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ABSTRACTThe main approach to preventing tick-borne encephalitis (TBE) is vaccination. Formaldehyde-inactivated TBE vaccines have a proven record of safety and efficiency but have never been characterized structurally with atomic resolution. We report a cryoelectron microscopy (cryo-EM) structure of the formaldehyde-inactivated TBE virus (TBEV) of Sofjin-Chumakov strain representing the Far-Eastern subtype. A 3.8 Å resolution reconstruction reveals the structural integrity of the envelope E proteins, specifically the E protein ectodomains. The comparative study shows a high structural similarity to the previously published structures of the TBEV European subtype strains Hypr and Kuutsalo-14. A fraction of inactivated virions exhibits asymmetric features including the deformations of the membrane profile. We propose that the heterogeneity is caused by inactivation and perform a local variability analysis on the small parts of the envelope protein shell to reveal membrane curvature features possibly induced by the inactivation. The results of this study will have implications for the design of novel vaccines against diseases caused by flaviviruses.

Relevance. The relevance of the research of deep structure of the Zmeinogorsky ore district is caused by the search for hidden and poorly manifested pyrite-polymetallic mineralization on the surface within the Rudny Altai minerogenic zone. This task is of particular prognostic interest due to the high searchability of the area on the surface and the prospects for detecting hidden mineralization at deeper horizons. Aim. Geotectonic modeling of structural and material inhomogeneities of the Earth's crust of the Zmeinogorsky ore district based on a comprehensive interpretation of geological and geophysical data with the identification of patterns of localization of hidden and poorly manifested pyrite-polymetallic mineralization on the surface. Objects. Regularities of localization of hidden and poorly manifested pyrite-polymetallic mineralization on the surface within the Zmeinogorsky ore district of the Rudny Altai. Methods. Processing of areal and profile materials of the study of the Rudny Altai, qualitative and quantitative interpretation of heterogeneous geological and geophysical information at the regional and detailed levels. The study of the history of development and geodynamic conditions of the formation of ore-bearing structures of the Zmeinogorsky ore district with the identification of geological and structural prognostic features at depths of practical interest. Results. Based on a comprehensive analysis of heterogeneous geological and geophysical data, the authors have carried out the historical-evolutionary and geodynamic interpretation of the mineragenic structures of the Zmeinogorsky ore district within the Rudny Altai; these materials can be used as the basis for regional forecast constructions using non-standard geological, structural and material (tectonic) signs; the special influence of tectonic events characterizing the situation of the active continental margin with complicating episodes of rifting was verified; the patterns of localization of pyrite-polymetallic ores in volcanogenic-sedimentary rocks were revealed with the justification of a set of predictive criteria.

Antibiotic-resistant bacteria represent a global issue that calls for novel approaches to diagnosis and treatment. Given the variety of genetic factors that determine resistance, multiplex methods hold promise in this area. We developed a novel method to covalently attach oligonucleotide probes to the wells of polystyrene plates using photoactivation with 4-azidotetrafluorobenzaldehyde. Then, it was used to develop the technique of microarrays in the wells. It consists of the following steps: activating polystyrene, hybridizing the probes with biotinylated target DNA, and developing the result using a streptavidin–peroxidase conjugate with colorimetric detection. The first microarray was designed to identify 11 different gene types and 16 single-nucleotide polymorphisms (SNPs) of clinically relevant ESBLs and carbapenemases, which confer Gram-negative bacteria resistance to β-lactam antibiotics. The detection of bla genes in 65 clinical isolates of Enterobacteriaceae demonstrated the high sensitivity and reproducibility of the technique. The highly reproducible spot staining of colorimetric microarrays allowed us to design a second microarray that was intended to quantify four different types of bla mRNAs in order to ascertain their expressions. The combination of reliable performance, high throughput in standard 96-well plates, and inexpensive colorimetric detection makes the microarrays suitable for routine clinical application and for the study of multi-drug resistant bacteria.

The information on geological structure as well as on the degree of contamination and geometrical parameters of a pollutant in oil-contaminated areas is necessary for risk assessment, planning of oil products recovery and territory remediation. Geophysical methods are actively used for solving such problems. The work considers the site on the Volga River bank, where soils are contaminated with petroleum products. The aim of the work is to delineate the distribution area of petroleum products. In order to achieve the goal, the set of near-surface geophysical methods (vertical electric sounding, seismic survey) and gas geochemistry were implemented. The results of a new approach to characterization of contaminated sites by RGB-data synthesis have been demonstrated as one of the ways of data interpretation. The method is based on the generalization of the available materials by optically mixing of the data of three spatially distributed characteristics presented in the form of three channels – red, green, and blue – for the purpose of localizing the lenses of gravity-mobile and immobilized oil products. According to the results of the qualitative interpretation of geophysical information, the authors have built a scheme with the proposed contour of oil products distribution in the studied territory. The proposed method can be used for the delineation of oil spills along with the sufficient information obtained by geophysical or other methods (at least three) at the stage of determining the spread of contamination for the sites. This approach can speed up the interpretation process, as such maps overlaying sets the color distribution of different petrophysical characteristics of the soils for the selected depth level, and also eases the task of determination of coordinates when correlating various anomalies, identified by different methods.

The use of the zonal-block model of the earth's crust for the construction of regional tectonic schemes and sections of the earth's crust based on a complex of geological and geophysical data makes it possible to consider the resulting maps and sections as tectonic models. The main elements of such models are blocks with an ancient continental base and interblock zones formed by complexes of island arcs, an accretionary prism, or oceanic crust. The developed geotectonic model of the Sea of Okhotsk region reflects the features of the deep structure, tectonics, and geodynamics. The Cimmerian Novosibirsk-Chukotka, Verkhoyansk-Kolyma, Kolyma-Omolon, and Amur folded regions and the Alpides of the Koryak-Kamchatka and Sakhalin-Sikhote-Alin folded regions are developed along the northern, western, and southern boundaries of the Sea of Okhotsk megablock with a continental crust type. From the east, the megablock is limited by oceanic basins and island arcs.

Link for citation: Mingaleva T.A., Shakuro S.V., Egorov A.S. Features of the structure and nature of pollution of the upper part of the section of oil storage facilities in the Volga River valley. Bulletin of the Tomsk Polytechnic University. Geo Аssets Engineering, 2023, vol. 334, no. 7, рр. 137-147. In Rus. The relevance of the study is caused by the fact that soil pollution with oil products has a complex dynamic character in the spatio-temporal region. Therefore, the physical properties of soils in solving geophysical problems of contouring and determining the thickness of pollution can change under the influence of various factors, expanding the range of search signs of pollution. Determination of physical parameters for areas of oil pollution, similar in nature of development and geological conditions, can help in the future for the effective parameterization of hydrocarbons in soils. The main aim is to build a generalized model with physical properties (electrical resistivity, сompressional and shear-wave velocities) for the soils of long-term oil depot territories. Methods: analysis of literary sources on the research topic; processing and interpretation of field geophysical material for tank farms located on the banks of the Volga River; building a generalized model with a description of the physical characteristics of soils based on the results of geophysics for the soils of tank farms. Results. The authors have studied the nature of soil pollution of two oil depots in the Volga River region using materials published in domestic and foreign literature, which made it possible to substantiate the parameters of a generalized physical-geological model of soil pollution of oil depots. In the general case, the distribution of pollution areas is subject to the features of the geological structure and hydrogeological regime of the areas under consideration and generally includes five zones (the upper area, the area of pollution above the free-flow horizon, the area of seepage in the hydrogeological window, the area of groundwater pollution, the zone of secondary accumulation). This model can be used to predict the nature of pollution in tank farms, loading and unloading points, car repair shops, washing sites and gas stations located near river and lake basins. The model of distribution of oil products in soils will be complex, which will also be expressed in geophysical sections.

The unprecedented in recent history global COVID-19 pandemic urged the implementation of all existing vaccine platforms to ensure the availability of the vaccines against COVID-19 to every country in the world. Despite the multitude of high-quality papers describing clinical trials of different vaccine products, basic detailed data on general toxicity, reproductive toxicity, immunogenicity, protective efficacy and durability of immune response in animal models are scarce. Here, we developed a β-propiolactone-inactivated whole virion vaccine CoviVac and assessed its safety, protective efficacy, immunogenicity and stability of the immune response in rodents and non-human primates. The vaccine showed no signs of acute/chronic, reproductive, embryo- and fetotoxicity, or teratogenic effects, as well as no allergenic properties in studied animal species. The vaccine induced stable and robust humoral immune response both in form of specific anti-SARS-CoV-2 IgG and NAbs in mice, Syrian hamsters, and common marmosets. The NAb levels did not decrease significantly over the course of one year. The course of two immunizations protected Syrian hamsters from severe pneumonia upon intranasal challenge with the live virus. Robustness of the vaccine manufacturing process was demonstrated as well. These data encouraged further evaluation of CoviVac in clinical trials.

In this work, we, for the first time, manufactured a plasma-chemical reactor operating at a frequency of 0.11 MHz. The reactor allows for the activation of large volumes of liquids in a short time. The physicochemical properties of activated liquids (concentration of hydrogen peroxide, nitrate anions, redox potential, electrical conductivity, pH, concentration of dissolved gases) are characterized in detail. Antifungal activity of aqueous solutions activated by a glow discharge has been investigated. It was shown that aqueous solutions activated by a glow discharge significantly reduce the degree of presence of phytopathogens and their effect on the germination of such seeds. Seeds of cereals (sorghum and barley) and fruit (strawberries) crops were studied. The greatest positive effect was found in the treatment of sorghum seeds. Moreover, laboratory tests have shown a significant increase in sorghum drought tolerance. The effectiveness of the use of glow-discharge-activated aqueous solutions was shown during a field experiment, which was set up in the saline semi-desert of the Northern Caspian region. Thus, the technology developed by us makes it possible to carry out the activation of aqueous solutions on an industrial scale. Water activated by a glow discharge exhibits antifungicidal activity and significantly accelerates the development of the grain and fruit crops we studied. In the case of sorghum culture, glow-discharge-activated water significantly increases drought resistance.

Background: Tick-borne encephalitis virus (TBEV) is a dangerous human pathogen which envelope structure is already known from cryoEM study. TBEV mature viral particle size (~50 nm in diameter) makes it suitable for single-particle imaging (SPI) on X-ray free-electron laser (XFEL). XFEL SPI studies are at the early stages of development; thus, a well-described and conformationally homogeneous sample is required to develop approaches for experimental setup and data analysis. Here we present the image analysis results of data collected in October 2019 during the European XFEL experiment #2316. Methods: The detector was placed at 1.62 m from the injector; photon energy was around 6 keV, pulse energy 4 mJ, beam diameter ~ 500 nm. All runs were processed to detect hits with threshold filter (5th percentile of lit pixels) and further filtered to omit low-intensity images and images that lack detector modules. Filtered hits were background and geometry corrected with SPImage library and custom python scripts. Then hits were azimuthally integrated using PyFAI library. Scattering profiles were further clustered using the affinity propagation algorithm with cosine similarity metric in log space. Extracted classes were used to build averaged images. All hit profiles were fitted with model scattering to estimate the diameter of the particle. Simulated diffraction patterns were prepared using Condor from the cryoEM electron density map (EMDB ID 3752). Results: During the analysis after the filtering, only 276 clean and bright hits were collected per 135 min of injection (from 27287 hits detected via lit pixels threshold). Thus the hit rate was around ~ 2 hits/min, which is expected to rise in the future. The majority of hits correspond to the 40-50 nm particles (Fig. 1a), which is expected for TBEV. However, the exact size may vary due to solvent evaporation, ion condensation, and possible variability in the sample. Conclusion: The averaged images and their scattering profiles correlate with the simulated scattering patterns, though not ideally (Fig. 1 bc). Such discrepancy is expected due to the absence of electron density in the center of modeled viral structures.

The evolutionary-genetic method, whereby modern sedimentary basins are interpreted as end-products of a long geological evolution of a system of conjugate palaeo-basins, enables the assessment of the petroleum potential of the Western sector of the Russian Arctic. Modern basins in this region contain relics of palaeo-basins of a certain tectonotype formed in varying geodynamic regimes. Petroleum potential estimates of the Western Arctic vary broadly—from 34.7 to more than 100 billion tons of oil equivalent with the share of liquid hydrocarbons from 5.3 to 13.4 billion tons of oil equivalent. At each stage of the development of palaeo-basins, favourable geological, geochemical and thermobaric conditions have emerged and determined the processes of oil and gas formation, migration, accumulation, and subsequent redistribution between different complexes. The most recent stage of basin formation is of crucial importance for the modern distribution of hydrocarbon accumulations. The primary evolutionary-genetic sequence associated with the oil and gas formation regime of a certain type is crucial for the assessment of petroleum potential. Tectonic schemes of individual crustal layers of the Western sector of the Russian Arctic have been compiled based on the interpretation of several seismic data sets. These schemes are accompanied by cross-sections of the Earth’s crust alongside reference geophysical profiles (geo-traverses). A tectonic scheme of the consolidated basement shows the location and nature of tectonic boundaries of cratons and platform plates with Grenvillian basement as well as Baikalian, Caledonian, Hercynian, and Early Cimmerian fold areas. Four groups of sedimentary basins are distinguished on the tectonic scheme of the platform cover according to the age of its formation: (1) Riphean-Mesozoic on the Early Precambrian basement; (2) Paleozoic-Cenozoic on the Baikalian and Grenvillian basements; (3) Late Paleozoic-Cenozoic on the Caledonian basement; (4) Mesozoic-Cenozoic, overlying a consolidated basement of different ages. Fragments of reference sections along geo-traverses illustrate features of the deep structure of the main geo-structures of the Arctic shelf and continental regions of polar Russia.

The relevance of the work is caused by the need to search for new industrial ore manifestations, due to the fact that most of the explored deposits have already been worked out. The aim of the research is to identify ore promising objects in deep horizons and flanking parts of the Ubinsk ore field of the Rudny Altai using electromagnetic methods of direct and alternating current. Methods of research. Transient electromagnetic method with inductive installations and DC electrical resistivity tomography were used to obtain field data. Interpretation was carried out using interactive simulation and inversion software complexes ERA, EMS, ZondTEM1D. The results were justified based on the analysis and comparison of geological and geophysical data. Results. According to the transient electromagnetic method the authors have plotted the sections along the observation profiles, area distributions of the electrical resistivity at several depth intervals, as well as three-dimensional models of promising zones of ore. For the first time, three types of anomalous zones were identified, corresponding to ore objects, differing in size and depth of occurrence. According to the results of electrical resistivity tomography, the manifestation of fault structures in the upper part of the section is traced. The subsequent detailed work is grounded by methods of electrical prospecting within the allocated perspective zones. Conclusions. The use of electroprospecting methods is effective for the search for polymetals in the area of Rudny Altai. According to the sounding, the authors confirmed the prospects for polymetallic rocks in the southeastern part of the Ubinsk area, where the greatest depths of ore occurrence objects have been obtained. Geological and electro-prospecting data were recommended for electric survey to of 700-1200 m depth.

Insulinomatosis is characterized by monohormonality of multiple macro-tumors and micro-tumors that arise synchronously and metachronously in all regions of the pancreas, and often recurring hypoglycemia. One of the main characteristics of insulinomatosis is the presence of insulin-expressing monohormonal endocrine cell clusters that are exclusively composed of proliferating insulin-positive cells, are less than 1 mm in size, and show solid islet-like structure. It is presumed that insulinomatosis affects the entire population of β-cells. With regards to molecular genetics, this phenomenon is not related to mutation in MEN1 gene and is more similar to sporadic benign insulinomas, however, at the moment molecular genetics of this disease remains poorly investigated. NGS sequencing was performed with a panel of 409 cancer-related genes. Results of sequencing were analyzed by bioinformatic algorithms for detecting point mutations and copy number variations. DNA copy number variations were detected that harbor a large number of genes in insulinoma and fewer genes in micro-tumors. qPCR was used to confirm copy number variations at ATRX , FOXL2 , IRS2 and CEBPA genes. Copy number alterations involving FOXL2 , IRS2 , CEBPA and ATRX genes were observed in insulinoma as well as in micro-tumors samples, suggesting that alterations of these genes may promote malignization in the β-cells population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Anoshkin, Vasilyev, Karandasheva, Shugay, Kudryavtseva, Egorov, Gurevich, Mironova, Serikov, Kutsev and Strelnikov.)

Objectives: Blood-based tests have been shown to be an effective strategy for colorectal cancer (CRC) detection in screening programs. This study was aimed to test the performance of 20 blood markers including tumor antigens, inflammatory markers, and apolipoproteins as well as their combinations. Methods: In total 203 healthy volunteers and 102 patients with CRC were enrolled into the study. Differences between healthy and cancer subjects were evaluated using Wilcoxon rank-sum test. Several multivariate classification algorithms were employed using information about different combinations of biomarkers altered in CRC patients as well as age and gender of the subjects; random sub-sampling cross-validation was done to overcome overfitting problem. Diagnostic performance of single biomarkers and multivariate classification models was evaluated by receiver operating characteristic (ROC) analysis. Results: Of 20 biomarkers, 16 were significantly different between the groups ( p -value ≤ 0.001); ApoA1, ApoA2 and ApoA4 levels were decreased, whereas levels of tumor antigens ( e.g . carcinoembriogenic antigen) and inflammatory markers (e.g., C-reactive protein) were increased in CRC patients vs. healthy subjects. Combinatorial markers including information about all 16 significant analytes, age and gender of patients, demonstrated better performance over single biomarkers with average accuracy on test datasets ≥95% and area under ROC curve (AUROC) ≥98%. Conclusions: Combinatorial approach was shown to be a valid strategy to improve performance of blood-based CRC diagnostics. Further evaluation of the proposed models in screening programs will be performed to gain a better understanding of their diagnostic value., (Copyright © 2020 Voronova, Glybochko, Svistunov, Fomin, Kopylov, Tzarkov, Egorov, Gitel, Ragimov, Boroda, Poddubskaya and Sekacheva.)

β-lactamases are hydrolytic enzymes primarily responsible for occurrence and abundance of bacteria resistant to β-lactam antibiotics. TEM type β-lactamases are formed by the parent enzyme TEM-1 and more than two hundred of its mutants. Positions for the known amino acid substitutions cover ∼30% of TEM type enzyme's sequence. These substitutions are divided into the key mutations that lead to changes in catalytic properties of β-lactamases, and the secondary ones, which role is poorly understood. In this study, Residue Interaction Networks were constructed from molecular dynamic trajectories of β-lactamase TEM-1 and its variants with two key substitutions, G238S and E240K, and their combinations with secondary ones (M182T and Q39K). Particular attention was paid to a detailed analysis of the interactions that affect conformation and mobility of the Ω-loop, representing a part of the β-lactamase active site. It was shown that key mutations weakened the stability of contact inside the Ω-loop thus increasing its mobility. Combination of three amino acid substitutions, including the 182 residue, leads to the release of R65 promoting its new contacts with N175 and D176. As a result, Ω-loop is fixed on the protein globule. The second distal mutation Q39K prevents changes in spatial position of R65, which lead to the weakening of the effect of M182T substitution and the recovery of the Ω-loop mobility. Thus, the distal secondary mutations are directed for recovering the mobility of enzyme disturbed by the key mutations responsible for expansion of substrate specificity. AbbreviationsESBLextended spectrum beta-lactamasesIRinhibitor resistant beta-lactamasesMDmolecular dynamicsRINresidue interaction networksRMSDroot mean square deviationRMSFroot mean square fluctuations.Communicated by Ramaswamy H. Sarma.

Bacterial resistance to β-lactams, the most commonly used class of antibiotics, poses a global challenge. This resistance is caused by the production of bacterial enzymes that are termed β-lactamases (βLs). The evolution of serine-class A β-lactamases from penicillin-binding proteins (PBPs) is related to the formation of the Ω-loop at the entrance to the enzyme's active site. In this loop, the Glu166 residue plays a key role in the two-step catalytic cycle of hydrolysis. This residue in TEM-type β-lactamases, together with Asn170, is involved in the formation of a hydrogen bonding network with a water molecule, leading to the deacylation of the acyl-enzyme complex and the hydrolysis of the β-lactam ring of the antibiotic. The activity exhibited by the Ω-loop is attributed to the positioning of its N-terminal residues near the catalytically important residues of the active site. The structure of the Ω-loop of TEM-type β-lactamases is characterized by low mutability, a stable topology, and structural flexibility. All of the revealed features of the Ω-loop, as well as the mechanisms related to its involvement in catalysis, make it a potential target for novel allosteric inhibitors of β-lactamases.

Highly mutable β-lactamases are responsible for the ability of Gram-negative bacteria to resist β-lactam antibiotics. Using site-directed mutagenesis technique, we have produced in vitro a number of recombinant analogs of naturally occurring TEM-type β-lactamases, bearing the secondary substitution Q39K and key mutations related to the extended-spectrum (E104K, R164S) and inhibitor-resistant (M69V) β-lactamases. The mutation Q39K alone was found to be neutral and hardly affected the catalytic properties of β-lactamases. However, in combination with the key mutations, this substitution resulted in decreased K values towards hydrolysis of a chromogenic substrate, CENTA. The ability of enzymes to restore catalytic activity after exposure to elevated temperature has been examined. All double and triple mutants of β-lactamase TEM-1 bearing the Q39K substitution showed lower thermal stability compared with the enzyme with Q39 intact. A sharp decrease in the stability was observed when Q39K was combined with E104K and M69V. The key R164S substitution demonstrated unusual ability to resist thermal inactivation. Computer analysis of the structure and molecular dynamics of β-lactamase TEM-1 revealed a network of hydrogen bonds from the residues Q39 and K32, related to the N-terminal α-helix, towards the residues R244 and G236, located in the vicinity of the enzyme's catalytic site. Replacement of Q39 by lysine in combination with the key drug resistance mutations may be responsible for loss of protein thermal stability and elevated mobility of its secondary structure elements. This effect on the activity of β-lactamases can be used as a new potential target for inhibiting the enzyme.M values towards hydrolysis of a chromogenic substrate, CENTA. The ability of enzymes to restore catalytic activity after exposure to elevated temperature has been examined. All double and triple mutants of β-lactamase TEM-1 bearing the Q39K substitution showed lower thermal stability compared with the enzyme with Q39 intact. A sharp decrease in the stability was observed when Q39K was combined with E104K and M69V. The key R164S substitution demonstrated unusual ability to resist thermal inactivation. Computer analysis of the structure and molecular dynamics of β-lactamase TEM-1 revealed a network of hydrogen bonds from the residues Q39 and K32, related to the N-terminal α-helix, towards the residues R244 and G236, located in the vicinity of the enzyme's catalytic site. Replacement of Q39 by lysine in combination with the key drug resistance mutations may be responsible for loss of protein thermal stability and elevated mobility of its secondary structure elements. This effect on the activity of β-lactamases can be used as a new potential target for inhibiting the enzyme.

We have demonstrated label-free and real-time detection of prostate specific antigen (PSA) in human serum using silicon nanowire field effect transistors (NW FETs) with Schottky contacts (Si-Ti). The NW FETs were fabricated from SOI material using high-resolution e-beam lithography, thin film vacuum deposition and reactive-ion etching processes eliminating complicated processes of doping and thermal annealing. This allowed substantial simplifying the transistors manufacturing. A new method for covalent immobilization of half-fragments of antibodies on silicon modified by 3-glycidopropyltrimethoxysilane with thiol groups and 5nm gold nanoparticles (GNPs) was established. NW FETs functionalized by GNPs revealed extremely high pH sensitivity of 70mV/pH and enhanced electrical performance in the detection of antigen due to enhanced surface/volume ratio, favorable orientation of antibody active sites and approaching the source of the electric field close to the transistor surface. Si NWFETs were applied for quantitative detection of PSA in a buffer and human serum diluted 1/100. Response time was about 5-10s, and analysis time per sample was 1min. The limit of PSA detection was of 23fg/mL, concentration range of 23fg/mL-500ng/mL (7 orders of magnitude). The PSA concentrations determined by the NW FETs in serum were compared with well-established ELISA method. The results matched well with the correlation coefficient of 0.97., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Gastrinomas are located more frequently in the pancreas, which normally has no cells that can produce gastrin. They have a more aggressive course than other pancreatic endocrine tumors and extrapancreatic gastrinomas associated with multiple endocrine neoplasia Type 1 syndrome. The current study analyzed immunophenotypes of gastrinomas and compared them with other pancreatic endocrine tumors., Methods: Twenty-one formalin-fixed, paraffin-embedded specimens (15-tumors in the pancreas, 1 in the duodenum, 1 in the stomach, 1 in the liver, and 3 of unknown primary location) accompanied by Zollinger-Ellison syndrome and 17 other pancreatic endocrine tumor specimens were investigated. They were stained immunohistochemically for gastrin, chromogranin A, synaptophysin, insulin, glucagon, somatostatin, pancreatic polypeptide, calcitonin, serotonin, chorionic gonadotropin, adrenocorticotropic hormone, carcinoembryonic antigen, epithelial membrane antigen, and cytokeratin 19., Results: Gastrinomas coexpressed neuroendocrine and exocrine markers, including chromogranin A, synaptophysin, carcinoembryonic antigen, cytokeratin 19, and epithelial membrane antigen. Carcinoembryonic antigen was found in all 17 gastrinomas (100%), cytokeratin 19 was found in 15 of 17 (88.2%) gastrinomas, and epithelial membrane antigen was found in 16 of 18 (88.9 %) gastrinomas. Cytokeratin 19, epithelial membrane antigen, and carcinoembryonic antigen were not found to be present in the pancreatic endocrine tumors, but chromogranin A and synaptophysin were. Chorionic gonadotropin was found in 16 gastrinomas (100%), but only in 2 of 17 other pancreatic endocrine tumors (11.8 %)., Conclusions: Pancreatic gastrinomas were characterized by the coexpression of neuroendocrine markers, exocrine markers, and chorionic gonadotropin. Therefore, pancreatic gastrinomas made a special intermediate group of tumors, which phenotypically combined features of neuroendocrine and exocrine neoplasms. These findings suggested that sporadic pancreatic gastrinomas and other pancreatic endocrine tumors are different phenotypically and are possibly of different origin., (Copyright 2003 American Cancer Society.)