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Efficacy of a technique for exposing the mouse lung to particles aspirated from the pharynx.

Recent studies have demonstrated that the mouse lung can be exposed to soluble antigens by aspiration of these antigens from the pharynx. This simple technique avoids the trauma associated with intratracheal instillation. In this study, the pharyngeal aspiration technique was validated for exposing the mouse lung to respirable particles. Using respirable fluorescent amine-modified polystyrene latex beads and beryllium oxide particles, we investigated the localization of aspirated particles within the lung and the relationship between the amount of material placed in the pharynx and the amount deposited in the lung. For exposure, mice were anesthetized with isoflurane in a bell jar, placed on a slant board, and the tongue was gently held in full extension while a 50-microl suspension of particles was pipetted onto the base of the tongue. Tongue restraint was maintained until at least two breaths were completed. Less than a minute after exposure, all mice awoke from anesthesia without visible sequela. There were no significant differences in particle distribution between the left and right side of the lung (p=.16). Particles were widely disseminated in a peribronchiolar pattern within the alveolar region. There was a linear and significant correlation (r2=.99) between the amount administered and the amount deposited in the lung. In beryllium-exposed mice, measurable lung beryllium was 77.5 to 88.2% of the administered beryllium. These findings demonstrate that following aspiration of pharyngeal deposited particles, exposures to the deep lung are repeatable, technically simple, and highly correlated to the administered dose.

Animals↗

Experimental beryllium-induced lung disease. II. Analyses of bronchial lavage cells in strains 2 and 13 guinea pigs.

In previous studies, we found that endotracheal administration of beryllium oxide (BeO) produced cell-mediated immunity and granulomatous lung disease in strain 2 but not strain 13 guinea pigs. This report describes phenotypic and functional studies of bronchial lavage cells from both guinea pig strains after BeO exposure. In BeO-treated strain 2 animals, the percentage of T (ER+)3 lymphocytes was significantly (p less than 0.05) elevated above normal by 2 weeks after BeO exposure, while T lymphocytes were not increased in strain 13. Giant cells containing crystalline material in fused, coalesced phagolysosomes were observed in treated animals of both strains. BeO-exposed strain 2 alveolar macrophages (AM) demonstrated enhanced killing of Listeria monocytogenes and enhanced chemiluminescence, while AM of strain 13 had responses below controls. Findings support the presence of BeO-induced cellular immunologic activity in strain 2 animals and, on the other hand, suggest BeO toxicity to lavage cells in strain 13.

Animals↗

Beryllium-induced lung disease in the dog following two exposures to BeO.

We have shown previously that dogs exposed once to aerosols of beryllium oxide (BeO) calcined at 500 or 1000 degrees C developed granulomatous lung lesions as well as Be-specific immune responses in the blood and lung. In this report, we investigate the immunopathologic consequences of exposing dogs twice to aerosols of BeO. Dogs previously exposed to aerosols of 500 or 1000 degrees C calcined BeO to achieve an initial lung burden (ILB) of either 50 or 17 micrograms/kg body wt were exposed a second time to BeO calcined at 500 degrees C, 2.5 years after the first exposure, to achieve an ILB of about 50 micrograms/kg body wt. Immune responses of peripheral blood and lung lymphocytes were measured at 0, 14, 30, 60, 90, 120, 150, 165, 180, and 210 days postexposure (dpe), and dogs were euthanized at 210 dpe. Be-specific immune responses occurred in blood at 30 dpe and again at 150 to 210 dpe. Only sporadic positive responses were seen among lung lymphocytes when cells were cultured in 10% fetal bovine serum. In contrast, samples collected at 165, 180, and 210 dpe and incubated with 10% dog serum showed a large number of positive responses in both blood and lung. Histologic lesions were characterized by perivascular and interstitial infiltrates of lymphocytes and macrophages with progression to patchy granulomatous pneumonia accompanied by focal septal fibrosis. We conclude that Be-induced granulomatous and fibrotic lung lesions are accompanied by Be-specific immune responses within the lung but these changes do not appear to be cumulative if enough time has elapsed between exposures.

Aerosols↗

Combined TL and 10B-alanine ESR dosimetry for BNCT.

The dosimetric technique described in this paper is based on electron spin resonance (ESR) detectors using an alanine-boric compound acid enriched with (10)B, and beryllium oxide thermoluminescent (TL) detectors; with this combined dosimetry, it is possible to discriminate the doses due to thermal neutrons and gamma radiation in a mixed field. Irradiations were carried out inside the thermal column of a TRIGA MARK II water-pool-type research nuclear reactor, also used for Boron Neutron Capture therapy (BNCT) applications, with thermal neutron fluence from 10(9) to 10(14) nth cm(-2). The ESR dosemeters using the alanine-boron compound indicated ESR signals about 30-fold stronger than those using only alanine. Moreover, a negligible correction for the gamma contribution, measured with TL detectors, almost insensitive to thermal neutrons, was necessary. Therefore, a simultaneous analysis of our TL and ESR detectors allows discrimination between thermal neutron and gamma doses, as required in BNCT.

Body Burden↗

The etiology of osteosarcoma. A review of current considerations.

Various agents have caused osteosarcoma in several experimental animal systems. These agents or initiators may be classified as chemicals, radiation, viruses, and miscellaneous. Zinc beryllium silicate with beryllium oxide in rabbits and FBJ virus in mice are two such initiating agents. The relevance of these animal experiments to the human situation is not known, but recent reports regarding a transmissible agent obtained from human osteosarcoma tissue suggest that a virus may be implicated. There is a theoretic indication that the various etiologic agents, including viruses, may affect the DNA of normal cells in such a way that further evolution and differentiation through several cell divisions may result in the clinical appearance of cancer.

Animals↗

Controllability of depth dose distribution for neutron capture therapy at the Heavy Water Neutron Irradiation Facility of Kyoto University Research Reactor.

The updating construction of the Heavy Water Neutron Irradiation Facility of the Kyoto University Research Reactor has been performed from November 1995 to March 1996 mainly for the improvement in neutron capture therapy. On the performance, the neutron irradiation modes with the variable energy spectra from almost pure thermal to epi-thermal neutrons became available by the control of the heavy-water thickness in the spectrum shifter and by the open-and-close of the cadmium and boral thermal neutron filters. The depth distributions of thermal, epi-thermal and fast neutron fluxes were measured by activation method using gold and indium, and the depth distributions of gamma-ray absorbed dose rate were measured using thermo-luminescent dosimeter of beryllium oxide for the several irradiation modes. From these measured data, the controllability of the depth dose distribution using the spectrum shifter and the thermal neutron filters was confirmed.

Antineoplastic Agents↗

The effects of CT drift on xenon/CT measurement of regional cerebral blood flow.

A systematic increase in computed tomography (CT) number of approximately 0.13 Hounsfield unit per scan (HU/scan) was observed when serial DeltaScan 2020 CT scans of a uniform water phantom were equally spaced at 0.5, 1.0, or 2.0 min and a shaped aluminum beam-hardening filter was employed. Much smaller drifts (less than 0.06 HU/scan) were observed with flat aluminum or shaped beryllium oxide filters. This machine drift, which was not associated with a rise in water phantom temperature and did not consistently correlate with estimated x-ray tube heat, could result in a significant overestimation of regional cerebral blood flow (rCBF) for a xenon/CT rCBF protocol involving 5-7 sequential scans obtained at 1-min interscan intervals.

Brain↗

Comparative study of proteins extracted form metal-induced allergic and foreign body granulomas in man.

In order to characterize proteins unique to organized epitheloid cells, proteins havebeen sequentially extracted form both foreign body and allergic granulomas in man at varoius times after intradermal injection of beryllium oxide suspension. Treitium-labeled l-tyrosine was injected intralesionally 2 weeks before excision of granulomas. Prolongedextraction with 8 m urea yeilded increases amounts of radioactivie protein form older (8-to 26-week) allergic granulomas but not from 4-to6-week-old or foreign body granulomas (consisting of mononuclear cells and phagocytes). Sephadex G-200 column chromatographyand sodium dodecyl sulfate (SDS)-polyacrylamide gel electrophoresis of the urea extractsfrom 8-week and older allergic granulomas revealed distinct readioactive protein peaks with molecular weights of approximately 172,000 to 208,000. Antisera raised to one of these proteins gave a precipitin line in agar gel diffusion with lines of identity againsturea extracts of several allergic granulomas but not against similiar extracts of foreignbody granulomas. The results suggest synthesis of distinctive high molecular weight proteins in allergic granulomas which may serve as "markers" for organized epitheloid cell granulomas as they transform from mononuclear cells.

Animals↗

Nitric oxide attenuates beryllium-induced IFNgamma responses in chronic beryllium disease: evidence for mechanisms independent of IL-18.

In chronic beryllium disease (CBD), a granulomatous lung disease characterized by hypersensitivity to beryllium salts (BE), BE challenge of bronchoalveolar lavage cells induces IFNgamma. Although nitric oxide (NO) is elevated in CBD airways, the effects of NO on CBD IFNgamma responses are unknown. Here we report that BE-stimulated IFNgamma production in CBD lavage cells was markedly reduced (74%) by the NO generator DETA NONOate. Investigation of IFNgamma-stimulatory cytokine involvement indicated that lavage cell IL-18 was significantly increased (fourfold) by BE and reduced (64%) by DETA NONOate but IL-12 was undetectable. IL-18 production was caspase-1-dependent but caspase 1 inhibition reduced IFNgamma only partially (43%). Specific antibody depletion of lavage cell IL-18 yielded marginal reduction (19%) of IFNgamma. Data are the first to show that: (1) BE stimulates IL-18 as well as IFNgamma in CBD; (2) BE cytokine responses are NO-sensitive; and (3) NO down-regulation of IFNgamma involves other sites in addition to IL-18.

Berylliosis↗

Lung clearance, translocation, and acute toxicity of arsenic, beryllium, cadmium, cobalt, lead, selenium, vanadium, and ytterbium oxides following deposition in rat lung.

Young adult rats were exposed via inhalation or intratracheal instillation to oxides of arsenic, beryllium, cadmium, cobalt, lead, selenium, vanadium, and ytterbium. Serial necropsies were performed to assess the metal content in organs at times up to several weeks after exposure. The lung clearance varied widely for these compounds, and the times to remove 50% of the initial burden ranged from 18 min for vanadium to 400 days for beryllium. Arsenic, cadmium, lead, selenium, and vanadium were initially soluble in lung, but a small fraction (1-20%) remained there over the long term. Extrapulmonary tissues often accumulated substantial amounts of the soluble oxides, and whole-body retention was often greater for compounds that were more soluble in lung. Arsenic, selenium, and vanadium translocated to carcass and bone. Arsenic, cadmium, lead, and selenium accumulated in the liver, and the kidney retained cadmium and lead. Beryllium, cobalt and ytterbium did not deposit at any extrapulmonary site in significant amounts. In general, the aqueous solubility of these compounds was a poor predictor for behavior in vivo because of their interaction with metabolic processes. Of the metal oxides tested for acute lethality following pulmonary deposition, cadmium was most toxic, followed by selenium, vanadium, and arsenic.

Animals↗

Electron dosimetry with thermally stimulated exoelectron emission (TSEE).

The dependence of exoelectron emission from BeO and Al2O3 on primary electron energy has been measured over the 200 keV to 1.2 MeV range. Two types of measurements are made, firstly with the isotopes 90Sr + 90Y, 147Pm, 204Tl, and secondly for BeO with monoenergetic electrons from an accelerator. The TSEE response of covered BeO-dosemeters (cover of 7 mg cm-2 polyethylene) is independent from electron energies in the 200 to 700 keV range for constant equivalent doses (ICRP 21). The experimental results for uncovered TSEE-dosemeters and electron fluences are in agreement with calculations performed using a Monte Carlo program developed by Seltzer and Berger. The TSEE responses for electrons and photons in equivalent dose units are very similar. A lower detection limit of 20 mu Gy (absorbed dose in air) is found for this dosemeter.

Aluminum Oxide↗

Role of lasertripsy in the management of ureteral calculi: experience with alexandrite laser system in 232 patients.

In 232 patients with ureteral stones, lasertripsy was used as primary treatment or as second-line therapy after extracorporeal shockwave lithotripsy (SWL). In all patients, a semirigid 6.5F ureteroscope or a flexible 6F ureteroscope was used. Lithotripsy was performed employing an alexandrite laser with an energy of 50 to 65 mJ. The immediate success rate was 67.5% for stones in the upper ureter, 86.1% for those in the midureter, and 94.5% for those in the distal ureter. In 16.5% of the treatments, it was necessary to insert a double-J stent. A perforation of the ureter happened in two patients (0.9%), but no laser-related complications were seen. Stone fragmentation was not dependent on stone composition or size. Using small semirigid or flexible ureteroscopes, lasertripsy of ureteral stones is a minimally invasive treatment with an insignificant complication rate. In case of midureteral stones, our results revealed a higher immediate stone-free rate than is reported in the literature after treatment by SWL, and we can therefore recommend lasertripsy as primary treatment. For upper ureteral stones, lasertripsy can be recommended as a helpful auxillary procedure. Furthermore, in cases of distal ureteral stones, lasertripsy challenges SWL as the primary treatment.

Adolescent↗

A radioluminescence study of spectral and dose characteristics of common luminophors.

Many synthetic materials are used as thermoluminescence dosemeters for the measurement of the absorbed dose from ionising radiation sources. A part of the absorbed energy leads to a prompt luminescence (radioluminescence, abbreviated RL) which dose behaviour mainly corresponds with the densitity of charge carriers in the respective traps or recombination sites. The RL reported in this study was stimulated using two 137Cs sources with activities of 3.7 MBq (spectral measurements) or 5 MBq (dosimetry studies), respectively, and was recorded steadily during stimulation. This presentation gives a comprehensive survey of the spectral and dose dependent RL properties of a number of luminescent materials like LiF:Mg,Ti, Al2O3:C, CaSO4:Dy, CaF2:Mn, Li2B4O7:Mn, BeO and ZnS:Ag. The spectral and dose dependent results were compared with thermoluminescence as well as other RL studies.

Aluminum Oxide↗

Treatment of nevus of Ota by the Q-switched alexandrite laser.

BACKGROUND: The Q-switched alexandrite laser (755 nm, 100 nanoseconds) selectively targets and destroys cutaneous pigment such as that found in dermal pigmented lesions and tattoos. The nevus of Ota is a benign dermal melanocytic lesion, which, due to its large size and periocular location, has been notoriously difficult to treat. Utilizing the principles of selective photothermolysis, the alexandrite laser could effect an excellent treatment for nevus of Ota. OBJECTIVE: To report the effectiveness of the Q-switched alexandrite laser in treating nevus of Ota. METHODS: Seven patients with nevus of Ota were treated with the Q-switched alexandrite laser (755 nm, 100 nanoseconds) with energy densities ranging from 4.75 to 7.0 J/cm2 at 8-12-week intervals. Response to therapy was evaluated through independent observation and rating of sequential photographs by two blinded observers. Histologic examinations of lesional skin biopsies before and after completion of laser treatments were performed. RESULTS: An average of two laser treatments were required to effect an average clinical improvement of 50%. Five patients showed 100% lesional clearance after an average of five treatments. No scarring, textural changes, or pigmentary side effects were observed in treated skin. Histology of laser-irradiated lesions revealed elimination of upper dermal pigmentation without epidermal disruption, and rare melanophages and pigmented spindle cells in the deep reticular dermis. No lesional recurrences were observed up to 1 year following treatment. CONCLUSION: The Q-switched alexandrite laser can effectively eliminate nevus of Ota without untoward side effects, such as scarring.

Adolescent↗