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PubMed1998

[The 13C-urea breath test in Helicobacter pylori gastric infection in children].

Helicobacter pylori gastric infection in children is a public health problem. Classical diagnostic tools such as endoscopy are excessively invasive in the usual clinical context. Serology at this age has multiple drawbacks. The urea-13C breath test seems today the most appropriate alternative method. The principle of the test relies upon the indirect detection of H pylori through its high urease activity. The test uses a stable (ie, non radioactive) isotope, which allows its repeated use. The main indications are the detection and the follow-up of H pylori infection.

Adult↗
PubMed1999

The influence of low doses 131I-induced maternal hypothyroidism on the development of rat embryos.

The aim of our research was to create and verify a model for studying the effects of a low dose of 131I and 131I-induced maternal hypothyroidism on the development of the embryo's thyroid gland and brain. The given dose (150 microCi) corresponds to the absorbed dose of 0.5 Gy. This dose is similar to that dose received by large numbers of the population of the C.I.S. regions polluted by radioactive isotopes of iodine as a result of the Chernobyl accident in 1985. Thirty-five female Wistar rats and their 168 newborn pups were used for observation. The females were divided into a control group and four experimental groups (each distinguished by the time of 131I injection: group I - no less than 12 days before mating; groups II, III and IV - on 5th, 10th and 16th days of gestation, respectively). In all the experimental female groups the incorporate dose of 131I led to hypothyroidism accompanied by a 43% reduction in the thyroxin level and by a nearly 8-fold increase in the TSH level. However, the influence of maternal hypothyroidism on the development of the thyroid gland and brain of embryos depends on the time when 131I took effect. There is a reduction in the weight of the newborns' brain and thyroid gland, total body mass. The hormonal status of the newborns' thyroid gland also changes. The proposed model will allow us to study many aspects of induced changes in the brain and thyroid gland of the embryos which develop under conditions of maternal hypothyroidism resulting from a low dose of 131I, administered at the critical times of development.

Animals↗
PubMed2002

Protein transduction technology.

Intracellular delivery of macromolecules remains problematic because of the bioavailability restriction imposed by the cell membrane. Recent studies on protein transduction domains have circumvented this barrier, however, and have resulted in the delivery of peptides, full-length proteins, iron beads, liposomes, and radioactive isotopes into cells in culture and animal models in vivo.

Animals↗
PubMed2003

An adjustable release rate linking strategy for cytotoxin-peptide conjugates.

Peptide hormones are often rapidly internalized after binding to and activation of their receptors which are sometimes over-expressed on tumor cells. Thus, peptide ligands are increasingly being utilized for specific tumor cell targeting and internalization of radioactive isotopes for tumor imaging and for specifically delivering and internalizing cytotoxic moieties. Here, we describe a new carbamate linker system containing a series of built-in nucleophile assisted releasing (BINAR) groups which enable the 'fine-tuning' of intracellular cleavage rates of free cytotoxic agents containing reactive OH groups. Release rates were found to fit well with the chemical model and several conjugates of camptothecin and one of combretastatin were shown to have potent cytotoxic effects on cultures of human neuroblastoma IMR-32 cells which over-express somatostatin receptors.

Amino Acid Sequence↗
PubMedDate not supplied

High-power CW LINAC for food irradiation.

The continuing high profile food poisoning incidents are beginning to attract food processors using electron and gamma-ray sterilization technologies. The present method of choice uses radioactive isotopes but high-power electron particle accelerators are proving an increasingly attractive alternative. We are developing a family of compact industrial continuous wave linear accelerators which produce electrons with energies from 600 keV in increments of approximately 600 keV and with beam power of 30 kW increasing in increments of 30 kW. Here, we describe the performance of our 1st section that accelerates 15 keV gun electrons to relativistic energies and then we sketch the design of the less demanding subsequent sections that we are now constructing.

Electrons↗
PubMed2002

A simplified technique to determine the self-absorption correction for sediment samples.

A self-absorption correction factor is required for the determination of the radioactive isotope concentration in sediment samples at the low-energy region. A simplified technique for this correction factor for a well-type HP germanium detector is described. This correction is especially important when the ratio between the sample density and reference sample density (rho(sa.)/rho(re)) is greater than approximately 1.4.

Journal Article↗
PubMed2003

New treatment modalities for end-stage emphysema.

The concept of nonresectional LVRS appears to be highly promising. Several strategies and approaches are currently available; however, the investigations to date are still just studies, and there remain many unanswered questions. No doubt new modifications and improvements in design will occur and these devices will continue to evolve. Appropriate patient selection is, as always, the key to good outcome. The studies so far have included only patients who have heterogenous disease; whether or not the procedures can be helpful for patients who have homogenous distribution of emphysema remains to be seen. Radioactive isotope scans are currently being used in an attempt to identify patients who have significant collateral flow, and these scans might eventually be useful in selecting patients who are unlikely to benefit from this approach. The preliminary data remain encouraging and suggest that a larger study with long-term follow-up care is warranted.

Biocompatible Materials↗
PubMedDate not supplied

Legal issues in human clinical investigation: a primer for physicians.

Human clinical investigation plays a central role in contemporary nuclear cardiology. It is a complex expensive endeavor triggering multiple responsibilities not otherwise encountered by physicians in clinical practice. Clinical investigators, drug and device manufacturers, hospitals and universities, governmental agencies, research subjects, patient advocacy groups, and investors all have a legitimate interest in the conduct and the outcome of clinical research. Past abuses of research subjects in many countries including those unknowingly exposed to radioactive isotopes have raised ethical concerns that are now addressed by overlapping laws, regulations, guidelines, and institutional policies that have evolved to guide the research enterprise. The policies underlying this legal and regulatory structure include protection of research subjects, protection of the integrity of research design and research data, and protection of the public and private purse. Knowledge of these laws and regulations is essential for physicians participating in clinical investigations to protect their professional and personal interests. This article reviews legal issues relevant to physicians conducting human clinical trials in the United States.

Clinical Trials as Topic↗
PubMed2002

The properties of gamma-radiation and high-energy neutron fluxes in "MIR" station orbit.

The study of radiation background components in the near-Earth space is very important for different branches of space research, in particular for space dosimetry and for the planning of gamma-astronomy experiments. Detailed information on the neutral components (gamma-quanta, neutrons) of background radiation was obtained during the Grif-1 experiment onboard Mir orbital station (OS). The measurements of fluxes of 0.05-50 MeV gamma-quanta and >30 MeV neutrons with a large area instrument (approximately 250 cm2 for gamma-quanta, approximately 30 cm2 for neutrons) as well as corresponding charged particle measurements (0.4-1.5 MeV electrons, 1-200 MeV protons) were made during this experiment. The background components induced by the station's own radiation as well as the albedo gamma-rays from the Earth's atmosphere were revealed as the result of data analysis for about 600 h of observation. A mathematical model describing the latitude and energy dependences of atmospheric albedo gamma-rays as well as of those of gamma-quanta produced in the material of the station due to cosmic ray interactions was developed. An analytical approximation of the spectrum of induced gamma-rays from radioactive isotopes stored in the station and instrument's materials is presented. The dynamics of gamma-quantum background fluxes during the geomagnetic disturbances of January 10-11, 1997 are discussed. An analytical representation of the latitude dependence of the integral flux of neutrons with >30 MeV is given.

Brazil↗
PubMed1998

Using GADlacZ transgenic mice as a marker system for homotopic transplantation.

Olfactory bulb (OB) transplantation is a well characterized model that has been widely used for studying neuronal plasticity and regeneration [G. Sekerková, Z. Katarova, E. Mugnaini, F. Joó, J.R. Wolff, S. Prodan, G. Szabó, Intrinsically labeled relay neurons of homotopic olfactory bulb transplants establish proper afferent and afferent synaptic connections with host neurons, Neuroscience, 80 (1997) 973-979 [10]; G. Sekerková, Z. Malatová, J. Orendácová, T. Zigová, Transplantation of dorsal root ganglion into the olfactory bulb of neonatal rats: a histochemical study, Restor. Neurol. Neurosci., 6 (1993) 1-8 [11]; E. Raceková, I. Vanický, T. Zigová, Correlation of functional alteration with lesion extent after olfactory bulbectomy in rats, Int. J. Neurosci., 79 (1994) 13-20 [12]; T. Zigová, P.P.C. Graziadei, A.G. Monti Graziadei, Olfactory bulb transplantation into the olfactory bulb of neonatal rats: an autoradiographic study, Brain Res., 539 (1991) 51-58 [13]]. In previous studies, the OB grafts have been routinely labeled by tritiated thymidine [S.M. Onifer, L.A. White, S.R. Whittemore, V.R. Holets, In vitro labelling strategies for identifying primary neural tissue and neuronal cell line after transplantation in the CNS, Cell Transplant., 2 (1993) 131-149 [7]; [13]] allowing distinction of graft from the surrounding tissue by the presence of silver grains over the cell nuclei of the transplant. However, this approach has some disadvantages, namely: partial or insufficient labeling of a defined neuronal subclasses due to the length of the period of their generation, variation in the number of labeled cells due to differences in the gestation stage between individual embryos at the time of i.p. injection of tritiated thymidine, inability to follow the dendritic arborization and axonal outgrowth of the transplanted neurons or to detect directly their actual synaptic contacts, and finally, the need to work with radioactive isotopes. In this paper, we describe an alternative approach, in which the donor OBs in a homotopic OB transplantation were derived from transgenic mice carrying the bacterial gene lacZ under control from the regulatory region of GAD67 gene. In these mice, beta-galactosidase (beta-gal), encoded by lacZ is stably, ectopically expressed in the vast majority of mitral/tufted (M/T) cells of the OB and served as their intrinsic cellular marker in the OB transplant. By using a simple histochemical reaction for beta-gal or immunocytochemistry with anti-beta-gal antibody, we could detect the cell bodies and processes of the donor M/T cells and their synaptic contacts with host neurons after long-term survival using both light and electron microscopy. Given the great number of existing transgenic mouse lines that express in the nervous system, this approach may have an even wider application in neural transplantation.

Animals↗
PubMed1984

Gastric emptying, glucose tolerance and associated hormonal changes in heroin addiction.

The gastric emptying rate of 8 heroin-dependent males was measured by means of a radioactive isotope method. A simultaneous oral glucose tolerance test was carried out. The glucose response showed a low, flat curve with a delayed peak, and increased secretion of insulin and growth hormone occurred. As the gastric emptying rate proved to be normal the observed metabolic abnormalities are not due to the effect of heroin on the gastro-intestinal tract, but must be attributed to some other effect of chronic heroin administration.

Adult↗
PubMedDate not supplied

General method to label antisense oligonucleotides with radioactive halogens for pharmacological and imaging studies.

Evaluation of oligonucleotides for biomedical applications requires different in vivo and in vitro approaches (pharmacokinetics, biodistribution, macro- and microimaging, metabolism,.), that are performed with different radioisotopes according to the temporal and spatial resolution needed. A method to introduce radioactive isotopes of halogens (fluorine, bromine, and iodine) in a small and stable molecule has been developed. Radiosynthons can then be conjugated with any given oligonucleotide in one step to create the appropriate radiotracer. This general radiolabeling procedure for oligonucleotides is efficient to synthesize (18)F-, (76)Br-, and (125)I-oligonucleotides for biological needs. Applications of the method to biodistribution, metabolism, in vivo and ex vivo imaging of (125)I- and (18)F-labeled oligonucleotides are reported.

Animals↗
PubMed1975

Fucosyl-glycoprotein and precursor polls in HeLa cells.

An enzymatic-radioactive isotope method has been developed for the direct quantitation of L-fucose in amounts as low at 0.5 plus or minus 0.05 nmol. Fucose kinase is used to transfer [32-P]phosphate from ATP to [3-H]fucose. The labeled enzymatic products are then separated electrophoretically and the amount and specific activity of the fucose are determined from the known specific activity of the phosphate donor. This assay has been used to measure the GDP-L-fucose and macromolecualar fucose in HeLa cells after extraction and purification of the sugar. It has been determined there are 0.5 nmol of GDP-L-fucose in 10-7 cells with a nine- to tenfold dilution of specific activity in converting L-[3-H] fucose to GDP-L-[3-H]fucose. After 2 to 3 days of labeling, the GDP-L-[3-H]fucose pool is essentially at equilibrium with the macromolecular pool, and hence it can be concluded that the dilution of label is due to a nine- to tenfold contribution to GDP-L-fucose from an endogenous source, as compared to exogenously supplied fucose. The fucosyl-glycoprotein pool has been shown to be much larger containing 6 to 8 nmol of fucose in 10-7 cells. It has further been shown that GDP-fucose is the only soluble fucose intermediate present in significant amount.

Cell Division↗
PubMed1981

Mice treated with strontium 90: an animal model deficient in NK cells.

Treatment of BALB/c mice with radioactive isotopes of the bone-seeking element strontium reduces the percentage of specific NK-cell cytotoxicity to only 2.6%, compared with 13.6% for normal BALB/c and 36.3% for athymic (nude) BALB/c. The syngeneic plasmacytoma NS-1 was used as target in a 4th in vitro NK-cell microassay. Marrow cellularity in treated mice is reduced to 12.5% of controls, but haemopoietic and stem-cell functions are taken over by the spleen and the peripheral blood picture remains relatively normal. Allogenic (H-2k) tumour transplants are rejected normally with good anti-H-2k alloantibody response. Haemopoietic and T- and B-cell functions are therefore substantially intact, and the defect seems confined to NK cells. In vivo, after s.c. inoculation of 10(6) NS-1 cells, 8/12 controls grew a solid tumour after a mean delay of 30.5 +/- 1.25 (s.e.) days, whereas 5/6 90Sr-treated mice grew the tumours after a delay of only 10.5 +/- 1.8 days. This markedly reduced delay in the 90Sr-treated mice lends support to suggestions that NK cells play an important role in resisting the establishment of tumour foci (i.e. in antitumour surveillance). Mice treated with 90Sr could be useful in evaluating the in vitro role of NK cells.

Animals↗
PubMed1988

Validation of the fluorescent dye Hoechst 33342 as a vascular space marker in tumours.

The DNA-binding fluorescent dye Hoechst 33342 (H33342) has been used in a series of investigations of the vascular parameters of two murine tumours. This dye has been shown, to have a short half-life in the circulation (T1/2 less than 2 min), but is stably bound for at least 2 h after it enters cells. It can be used in morphometric studies on frozen sections to determine the effective vascular volume, the capillary fraction and the size distribution of blood vessels in each tumour. These latter two parameters cannot be deduced from the less labour intensive techniques using radioactive isotopes. The effective vascular volume perfused in 1 min by H33342 was compared with the volume perfused in 30 min with 51Cr labelled erythrocytes. Similar volumes were estimated with the two techniques in a murine carcinoma and in a sarcoma. Both techniques showed that the vascular volume decreased in larger tumours. The H33342 analysis of vessel size showed the decrease in capillary vessels in the carcinomas was even greater, falling from 70% in small tumours to 20% in larger tumours. The deteriorating vascular network in larger tumours is associated with an increasing fraction of necrotic tissue. Experiments in which the isotopes and dye were co-injected suggest that at 40 mgkg-1 the dye may rapidly lead to a partial shutdown of the tumour vascular bed. This is less marked with 20 mg kg-1. In spite of this effect there is in general a close correlation between the volumes perfused by labelled red blood cells and the fluorescent dye.

Adenocarcinoma↗
PubMed1995

Renal accumulation of streptavidin: potential use for targeted therapy to the kidney.

Streptavidin exhibits a remarkable accumulation in the kidney. Biodistribution studies with radio-iodinated streptavidin showed that 70 to 80% of the injected dose per gram tissue (%/g) were retained in kidneys of Balb/C mice for three to four days compared to less than 5%/g levels in other tissues. This observation means that 15 to 20% of the injected dose is accumulated in the kidney, an organ that constitutes less than 1% of total body weight. Similar results of percent radioactivity per total kidney were obtained in other mouse strains as well as in rats and rabbits. Avidin, or the post-secretory form of streptavidin which is of a higher molecular weight, do not show any preferential affinity to the kidney. The kidney-accumulated streptavidin was mostly confined to the cortex, concentrated in the proximal tubular cells. Accumulation of streptavidin in the kidney was independent of biotin, since addition of biotin to radio-iodinated streptavidin prior to injection did not affect its kidney uptake. Therefore, streptavidin, which aquires its kidney accumulation property following truncation of the native form, may be utilized for renal specific delivery of chemotherapeutic agents, radioactive isotopes and other effector molecules. Such ligands can be linked to streptavidin via conventional coupling methods or following their biotinylation. Preliminary experiments showed that streptavidin can target to the kidney biotinylated ligands or high doses of chemically linked radionuclides.

Animals↗
PubMed2003

Indium-111-labelled octreotide scintigraphy in the diagnosis and management of non-iodine avid metastatic carcinoma of the thyroid.

Treatment of differentiated thyroid cancer is a success of modern medicine with the use of radioiodine ((131)I). However, a significant proportion of thyroid cancers may be non-iodine avid. Thyroid tumours are known to express somatostatin receptors. Octreotide, an analogue of somatostatin, can be combined with a radioactive isotope, such as (111)In-DTPA(0) to visualise tumours with high concentrations of somatostatin receptors. We assessed 18 patients with histologically proven metastatic or locally recurrent non-iodine avid thyroid carcinoma to determine the usefulness of (111)In-DTPA(0) octreotide scintigraphy compared to conventional radiology in diagnosing sites of metastasis. The diagnosis of metastatic disease was made using conventional radiology and all had prospective scintigraphy using (111)In-DTPA(0)octreotide. Of the 18 patients, 14 had octreotide-positive scans. In eight, the octreotide scans identified the same sites of metastases as conventional radiology, that is, were concordant. In nine patients, conventional radiology showed more extensive disease than revealed on the octreotide scans. In one patient with widespread bone metastases, octreotide gave a more detailed assessment of metastatic disease than conventional radiology. These data indicate that (111)In-DTPA(0)octreotide imaging for patients with non-iodine avid carcinoma of the thyroid may be a useful diagnostic and staging tool. One patient with Hurthle cell carcinoma metastatic to bone and a positive octreotide scan has been treated with (90)yttrium-labelled octreotide.

Antineoplastic Agents, Hormonal↗
PubMed1971

Induction of cyst coat protein synthesis by starvation in the ciliate Colpoda steinii.

1. At 28 degrees C, synthesis of protein cyst coat in ciliates of Colpoda steinii is induced by washing with water and, as judged by glutamic acid assays and incorporation studies with l-[U-(14)C]leucine, starts about 30min after the cells have stopped swimming and is largely complete 90min later. During this time up to 70% of the protein synthesized by the cell is coat protein. 2. When cells were placed in l-[U-(14)C]leucine at low concentrations (0.25-0.76mm) during the period of coat synthesis there was no lag in uptake. Only a small proportion of the leucine incorporated into the coat was from the external substrate, implying that the rate of radioactive isotope incorporation measured the rate of transport of amino acid into the cell. Transport of l-[U-(14)C]leucine into the cell was markedly stimulated by l-glutamic acid and l-lysine. 3. When cells were placed in l-[U-(14)C]leucine at high concentrations (38mm) the rate of incorporation was considered to measure the rate of protein synthesis, but because the latter may have been affected by substrate it is concluded that such measurements are of doubtful value.

Amino Acids↗