with the American strain of PRRSV. Sentinel pigs were placed in-contact with the group of receiver pigs fed spiked muscle. All receiver pigs became viraemic by 6 days post-feeding (dpf). There was evidence of horizontal transmission with sentinel pigs, in-contact with receiver pigs, becoming viraemic. The study demonstrates that PRRSV could be infectious through the oral route via the feeding of meat obtained from recently infected pigs.