Effective dose rate coefficients for exposure to contaminated soil.

The Oak Ridge National Laboratory Center for Radiation Protection Knowledge has undertaken calculations related to various environmental exposure scenarios. A previous paper reported the results for submersion in radioactive air and immersion in water using age-specific mathematical phantoms. This paper presents age-specific effective dose rate coefficients derived using stylized mathematical phantoms for exposure to contaminated soils. Dose rate coefficients for photon, electron, and positrons of discrete energies were calculated and folded with emissions of 1252 radionuclides addressed in ICRP Publication 107 to determine equivalent and effective dose rate coefficients. The MCNP6 radiation transport code was used for organ dose rate calculations for photons and the contribution of electrons to skin dose rate was derived using point-kernels. Bremsstrahlung and annihilation photons of positron emission were evaluated as discrete photons. The coefficients calculated in this work compare favorably to those reported in the US Federal Guidance Report 12 as well as by other authors who employed voxel phantoms for similar exposure scenarios.

Transformation by the v-fms oncogene product: role of glycosylational processing and cell surface expression.

The effect of glycosylational-processing inhibitors on the synthesis, cell surface expression, endocytosis, and transforming function of the v-fms oncogene protein (gp140fms) was examined in McDonough feline sarcoma virus-transformed Fischer rat embryo (SM-FRE) cells. Swainsonine (SW), a mannosidase II inhibitor, blocked complete processing, but an abnormal v-fms protein containing hybrid carbohydrate structures was expressed on the cell surface. SW-treated SM-FRE cells retained the transformed phenotype. In contrast, two glucosidase I inhibitors (castanospermine [CA] and N-methyl-1-deoxynojirimycin [MdN]) blocked carbohydrate remodeling at an early stage within the endoplasmic reticulum and prevented cell surface expression of v-fms proteins. CA-treated SM-FRE cells reverted to the normal phenotype. Neither SW, CA, nor MdN affected either endocytosis or the tyrosine kinase activity associated with the v-fms gene product in vitro. These results demonstrate the necessity of carbohydrate processing for cell surface expression of the v-fms gene product and illustrate the unique ability to modulate the transformed state of SM-FRE cells with the glycosylational-processing inhibitors CA and MdN.

Behavioral anomalies of highly malignant respiratory tract epithelial cells.

In previous work, we undertook a comparison of cells from three highly malignant in vitro epithelial lines with cells from three lines showing little or no evidence of tumorigenicity, to see if consistent structural perturbations were present. Cells from highly malignant lines showed common anomalies in the organization of the lamellar cytoplasm. The objective of the present studies was to determine whether these anomalies were correlated with common adhesive or motile properties of the cells. The cells were cultured in a special chamber on the stage of an inverted microscope, and their movements were recorded by a time-lapse video process. Cells selected at the 24.0-hr interval after plating were subjected to a progressive analysis of movement by entering their sequential positions on the digitizing tablet of a Videoplan image analyzer. For each frame analyzed, representing a 15-min real-time interval, the distance traveled and the angle of travel relative to a fixed axis were measured, and the extent of contact between the subject cell and its neighbors was estimated. For the great majority of cells, the direction of translocative movement was random. The mean velocities were in the range of 17 to 60 mum/hr and tended to be greater for cells from the highly malignant lines. Although the frequency of cell-cell contact varied little among lines, the frequency of cells overlapping during contact was much greater for lines of high malignant potential than for lines of negligible tumorigenicity. Striking differences were observed in the behavior of cells plated on glass and plastic substrata. While cells from lines of negligible tumorigenicity adhered well to both substrates, cells from all of the three highly malignant lines became rounded or formed spheroidal masses when plated on glass surfaces. The results indicated that gradations of adhesive, although not necessarily motile, properties were correlated with gradations of tumorigenicity in these epithelial model systems.

Selective elimination of breast cancer cells from human bone marrow using an antibody-Pseudomonas exotoxin A conjugate.

A pancarcinoma monoclonal antibody (NR-LU-10), homogeneously reactive with human breast cancer cells, was conjugated to Pseudomonas exotoxin A. The immunotoxin was evaluated for its potential for purging breast cancer cells from human bone marrow. The immunotoxin NR-LU-10 antibody did not react with normal bone marrow preparations yet readily detected 1% contamination of bone marrow by MCF-7 breast cancer cells added to normal bone marrow without significantly inhibiting the colony-forming ability of bone marrow progenitor cells. NR-LU-10-Pseudomonas exotoxin A has potential for purging bone marrow of breast cancer cells without impairing the growth of bone marrow progenitor cells.

Enhanced therapeutic efficacy of an immunotoxin in combination with chemotherapy against an intraperitoneal human tumor xenograft in athymic mice.

A mouse IgG2b anti-pan carcinoma monoclonal antibody, NR-LU-10, was shown to bind homogeneously to ascites xenografts of both ovarian and colon carcinoma. Following linkage to a highly potent holotoxin, Pseudomonas exotoxin A (PE), NR-LU-10 demonstrated high potency and selectivity in vitro (ID50 = 100 pg/ml; elimination of greater than or equal to 4.5 logs of cells). The conjugate was evaluated for therapeutic efficacy against a human colon tumor (HT-29) transplantable in the peritoneal cavity of nude mice. Beginning 3 days after HT-29 injection, mice received either three or six i.p. injections of 0.5 micrograms of unconjugated NR-LU-10 or immunotoxin conjugate (NR-LU-10/PE) every other day. Mice that received three or six treatments of NR-LU-10 alone had median survival times (MSTs) of 39 and 40 days, respectively, which did not differ significantly from the MST observed for the untreated control groups (MST = 35 days). In contrast, treatment with three or six injections of 0.5 micrograms NR-LU-10/PE exhibited significantly increased MSTs (P = 0.002) of 50 and 60 days, respectively. Coinjection of unconjugated NR-LU-10 (20 micrograms) and 0.5 micrograms of NR-LU-10/PE blocked the therapeutic effect of the immunotoxin (MST = 33 days). The therapeutic efficacy of NR-LU-10/PE was further enhanced against HT-29 when administered i.p. during and after cytoreductive chemotherapy. The i.p. administration of 300 mg/lg of cyclophosphamide plus 100 mg/kg of the chemoprotective drug, WR-2721, 10 and 17 days posttumor cell inoculation induced a significant increase in MST from 36 days to 59 days (P = 0.002). Interestingly, groups of mice that received either two, four, or seven treatments of NR-LU-10/PE following cytoreductive therapy exhibited a further significant increase (P = 0.001) in MSTs of 89, 97, and 105 days, respectively. Therefore, the use of immunotoxin therapy following cytoreductive chemotherapy significantly prolonged survival time of mice bearing the HT-29 colon tumor over that observed with chemotherapy or NR-LU-10/PE alone.

ICRP Publication 133: The ICRP computational framework for internal dose assessment for reference adults: specific absorbed fractions.

Abstract ­: Dose coefficients for assessment of internal exposures to radionuclides are radiological protection quantities giving either the organ equivalent dose or effective dose per intake of radionuclide following ingestion or inhalation. In the International Commission on Radiological Protection's (ICRP) Occupational Intakes of Radionuclides (OIR) publication series, new biokinetic models for distribution of internalised radionuclides in the human body are presented as needed for establishing time-integrated activity within organs of deposition (source regions). This series of publications replaces Publications 30 and 68 (ICRP, 1979, 1980, 1981, 1988, 1994b). In addition, other fundamental data needed for computation of the dose coefficients are radionuclide decay data (energies and yields of emitted radiations), which are given in Publication 107 (ICRP, 2008), and specific absorbed fraction (SAF) values ­ defined as the fraction of the particle energy emitted in a source tissue region that is deposited in a target tissue region per mass of target tissue. This publication provides the technical basis for SAFs relevant to internalised radionuclide activity in the organs of Reference Adult Male and Reference Adult Female as defined in Publications 89 and 110 (ICRP, 2002, 2009). SAFs are given for uniform distributions of mono-energetic photons, electrons, alpha particles, and fission-spectrum neutrons over a range of relevant energies. Electron SAFs include both collision and radiative components of energy deposition. SAF data are matched to source and target organs of the biokinetic models of the OIR publication series, as well as the Publication 100 (ICRP, 2006) Human Alimentary Tract Model and the Publication 66 (ICRP, 1994a) Human Respiratory Tract Model, the latter as revised within Publication 130 (ICRP, 2015). This publication further outlines the computational methodology and nomenclature for assessment of internal dose in a manner consistent with that used for nuclear medicine applications. Numerical data for particle-specific and energy-dependent SAFs are given in electronic format for numerical coupling to the respiratory tract, alimentary tract, and systemic biokinetic models of the OIR publication series.

[Natural orifice transluminal endoscopic surgery in Germany: Data from the German NOTES registry]. / "Natural orifice transluminal endoscopic surgery" in Deutschland : Daten aus dem deutschen NOTES-Register.

BACKGROUND: The German NOTES registry (GNR) was initiated by the German Society for General and Visceral Surgery (DGAV) as a treatment and outcome database for natural orifice transluminal endoscopic surgery (NOTES). AIM: The aim of this study was the descriptive analysis of all GNR data collected over a 5-year period since its start in 2008 with more than 3000 interventions. MATERIAL AND METHODS: The GNR is an online database with voluntary participation available to all German-speaking clinics. Demographic data, therapy details, complications and data on the postoperative course of patients are recorded. All cases in the GNR between March 2008 and November 2013 were included in the analysis. RESULTS: From a total of 3150 data sets 2992 (95 %) were valid and suited for the analysis. Hybrid transvaginal cholecystectomy was the most frequently used procedure (88.7 %), followed by hybrid transvaginal/transgastric appendectomy (6.1 %) and hybrid transvaginal/transrectal colon procedures (5.1 %). Intraoperative complications occurred in 1.6 %, postoperative complications in 3.7 % and conversions were reported in 1.5 %. Intraoperative bladder injuries and postoperative urinary tract infections were identified as method-specific complications of transvaginal procedures. Bowel injuries occurred as a rare (0.2 %) but potentially serious complication of transvaginal operations. CONCLUSION: The German surgical community ensures a safe and responsible introduction of the new NOTES operation techniques with its active participation in the GNR. Despite an overall low complication rate, the high number of procedures in the GNR permitted the identification of method-specific complications. This knowledge can be used to further increase the safety of NOTES in practice.

Template preparation for PCR and RFLP of amplification products for the detection and identification of Cyclospora sp. and Eimeria spp. Oocysts directly from raspberries.

Raspberries were epidemiologically associated with cyclosporiasis outbreaks during 1996 and 1997. The 18S rRNA genes of Cyclospora cayetanensis and several species of a closely related genus, Eimeria, were sequenced and primers for a nested PCR developed in a previous study. The ability to distinguish amplified products of Cyclospora sp. from those of Eimeria spp. is important for testing food and environmental samples. Therefore, an RFLP analysis of amplified products was used to differentiate Cyclospora cayetanensis from Eimeria spp. PCR inhibitors and the low levels of Cyclospora oocysts present in raspberries make template preparation for PCR challenging. Several approaches for PCR template preparation from raspberry samples were evaluated. Template preparation methods using various washing and concentration steps, oocyst disruption protocols, resin matrix treatment, DNA precipitation, and/or the addition of nonfat dried milk solution to a PCR using modified primers were evaluated first with oocysts of Eimeria tenella then refined with oocysts of C. cayetanensis. Approximately 10 E. tenella oocysts per PCR or approximately 19 C. cayetanensis oocysts per PCR were detected with the optimized template preparation method. The addition of 20 microliters of raspberry wash sediment extract and nonfat dried milk solution did not inhibit the amplification of DNA from as few as 10 E. tenella and 25 C. cayetanensis oocysts in a 100-microliter PCR. The nucleotide sequences of C. cayetanensis and the Eimeria spp. are 94 to 96% similar in the amplified region, but the amplification products from the two genera were distinguished using an RFLP analysis with the restriction enzyme MnlI.

Heavy metals, lipid peroxidation, and ciguatera toxicity in the liver of the Caribbean barracuda (Sphyraena barracuda).

Human consumption of over 400 species of tropical fish containing polyether toxins (e.g. ciguatoxins, maitotoxins) causes ciguatera fish poisoning. The Caribbean barracuda (Sphyraena barracuda) is one of the most potent ciguatoxic fish. The objective of this study was to determine whether toxicity of 14 barracuda livers was correlated with lipid peroxidation. A significant correlation (p = 0.015, Pearson's correlation) between lipid peroxidation and toxicity of barracuda liver was found. Because iron and copper are well-known catalysts of hydroxyl radical production and lipid peroxidation in biological systems, the correlation between the concentrations of these metals in barracuda liver and lipid peroxidation and toxicity was also investigated. Cadmium was significantly correlated (p = 0.014) with the toxicity of barracuda livers. This study provides the first data concerning the concentration of iron, copper, and cadmium in the liver of the Caribbean barracuda. Of the three metals studied in barracuda liver, iron was the most abundant, followed by copper and cadmium. Lipid peroxidation was highly variable and detected in five (36%) of the liver samples. Lipid peroxidation was not statistically significantly correlated (p > 0.05) with concentrations of iron, copper, and cadmium in barracuda liver. Collectively, these findings provide additional evidence that lipid peroxidation can be a mechanistic component of ciguatera toxicity in the Caribbean barracuda.

Detection of sodium channel toxins: directed cytotoxicity assays of purified ciguatoxins, brevetoxins, saxitoxins, and seafood extracts.

Neuroblastoma cells in culture were used to detect sodium channel-specific marine toxins based on an end-point determination of mitochondrial dehydrogenase activity. The assay responds in a dose-dependent manner to ciguatoxins, brevetoxins, and saxitoxins, and delineates the toxic activity as either sodium channel enhancing or sodium channel blocking. The assay responds rapidly to sodium channel activating toxins, allowing dose dependent detection in 4 to 6 h. Brevetoxins can be detected at 250 pg, and purified ciguatoxins are detected in the low picogram and subpicogram levels. The results obtained from cell bioassay of ciguatoxic finfish extracts correlates with those obtained from mouse bioassays. Sodium channel blocking toxins can also be detected with an approximate sensitivity of 20 pg in 24 to 48 h. This cell-based technique is simple, sensitive, demonstrates potential as an alternative to animal testing for sodium channel activating and blocking toxins, and can be automated.

Developing a centre for health information and promotion.

Following the successful application for nursing development unit funding, the children's outpatient department within the Child Health Directorate of the University Hospital, Southampton, has developed a number of ambitious plans to promote nursing initiatives, one of which was the creation of a centre for health information and promotion. This article describes this development.

Dose conversion coefficients for neutron exposure to the lens of the human eye.

Dose conversion coefficients for the lens of the human eye have been calculated for neutron exposure at energies from 1 × 10(-9) to 20 MeV and several standard orientations: anterior-to-posterior, rotational and right lateral. MCNPX version 2.6.0, a Monte Carlo-based particle transport package, was used to determine the energy deposited in the lens of the eye. The human eyeball model was updated by partitioning the lens into sensitive and insensitive volumes as the anterior portion (sensitive volume) of the lens being more radiosensitive and prone to cataract formation. The updated eye model was used with the adult UF-ORNL mathematical phantom in the MCNPX transport calculations.

Evaluation of internal contamination levels after a radiological dispersal device incident using portal monitors.

Following a radioactive dispersal device (RDD) incident, it may be necessary to evaluate the internal contamination levels of a large number of potentially affected individuals to determine if immediate medical follow-up is necessary. Since the current laboratory capacity to screen for internal contamination is limited, rapid field screening methods can be useful in prioritising individuals. This study evaluated the suitability of a radiation portal monitor for such screening. A model of the portal monitor was created for use with models of six anthropomorphic phantoms in Monte Carlo N-Particle Transport Code Version 5 (MCNP) X-5 Monte Carlo Team (MCNP-A General Monte Carlo N-Particle Transport Code Version 5. LA-CP-03-0245. Vol. 2. Los Alamos National Laboratory, 2004.). The count rates of the portal monitor were simulated for inhalation and ingestion of likely radionuclides from an RDD for each of the phantoms. The time-dependant organ concentrations of the radionuclides were determined using Dose and Risk Calculation Software Eckerman, Leggett, Cristy, Nelson, Ryman, Sjoreen and Ward (Dose and Risk Calculation Software Ver. 8.4. ORNL/TM-2001/190. Oak Ridge National Laboratory, 2006.). Portal monitor count rates corresponding to a committed effective dose E(50) of 10 mSv are reported.

Using handheld plastic scintillator detectors to triage individuals exposed to a radiological dispersal device.

After a radiological dispersal device (RDD) event, people could become internally contaminated by inhaling dispersed radioactive particles. A rapid method to screen individuals who are internally contaminated is desirable. Such initial screening can help in prompt identification of those who are highly contaminated and in prioritising individuals for further and more definitive evaluation such as laboratory testing. The use of handheld plastic scintillators to rapidly screen those exposed to an RDD with gamma-emitting radionuclides was investigated in this study. The Monte Carlo N-Particle transport code was used to model two commercially available plastic scintillation detectors in conjunction with anthropomorphic phantom models to determine the detector response to inhaled radionuclides. Biokinetic models were used to simulate an inhaled radionuclide and its progression through the anthropomorphic phantoms up to 30 d after intake. The objective of the study was to see if internal contamination levels equivalent to 250 mSv committed effective dose equivalent could be detected using these instruments. Five radionuclides were examined: (60)Co, (137)Cs, (192)Ir, (131)I and (241)Am. The results demonstrate that all of the radionuclides except (241)Am could be detected when placing either one of the two plastic scintillator detector systems on the posterior right torso of the contaminated individuals.

A generic biokinetic model for Carbon-14.

The generic biokinetic model currently recommended by the International Commission on Radiological Protection (ICRP) for the treatment of systemic radiocarbon assumes uniform distribution of activity in tissues and a biological half-time of 40 d. This model is intended to generate cautiously high estimates of dose per unit intake of C-14 and, in fact, generally predicts a much higher effective dose than systemic models that have been developed on the basis of biokinetic studies of specific carbon compounds. The simplistic model formulation precludes its application as a bioassay model or adjustment to fit case-specific bioassay data. This paper proposes a new generic biokinetic model for systemic radiocarbon that is less conservative than the current ICRP model but maintains sufficient conservatism to overestimate the effective dose coefficients generated by most radiocarbon-compound-specific models. The proposed model includes two systemic pools with different biological half-times representing an initial systemic form of absorbed radiocarbon, a submodel describing the behaviour of labelled carbon dioxide produced in vivo, and three excretion pathways: breath, urine and faeces. Generic excretion rates along each path are based on multi-phase excretion curves observed in experimental studies of radiocarbons. The generic model structure is designed so that the user may adjust the level of dosimetric conservatism to fit the information at hand and may adjust parameter values for consistency with subject-specific or site-specific bioassay data.

[Problem discussion of allergic reactions in patients with infection-induced bronchial asthma in Candida colonization outside the respiratory tract]. / Problemdiskussion über allergische Reaktionen von Patienten mit infektbedingtem Asthma bronchiale bei Candida-Besiedlung ausserhalb des Respirationstraktes.

Candida albicans colonization outside from the respiratory tract can occur as a side-effect of long lasting antibiotica therapy in patients with infection-induced asthma bronchiale and may induce in them allergic reactions. Based on own experiences the author reports on the frequency of Candida infections following antibiotica therapy and the effect of a therapy with Fungicidin on the number of dyspnoe attacks.

[Causes of outpatient dropouts in the dispensary care of a chest clinic (author's transl)]. / Eine Untersuchung der Gründe für das Fernbleiben ambulanter Patienten

An investigation was made to point out, why 397 of total 2773 patients with 5524 consultations failed the fixed next consultation. 29 patients had died meanwhile. A special invitation was necessary in 368 (= 13%) of 2744 patients. The further behaviour of these patients after suitable advice and the importance of the diagnosis of their diseases in this connection were investigated. Failing of the patients can be diminished by systematical instructions.

Localization of the feline sarcoma virus fgr gene product (P70gag-actin-fgr): association with the plasma membrane and detergent-insoluble matrix.

The v-fgr oncogene codes for a unique transforming protein (P70gag-actin-fgr) that contains virus-specific determinants and cell-derived sequences for both a tyrosine-specific kinase domain and an actin domain. We examined the subcellular distribution of the v-fgr protein by immunofluorescence microscopy and various cell fractionation techniques. By immunofluorescence, the v-fgr protein was localized in a diffuse cytoplasmic pattern within transformed cells. The v-fgr protein was not detectable at substratum adhesion sites. Crude membrane preparations (P100) obtained from fgr-transformed cells contained elevated levels of P70gag-actin-fgr. Further analysis of membranes on discontinous sucrose gradients revealed that P70gag-actin-fgr cofractionated with plasma membranes. Using an alternate method of fractionation, we found that the majority of the v-fgr protein remained with the insoluble matrix obtained by treating cells with a buffer containing Triton X-100. When membranes were similarly treated with detergent, nearly all of v-fgr protein remained with the residual insoluble matrix. These results suggest that the transforming activity of P70gag-actin-fgr may be directed to subcellular cytoskeletal targets at or near the cytoplasmic face of the plasma membrane.