Risk of thyroid cancer after exposure to 131I in childhood.
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BACKGROUND: After the Chernobyl nuclear power plant accident in April 1986, a large increase in the incidence of childhood thyroid cancer was reported in contaminated areas. Most of the radiation exposure to the thyroid was from iodine isotopes, especially 131I. We carried out a population-based case-control study of thyroid cancer in Belarus and the Russian Federation to evaluate the risk of thyroid cancer after exposure to radioactive iodine in childhood and to investigate environmental and host factors that may modify this risk. METHODS: We studied 276 case patients with thyroid cancer through 1998 and 1300 matched control subjects, all aged younger than 15 years at the time of the accident. Individual doses were estimated for each subject based on their whereabouts and dietary habits at the time of the accident and in following days, weeks, and years; their likely stable iodine status at the time of the accident was also evaluated. Data were analyzed by conditional logistic regression using several different models. All statistical tests were two-sided. RESULTS: A strong dose-response relationship was observed between radiation dose to the thyroid received in childhood and thyroid cancer risk (P<.001). For a dose of 1 Gy, the estimated odds ratio of thyroid cancer varied from 5.5 (95% confidence interval [CI] = 3.1 to 9.5) to 8.4 (95% CI = 4.1 to 17.3), depending on the risk model. A linear dose-response relationship was observed up to 1.5-2 Gy. The risk of radiation-related thyroid cancer was three times higher in iodine-deficient areas (relative risk [RR]= 3.2, 95% CI = 1.9 to 5.5) than elsewhere. Administration of potassium iodide as a dietary supplement reduced this risk of radiation-related thyroid cancer by a factor of 3 (RR = 0.34, 95% CI = 0.1 to 0.9, for consumption of potassium iodide versus no consumption). CONCLUSION: Exposure to (131)I in childhood is associated with an increased risk of thyroid cancer. Both iodine deficiency and iodine supplementation appear to modify this risk. These results have important public health implications: stable iodine supplementation in iodine-deficient populations may substantially reduce the risk of thyroid cancer related to radioactive iodines in case of exposure to radioactive iodines in childhood that may occur after radiation accidents or during medical diagnostic and therapeutic procedures. (+info)
Yolk granule tethering: a role in cell resealing and identification of several protein components.
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Homotypic fusion among echinoderm egg yolk granules has previously been reconstituted in vitro, and shown to be a rapid, Ca2+-triggered reaction that can produce extremely large (>10 microm diameter) fusion products. We here show that, prior to Ca2+-triggered fusion, yolk granules in vitro, if isolated in an appropriate buffer, became tethered to one another, forming large aggregates of more than 100 granules. Granule washing with mildly chaotropic salt abolished this tethering reaction, and prevented Ca2+-triggered formation of the large fusion products characteristic of tethered granules. Protein factors present in the wash restored tethering activity and these factors could be substantially enriched by anion exchange chromatography. The enriched fraction behaved under native conditions as a high molecular weight (approximately 670 kDa), multisubunit complex of at least seven proteins. Monoclonal antibodies directed against this complex of proteins were capable of immunodepleting tethering activity, confirming the role of the complex in granule tethering. These antibodies selectively stained the surface of yolk granules in the intact egg. We therefore propose a new role for tethering: it can promote the formation of large vesicular fusion products, such as those required for successful resealing. We have, moreover, identified several proteins that may be critical to this tethering mechanism. (+info)
Mycoplasma pneumoniae cytadherence phase-variable protein HMW3 is a component of the attachment organelle.
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The subcellular location of the phase-variable cytadherence-accessory protein HMW3 in Mycoplasma pneumoniae has been examined by biochemical and immunoelectron microscopic techniques. Analysis by Western blot (immunoblot) with HMW3-specific antiserum established the presence of this protein within the M. pneumoniae Triton X-100-insoluble fraction or triton shell. Immunogold labeling of Triton-extracted mycoplasmas with affinity-purified antibodies localized HMW3 to the terminal knob on the rodlike extensions of the triton shell, a location that would correspond to the adherence organelle in whole mycoplasmas. Treatment of triton shells with KI resulted in the selective removal of the adherence-accessory proteins HMW1 to HMW4. Analysis of these triton shells by transmission electron microscopy revealed dramatic ultrastructural changes in the filamentous network and core structure. Immunogold labeling of KI-extracted shells reflected the removal of HMW3 from the disrupted tip structure. An examination of ultrathin sections of wild-type cells by transmission electron microscopy following labeling with HMW3-specific antibodies provided further evidence for the nonrandom distribution of HMW3 and its localization to the terminal portion of filamentous cell extensions. Most colloidal gold molecules were associated with the cell interior, but limited peripheral labeling of the terminal region was also observed. Postfixation antibody labeling of whole cells suggested limited exposure of HMW3 on the mycoplasma surface at the tip structure. However, prefixation antibody labeling failed to indicate surface exposure, raising some uncertainty regarding the relationship of HMW3 with the mycoplasma membrane. (+info)
Activation of the endothelial store-operated ISOC Ca2+ channel requires interaction of protein 4.1 with TRPC4.
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Store-operated calcium (SOC) entry represents the principal Ca2+ entry pathway into nonexcitable cells. Despite intensive investigation, mechanisms underlying activation of SOC entry have remained elusive. The endothelial ISOC channel is a Ca2+-selective SOC entry channel to which the transient receptor potential (TRP) proteins TRPC1 and TRPC4 contribute subunits. Activation of ISOC is specifically regulated by the spectrin-actin membrane skeleton; however, the nature of coupling between the ISOC channel and membrane skeleton is unknown. Here we demonstrate that protein 4.1 is an essential component of the ISOC channel gating mechanism. Protein 4.1 interacts with TRPC4 and the membrane skeleton. Deletion of the protein 4.1 binding domain on TRPC4 or peptide competition to the protein 4.1 binding domain prevents ISOC activation. These findings reveal that interaction of protein 4.1 with TRPC4 is required for activation of the endothelial ISOC channel. (+info)
In southern Brazil, cattle are affected by a disease known locally as Lechiguana and characterized by large subcutaneous swellings. Eighteen cases were examined clinically; 17 of the cattle had a single swelling, and one had two swellings. In 14 of the 18 cases, the swellings were located over the scapula and adjacent regions. The subcutaneous masses reached maximum dimensions of 45 x 50 cm, with heights above the skin surface of 5-25 cm. Growth was rapid, often taking place in 15 to 60 days. Histologically, all lesions were focal proliferative fibrogranulomatous panniculitis and consisted of focal proliferation of fibrous tissue that was infiltrated by plasma cells, eosinophils, lymphocytes, and sometimes neutrophils. An eosinophilic lymphangitis was also present, which sometimes resulted in the destruction of the lymphatics and the formation of eosinophilic microabscesses. Small granulomas, sometimes containing radiating clubs, and Splendore-Hoeppli material were present in the regional lymph node. Pasteurella granulomatis was isolated from the subcutaneous masses of 14 of the 18 natural cases. All 11 of these cases recovered following treatment with 3 g of chloramphenicol daily for 5 days. Untreated animals died. Because the area of anatomic distribution is similar to that infested by Dermatobia hominis, we postulate that this insect may transmit the causative agent. In one steer, a subcutaneous injection of P. granulomatis caused a large subcutaneous swelling consisting of interlacing bundles of collagen infiltrated by neutrophils, eosinophils, and some lymphocytes. Microabscesses, but not lymphangitis and granulomas, were detected. In all 11 cattle inoculated either intramuscularly or subcutaneously with P. granulomatis, purulent abscesses were produced at the sites of the injection, and P. granulomatis was recovered from all lesions. (+info)
Quantitative analysis of irbesartan in commercial dosage forms by kinetic spectrophotometry.
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The objective of this work is to develop a new kinetic spectrophotometric method for the determination of irbesartan in pharmaceutical formulations. The method is based on the reaction of carboxylic acid group of the oxidized irbesartan with a mixture of potassium iodate (KIO(3)) and iodide (KI) to form yellow colored triiodide ions in aqueous medium at 30+/-1 degrees C. The reaction is followed spectrophotometrically by measuring the rate of change of absorbance at 352 nm. The initial-rate and fixed-time (DeltaA) methods are adopted for constructing the calibration curves, which were found to be linear over the concentration ranges of 10.0-60.0 and 7.5-60.0 microg ml(-1) respectively. The regression analysis of calibration data yielded the linear equations: rate=-2.138 x 10(-6)+1.058 x 10(-4)C and DeltaA=-3.75 x 10(-3)+3.25 x 10(-3)C for initial rate and fixed time (DeltaA) methods, respectively. The limit of detection for initial rate and fixed time methods are 0.21 and 2.40 mug ml(-1), respectively. The various activation parameters such as E(a), DeltaH++, DeltaS++ and DeltaG++ are also calculated for the reaction and found to be 70.95+/-0.43 kJ mol(-1), 68.48+/-0.21 kJ mol(-1), 16.54+/-0.24 J K(-1) mol(-1) and -4.94+/-0.07 kJ mol(-1), respectively. The proposed methods are optimized and validated as per the guidelines of International Conference on Harmonisation (U.S.A.). The point and interval hypothesis tests have been performed which indicate that there is no significant difference between the proposed methods and the reference method. The methods have been successfully applied to the determination of irbesartan in commercial dosage forms. (+info)
Rhinoentomophthoromycosis.
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A sixty year old patient presented with a slowly progressive swelling of the nose, of one year duration, suggesting a clinical diagnosis of subcutaneous zygomycosis. On investigation, the tissue fungal culture grew Conidiobolus coronatus, confirming the diagnosis as rhinoentomophthoromycosis. He was treated with a combination of oral fluconazole and oral potassium iodide for a total period of 5 months. His symptoms subsided completely. Serial CT scanning of paranasal sinuses showed the gradual resolution of the swelling, in response to the treatment. Early detection of the disease and combination therapy gave rapid and good results. This is the first case of its kind to be reported from Kerala, the southern state of India. (+info)
Quantitation of myosin light chain phosphorylation in intact smooth muscle.
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An improved method for quantitating the extent of myosin light chain (P-LC) phosphorylation in small smooth muscle samples is described. Native myosin was isolated from other cellular proteins in a crude supernatant fraction prepared from a few milligrams of bovine tracheal smooth muscle by polyacrylamide gel electrophoresis (PAGE) in the presence of sodium pyrophosphate (PPi). When potassium iodide (KI, 0.6 M) was added to the crude supernatant fraction, myosin migrated into the gels during electrophoresis. Without adding KI, myosin remained at the top of the gel so that the myosin content in the gel was 20 times less than in the presence of KI. After the PPi-PAGE, myosin was subjected to isoelectric focusing (IEF) on polyacrylamide slab gels to separate the phosphorylated from the nonphosphorylated forms of the P-LC. The extent of P-LC phosphorylation was quantitated after densitometric scanning of silver-stained IEF gels. Examination of the temporal changes in carbachol-induced contraction and P-LC phosphorylation in tracheal smooth muscle strips exhibited a relatively transient change in the P-LC phosphorylation as shown in other smooth muscle preparations. This procedure is applicable to investigations on the role of Ca2+.calmodulin-induced activation of myosin light chain kinase and phosphorylation of smooth muscle myosin. (+info)