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PubMed1976

[Pathological anatomy, etiology and pathogenesis of remote sequelae of radiation dust exposure].

Thorium (Th) is one of the widely spread radioactive substances in nature, and together with other aerosols it can penetrate into the organism. The article considers relationships between various histological forms of neoplasms induced by a radioactive dust agent containing Th and the power of this etiological factor (total body dose and its power). In experiments with 3000 white rats a 150 rad dose accumulated in the lungs during 15--21 months led to an increase in the number of cases of reticulosarcoma, a 300 rad dose produced no such effects. Doses as big as 1000--2700 rad brought about multicentrical adenomas and glandular cancerous tumours against the background of pneumocirrhosis. But no reticulosarcomas of the lung were noted. Adenocarcinomas and squamous-cell carcinomas were distributed most often in the neighbourhood of accumulated radioactive dusts. The question is raised about the need for taking into account the microdistribution of energy in the lung tissue in exposure to alpha-active aerosols with subsequent microdosimetry; due account also should be made of detailed registration of forms of tumours and degree of their malignancy, which is not also observed by researchrs in radiobiological investigations.

Adenocarcinoma↗
PubMed1993

Leukemia and other related hematological disorders among Danish patients exposed to Thorotrast.

At least 60 case studies of leukemia among people exposed to chronic low-dose alpha-particle radiation from injections with the radiographic contrast medium Thorotrast and 115 cases from follow-up studies have been described in the literature. In the present study, malignant hematological diseases among 1003 Danish patients injected during 1935-1947 and followed to 1992 accruing 20,433 person-years were assessed and available histopathological specimens revised. The mean cumulative bone marrow alpha-particle radiation dose (1.34 Gy) was estimated from records of the amount of Thorotrast injected (mean 18.7 ml). Sixteen cases of acute myelogenous leukemia (AML) and seven cases of myelodysplastic syndrome (MDS) were diagnosed 8-40 years after injection, the cumulative frequency reaching 7.6%. No significant relationship was seen between the cumulative frequency of AML + MDS and the age at injection, gender, or amount of Thorotrast injected, but a multivariate analysis described data best by a model with the bone marrow dose and the power of the attained age. The risk estimate for AML + MDS was 173 cases/10(4) persons per Gy. If also considering cases of acute lymphocytic leukemia (1), chronic myelogenous leukemia (3), non-Hodgkins lymphoma (4), and multiple myeloma (2), the risk estimate became 248 cases/10(4) persons per Gy. It is suggested that RBE of alpha particles from thorium may be lower than 20.

Adolescent↗
PubMed1996

Intermittent diplopia and strabismus caused by ocular neuromyotonia.

PURPOSE: Two cases illustrate the symptoms, signs, etiologies, and treatment of ocular neuromyotonia (ONM). METHODS: The histories, neuroradiologic tests, and/or biopsy revealed the etiologies of ONM in both patients. Clinical observations, videotaping, and electronic eye movement recordings documented the eye movements. RESULTS: A 72-year-old man with chronic arachnoiditis following myelography with thorium dioxide (Thorotrast) developed intermittent diplopia and a partial right third nerve palsy. Left gaze induced spasm of the right medial rectus. Right gaze produced right lateral rectus spasm. A 66-year-old woman, who had radiation treatment for a pituitary tumor and acromegaly, had intermittent spasm of the left medial rectus muscle and left esotropia. The episodes occurred spontaneously and were induced by right gaze. A left internuclear ophthalmoplegia was also found. Carbamazepine (Tegretol) abolished the ONM in both patients. CONCLUSIONS: Although ONM is an unusual cause of intermittent diplopia and strabismus, its distinctive clinical features identify it. Injury to the peripheral cranial nerves probably leads to segmental demyelination, axonal hyperexcitability, and a self-perpetuating, reverberating circuit, which causes spasms of the extraocular muscles.

Aged↗
PubMed1976

Residual splenic function in the presence of thorotrast-associated hepatic tumor: case report.

A 50-year-old man had received intravenous colloidal thorium dioxide (thorotrast) 27 years previously. Scintiscans with both 99mTc-sulfur colloid and 131I-rose bengal revealed an extensive intrahepatic defect. At operation, the lesion proved to be an infiltrating hemangiosarcoma. The spleen was small but the chronic internal radiation of the spleen had not completely destroyed the function of radiocolloid uptake. Review of the literature disclosed other cases in which the spleen was still capable of accumulating radiocolloid some years after thorotrast administration. In at least one other instance, radiocolloid uptake was not accompanied by splenic ability to clear Howell-Jolly bodies: a disassociation of splenic functions. The effects of the internal radiation dose to the spleen from thorotrast are discussed and compared with the effects of external radiation. The discrepancy between the effects of the two doses may be related to the high relative biologic effectiveness of the alpha rays from thorotrast compared with gamma-radiation, to nonuniformity of distribution, and to the effects of reticuloendothelial blockade.

Colloids↗
PubMed1981

Cerebral abscess in children.

We reviewed 94 consecutive episodes of pyogenic brain abscess seen at Children's Hospital Medical Center, Boston, between 1945 and 1980. After 1970, the mortality as reduced from 36% to 14%. Predisposing factors included congenital heart disease, otitic and sinus infections, closed head injuries, and cystic fibrosis. There were seven patients younger than 5 months of age. In one patient with Fallot's tetralogy, an abscess recurred at the site of retained thorium dioxide (Thorotrast) after an 11-year interval. The continuing substantial mortality is attributed to the presence of coma at the time of treatment, hemorrhagic complications of tapping abscesses, and the location of abscesses in deep brain structures. The early detection and successful treatment of brain abscesses in children remains a clinical challenge.

Adolescent↗
PubMedDate not supplied

Measurement of the concentration of radon gas in the Toirano's caves (Liguria).

The radioactive gas radon, intermediate term of the decay series of uranium and thorium, is the main contamination source of underground places and may be a risk for high concentration and long exposure time. European and Italian law requires radon concentration to be measured in workplaces and, if the "action level" of 500 Bq/m3 is reached, proper actions must be made in order to decrease the dose commitment. Considering natural showcaves or artificial cavities open to public, the exposition of the visitors is frequently small, due to the short residence time, but accompanying people, remaining underground for long time, may be subject to appreciable dose and the radon concentration should therefore be monitored. The high humidity in natural caves may impair the use of some measuring devices. Therefore, different detection methods were compared (ZnS scintillation counters, E-PERM electret ionisation chambers, cellulose nitrate alpha-track dosimeters) to select the best procedure for long-term investigation. The LR-115 (Kodak) alpha-track dosimeters were insensitive to humidity and permitted to monitor a great number of places at the same time. Measurements have been carried out in the speleological and archaeological site of the Toirano's Caves (Savona, Liguria, Italy) and several points were monitored for two years. Radon concentration strongly depends on the site and changes during the year, due to the difference between internal and external temperature. The maximum dose commitment during the visitors tour, considering the average yearly value of radon concentration, was found to be between 1.5 and 4 microSv. It was found that no risk exists for visitors, but the evaluation of the dose absorbed by the guides and their classification according to the radiation protection law requires a complete monitoring of the average yearly concentration of radon and of the total time spent by each worker into the cave.

Air Pollutants, Radioactive↗
PubMed1981

Periarterial macrophage sheaths (ellipsoids) in cat spleen--an electron microscope study.

Periarterial macrophage sheaths (PAMS), a term we introduce to replace "ellipsoids," surround arterial capillaries in the red pulp of the spleen and are major sites for clearance of blood-borne particles. PAMS and their arterial capillaries in cat spleens in various states of congestion and contraction were studied by transmission electron microscopy. Thorotrast, a colloidal suspension of thorium dioxide, was injected to label macrophages. A PAMS consisted of a fine meshwork of reticular cells and reticular fibers which held macrophages and formed a cylindrical sheath around an arterial capillary lying in its longitudinal axis. Some PAMS were spongy due to loosening of cell associations by plasma infiltration; others were tightly compressed. Blood cells were both free in the interstices of the PAMS and attached to macrophages. Reticular cells formed a closely applied but incomplete layer adventitial to the arterial capillary and extended branches which contributed to the meshwork. Small villous processes on the major branches of reticular cells approached each other, sometimes forming intercellular junctions, and fit into complementary indentations in the surfaces of macrophages and endothelial cells. Thin filaments within reticular cells filled the villous processes and formed a border beneath the plasmalemma; intermediate filaments ran through the centers of the branches. Reticular fibers lay between reticular cells. Basement membrane fabricated of the same material as reticular fibers lay between the endothelium and reticular cells. Macrophages contained Thorotrast and abundant debris of phagocytized cells and were joined by extensive interdigitation of micropseudopodia. Endothelial cells were long rods which lay parallel and were joined along their bases by interdigitating lateral processes. Intercellular junctions were present at some points, but at others lateral processes were everted to form open interendothelial slits through which blood cells could pass. Endothelial cells possessed great numbers of randomly oriented intermediate filaments and small patches of thin filaments scattered along the basal plasmalemma and in lateral processes. Thin filaments may function to attach cells to one another and to the basement membrane and may assist in closing interendothelial slits. We believe that the endothelium responds to changes in arterial blood pressure and blood flow. It stretches to allow dilatation and recoils, probably due to the intermediate filaments, squeezing blood cells through interendothelial slits.

Animals↗
PubMed1984

Glycogen autophagosomes in polymorphonuclear leukocytes induced by rickettsiae.

Guinea pig polymorphonuclear leukocytes (PMNs), rich in glycogen granules, were collected from sodium-caseinate-induced peritoneal exudate. When these cells were incubated with rickettsiae, many microorganisms were phagocytized within 30 minutes at 35 degrees C and vacuoles up to 5 microns in diameter containing glycogen granules were present. Contained within these vacuoles were phagocytized extracellular material and a dense, lysosomelike substance that was acid phosphatase positive. These vacuoles, which were interpreted to be autophagosomes, were absent from PMNs that had not been stimulated with microorganisms. The number of rickettsiae in the PMN did not appear to be related to the number of autophagosomes. About 8% and 80% of thin-sectioned profiles of PMNs contained these vacuoles after 30 minutes and 4 hours incubation, respectively. After 4 hours, the PMNs contained multiple autophagosomes. Almost all of the glycogen granules were in autophagosomes in some of the cells. In some PMNs, discontinuous membranes encircled some glycogen. When PMNs were initially incubated with thorium dioxide and ferritin, and extensively washed prior to incubation with rickettsiae, glycogen was found surrounded by flattened secondary lysosomes containing the dense tracers. Some autophagosomes also contained the electron-dense tracers. These results suggest that rickettsiae induce the rapid formation of glycogen-containing autophagosomes in guinea pig peritoneal PMNs in vitro.

Animals↗
PubMed2005

High-electron-density C6H6 units: stable ten-pi-electron benzene complexes.

The first stable benzene molecule with ten pi electrons is predicted. Stability is achieved through barium atoms acting as an electron-donating "matrix" to C6H6 in the inverted sandwich complex [Ba2(C6H6)]. The bis(barium)benzene complex has been computed at the density functional level of theory by using the hybrid functional mPW1PW91. Ab initio calculations were performed by using the coupled-cluster expansion, CCSD(T). Nucleus independent chemical shift (NICS) indices imply distinct aromatic character in the benzene ring of bis(barium)benzene. The D6h-symmetric structure with a 1A(1g) electronic ground state represents a thermochemically stable, aromatic benzene molecule with four excess pi electrons, stabilised by two barium ions. A possible molecular wire, built up from Ba end-capped thorium-benzene "sandwiches", is discussed.

Journal Article↗
PubMedDate not supplied

Mass spectrometry and isotopes: a century of research and discussion.

In 1815, the British physician William Prout had advanced the theory that the molecular masses of elements were multiples of the mass of hydrogen. This "whole number rule" (and especially deviations from it) played an important role in the discussion whether elements could be mixtures of isotopes. F. Soddy's discovery (1910) that lead obtained by decay of uranium and of thorium differed in mass was considered a peculiarity of radioactive materials. The question of the existence of isotopes came up when the instruments developed by J.J. Thomson and by W. Wien to study cathode and canal rays by deflection in electric and magnetic fields were steadily improved. In 1913, Thomson mentioned a weak line at mass 22 accompanying the expected one at mass 20 when he analyzed the mass spectrum of neon. Subsequently Aston obtained the mass spectrum of chlorine with masses at 35 and 37. Still in 1921, Thomson objected heavily to the idea of isotopes. The isotope problem was finally settled, but more accurate mass measurements showed that even isotopic weights differed to some extent from the whole numbers. Based on earlier ideas of P. Langevin and J.-L. Costa, F.W. Aston and A.J. Dempster developed the idea of packing fractions and mass defects due to the transformation of a portion of the matter comprising the atomic nucleus into energy. While the determination of the exact isotopic masses had improved over the years, the accurate determination of isotopic abundances remained a problem as long as photographic recording was used. Here especially A.O. Nier pioneered using dual collectors and compensation measurements. This was the prerequisite for the discovery that isotopic ratios varied somewhat in nature. M. Dole discovered the fractionation of oxygen isotopes by photosynthesis and respiration. Today 13C/12C-ratios are employed to detect adulterations of food and in doping analysis, and 14C/13C-ratios obtained by accelerator mass spectrometry are used for dating historical objects, just to give some examples.

Biomedical Research↗
PubMed1998

Trace metals in urine of United States residents: reference range concentrations.

We measured 13 metals in the urine of 496 United States residents to establish reference range concentrations using inductively coupled argon plasma mass spectrometry and Zeeman graphite furnace atomic absorption spectrometry. We frequently found 8 of these analytes at detectable concentrations in urine specimens: molybdenum (in 99.8%); lead (98.8%); tin (89%); thallium (77%); antimony (73.5%); manganese (73%); cesium (71%); tungsten (70%); and platinum (69.7%). The 95th percentile concentration for molybdenum was 168 micrograms/L; concentrations ranged up to 688 micrograms/L. Lead concentrations ranged up to 67 micrograms/L, and the 95th upper percentile was 6.4 micrograms/L. Tin had 95th upper percentile of 20.1 micrograms/L. Other analytes measured at detectable concentrations included barium (in 67% of the specimens); beryllium (67%); chromium (54%); thorium (44%); and cobalt (43%). In almost every case, the 95th upper percentiles of these analytes were less than 15 micrograms/L.

Adult↗
PubMed1998

Structural Environment of Uranium (VI) and Europium (III) Species Sorbed onto Phosphate Surfaces: XPS and Optical Spectroscopy Studies.

In order to characterize the structure of the surface complexes formed by interaction between uranyl and europium (III) ions and the surface of solid matrices, optical and X-ray photoelectron spectroscopies experiments on uranyl/europium loaded phosphate solids (Th4P2O7(PO4)4, ZrP2O7, and Zr2O(PO4)2) have been performed. The use of complimentary spectroscopic techniques allows an identification of the sorption mechanism and a structural characterization of the sorption sites and the sorbed species on phosphate surfaces. The samples were prepared from aqueous uranyl or europium solutions in the pH range from 1.5 to 6.0. The surface coverage was varied from 1 to 40 % of a monolayer. The differences between the emission spectra of europium ions either sorbed on the surface of phosphate samples or doped inside the solid unambiguously indicates that these sorbed ions are exclusively located on the surface and that they do not migrate inside the matrix, which shows clearly that surface complexation is involved during the sorption process. The U4f XPS spectrum of uranyl ions sorbed on zirconium diphosphate exhibits only one component, while the spectrum corresponding to uranium on thorium matrix shows two different unresolved peaks attributed to two different chemical environments. These results, corroborated by the uranyl emission spectra and the associated decay times and those obtained by optical spectroscopy of europium sorbed on the same solids, have been interpreted in terms of two sorption sites probably formed by the oxygens of the PO4 and P2O7 surface groups. Copyright 1998 Academic Press.

Journal Article↗
PubMed1999

Measurement and Modeling of Th Sorption onto TiO(2).

The sorption and desorption of Th onto TiO(2) (10 g/L) was studied as a function of pH (1-11), ionic strength (0.005-0.1 M NaCl, NaClO(4)), thorium concentration (from 1 x 10(-9) to 3 x 10(-2) M), and carbonate concentration (up to 10(-2) M) using (234)Th tracer. The results indicate the reversible formation of an inner sphere complex with a strong pH dependence. No effect of the carbonate on sorption could be measured in the pH range investigated (5-10.5). The data were fitted with five different conceptual models (constant capacitance, diffuse layer, Stern, triple layer, and a nonelectrostatic model) using FITEQL. Different hydroxy complex surface reactions were tried, one at a time, varying the site density (1-12 sites/nm(2)). The reaction that provided the best fit depended strongly on the surface site density and the model used. To be able to fit a reaction to the pH-dependent data with the compact layer models, the effect of the electrostatic term had to be decreased by decreasing the site density below 5 sites/nm(2). None of the electrostatic models could be used to fit all of the isotherm data. The nonelectrostatic model could be used to reasonably fit both the pH-dependent and isotherm data. Copyright 1999 Academic Press.

Journal Article↗
PubMed1989

On the origin of lipofuscin; the iron content of residual bodies, and the relation of these organelles to the lysosomal vacuome. A study on cultured human glial cells.

Cultured human glial cells constitute a suitable model system for the study of lipofuscinogenesis in vitro. These cells, although not post-mitotic, can be kept for several months in stable monolayers due to their display of very pronounced density-dependent inhibition of cell growth. Residual bodies, or lipofuscin pigment granules, accumulate over time in this "pseudo" post-mitotic cell system. I. In early dense cultures, exposed to purified rat liver mitochondriae, it was possible to follow the uptake of mitochondriae and their degradation, which was found to be incomplete and result in the formation of numerous residual bodies containing lipofuscin-type material. It was concluded that incomplete degradation of mitochondriae may be an important origin of lipofuscin. II. Dense, older cultures exposed to electron dense marker particles (colloidal thorium dioxide) accumulated these markers within endosomes, and later in secondary lysosomes of various types, including residual bodies. It was concluded that residual bodies constitute an integral part of the lysosomal vacuome system. III. Phase III glial cells were cultured on formvar-coated gold EM-grids and studied by whole cell transmission electron microscopy using TEM and STEM techniques in combination with energy dispersive X-ray microanalysis. It was found that residual bodies contained iron. This fact was taken as a further indication that lipofuscin has its origin in autophagocytosed mitochondriae and ER-material rich in metallo-enzymes. Due to their high concentration of iron, residual bodies may constitute unstable structures within the cells. Since iron is a well known catalyst of various peroxidative processes, the surrounding lysosomal membrane might be damaged, e.g. by oxidative stress, with risk for leakage of degradative lysosomal enzymes into the cell sap.

Cell Line↗
PubMed1976

Effect of cholecystokinin-pancreozymin (CCK-PZ) on glycoprotein secretion from mouse gallbladder epithelium: an ultrastructural and cytochemical study.

Structural changes in the gallbladder epithelial cells of the mouse were studied following in vivo and in vitro stimulation of the gallbladder with the gastrointestinal hormone cholecystokinin-pancreozymin (CCK-PZ). Signs of increased secretory activity were observed within the first 2-3 min after hormone administration. At the ultrastructural level, best visualized with the PA-CrA-silver technique, granule discharge was observed, as was an overall increase in size of the granules. After prolonged in vitro incubation or repeated in vivo stimulation, there was an almost total depletion of secretory granules. This phenomenon is accompanied by an enhanced uptake of extracellular thorium dioxide by endocytotic vesicles at the apical cell surface. An exocytosis-endocytosis coupling mechanism may be important for membrane conservation in the gallbladder epithelial cells. The findings establish that the hormone CCK-PZ stimulates the secretion of glycoproteins from the mouse gallbladder epithelium.

Animals↗
PubMed1977

Fine structure of rabbit ear chondrocytes in vitro and after autotransplantation.

Chondrocytes were isolated enzymatically from rabbit ear cartilage, grown in vitro or as autotransplants for 1, 2 or 5 weeks and then examined by transmission electron microscopy. A confluent monolayer formed rapidly in vitro and the cells later grew in multiple overlapping layers, producing thick sheets of cartilaginous tissue. The cells retained a normal structure throughout the period of observation and, like the chondrocytes in intact cartilage, showed numerous microfilaments, and extensive granular endoplasmic reticulum and a prominent Golgi complex. Large amounts of intercellular matrix were laid down in vitro consisting of thin collagen fibrils, small rounded or polygonal granules believed to represent proteoglycans and patches and fibres of elastin. Chondrocytes in intramuscular autotransplants reconstituted an elastic cartilage. The exogenous origin of the cells in the transplants was verified by labeling of the lysosomes by exposure of the cells to colloidal thorium dioxide particles prior to injection. Structurally, the cells and the matrix of the transplants conformed to the above description. Accumulations of elastin-like material were sometimes observed in the Golgi vacuoles of the cells. Extracellularly, such conglomerates aggregated in connection with bundles of microfibrils, building up mature elastic fibres with a dense amorphous structure. The culture and transplant systems characterized here provide suitable experimental models for studies on development, growth and aging of elastic cartilage, including various aspects of the formation and turnover of elastic fibres and other macromolecular matrix components.

Animals↗
PubMed1984

Influence of proteolytic enzymes and calcium-binding agents on nuclear and cell surface topography.

Transmission electron microscopy was used to study the effects of proteolytic enzymes (collagenase, trypsin, clostripain), the calcium chelator ethyleneglycol-bis-(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA), and the calcium ionophore A 23187 on substrate adhesion and fine structure of chondrocytes and fibroblasts. Monolayer-cultured cells responded to treatment with the proteolytic enzymes followed by EGTA or A 23187 by rounding and detaching from the substrate. This was accompanied by the formation of a microvillous surface, deep nuclear folds, and numerous cytoplasmic vacuoles. Labeling experiments with colloidal thorium dioxide indicated that the vacuoles were formed by endocytosis and fusion of endocytic vesicles with preexisting lysosomes. To a variable extent, similar changes were produced by trypsin or EGTA alone. The cells regained their normal fine structure after withdrawal of the reagents and when seeded onto a substrate. In suspension culture, recovery was incomplete; the cells retained a rounded shape and an increased number of cytoplasmic vacuoles. The results suggest that changes in plasma membrane composition and its permeability to calcium represent the primary signal for cell rounding and detachment. The cellular mechanisms responsible for the associated folding of the nuclear envelope and the cell surface remain unidentified. Nevertheless, this is believed to represent a means of handling of excess membrane during sudden transition from a flattened to a rounded shape. Membrane stored in folds and vacuoles is reutilized when the cells reattach and spread out on a substrate.

Animals↗
PubMed1977

Pressure effects on the distribution of extracellular materials in the rhesus monkey outflow apparatus.

An electron-microscopic investigation was conducted to determine the distribution of extracellular materials in the rhesus monkey outflow apparatus at various maintained levels of intraocular pressure. Intraocular pressure was maintained at either 0,8, 15, 22, 30, or 50 mm Hg, by an intracameral needle attached to a reservoir system for a period of 1 h. Thereafter the eyes were fixed either by intracameral perfusion of glutaraldehyde at the appropriate pressure level, or by carotid perfusion of the fixative, or by rapid enucleation and immersion fixation. The electron-dense cationic stains, colloidal thorium and colloidal iron were used to indicate the presence of carbohydrate-rich extracellular materials in the drainage tissues. In the control tissue (15 mm Hg), heavy concentrations of stain were detected within the cores of the trabeculae and in the extracellular spaces of the endothelial meshwork. With pressure elevation there was a progressive decrease in the surface staining on the meshwork cells, an increase in staining intensity within the trabecular cores, and a 'washout' of extracellular materials from the spaces of the endothelial meshwork. The washout was thought to occur via giant vacuoles up to 30 mm Hg, but at 50 mm Hg the process was accelerated by loss of association between the cells of the canal endothelial monolayer. Over the entire pressure range 0 to 50 mm Hg, there was an increase in the staining on the apical surface of the canal endothelium which was associated with a decrease in the incidence of micropinosomes.

Animals↗