bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparing Acceleration and Speed Tuning in Macaque MT: Physiology and Modeling
Authors: Price N.S.C. , Ono S. , Mustari M. J. , Ibbotson M. R.
Published: August 2005

Studies of individual neurons in area MT have traditionally investigated their sensitivity to constant speeds. We investigated acceleration sensitivity in MT neurons by comparing their responses to constant steps and linear ramps in stimulus speed. Speed ramps constituted constant accelerations and decelerations between 0 and 240°/s. Our results suggest that MT neurons do not have explicit acceleration sensitivity, although speed changes affected their responses in three main ways. First, accelerations typically evoked higher responses than the corresponding deceleration rate at all rates tested. We show that this can be explained by adaptation mechanisms rather than differential processing of positive and negative speed gradients. Second, we inferred a cell's preferred speed from the responses to speed ramps by finding the stimulus speed at the latency-adjusted time when response amplitude peaked. In most cells, the preferred speeds inferred from deceleration were higher than those for accelerations of the same rate or from steps in stimulus speed. Third, neuron responses to speed ramps were not well predicted by the transient or sustained responses to steps in stimulus speed. Based on these findings, we developed a model incorporating adaptation and a neuron's speed tuning that predicted the higher inferred speeds and lower spike rates for deceleration responses compared with acceleration responses. This model did not predict acceleration-specific responses, in accordance with the lack of acceleration sensitivity in the neurons. The outputs of this single-cell model were passed to a population-vector–based model used to estimate stimulus speed and acceleration. We show that such a model can accurately estimate relative speed and acceleration using information from the population of neurons in area MT.
Digital transcriptome analysis indicates adaptive mechanisms in the heart of a hibernating mammal
Authors: Brauch Katharine M. , Dhruv Nirish D. , Hanse Eric A. , Andrews Matthew T.
Published: August 2005

Survival of near-freezing body temperatures and reduced blood flow during hibernation is likely the result of changes in the expression of specific genes. In this study, we described a comprehensive survey of mRNAs in the heart of the thirteen-lined ground squirrel ( Spermophilus tridecemlineatus) before and during hibernation. The heart was chosen for this study because it is a contractile organ that must continue to work despite body temperatures of 5°C and the lack of food for periods of 5–6 mo. We used a digital gene expression assay involving high-throughput sequencing of directional cDNA libraries from hearts of active and hibernating ground squirrels to determine the identity and frequency of 3,532 expressed sequence tags (ESTs). Statistical analysis of the active and hibernating heart expression profile indicated the differential regulation of 48 genes based on a P ≤ 0.03 threshold. Several of the differentially expressed genes identified in this screen encode proteins that likely account for uninterrupted cardiac function during hibernation, including those involved in metabolism, contractility, Ca2+handling, and low-temperature catalysis. A sampling of genes showing higher expression during hibernation includes phosphofructokinase, pancreatic triacylglycerol lipase, pyruvate dehydrogenase kinase 4 (PDK4), aldolase A, sarco(endo)plasmic reticulum Ca2+-ATPase 2a (SERCA2a), titin, and four-and-a-half LIM domains protein 2 (FHL2). Genes showing reduced levels of expression during hibernation include cyclin-dependent kinase 2-associated protein 1 (CDK2AP1), troponin C, phospholamban, Ca2+/calmodulin-dependent protein kinase II (CaMKII), calmodulin, and four subunits of cytochrome c oxidase.
No evidence that FLT3 status should be considered as an indicator for transplantation in acute myeloid leukemia (AML): an analysis of 1135 patients, excluding acute promyelocytic leukemia, from the UK MRC AML10 and 12 trials
Authors: Gale Rosemary E. , Hills Robert , Kottaridis Panagiotis D. , Srirangan Sivatharsini , Wheatley Keith , Burnett Alan K. , Linch David C.
Published: August 2005

Fetal liver tyrosine kinase 3 (FLT3) internal tandem duplications (ITDs) are powerful adverse prognostic indicators for relapse in acute myeloid leukemia (AML) but the most efficacious therapy for FLT3/ITD+ patients is currently unknown. We evaluated outcome according to FLT3/ITD status in 1135 adult patients treated according to United Kingdom Medical Research Council (UK MRC) AML protocols: 141 received an autograft, and 170 received a matched sibling allograft in first complete remission (CR). An FLT3/ITD was detected in 25% of patients and was an independent predictor for relapse (P < .001). It remained prognostic for increased relapse in patients who received a transplant (odds ratio [OR] = 1.91; 95% confidence intervals [CIs] = 1.13-3.21; P = .02), with no evidence of a difference in effect between patients who received an autograft (OR = 2.39; CIs = 1.24-4.62) and patients who received an allograft (OR = 1.31; CIs = 0.56-3.06) (test for interaction, P = .3) or between patients who did or did not receive a transplant (P = .4). These results were confirmed in an analysis of 186 patients randomized to receive or not receive an autograft in first CR and in a donor-versus–no donor analysis of 683 patients to assess the role of allograft (for latter, FLT3/ITD- OR = 0.70, CIs = 0.53-0.92; FLT3/ITD+ OR = 0.59, CIs = 0.40-0.87; test for interaction, P = .5). These results suggest that at present there is no strong evidence that FLT3 status should influence the decision to proceed to transplantation.
Functional annotation by identification of local surface similarities: a novel tool for structural genomics
Authors: Ferrè Fabrizio , Ausiello Gabriele , Zanzoni Andreas , Helmer-Citterich Manuela
Published: August 2005

Background

Protein function is often dependent on subsets of solvent-exposed residues that may exist in a similar three-dimensional configuration in non homologous proteins thus having different order and/or spacing in the sequence. Hence, functional annotation by means of sequence or fold similarity is not adequate for such cases.

Results

We describe a method for the function-related annotation of protein structures by means of the detection of local structural similarity with a library of annotated functional sites. An automatic procedure was used to annotate the function of local surface regions. Next, we employed a sequence-independent algorithm to compare exhaustively these functional patches with a larger collection of protein surface cavities. After tuning and validating the algorithm on a dataset of well annotated structures, we applied it to a list of protein structures that are classified as being of unknown function in the Protein Data Bank. By this strategy, we were able to provide functional clues to proteins that do not show any significant sequence or global structural similarity with proteins in the current databases.

Conclusion

This method is able to spot structural similarities associated to function-related similarities, independently on sequence or fold resemblance, therefore is a valuable tool for the functional analysis of uncharacterized proteins. Results are available at http://cbm.bio.uniroma2.it/surface/structuralGenomics.html
Infants' Ability to Distinguish Between Intentional and Accidental Actions and Its Relation to Internal State Language
Authors: Olineck Kara M. , Poulin‐Dubois Diane
Published: August 2005

The experiment reported here investigated infants' concept of intention, as well as the relation among intention understanding, general productive vocabulary, and internal state language production during the 2nd year. Results from an imitation task indicated that 18‐month‐olds are better able to differentiate between intentional and accidental actions than 14‐month‐olds. Although there was no relation between infants' performance on the intention task and their general productive vocabulary, internal state language production at 30 months was predicted by infants' ability to differentiate between intentional and accidental actions about a year earlier. These findings shed light on the developmental progression of infants' concept of intention, as well as on the continuity between infants' understanding of intentional action and their ability to use internal state words.
G-protein-coupled glucocorticoid receptors on the pituitary cell membrane
Authors: Maier Christina , Rünzler Dominik , Schindelar Julia , Grabner Gottfried , Waldhäusl Werner , Köhler Gottfried , Luger Anton
Published: August 2005

Rapid, nongenomic actions of glucocorticoids (GCs) have been well documented, but information about putative membrane receptors that mediate them is scarce. We used fluorescence correlation spectroscopy to search for membrane GC-binding on the mouse pituitary cell line AtT-20. A slowly diffusing fraction (τ3; diffusion constant 3×10-10 cm2 s-1) of fluorescein-labeled dexamethasone on the cell membrane corresponds to fluorescein-dexamethasone binding. Preincubation experiments were performed to test binding specificity: a 500-fold excess of unlabeled dexamethasone abolished subsequent fluorescein-dexamethasone membrane binding from 58±2 (control) to 8±1 (% of τ3, mean ± s.e.m.), the natural ligand corticosterone prevented it partially (29±2), while the sex steroids estradiol (56±4) and progesterone (50±4) and the GC-receptor antagonist RU486 (56±2) had no effect. Preincubation with pertussis toxin resulted in disappearance of the slowest diffusion component (11±4) suggesting association of the receptor with a G-protein. Varying the concentration of fluorescein-dexamethasone showed that membrane binding is highly cooperative with an apparent Kd of 180 nM and Bmax of 230 nM. Taken together, these results demonstrate high-affinity GC-binding on the cell membrane of AtT-20 cells with characteristics distinct from intracellular binding.
Coxsackievirus-adenovirus receptor (CAR) is essential for early embryonic cardiac development
Authors: Dorner Armin A. , Wegmann Frank , Butz Stefan , Wolburg-Buchholz Karen , Wolburg Hartwig , Mack Andreas , Nasdala Ines , August Benjamin , Westermann Jürgen , Rathjen Fritz G. , Vestweber Dietmar
Published: August 2005

The coxsackievirus-adenovirus receptor (CAR) is a cell contact protein on various cell types with unknown physiological function. It belongs to a subfamily of the immunoglobulin-superfamily of which some members are junctional adhesion molecules on epithelial and/or endothelial cells. CAR is dominantly expressed in the hearts and brains of mice until the newborne phase after which it becomes mainly restricted to various epithelial cells. To understand more about the physiological function of CAR, we have generated CAR-deficient mice by gene targeting. We found that these mice die between E11.5 and E13.5 of embryonal development. Ultrastructural analysis of cardiomyocytes revealed that the density of myofibrils was reduced and that their orientation and bundling was disorganized. In addition, mitochondria were enlarged and glycogen storage strongly enriched. In line with these defects, we observed pericardial edema formation as a clear sign of insufficient heart function. Developmental abnormalities likely to be secondary effects of gene ablation were the persistent singular cardial atrio-ventricular canal and dilatations of larger blood vessels such as the cardinal veins. The secondary nature of these defects was supported by the fact that CAR was not expressed on vascular cells or on cells of the vascular wall. No obvious signs for alterations of the histological organization of the placenta were observed. We conclude that CAR is required for embryonal heart development, most likely due to its function during the organization of myofibrils in cardiomyocytes.
Effective Role Resolution in Workflow Management
Authors: Zeng Daniel D. , Zhao J. Leon
Published: August 2005

Workflow systems provide the key technology to enable business-process automation. One important function of workflow management is role resolution, i.e., the mechanism of assigning tasks to individual workers at runtime according to the role qualification defined in the workflow model. Role-resolution decisions directly affect the productivity of workers in an organization, and consequently affect corporate profitability. Therefore it is important to develop effective policies governing these decisions. However, there has not been a formal treatment of role-resolution policies in the literature. In this paper, we analyze role-resolution policies used in current workflow practice and propose new optimization-based policies that utilize online batching. Through a computational study, we examine three workflow-performance measures including maximum flowtime, average workload, and workload variation under these policies in different business scenarios. These scenarios vary by overall system load, task-processing-time distribution, and the number of workers. Based on computational results, we obtain the following insights that can help guide the selection of role-resolution policies. (a) As the overall system load increases, the benefit of using batching-based online optimization policies becomes more significant. (b) Processing-time variation has a major impact on workflow performance, and higher variation favors optimization-based policies. (c) Online optimization has the potential to reduce average workload significantly, and to reduce workload variation significantly as well.
Degradation of Chondroitin Sulfate Proteoglycans Induces Sprouting of Intact Purkinje Axons in the Cerebellum of the Adult Rat
Authors: Corvetti Luigi , Rossi Ferdinando
Published: August 2005

Chondroitin sulfate proteoglycans are major constituents of the extracellular matrix and form perineuronal nets. Information regarding the growth-inhibitory activity of these molecules after injury is rapidly expanding. However, less is known about their physiological role in the adult undamaged CNS. Here, we investigated the function of chondroitin sulfate proteoglycans in maintaining the proper structure of Purkinje axons in the cerebellum of adult rats. To this end, we examined the morphology and distribution of intracortical Purkinje neurites after intraparenchymal injection of chondroitinase ABC. Staining with the lectinWisteria floribundaagglutinin or 2B6 antibodies showed that this treatment efficiently removed chondroitin sulfate proteoglycans from wide areas of the cerebellar cortex. In the same sites, there was a profuse outgrowth of terminal branches from the Purkinje infraganglionic plexus, which invaded the deeper regions of the granular layer. In contrast, myelinated axon segments were not affected and maintained their normal relationship with oligodendroglial sheaths. Purkinje axon sprouting was first evident at 4 d and increased further at 7 d after enzyme application. Within 42 d, the expression pattern of chondroitin sulfate proteoglycans gradually recovered, whereas axonal modifications progressively regressed. Our results show that, in the absence of injury or novel external stimuli, degradation of chondroitin sulfate proteoglycans is sufficient to induce Purkinje axon sprouting but not the formation of long-lasting synaptic contacts. Together with other growth-inhibitory molecules, such as myelin-associated proteins, chondroitin sulfate proteoglycans restrict structural plasticity of intact Purkinje axons to maintain normal wiring patterns in the adult cerebellar cortex.
Short-Term Depression in Thalamocortical Synapses of Cat Primary Visual Cortex
Authors: Boudreau C. Elizabeth , Ferster David
Published: August 2005

Neurons in primary visual cortex exhibit several nonlinearities in their responses to visual stimuli, including response decrements to repeated stimuli, contrast-dependent phase advance, contrast saturation, and cross-orientation suppression. Thalamocortical synaptic depression has been implicated in these phenomena but has not been examined directly in visual cortexin vivo. We assessed depression of visual thalamocortical synapsesin vivousing 20-100 Hz trains of electrical stimuli delivered to the LGN. Cortical cells receiving direct input from the LGN, identified by short latency and low jitter of LGN-evoked PSPs, showed moderate reductions in PSP amplitude during the fastest trains. Cells receiving indirect input from the thalamus via other cortical excitatory neurons show a marked reduction in PSP amplitude during a train, which could be explained either by synaptic depression in corticocortical synapses or by an inhibition-mediated suppression of the firing of their afferents. Reducing spontaneous activity in the LGN (by retinal blockade) unmasked additional depression at the thalamocortical synapse but only for the first stimulus in the train. That is, the first PSP was increased in amplitude relative to the unblocked condition, but subsequent responses were essentially unchanged. Thus, the synapses are maintained at significant levels of depression by spontaneous activity. These findings constrain the role that thalamocortical depression can play in shaping cortical responses to visual stimuli.
FDA Drug Approval Summary: Erlotinib (Tarceva®) Tablets
Authors: Cohen Martin H. , Johnson John R. , Chen Yeh-Fong , Sridhara Rajeshwari , Pazdur Richard
Published: August 2005

On November 18, 2004, erlotinib (Tarceva®; OSI Pharmaceuticals, Inc., Melville, NY, http://www.osip.com, and Genentech, Inc., South San Francisco, CA, http://www.gene.com) received regular approval as monotherapy for the treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) after failure of at least one prior chemotherapy regimen. Survival of erlotinib-treated patients was superior to that of placebo-treated patients. The median survival duration of erlotinib-treated patients was 6.67 months, compared with 4.70 months for placebo-treated patients. Exploratory univariate analyses showed a larger survival prolongation in two subsets of patients: those who never smoked and those with epidermal growth factor receptor (EGFR)-positive tumors. Patients who never smoked and were EGFR-positive had a large erlotinib survival benefit. Erlotinib was also superior to placebo for progression-free survival and a response rate of 8.9% versus 0.9%. Skin rash and diarrhea were the most common erlotinib adverse events. Severe rash occurred in 8%, and severe diarrhea occurred in 6% of erlotinib-treated patients. In the first-line treatment of NSCLC, two large, controlled, randomized trials showed no benefit from adding erlotinib to doublet, platinum-based chemotherapy. Therefore, erlotinib is not indicated for use in this setting.
Management of Cancer-Related Anemia with Erythropoietic Agents: Doubts, Certainties, and Concerns
Authors: Stasi Roberto , Amadori Sergio , Littlewood Timothy J. , Terzoli Edmondo , Newland Adrian C. , Provan Drew
Published: August 2005

The management of cancer-related anemia with erythropoietic agents presents many unresolved issues. We reviewed the literature relating to epoetin alfa (Eprex®/Epypo®; Ortho Biotech/Janssen-Cilag, High Wycombe, United Kingdom, http://www.orthobiotech.co.uk; Procrit®; Ortho Biotech Products, L.P., Bridgewater, NJ, http://www.orthobiotech.com), epoetin beta (NeoRecormon®; Hoffman-La Roche, Basel, Switzerland, http://www.roche.com), and darbepoetin alfa (Aranesp®; Amgen Inc., Thousand Oaks, CA, http://www.amgen.com) highlighting the results of published clinical trials, safety, and cost-effectiveness. Studies were identified through MEDLINE and the bibliographies of relevant articles. Epoetin alfa, epoetin beta, and darbepoetin alfa have differing pharmacokinetic and pharmacodynamic profiles. They are all effective at reducing transfusion requirements and improving health-related quality-of-life parameters, irrespective of tumor response. A direct comparison between epoetin alfa and darbe poetin alfa is based on limited evidence, which does not allow definitive conclusions about relative efficacy and cost-effectiveness. No predictive factors for response to erythropoietic agents have been validated in prospective trials. The most consistent adverse events are thrombotic and may occur irrespective of an increase in hemoglobin. Recent research indicates that the erythropoietin receptor is expressed in several cancer cell lines, raising the concern of possible stimulation of tumor cell growth by these drugs. Studies on the cost-effectiveness of erythropoietins, particularly compared with transfusion therapy, have been challenging to conduct and analyze and have generated ambiguous results. The use of erythropoietins needs to be optimized in terms of cost-effectiveness, and issues surrounding safety need to be clarified. A stronger methodology for clinical studies and the design of new, randomized, clinical trials is a major priority.
Surgical liver resection in multimodal therapy of hepatic malignat affections: A 4-year study
Authors: Krejci Tomas , Skricka Tomas , Ruzicka Milos , Stracar Martin
Published: August 2005

BACKGROUND: The goal of our study was to evaluate our hitherto 4-year surgical treatment of liver malignancies. METHODS: Our team performed 43 liver resections from 1997 to 2000. Of these, 10 were primary tumours and 33 metastases. The most frequent indication for resection in our sample was for colorectal cancer - in total 27 patients. Metastatic pancreatic cancer or metastases of malignant melanoma account for rarer indications to surgery We considered CT arterioportography (CTAP) as the most significant preoperative examination from all available radiological methods. RESULTS Proper resection of the liver is possible even without special technical equipment. No patient between the ages of 22 - 82 years died in the 30-day postoperative period. Our postoperative morbidity was 18.6%. The most frequent complication was prolonged biliary secretion from drains. In our study, recurrent liver malignancies occurred most frequently within 6 months from the primary resection. CONCLUSION: Radical resection procedure may be facilitated for the greatest number of patients with primary or metastatic liver malignancies by the cohesive cooperation of a number of specialists.
The role of postoperative radiotherapy after radical mastectomy in treatment of early breast cancer
Authors: Mladenovic Jasmina , Borojevic Nenad
Published: August 2005

BACKGROUND: Radical or modified radical mastectomy was considered for many years the standard therapy for operable patients. Following radical mastectomy, postoperative irradiation of the chest wall and peripheral lymphatics is indicated in selected highrisk patients. Some studies on breast cancer patients who underwent radical mastectomy and received adjuvant chemotherapy tried to find out whether the addition of irradiation treatment to the chest wall and regional lymph nodes increases survival. The hypothesis in favor of irradiation is that chemotherapy can eliminate distant micrometastases, but is less effective against local and regional diseases, which are better controlled by radiotherapy. METHODS: In one year period, 110 patients with early stage of breast cancer were treated with radical mastectomy, and postoperative radiotherapy. Forty one patients had only postoperative radiotherapy, 27 received also adjuvant chemotherapy, 40 received adjuvant hormonal therapy and 2 patients received both adjuvant chemo and hormonotherapy. Postoperative irradiation was given on the regional lymph nodes (supra and infraclavicular, axillary and internal mammary nodes) with the tumor dose 48 Gy in 22 fractions over a period of four and a half weeks. All fields were treated with Cobalt 60. RESULTS After the median follow up of 67 months, 33 patients (30 %) had some kind of failure in form of local recurrence, distant metastases or both Locoregional relapse alone or associated with distant metastases occurred in 10 patients (9.1 %). Only 1.8 % of patients had local recurrence as the first failure. Distant metastases occurred in 32 patients (29.1%). After the end of follow up, 60 % patients are alive without evidence of disease while 16.4 % patients are alive with disease. The 5 year overall survival rate was 78.19% and 5 year disease free survival rate was 67.44%. CONCLUSION: Postoperative radiotherapy after radical mastectomy has important role in adjuvant treatment of early breast cancer in combination with adjuvant chemotherapy and hormonotherapy.
Testicular metastasis Of dermatofibrosarcoma protuberans: A case report - An Ultrasonography approach
Authors: Chryssogonidis Ioannis , Vorkas George , Papadopoulos Christos , Lytras Constantinos
Published: August 2005

Dermatofibrosarcoma protuberans (DFSP) is a highly recurrent low-grade soft tissue sarcoma, which is usually located on the trunk. In a review of the literature there were several reports of patients with dermatofibrosarcoma with histologically documented metastasis. In all of these, there was local recurrence and subsequent metastasis to local lymph nodes and heamatogenous spread to the lungs. We present a case of dermatofibrosarcoma protuberans first time reported in the literature with metastasis to the testis evaluated by Colour Doppler sonography.
The use of transdermal fentanyl in the treatment of cancer pain
Authors: Radovanovic Dragana , Pjevic Miroslava , Malbasa Zlatica , Stosic Aleksandar
Published: August 2005

The management of pain is complex having to take into consideration patient specific characteristics. Drug therapy should be individualized and managed based on numerous factors. The opioid of first choice for the treatment of cancer pain is morphine, according to the European Association for Palliative Care (2000). Transdermally administered fentanyl is one alternative to oral morphine in the treatment of cancer pain. The transdermal systems are designed to deliver fentanyl at a constant rate for periods of 72 hours. Patches with a delivery rate of 25, 50, 75 and 100 ?g/h are available. Treatment with transdermal fentanyl is safe and acceptable to many cancer patients. Significantly more patients expressed a preference for transdermal fentanyl than for sustained release oral morphine. The global score of adverse effects was significantly lower in patients receiving transdermal fentanyl than in those receiving sustained release oral morphine. The transdermal fentanyl patch is as effective as oral opioids in relieving cancer related pain, with a safety and side effect profile equal to or better than that of oral opioids.
Gastrointestinal stromal tumors (gists): Definition, clinical, histological, immunohistochemical and molecular genetic features and predictors of malignant potential and differential diagnosis
Authors: Zivkovic Vesna , Katic Vuka , Nagorni Aleksandar , Velickovic Ljubinka , Milentijevic Maja , Djordjevic Biljana
Published: August 2005

Gastrointestinal stromal tumors (GISTs) represent a distinct and the most important subset of mesenchymal tumors of the gastrointestinal (GI) tract GISTs occur throughout the GI tract but are usually located in the stomach and small intestine. The cellular origin, differentiation, nomenclature and prognosis of GISTs are controversial. Because GISTs, like the interstitial cells of Cajal, the GI pacemaker cells, express CD117 (c-kit protein), the origin of GISTs from the Cajal cells has recently been suggested. GISTs are also known for their wide variability in clinical behavior and for the difficulty to determine their malignant condition The most reproducible predictors of malignancy are mitotic count >1-5 per10 high-powered fields (HPF), size >5 cm, tumor necrosis, infiltration and metastasis to other sites. However, some tumors with mitotic activity <1/10 HPF may metastasize indicating some uncertainty in malignant potential of GISTs, especially those larger than 5 cm. Recently, mutations in c-kit gene (exon 11) preferentially occur in malignant GISTs and may be a clinically useful adjunct marker in evaluation of GISTs. In conclusion, the strong CD117 expression mostly defines primary GI mesenchymal tumors as GIST. Specific identification of GIST may become clinically important if therapies targeting the c-kit tyrosine kinase activation become available.
Tularemia live vaccine as a modifier of genotoxic and carcinogenic action of environmental factors
Authors: Nersesyan Armen , Galstyan Hairapet , Adamyan Robert
Published: August 2005

In this review we presented the data concerning the influence of tularemia live vaccine (TLV, produced in the USSR and Russia) on mutagenesis and carcinogenesis. The data show that rodents immunized with TLV are resistant to mutagen of any origin (chemical, physical, biological) independently of species (rats, mice, gray hamsters, guinea pigs). Exposure of immunized rodents to carcinogens decreased the incidence of tumors, prolonged the mean latency period of tumor development, and decreased the mean tumor weight. The most pronounced effect was observed when rodents were exposed to mutagens/carcinogens on day 15 after immunization. This universal antimutagenic/anticarcinogenic effect is associated with increased resistance of DNA of immunized rodents to genotoxic action of environmental agents, the influence on the process of metabolic activation of xenobiotics, and increased synthesis of interferon, catalase and superoxide dismutase. The problem of influence of vaccines against dangerous infections on mutagenesis and carcinogenesis is a topical issue because the best way of protection against dangerous infections in case of epidemic or terrorist act is vaccination.
Male breast cancer in Armenia 1980-2000
Authors: Galstyan Hairapet , Khachatouryan Irina , Nersesyan Armen
Published: August 2005

We analyzed the incidence of male breast cancer in Armenia over the period of 20 years (1980-2000). The obtained data showed that, unlike female BC, male BC incidence also varies in Armenia as in most developed and developing countries, but without any regularity. The mean crude rate for the observed period is lower than in developed but comparable with developing countries. The most important peculiarity of male BC in Armenia is young age of patients.
Elevated plasma levels of TGF-beta1 in patients with locally advanced breast cancer related to other clinical stages
Authors: Todorovic-Rakovic Natasa , Ivanovic Vesna , Demajo Miroslav , Neskovic-Konstantinovic Zora , Nikolic-Vukosavljevic Dragica
Published: August 2005

Background: The application of plasma tumor markers is mainly during the follow-up of cancer patients and especially in monitoring of advanced disease. These biomarkers do not require surgical intervention and provide relatively simple monitoring at any time during the disease course. TGF-beta1 is a pluripotent cytokine, with diverse effects in normal physiology and a role in both normal mammary gland development and progression of breast cancer. In early stages of breast carcinomas TGF-beta1 acts as tumor suppressor, while in later stages, when tumor cells become resistant to growth inhibition by TGF-beta1, it acts as tumor promoter. For that reason, the aim of this study was to assess the stage-related TGF-beta1 elevation in circulation of breast cancer patients, during disease progression. Methods: We analyzed 52 breast cancer patients of different stages (I/II, III, IV) and 36 healthy donors. TGF-beta1 levels were determined by enzyme-linked immunosorbent assay (ELISA, R&D). Results Although there was no increase in plasma TGF-beta1 in stage I/II patients (n =10, median value = 0.89 ng/ml), statistically significant elevation of plasma TGF-beta1 was found in locally advanced breast cancer (stage III, n = 9, median value = 2.30 ng/ml) and also in metastatic breast cancer (stage IV, n = 33, median value = 2.46 ng/ml) in relation to healthy donors and stage I/II. Conclusion: This elevation of plasma TGF-beta1 in locally advanced breast cancer is probably the result of increased tumor mass and tumor-stromal interactions in this stage, as well as a possible cause of greater metastatic potential of tumor cells which lead to metastatic breast cancer. Prognostic role of TGF-beta1 is not fully understood, but from these results we could say that it could be a marker for monitoring patients disease course, as well as for understating the biology of breast cancer.
Maintaining treatment of locally advanced breast cancer
Authors: Muzikravic Ljubomir , Donat Dragutin , Pesic Jasna , Trifunovic Jasna
Published: August 2005

Locally advanced breast cancer is a specific clinic entity, comprising various degrees of breast cancer local and regional extension. This term is applied to nonmetastatic large primary tumors (including inflammatory breast carcinoma), with or without extensive regional lymph node involvement, with a rapid or slow evolution, and usually with poor prognosis. This clinical presentation of mammary carcinoma is common in developing countries (30% to 60%), but also with a remarkable incidence in developed countries (10% to 20%). During many decades patients were treated with radical surgery or radiation therapy and with their combination, but always with poor results. The inclusion of neoadjuvant chemotherapy in the treatment enabled more favorable treatment results. The mortality from disseminated disease is the main problem in these patients, inducing the question of need for additional postoperative adjuvant systemic therapy. For steroid receptor positive patients hormonotherapy is a convenient choice of maintaining treatment. In endocrine non-responsive tumors, the role of postoperative chemotherapy is doubtful, having in mind preoperative chemotherapy and cumulative toxic effects. New trials including the large number of patients are necessary to obtain the definite answer whether the maintaining chemotherapy is useful but today it seems that additive postoperative treatment is not more efficient than preoperative alone.
Publication ethics: The editor-author relationship
Authors: Bogdanovic Gordana
Published: August 2005

Publication is considered the end point of the research project. New scientific results may be assessed, corrected and further developed by the scientific community only if they are published. Guidelines on responsible research and publication are now set, to encourage and promote high ethical standards in the conduct of research and in biomedical publications. They address various aspects of the research and publishing including duties of editors and authorship determination. This paper brings a short survey of editor-author relationship in the process of publication.
Cervical acid phosphatase: A new biomarker of cervical dysplasia
Authors: Markovic Olivera , Markovic Nenad
Published: August 2005

BACKGROUND: Cervical acid phosphatase (CAP) has recently been described as a biomarker labeling abnormal squamous cells on Pap smears (USPTO #6,143,512). The enzyme activity is presented as a red, granular deposit on a modified Papanicolaou background. This unique property was utilized for development of a test and tools intended for cervical cancer screening. METHODS: We conducted a multicenter, random assignment, assessor blinded, 2-group (test and control), and split-sample design clinical trial on 1,500 subject/specimens to assess safety and efficacy of the new test in comparison with the control for cervical cancer screening in standard Pap test environment. Safety was measured with frequency, severity and relation of adverse events. Efficacy was measured with primary endpoints (portion of positive/abnormal specimens detected, and the false negative rate), and with accuracy (sensitivity/specificity) and predictive values as secondary efficacy endpoints. RESULTS: In March 2003, the recruitment was completed and the first thousand cases were evaluated. There were no serious or related adverse events in both groups. Minor, unrelated adverse events were rare and insignificantly distributed in both groups. Primary endpoints: A Portion of positive/abnormal specimens detected: Pe (new test) = 0.17, Ps (pap test): 0.082; Ps' (American standard): 0.07. Pe >=Ps + beta, for beta = 0.5Ps. B. False negative rate: Pe = 0.05, Ps' = 0.10. Test sensitivity 0.81, specificity: 0.97, PPV: 0.83, NPV: 0.96. Chi-square between test and controls 40.69101 was greater than the critical value of 3.841 (p<0.05). CONCLUSION: We concluded that CAP had added to visibility of Pap test and has enabled cytoscreeners to significantly improve detection of positive/abnormal specimens and reduce false negative rate.
Problems in radon measurements in context of epidemiological studies
Authors: Yarmoshenko Ilia , Kirdin Ivan
Published: August 2005

Epidemiological case control study is considered to be primary instrument to investigate the relationship between population indoor radon exposure and risk of lung cancer. A number of such studies had been completed in last 15 years and others are running now. Considering indoor radon and progeny some specific efforts should be undertaken to assess the exposure. While the lungs exposure after inhalation arises mainly due to radon progeny, in the case of the radon gas measurements application the researchers have to address the disequilibrium between radon and radon progeny. It is widely accepted by researchers and approved by ICRP that worldwide average value of equilibrium factor is 0.4 though real equilibrium factor value can deviate significantly from average. Temporal variation of indoor radon concentration complicates the evaluation of exposure as well. Three types of variation can be emphasized: diurnal, seasonal and long time. Experimental and modeling investigation of radon entry shown that pattern of indoor radon temporal variation firmly depends on relationship between entry rates of primary radon sources (diffusive and advective) and influencing factors are construction characteristics, climatic condition and life style. To find appropriate parameters describing radon disequilibrium and temporal variation it is necessary to perform special investigation in the representative sample of houses.
Postmastectomy radiotherapy and locoregional recurrence rate in high-risk breast cancer patients
Authors: Scepanovic Danijela , Bajic Nada , Babic Jovan
Published: August 2005

BACKGROUND: Postmastectomy radiotherapy has been the topic for many debates over several years about its role on locoregional control as well as overall survival in premenopausal and postmenopausal breast cancer patients. METHODS: From 1994 till 1999, 233 patients underwent modified radical mastectomy for breast cancer. Among them there was 92 premenopausal patients (median age was 44 years) and 141 postmenopausal patients (median age was 60 years). Traditional prognostic factors were used to assess risk of locoregional recurrence: 84 patients were node-negative, 71 patients had 1 to 3 lymph nodes positive, and 71 patients had 4 and more positive lymph nodes; 103 patients had tumor less than 3 cm diameter and 130 patients had tumors grater than 3 cm. According to this, postmastectomy radio- therapy was applied in 125 patients of whom 117 patients (94%) had also adjuvant systemic therapy (chemotherapy and/or hormonal therapy). RESULTS: The locoregional recurrence was observed in 42 patients while 191 patients were free of (median follow-up time was 49 months). Locoregional recurrence developed in 10 patients who had postmastectomy radiotherapy and in 32 patients who did not had postmastectomy radiotherapy (p=0.0001). In the group of patients with locoregional recurrence event 5-year overall survival was 28% while 70% in the group of patients free of (p=0.00001). There was statistically significant advantage for post- mastectomy radiotherapy in the group of patients with 1 to 3 positive lymph nodes as well as for 4 and more positive lymph nodes group (p=0.0008). In addition there was statistically significant difference among postmastectomy radiotherapy group and no postmastectomy radiotherapy group for disease free survival (74% vs. 50%, 5-year disease free survival, p=0.0001) and overall survival (71% vs. 53%, 5-year overall survival, p=0.0422). CONCLUSION: Postmastectomy radiotherapy reduces locoregional recurrence rate and improves overall survival in premenopausal and postmenopausal breast cancer patients with tumors grater than 3cm diameter and positive axillary lymph nodes.
The ultrastructural investigation of mitochondria in B-CLL cells during apoptosis
Authors: Brajuskovic Goran , Skaro-Milic Andjelija , Marjanovic Slobodan , Cerovic Snezana , Knezevic-Usaj Slavica
Published: August 2005

BACKGROUND: B-chronic lymphocytic leukemia (B-CLL) is an example of human malignancy caused by alternations in the pathways of apoptosis. Mitochondria play a critical role in the regulation of this process. The B-CLL cells dying in apoptosis showed typical morphological characteristics: the reduction of the nuclear volume is accompanied with the reduction of the cytoplasmatic volume, while many of organelles remain intact. The aim of our study was ultrastructural investigation of mitochondrial morphology in apoptotic B- CLL cells. METHODS: Our study included peripheral blood samples from 32 B-CLL patients. The samples were fixed in 4% glutar-aldehyde buffered in 0.1 cacodylate buffer and postfixed in 1% osmium tetroxide in the same buffer. The specimens were dehydrated in a graded series of alcohol and embedded in EPON 812. The ultra-thin sections were stained with uranyl acetate and lead citrate. Ultrastructural analysis of sections was performed on Philips electron microscope 208S at 80 kV. RESULTS: The most frequent mitochondrial abnormalities in apoptotic B-CLL cells were a reduction of size with a hyperdensity of their matrix (mitochondrial pyknosis), or markedly swollen mitochondria with peripherally placed, disorientated, and disintegrated cristae. In some apoptotic cells, we also detected close association of mitochondria with loops of rough endoplasmatic reticulum. CONCLUSION: The results of our study showed the numerous of mitochondria damages in B-CLL cells during apoptotic process. The correlation between ultrastructural damage and functional activity of mitochondria in apoptotic B-CLL cells is still not clear and requires further investigation.
Some epidemiological characteristics of malignant fibrous histiocytoma in the Province of Vojvodina
Authors: Nikolin Borislava , Dugandzija Tihomir , Salma Svetlana , Trifunovic Jasna , Vojnovic Dragana
Published: August 2005

BACKGROUND: Malignant fibrous histiocytoma is most common soft tissue sarcoma occurring in late adult life, most in the extremities and in the retroperitoneum, usually developing in deep fascia or skeletal muscle. Because of the aggressive nature of the tumor early and complete surgical removal is indicated. The overall survival rate of patients with malignant fibrous histiocytoma ranges from 36% to 58% at 5 years. Malignant fibrous histiocytoma in Vojvodina is still rare malignancy either in incidence or in mortality in both sexes. The population of Vojvodina is about 2 100 000. METHODS: We used a descriptive epidemiological method to analyze incidence and mortality from malignant fibrous histiocytoma in Vojvodina. This study is based on the Cancer Registry data for the ten-year period from 1993 to 2002. RESULTS: During the observed period 37 cases of malignant fibrous histiocytoma were reported (19 men and 18 women). The average age of patients was 50 years. The body site distribution differed between sexes and malignant fibrous histiocytoma was more common on the trunk (retroperitoneum) in men and on the lower limbs in women. The average annual incidence rate for the observed period was 1.82 per 1 000 000 for both sexes. The incidence rate changed irregularly over the observed period with the peak of 9 cases (4.55 per 1 000 000) in 2001. The overall linear trends of incidence and of mortality showed a slight increasing tendency in both sexes, but not significantly. Concerning mortality, the similar patterns were noticed. The mortality rate was 0.83 per 1 000 000. CONCLUSION: According to epidemiological data we obtained it can be concluded that Province of Vojvodina is not a region with an important risk for malignant fibrous histiocytoma; however, the increase of incidence appearing in both men and women should be taken into account very seriously in future.
Magnetic resonance mammography in diagnostics of breast tumor
Authors: Bogdanovic Dragana
Published: August 2005

Breast cancer is the most common malignant neoplasm in female population. The complexity of early breast carcinoma diagnostics is conditioned by the variability of the breast structure during life, as well as cyclic, hormone conditioned changes. Today, the most important and the most widely applied radiological modality is mammography, which value has been proved by many studies. Up-to-date diagnostic algorithm also includes the breast evaluation by ultrasound with the probes of 7.5 and 10 MHz that provide for high tissue resolution. Magnetic resonance currently presents the most up-to-date visualization modality. Its basic technical possibilities: multiplanarity, high area, and tissue resolution combined with biological noninvasiveness, unambiguously make MR the most sensitive and the most specific radiological method for evaluation of the majority of organism regions.
On direct sequential analysis of heart rate variability signals
Authors: Bajic Dragana , Loncar-Turukalo Tatjana , Sibarevic Olijandra
Published: August 2005

Heart rate variability analysis represents one of the most promising and the most commonly used quantitative measures of the cardiovascular autonomic regulatory system. The analysis includes traditional statistical analytical tools and a number of new methods based on nonlinear system theory, recently developed to give better insight into complex HR. This paper introduces a direct sequential analysis.
Sintering of Astroloy-Y2O3 particulate composites
Authors: Roy S. , Upadhyaya G.S.
Published: August 2005

The present paper describes the preparation and properties of Astroloy-Y2O3 (up to 8 vol%) sintered composites. A dilatometric study of green composites carried out in argon up to 1325?C, revealed that maximum shrinkage occurs in a 6 vol% Y2O3 composite, while the lowest shrinkage was noted in an 8 vol% composite. It is observed that the greater the volume fraction of Y2O3, the higher is the onset of temperature for the beginning of the shrinkage process. A post sintering hot forging operation serves very well as an alternative to repressing-resintering. Mechanical properties have better values for 6 vol% Y2O3 composite as compared to other composites.
Low temperature sintering of mechanically activated BaCO3-TiO2
Authors: Pavlovic Vera , Stojanovic Biljana , Pavlovic Vladimir , Zivkovic Ljiljana , Ristic Momcilo
Published: August 2005

In this article low temperature sintering of mechanically activated BaCO3-TiO2 system was studied. A stoichiometric mixture of BaCO3 and TiO2 powders was mechanically activated in a high-energy vibromill for 0, 30, 90 and 180 min, calcined at 800oC for 1 h and reaction sintered at 1100oC and 1200oC for 2 h (heating rate of 10oC/min). Phase compositions and crystallographic data of initial, activated, calcinated and sintered specimens were obtained by the XRPD method. It was noticed that mechanical activation enhanced and lowered the temperature of the formation of tetragonal BaTiO3. Scanning electron microscopy was used to study and characterize microstructures of the samples.
Characterisation of dispersive systems using a coherer
Authors: Nikolic Pantelija , Djuric S. , Radulovic K. , Vasiljevic-Radovic D. , Nikolic M.V. , Ristic Momcilo
Published: August 2005

The possibility of characterization of aluminium powders using a horizontal coherer has been considered. Al powders of known dimension were treated with a high frequency electromagnetic field or with a DC electric field, which were increased until a dielectric breakdown occurred. Using a multifunctional card PC-428 Electronic Design and a suitable interface between the coherer and PC, the activation time of the coherer was measured as a function of powder dimension and the distance between the coherer electrodes. It was also shown that the average dimension of powders of unknown size could be determined using the coherer.