Biomedical subjects

Xiaowei Liu

Publications and source records attributed to Xiaowei Liu.

At least 19 recordsLinked to original sources

PubMed2026

Spatiotemporal genomic analysis and risk assessment of the plasmids carrying blaOXA-48-like genes based on a large-scale international dataset.

BACKGROUND: The spread of OXA-48-like carbapenemases represents a major public health challenge. Although previous studies have investigated OXA-48-like carbapenemases risk factors, nosocomial dissemination, and plasmid dynamics, an integrated plasmid-centered framework combining complete plasmid mining, transmission-unit analysis, phylogenetic reconstruction, and machine learning-based risk assessment remains limited. METHODS: We systematically collected 747 complete plasmid sequences carrying blaOXA-48-like genes from the NCBI database, establishing the largest collections of complete plasmid sequences to date. Using an integrative framework of population genomics, phylogenetic dating, and machine learning, this study aimed to characterize the dissemination patterns, plasmid replicon diversity, transmission units, mobile genetic elements, co-resistance profiles, and risk classification of these plasmid. RESULTS: Plasmids carrying blaOXA-48-like genes were detected across 50 countries on six continents, with blaOXA-48 predominating in Europe, blaOXA-181 in South Asia, and blaOXA-232 largely in Asia. IncL and ColKP3/IncX3 replicons, together with Tn1999.2 and other MGEs, were central drivers of plasmid maintenance and spread. Sixteen transmission units were defined, with AA068_Cluster3 estimated to have originated in the Netherlands around 2005 before expanding to Europe, the Middle East, Asia, and North America. Co-resistance analyses revealed frequent modules involving aminoglycoside and quinolone resistance, with qnrS1 and aph(3'')-Ib most prevalent. Notably, high-risk transposon structures were often identified in non-clinical environments, underscoring their cross-ecological transmission potential. Machine learning-based classification models showed good internal performance for predefined composite-risk categories, with plasmid mobility, clinical/non-clinical source composition, and host background contributing to the classification results. CONCLUSIONS: This study provides a large-scale plasmid-centered genomic analysis of publicly available complete plasmid sequences carrying blaOXA-48-like genes, integrating transmission-unit inference, phylogeographic reconstruction, mobile genetic element and co-resistance profiling, and composite genomic risk stratification. This gene-centered framework may support future One Health-oriented antimicrobial resistance surveillance and prioritization of plasmids with higher dissemination and resistance potential.

Plasmids↗

PubMed2025

Malonate promotes CD8+ T cell memory formation via protein malonylation.

Protein malonylation represents a recently identified posttranslational modification whose role in CD8+ T cell differentiation and functionality remains incompletely understood. In this study, we demonstrate that enhancing protein malonylation through sodium malonate (SM) treatment promotes CD8+ T cell memory formation in response to bacterial infection, subsequently potentiating recall responses. Comparative metabolomic analysis between SM-treated and control CD8+ T cells revealed significant metabolic alterations associated with protein malonylation. We present the first comprehensive proteomic analysis of lysine malonylation in murine CD8+ T cells, identifying 77 malonylation sites across 64 proteins involved in diverse cellular processes, particularly metabolic pathways. Malonylation of STAT6 was confirmed via the use of a specific chemical probe. Notably, we established that malonylation at the lysine 374 site of STAT6 results in increased TCF1 expression, due to alleviated transcriptional repression of TCF1 by STAT6. Collectively, our findings provide compelling evidence that protein malonylation plays a significant role in regulating CD8+ T cell memory formation.

Animals↗

PubMed2006

A human monoclonal antiprothrombin antibody is thrombogenic in vivo and upregulates expression of tissue factor and E-selectin on endothelial cells.

Prothrombin is now accepted as one of the target antigens recognised by antiphospholipid (aPL) antibodies. However, it is not clear whether anti-prothrombin antibodies are pathogenic in vivo and if so, the possible mechanism(s) involved. Here, we examined the pathogenic effects of the IS6 monoclonal anti-prothrombin antibody isolated from a patient with Antiphospholipid Syndrome (APS). IS6 antibody was purified from hybridoma supernatant. Its pathogenic potentials were studied in an in vivo model of induced thrombosis. The expression of tissue factor (TF) and E-selectin on human umbilical vein endothelial cells (HUVEC) was determined by cyto-enzyme-linked immunosorbent assay. Transcription of TF mRNA was determined by quantitative real time-polymerase chain reaction (RT-PCR). In vivo, the thrombus size increased significantly when treated with IS6 compared with control-treated mice (5388 +/- 1035 microm2 vs. 2845 +/- 1711 microm2). In vitro, IS6 induced significant expression of TF and E-selectin on HUVEC, when compared with control preparation (3.1- and 5.1-fold increase compared with the control-treated cells). RT-PCR analysis of TF mRNA transcription showed a 2.5-fold increase of IS6-treated cells over the value obtained with control-treated cells. Taken together, these data show that IS6 monoclonal anti-prothrombin antibody promotes thrombosis and this is associated with TF and E-selectin expression.

Adolescent↗

PubMed2006

Effects of dissolved oxygen on survival and immune responses of scallop (Chlamys farreri Jones et Preston).

This experiment investigated the effects of dissolved oxygen (DO) on the survival and immune responses of scallop Chlamys farreri. The scallops (initial mean dry weight of soft tissue 1.52+/-0.10 g) were cultivated in the seawater with different DO levels (8.5, 6.5, 4.5, and 2.5mg l(-1), respectively) for 21 d. Each treatment had triplicate groups of 35 animals. During the experimental period, the scallops were fed with Spirulina maxima, and water temperature ranged from 15.2 degrees C to 17.5 degrees C, salinity from 29.5 per thousand to 32.5 per thousand and pH from 7.5 to 8.2. Survival, specific growth rate (SGR) and total haemocyte count (THC) were examined at the end of the study, and superoxide dismutase (SOD), acid phosphatase (ACP) and alkaline phosphatase (ALP), were examined at 12 h, 24 h, Day 7, Day 14 and Day 21 after being exposed to the graded DO levels. The lower DO levels (2.5 and 4.5mg l(-1))resulted in lower survivals of scallops, and the survival (81.7%) at 2.5mg 1(-1)DO was significantly lower than those (100.0%) at 8.5 and 6.5mg l(-1) DO. Similarly, the SGR and THC of scallop gradually reduced with decreasing DO levels, and reached significant levels at 2.5mg l(-1) DO (P<0.05). At higher DO levels (8.5 and 6.5mg l(-1)), the SOD activity maintained rather stable during the entire sampling period. At lower DO levels (4.5 and 2.5mg l(-1)), however, the SOD activity significantly increased at 12 h, and then significantly decreased to the levels below the normal. At the two lower DO levels, ACP activities had no significant changes before Day 7, and then declined to the levels that were significantly lower than the normal. Significantly higher ALP activity was only observed at 12 h in the treatment of 2.5mg l(-1) DO, but in all other treatments and sampling times it fluctuated in a narrow range. In conclusion, less than 4.5mg l(-1) DO reduced the survival and depressed the immune responses of C. farreri.

Acid Phosphatase↗

PubMed2005

Requirement of activation of complement C3 and C5 for antiphospholipid antibody-mediated thrombophilia.

OBJECTIVE: Antiphospholipid antibodies (aPL) have been shown to induce thrombosis, activate endothelial cells, and induce fetal loss. The pathogenesis of aPL-induced thrombosis, although not completely understood, may involve platelet and endothelial cell activation as well as procoagulant effects of aPL directly on clotting pathway components. Recent studies have shown that uncontrolled complement activation leads to fetal death in aPL-treated mice. In this study, we tested the hypothesis that aPL are responsible for activation of complement, thus generating split products that induce thrombosis. METHODS: To study thrombus dynamics and adhesion of leukocytes we used in vivo murine models of thrombosis and microcirculation, in which injections of aPL were used. RESULTS: Mice deficient in complement components C3 and C5 were resistant to the enhanced thrombosis and endothelial cell activation that was induced by aPL. Furthermore, inhibition of C5 activation using anti-C5 monoclonal antibodies prevented thrombophilia induced by aPL. CONCLUSION: These data show that complement activation mediates 2 important effectors of aPL, induction of thrombosis and activation of endothelial cells.

Animals↗

PubMed2005

Complement activation: a novel pathogenic mechanism in the antiphospholipid syndrome.

Antiphospholipid antibodies (aPLs) have been shown to induce thrombosis, activate endothelial cells, and induce fetal loss. The pathogenesis of aPL-induced thrombosis is incompletely understood, but it is thought to involve platelet and endothelial cell activation as well as pro-coagulant effects of aPL antibody directly on clotting pathway components. Recent studies have shown that uncontrolled complement activation leads to fetal death in aPL-antibody treated mice. We hypothesized that aPL antibodies activate complement, generating split products that induce thrombosis. To test this hypothesis, we used an in vivo model of thrombosis in which aPL antibodies induce a significant increase in thrombus size and a mouse model of endothelial cell activation in which aPLs induce significant adhesion of leukocytes (WBCs) to endothelial cells. We found that mice deficient in complement components C3 and C5 were resistant to enhanced thrombosis and endothelial cell activation induced by aPL antibodies. Furthermore, inhibition of C5 activation using anti-C5 mAb prevented thrombophilia induced by aPL antibodies. Our data show that complement activation mediates two important effectors of aPL antibodies: induction of thrombosis and endothelial activation.

Animals↗

PubMed2004

A peptide that shares similarity with bacterial antigens reverses thrombogenic properties of antiphospholipid antibodies in vivo.

OBJECTIVE: The factors causing production of antiphospholipid (aPL) antibodies remain unidentified. Recently, studies have shown that aPL and anti-beta2Glycoprotein I (anti-beta2GPI) antibodies with pathogenic properties can be generated with peptides from bacterial and viral origin, that mimic regions of beta2GPI. These data suggest a molecular mimicry between bacterial/viral antigens and self-proteins. In this study we examined the ability of a synthetic peptide (named peptide A, NTLKTPRVGGC) that shares similarity with common bacterial antigens, to reverse aPL-mediated thrombosis in mice in vivo. Peptide A is also found in region I/II of beta2GPI. A scrambled form of peptide A (named scA, GTKGCPNVRLT) was used as a control. METHODS AND RESULTS: Sera from 29 patients with APS bound to peptide A but not to peptide scA by ELISA in a dose-dependent fashion. Cardiolipin (CL) liposomes inhibited the binding of IgG-APS by ELISA to peptide A by 35% and to CL by 56%. The inhibition of binding to cardiolipin and to peptide A was enhanced by addition of beta2GPI to the liposomes. CL/peptide A liposomes but not peptide A alone inhibited the binding of IgG-APS to peptide A. beta2GPI alone did not inhibit binding of IgG-APS to peptide A, to beta2GPI or to CL. For the in vivo experiments, CD1 mice in groups of 20 were injected with affinity purified aPL antibodies or with control IgG-NHS twice intraperitoneally. Seventy hours after the first injection, and 30 min before the surgical procedure (induction of experimental thrombus) mice were infused i.v. in each group with either peptide A or with peptide scA. The femoral vein of the anesthetized mice were dissected to examine the dynamics of an induced thrombus in treated and control mice. The mean aCL titer of mice injected with aPL was 60 GPL units. Mice treated with aPL and infused with peptide scA produced significantly larger thrombi when compared to mice treated with IgG-NHS and peptide scA (2466+/-462 microm2 vs 772.5+/-626.4 microm2). Treatment with peptide A significantly decreased thrombus size in mice injected with aPL antibodies (1063+/-890 microm2 compared to 2466+/-462 microm2). CONCLUSION: The data indicates that a synthetic peptide that shares similarity with common bacterial antigens and with regions of beta2GPI is capable to inhibit thrombogenic properties of aPL in mice. This may have important implications in designing new modalities of prevention and/or treatment of thrombosis in APS.

Antigens, Bacterial↗

PubMed2004

Absorbed dose distribution in glioma tumors in rat brain after therapeutic intratumoral injection of 201Tl-chloride.

Studies on animals with gliomas inoculated in the brain and treated with intratumoral injections of 201Tl-chloride have previously shown very promising results, with a survival several weeks longer than controls. Total regression was found in some animals, and necrosis was found in all the 201Tl-treated brain tumors. This study was undertaken to estimate the absorbed dose and dose distribution to the tumor based on the localization and clearance properties obtained from images with two high-resolution imaging techniques; pinhole single photon emission computed tomography (SPECT) and beta-camera. The images from the beta-camera were used to calculate the absorbed dose rate, using an in-house-developed, voxel-based Monte Carlo program, based on the EGS4 package. To evaluate the effects of different beta-particle energies on the absorbed dose rate distribution, simulations of medium- and high-energy electrons were conducted. Dose-volume histograms from these simulations show that the energy absorption is very locally distributed for 201Tl and medium energy, whereas high-energy beta emitters show a broader dose-volume distribution. The calculated total absorbed dose of 2-8 Gy in the tumor seems to be relativity low when considering the therapeutic effect that was seen. Further investigations, to determine the cause of the high therapeutic efficacy, are needed.

Animals↗

PubMed2003

Conformation of CCAAT/enhancer-binding protein alpha dimers varies with intranuclear location in living cells.

The structure of a protein defines its biochemical properties, but the impact of intracellular location and environment on protein structure remains poorly defined. CCAAT/enhancer-binding protein alpha (C/EBPalpha) is a master regulator of transcription and cellular proliferation that concentrates and is kept inactive at transcriptionally quiescent, pericentromeric regions in mouse cell nuclei. C/EBPalpha dimer structure was measured in living cells from the amounts of fluorescence energy transferred between derivatives of the green fluorescent protein attached to different C/EBPalpha domains. Comparing the levels of fluorescence resonance energy transfer at pericentromeric and nonpericentromeric regions of the nucleus indicated that the DNA binding domains of C/EBPalpha dimers were further apart and interacted more poorly at pericentromeric heterochromatin than in the more euchromatic regions of the nucleus. In contrast, the position and interactions of the transcriptional activation domains were similar throughout the nucleus. Phorbol ester treatment caused a shift in the position of the transcriptional activation domain relative to the DNA binding domain. Thus, C/EBPalpha conformation varies with intranuclear location and with cellular environment. These "fluorescence resonance energy transfer nanoscopy" techniques will be broadly applicable for associating conformational and kinetic variations to subcompartment-specific actions of C/EBPalpha or any protein in the dynamic intracellular environment.

3T3 Cells↗

PubMed2003

Inhibition of the thrombogenic and inflammatory properties of antiphospholipid antibodies by fluvastatin in an in vivo animal model.

OBJECTIVE: Antiphospholipid antibodies (aPL) have thrombogenic properties in vivo, through their interactions with soluble coagulation factors and their ability to modulate the functions of cells involved in coagulation homeostasis. These antibodies have also been shown to enhance the adhesion of leukocytes to endothelial cells (ECs) in vivo. New lipophilic statins such as fluvastatin have antiinflammatory and antithrombogenic effects. This study uses an in vivo mouse model to investigate whether fluvastatin has an effect on decreasing both the adhesion of leukocytes to ECs and the thrombus formation induced by aPL. METHODS: Two groups of CD-1 male mice, each comprising approximately 18 mice, were fed either normal saline solution or 15 mg/kg fluvastatin for 15 days. Each of the 2 groups was further subdivided to receive either purified IgG from patients with the antiphospholipid syndrome (IgG-APS) or normal IgG from healthy subjects. Analysis of thrombus dynamics was performed in treated and control mice, using a standardized thrombogenic injury procedure, and the area (size) of the thrombus was measured. Adhesion of leukocytes to ECs was analyzed with a microcirculation model of exposed cremaster muscle. Baseline and posttreatment soluble intercellular adhesion molecule 1 (sICAM-1) levels were determined by enzyme-linked immunosorbent assay. RESULTS: IgG-APS mice treated with fluvastatin showed significantly smaller thrombi, a reduced number of adherent leukocytes, and decreased levels of sICAM-1 compared with IgG-APS animals treated with placebo. CONCLUSION: These findings indicate that fluvastatin significantly diminishes aPL-mediated thrombosis and EC activation in vivo. These results may have important implications for the design of new treatment strategies aimed at preventing recurrent thrombosis in patients with APS.

Administration, Oral↗

PubMed2003

3D absorbed dose calculations based on SPECT: evaluation for 111-In/90-Y therapy using Monte Carlo simulations.

A general method is presented for patient-specific three-dimensional (3D) absorbed dose calculations based on quantitative SPECT activity measurements. The computational scheme includes a method for registration of the CT study to the SPECT image, and compensation for attenuation, scatter, and collimator-detector response including septal penetration, performed as part of an iterative reconstruction method. From SPECT images, the absorbed dose rate is calculated using an EGS4 Monte Carlo code, which converts the activity distribution to an absorbed dose rate distribution. Evaluation of the accuracy in the activity quantification and the absorbed dose calculation is based on realistic Monte Carlo simulated SPECT data of a voxel-computer phantom and (111)In and (90)Y. Septal penetration was not included in this study. The SPECT-based activity concentrations and absorbed dose distributions are compared to the actual values; the results imply that the corrections for attenuation and scatter yield results of high accuracy. The presented method includes compensation for most parameters deteriorating the quantitative image information. Inaccuracies are, however, introduced by the limited spatial resolution of the SPECT system, which are not fully compensated by the collimator-response correction. The proposed evaluation methodology may be used as a basis for future inter-comparison of different dosimetry calculation schemes.

Humans↗

PubMed2003

Crypt cell dosimetry for 99Tcm-sestamibi in a new small intestinal dosimetry model.

The aim of the study was to calculate the absorbed dose to the crypt cells in the small intestine from (99)Tc(m)-sestamibi excreted through the intestinal tract. The absorbed dose was calculated taking into consideration the biodistribution of the radiopharmaceutical in the small intestinal wall and its contents, based on data gathered in rats. Absorbed dose calculations were performed using a new intestinal model in which S values for crypt cells are given both for the intestinal wall and for the intestinal contents as source organs. A maximum of 6% of the injected activity was found to be located in the intestinal wall at 30 minutes after injection and 13% in the intestinal contents at 2 h, resulting in an absorbed dose of 8.9 microGy/MBq to the crypt cells. Assuming the activity to be located only in the wall, we calculate an absorbed dose to the crypt cells 2.5 times higher than if all the activity is assumed to be present in the intestinal contents. Using the new intestinal dosimetry model, together with detailed biokinetic data for the radiopharmaceutical from animal studies, it is possible to calculate the absorbed dose to the crypt cells, which is not possible when using external imaging.

Animals↗

PubMed2003

Secular trends in adolescent never smoking from 1990 to 1999 in California: an age-period-cohort analysis.

OBJECTIVES: We analyzed age, time period, and cohort effects on trends in adolescent cigarette smoking in California from 1990 to 1999. METHODS: Data from subjects aged 12 to 17 years (n = 26 536; 50.4% male) from the California Tobacco Survey and the California Youth Tobacco Survey were analyzed, and never smokers were used as the outcome measure. RESULTS: The proportion of never smokers increased from 60% for males and 66% for females in 1990 to around 70% for both sexes in 1999. Respondents were more likely to be never smokers if born in 1978 or later (i.e., aged 12 years or younger in 1990, when most tobacco control programs started in California). CONCLUSIONS: The statewide antitobacco programs prevented adolescents from starting to smoke, primarily through a cohort effect.

Adolescent↗

PubMed2002

Ischemia elicits a coordinated expression of pro-survival proteins in mouse myocardium.

Cardiomyocytes are post-mitotic, long-lived cells until disruptions to pro-survival factors occur after myocardial ischemia. To gain an understanding of the factors involved with ischemic injury, we examined expression changes in pro-survival and opposing pro-apoptotic signals at early and chronic periods of ischemia using an in vivo murine model. Alterations of pro-survival proteins such as the inhibitor of apoptosis protein on chromosome X (xIAP) and the apoptotic repressor protein (ARC) have not been evaluated in a murine model of cardiac ischemia. Early ischemia (1 day) resulted in a 50% reduction in ARC protein levels relative to sham-operated left ventricles, without significant changes in the expression of xIAP or other pro-survival factors. In contrast, a deficiency of xIAP expression was found in cardiac infarcts starting after 1 week, concomitant with significant evidence of apoptotic cell death and an up-regulation of pro-apoptotic signals including Bax, tumor necrosis factor-a, and caspase-8 activation. Chronic ischemia (after 2 weeks) was associated with elevated levels of other pro-survival factors such as Bcl-xL and the phosphorylated form of Akt, as part of the adaptive remodeling of the myocardium. Altogether, these findings suggest that strategies to increase IAP expression may promote myocyte survival after chronic ischemia.

Acute Disease↗

PubMed2002

Antiphospholipid antibodies induced in mice by immunization with a cytomegalovirus-derived peptide cause thrombosis and activation of endothelial cells in vivo.

OBJECTIVE: To characterize the binding and functional properties of antiphospholipid antibodies (aPL) induced by immunization with a viral peptide and to determine whether aPL are pathogenic in vivo. METHODS: Ten murine monoclonal aPL were generated from spleen cells of PL/J mice immunized with TIFI, a phospholipid-binding peptide spanning Thr(101)-Thr(120) of ULB0-HCMVA from human cytomegalovirus (CMV), which shares structural similarity with the phospholipid-binding site of beta(2)-glycoprotein I (beta(2)GPI). RESULTS: The antibodies generated had aPL activity that was inhibited by cardiolipin liposomes, and this inhibition was enhanced in the presence of beta(2)GPI. Some of the antibodies exhibited binding to cultured endothelial cells in vitro, and some had lupus anticoagulant activity. Injection with 2 of the monoclonal aPL in mice resulted in a significant increase in the number of leukocytes adhering to endothelial cells and enhanced thrombus formation in vivo. CONCLUSION: These results indicate that aPL induced by immunization with a phospholipid-binding CMV peptide are pathogenic in vivo. The results also suggest a mechanism (molecular mimicry) by which pathogenic aPL may be generated in patients with antiphospholipid syndrome.

Amino Acid Sequence↗

PubMed2002

A 3-dimensional absorbed dose calculation method based on quantitative SPECT for radionuclide therapy: evaluation for (131)I using monte carlo simulation.

UNLABELLED: A general method is presented for patient-specific 3-dimensional absorbed dose calculations based on quantitative SPECT activity measurements. METHODS: The computational scheme includes a method for registration of the CT image to the SPECT image and position-dependent compensation for attenuation, scatter, and collimator detector response performed as part of an iterative reconstruction method. A method for conversion of the measured activity distribution to a 3-dimensional absorbed dose distribution, based on the EGS4 (electron-gamma shower, version 4) Monte Carlo code, is also included. The accuracy of the activity quantification and the absorbed dose calculation is evaluated on the basis of realistic Monte Carlo-simulated SPECT data, using the SIMIND (simulation of imaging nuclear detectors) program and a voxel-based computer phantom. CT images are obtained from the computer phantom, and realistic patient movements are added relative to the SPECT image. The SPECT-based activity concentration and absorbed dose distributions are compared with the true ones. RESULTS: Correction could be made for object scatter, photon attenuation, and scatter penetration in the collimator. However, inaccuracies were imposed by the limited spatial resolution of the SPECT system, for which the collimator response correction did not fully compensate. CONCLUSION: The presented method includes compensation for most parameters degrading the quantitative image information. The compensation methods are based on physical models and therefore are generally applicable to other radionuclides. The proposed evaluation methodology may be used as a basis for future intercomparison of different methods.

Humans↗

PubMed2002

[Analysis of a family pedigree with primary shunt hyperbilirubinaemia].

OBJECTIVE: To identify whether primary shunt hyperbilirubinaemia is a genetic disorder or not and the pattern of the inheritance. METHOD: Clinical case data were studied with analysis of family pedigree of a case. RESULTS: Although the patient with primary shunt hyperbilirubinaemia presented an elevated unconjugated serum bilirubin, anemia and splenomegaly, the patient also presented decline of amount of peripheral white cells and normal amount of reticulocytes. The mature erythrocytes in peripheral blood and bone marrow were irregular in shape and size. There were also some target-, rod-, and mouth-shaped peripheral red cells in blood smear. With analysis of family pedigree, we can find that there were some patients with the primary shunt hyperbilirubinaemia in every generation of the family with equal distribution in male and female. The pattern of inheritance was transmitted from one generation to the next generation directly. Almost any manifestation of the disease may be found in adult patients, but the severity of the disorder was not the same among these patients. CONCLUSIONS: The primary shunt hyperbilirubinaemia is a genetic disease; its pattern of inheritance is autosomal dominant. It is suggested that the disease of primary shunt hyperbilirubinaemia could be renamed as hereditary shunt hyperbilirubinaemia.

Adult↗

PubMed2002

A dosimetry model for the small intestine incorporating intestinal wall activity and cross-doses.

UNLABELLED: Current internal radiation dosimetry models for the small intestine, and for most walled organs, lack the ability to account for the activity uptake in the intestinal wall. In existing models the cross-dose from nearby loops of the small intestine is not taken into consideration. The aim of this investigation was to develop a general model for calculating the absorbed dose to the radiation-sensitive cells in the small intestinal mucosa from radionuclides located in the small intestinal wall or contents. METHODS: A model was developed for calculation of the self-dose and cross-dose from activity in the intestinal wall or contents. The small intestine was modeled as a cylinder with 2 different wall thicknesses and with an infinite length. Calculations were performed for various mucus thicknesses. S values were calculated using the EGS4 Monte Carlo simulation package with the PRESTA algorithm and the simulation results were integrated over the depth of the radiosensitive cells. The cross-organ dose was calculated by summing the dose contributions from other intestinal segments. Calculations of S values for self-dose and cross-dose were made for monoenergetic electrons, 0.050-10 MeV, and for the radionuclides (99m)Tc, (111)In, (131)I, (67)Ga, (90)Y, and (211)At. RESULTS: The self-dose S value from activity located in the small intestinal wall is considerably greater than the S values for self-dose from the contents and the cross-dose from wall and contents except for high electron energies. For all radionuclides investigated and for electrons 0.10-0.20 MeV and 8-10 MeV in energy, the cross-dose from activity in the contents is higher than the self-dose from the contents. The mucus thickness affects the S value when the activity is located in the contents. CONCLUSION: A dosimetric model for the small intestine was developed that takes into consideration the localization of the radiopharmaceutical in the intestinal wall or in the contents. It also calculates the contribution from self-dose and cross-dose. With this model, more accurate calculations of absorbed dose to radiation-sensitive cells in the intestine are possible.

Electrons↗