B6C3F1mice chronically exposed to 3,3′,4,4′-tetrachloroazobenzene (TCAB), a contaminant of dichloroaniline-derived herbicides, developed a number of neoplastic and nonneoplastic...Full Text Available
Toxicity and potential carcinogenicity studies of boric acid were investigated in mice to verify in a second rodent species that this was a noncarcinogenic chemical. Earlier chronic studies in rats...Full Text Available
Subchronic exposure to pharmacological levels of estrogenic compounds, including 17 beta-estradiol, diethylstilbestrol, and alpha-dienestrol, significantly increased the mortality of B6C3F1 female mice...Full Text Available
The objective of this study was to determine if genistein (GEN) modulation of the immune responses might contribute to the increased host resistances to tumors. A time-course study was performed...Full Text Available
Metabolism of benzene is thought to be necessary to produce the toxic effects, including carcinogenicity, associated with benzene exposure. To extrapolate from the results of rodent studies to potential health risks in man, one must know how benzene metabolism is affected by species, dose, dose rate, and repeated versus single exposures. The purpose of our studies was to determine the effect of repeated inhalation exposures on the metabolism of [14C]benzene by rodents. Benzene metabolism was assessed by characterizing and quantitating urinary metabolites, and by quantitating 14C bound to hemoglobin and micronuclei induction. F344/N rats and B6C3F1mice were exposed, nose-only, to 600 ppm benzene or to air (control) for 6 hr/day, 5 days/week for 3 weeks. On the last day, both benzene-pretreated and control animals were ...
Short and long-term pulmonary response to inhaled nickel hydroxide nanoparticles (nano-Ni(OH)2, CMD = 40 nm) in C57BL/6 mice was assessed using a whole body exposure system. For short-term...Full Text Available
Exposure of mice to 1000 ppm of vinyl chloride (VC), 6 hr/day, 5 days/week, caused some acute deaths with toxic hepatitis and marked tubular necrosis of the renal cortex. Starting the sixth month,...Full Text Available
1,1-Dichloroethylene is reported to produce renal tumors in male mice. It is an hepatotoxin in fasted rats after inhalation. We found that trichloropropane epoxide, an inhibitor of epoxide hydrase,...Full Text Available
The abuse of volatile solvents may be due to their ability to produce an intoxication similar to that produced by classical central nervous system depressants such as the barbiturates and ethanol. To evaluate this hypothesis, mice were trained to discriminate pentobarbital from saline injections in a two-lever operant task. Stimulus generalization was examined following 20-min inhalation exposures to toluene (300-5400 ppm). In 8 of 10 subjects, pentobarbital-lever responding occurred following toluene exposure indicating an overlap in the discriminative stimulus properties of toluene and pentobarbital.
Exposure to urban air pollution is an independent risk factor for increased cardiovascular diseases. Heat shock protein 70 (HSP70) has been implicated in the pathogenesis of vascular dysfunction and cardiovascular diseases. This study has been designed to determine whether inhalation of urban air induces HSP70 expression in the lung and blood as well as the association of HSP70 and air pollution-induced vascular dysfunction. Apolipoprotein E (Apo-E) deficient mice were exposed to diesel exhaust (DE) either acutely (3 days, 200 or 400 g/m3 for 6 h/day) or chronically (7 weeks, 200 or 400 g/m3 for 6 h/day). HSP70 was measured in the lung using immunohistochemistry, and in the plasma by ELISA. Abdominal aorta rings were used to determine vascular functional responses. Chronic DE-exposure incr...
Rats or mice acutely exposed to high concentrations of ozone show an immediate and significant weight loss, even when allowed free access to food and water. The mechanisms underlying this systemic response to ozone have not been previously elucidated. We have applied the technique of global gene expression analysis to the livers of C57BL mice acutely exposed to ozone. Mice lost up to 14% of their original body weight, with a 42% decrease in total food consumption. We previously had found significant up-regulation of genes encoding proliferative enzymes, proteins related to acute phase reactions and cytoskeletal functions, and other biomarkers of a cachexia-like inflammatory state in lungs of mice exposed to ozone. These results are consistent with a general up-regulation of different gene families responsive to NF-#kappa#B in the lungs of the exposed mice. In the present study, we ...
A comparison of the concentration-response effects of inhaled ozone (O/sub 3/) and phosgene (COCl/sub 2/) in different species of laboratory animals was made in order to better understand the influence of the choice of species in inhalation toxicity studies. The effect of 4-h exposures to ozone at concentrations of 0.2, 0.5, 1.0, and 2.0 ppm, and to COCl/sub 2/ and 0.1, 0.2, 0.5, and 1.0 ppm was determined in rabbits, guinea pigs, rats, hamsters, and mice. Lavage fluid protein (LFP) accumulation 18-20 h after exposure was used as the indicator of O3- and COCl/sub 2/-induced pulmonary edema. All species had similar basal levels of LFP (250-350 mg/ml) when a volume of saline that approximated the total lung capacity was used to lavage the collapsed lungs. Ozone effects were most marked in guinea pigs, which showed significant effects at 0.2 ppm and above. Mice, hamsters, and rats showed effects at 1.0 ppm ...
A comparison of the concentration-response effects of inhaled ozone (O/sub 3/) in different species of laboratory animals was made in order to better understand the influence of the choice of species in inhalation studies of this gas. The effect of 4-hour exposure to ozone (O/sub 3/) at concentrations of 0.0, 0.2, 0.5, 1.0, and 2.0 ppm was determined in rabbits, guinea pigs, rats, hamsters and mice. Lavage fluid protein (LFP) accumulation 18 hr after exposure was used as the indicator of O/sub 3/-induced pulmonary edema. All species had similar basal levels of LFP (250-350 ug/ml) when a volume of saline which approximated the total lung capacity was used for lavage of the collapsed lungs. Exponential dose-response curves were seen in all species except guinea pigs, which showed significant increases in LFP at low O/sub 3/ concentrations (0.2 ppm) and a leveling off of response at the higher O/sub 3/ levels. Other species ...
Cigarette smoking is the major environmental risk factor for bladder cancer in humans. Aromatic amines, potent DNA-reactive bladder carcinogens present in cigarette smoke, contribute significantly. However, increased cell proliferation, caused by direct mitogenesis or in response to cytotoxicity, may also play a role since urothelial hyperplasia has been observed in human cigarette smokers. We examined the urothelial effects of cigarette smoke (whole body inhalation exposure (Teague) system) in female C57BL/6 mice at various times in two studies, including reversibility evaluations. In both studies, no urothelial hyperplasia was observed by light microscopy in any group. However, in study 1, the Ki-67 labeling index (LI) of the urothelium was significantly increased in the smoke exposed group compared to controls through 3 months, but was not present at 6, 9 or 12 months even with continued exposures. In the groups that discontinued smoke ...
Additional measurements have been made of deposition and retention of inhaled radioactively labeled iron oxide aerosols generated by a spinning top aerosol generator.
Olfactory tract has been demonstrated to be an important portal for inhaled solid nanoparticle transportation into the central nervous system (CNS). We have previously demonstrated that intranasally instilled Fe_2O_3 nanoparticles could transport into the CNS via olfactory pathway. In this study, we investigated the neurotoxicity and size effect of repeatedly low-dose (130 #mu#g) intranasal exposure of nano- and submicron-sized Fe_2O_3 particles (21 nm and 280 nm) to mice. The biomarkers of oxidative stress, activity of nitric oxide synthases and release of monoamine neurotransmitter in the brain were studied. Our results showed that significant oxidative stress was induced by the two sizes of Fe_2O_3 particles. The activities of GSH-Px, Cu,Zn-SOD, and cNOS significantly elevated and the total GSH and GSH/GSSG ratio significantly decreased in the olfactory bulb and hippocampus after the nano- and submicron-sized Fe_2O_3 particle treatment (p ...
Inhaled corticosteroids (ICS) are often prescribed as first-line therapy for patients with asthma Despite their efficacy and improved safety profile compared with oral corticosteroids, the potential...Full Text Available
ObjectivesTo study inhalation and dermal exposure to hexamethylene diisocyanate (HDI) and its oligomers as well as personal protection equipment (PPE) use during task performance...Full Text Available
A review of the literature on chronic inhalation studies in which rats were exposed to mineral fibres at known fibre number concentrations was undertaken to examine the specific roles of fibre length...Full Text Available
Lipopolysaccharides from different bacteria isolated from cotton were purified and chemically analyzed. Their pulmonary toxicity to animals was tested in inhalation tests. Lipopolysaccharides from Agrobacterium...Full Text Available
Hypersensitivity pneumonitis (HP) is an inflammatory lung disease caused by repeated inhalation of aerosolized antigens. With chronic exposure to an inhaled antigen, patients are at risk of...Full Text Available
Rats that inhaled "2"3"9Pu(NO_3)_4 or "2"3"8Pu(NO_3)_4 developed lung tumors and bone tumors. Lung tumors were clearly associated with Pu inhalation (accumulated dose to lung, 1 rad to 5000 rads); bone tumors could not be unequivocally related to the radiation insult.
Preliminary results suggest that Pu(NO_3)_4 inhaled as crystalline solid aerosol is retained more tenaciously in the lung and excreted less in urine than inhaled Pu(NO_3)_4 aerosols generated from a nitric acid solution.
Objective: To establish a computer program for rapid calculation of internal committed effective close through inhalation and ingestion pathways under radiological emergency. Methods: Visual Basic 6.0 is used to compile the generic procedures of internal committed effective dose by inhalation and ingestion in IAEA-TECDOC-1162, Generic Procedures for Assessment and Response during a Radiological Emergency. Results: The assessment methodology of internal committed effective dose by inhalation and ingestion under radiological emergency in the report IAEA-TECDOC-1162 can be coded into a computer program. Conclusions: This research provides a rapid method of assessment for internal committed effective dose by inhalation and ingestion under radiological emergency, and it may provide needed dosimetry data for treatment under emergency response. (authors)
Toxic studies were conducted with rats, mice, and guinea pigs to determine acute effects from single exposures to M60A1-tank-generated DF2 and DF1 (diesel fuel) smoke and/or exhaust clouds under static airflow conditions. Emissions were disseminated with the Vehicle Engine Exhaust Smoke System (VEESS) and exposure periods ranged from 15 to 300 minutes. At attempted airborne concentrations of 10.0 to 12.0 mg/i (10,000 cu.m to 12,000 cu.m) of the DF2 and DF1 smoke/exhaust mixtures and 0.2 mg/1 (200 mg/cu.m) of the exhausts, toxic signs (excluding death) and lung compliance changes were observed after 15-minute exposures. Death and pathological abnormalities of the lung were seen after 16-minute exposures to DF2 smoke and/or exhaust. Exposures to DF1 smoke/exhaust showed lung pathology and death by 120 minutes while death and turbinate lesions were observed in animals exposed to DF1 exhaust for 60 minutes. Experimental evidence suggests that a principal toxic ...
We describe a 16-month-old boy presenting with stridor and fever. The chest X-ray suggested inhalation of a foreign body but here was no history of this. A high spot a T_1-weighted chest MRI was due to a peanut which was seen to have moved from the right main bronchus to the left inferior bronchus, between the two MRI studies. MRI can provide information on position and size of the peanut, the conditons of the surrounding tissues and may be also useful in treatment. We consider MRI to be a valuable new method for the diagnosis of peanut inhalation. (orig./GDG).
Inhaled beryllium oxide results in impaired alveolar clearance of inhaled "2"3"9PuO_2 and induces an inflammatory reaction in the lung. However, only one of 184 rats exposed to beryllium developed a lung tumor; none of 128 unexposed rats developed a lung tumor. Fifty-six lung tumors were induced in 181 rats exposed to plutonium. A total of 37 lung tumors were found in 119 rats given combined exposures to beryllium and plutonium. Only in rats given the highest levels of both beryllium and plutonium was there an incidence of lung tumors greater than that seen with exposure to plutonium only.
Hypersensitivity Pneumonitis (HP) is an interstitial lung disease that develops following repeated exposure to inhaled environmental antigens. The disease is characterized by alveolitis, granuloma formation...Full Text Available
... Bisgard, GE, Ruiz, AV, Grover, RF & Will, JA, "Ventilatory control in the ... Watkins, BE, Riegle, GD & Heisey, SR, "Respiratory responses to ACTH and ...
Cell cultures were prepared from lung tumors occurring in beagles following exposure to inhaled plutonium. Morphologic and growth characteristics of two of these cell lines are described.
Dosimetry parameters such as deposition, clearance, retention, and translocation and dissolution of inhaled particles in and to different lung compartments may be important for the persistence of particles...Full Text Available
Simultaneous exposures of rats and hamsters to inhaled radon daughters, with and without uranium ore dust, were performed daily for five months. Pulmonary pathology developing in 6 to 13 mo after cessation of daily exposures included interstitial fibrosis, emphysema, epithelial hyperplasia, squamous metaplasia, and malignant neoplasia. Rats showed a greater variety and more severe response to these uranium mine inhalation exposures than did hamsters. Inhalation of radon daughters with uranium ore dust displayed the site of greatest damage, including squamous carcinoma, from the nasopharynx to the lungs. Sixty percent of the rats exposed to radon daughters with ore dust developed primary pulmonary carcinomas, providing an appropriate short-term experimental animal model for investigation of respiratory tract carcinogenesis in uranium miners.
BackgroundThe scent from receptive female mice functions as a signal, which stimulates male mice to search for potential mating partners. This searching behavior is coupled with...Full Text Available
The use of mice for the assay of tetanus toxoids would offer considerable advantages over the use of guinea-pigs, but mice cannot readily be immunized with the fluid tetanus toxoid at present designated...Full Text Available
Plasma samples were collected from mice infected with Trypanosoma musculi at different times postinfection and administered to naive recipient mice either before or during T. musculi infection. The...Full Text Available
Mice injected with rat erythrocytes developed anti-erythrocyte autoantibodies which reached a plateau at 4-12 weeks, then gradually declined until at about 24 weeks the majority of mice were negative....Full Text Available
Mice are an ideal mammalian model for studying the genetics of aging: considerable resources are available, the generation time is short, and the environment can be easily controlled, an important...Full Text Available
Studies were initiated to examine in rats the effects of a protracted exposure to inhaled "2"3"9PuO_2. Graphs are presented to show effect of multiple exposures to "2"3"9PuO_2 on the deposition and clearance of "2"3"9Pu in the alveoli.
Daily exposures of adult beagle dogs to inhaled radon daughters plus uranium ore dust, with and without concurrent cigarette smoking, for 2 to 5-1/2 yr have produced massive pulmonary fibrosis and severe emphysema. The cumulative exposure doses are similar to those associated with a 5-fold or greater increase in death rate of uranium miners due to chronic respiratory insufficiency, including pneumoconiosis, pulmonary fibrosis, and emphysema.
Beagle dogs given a single inhalation exposure to "2"3"9Pu(NO_3)_4 are being observed for life-span dose-effect relationships. Over half of the dogs planned for "2"3"9Pu(NO_3)_4 exposure have been exposed and the remaining dogs will be exposed as they reach adult age.
Uranyl nitrate ("2"3"3U) was retained mainly in lung, skeleton, pelt and kidney 60 days after inhalation exposure. The concentration in lung exceeded that in other tissues. Preliminary results with "2"3"2U indicate retention in lung similar to that of "2"3"3U, at total deposited mass levels of 0.1 #mu#g or less.
Daily exposures of adult beagle dogs to inhaled radon daughters and to uranium ore dust for 4-1/2 to 6 yr have produced respiratory tract carcinomas, at similar cumulative working level months (WLM) of exposures to those which induced carcinomas in uranium miners. Biological data from the beagle-dog experiments can therefore be used for prediction of carcinogenic risk under changing exposure conditions in future uranium miners.
This study in human volunteers was designed to compare the retention of diethylenetriaminepentaacetic acid (DTPA) in the body after intravenous (i.v.) injection with that following inhalation by using a /sup 14/C labelled tracer. After i.v. injection retention in the blood could be described by three exponential components with half-times of about 1.4 min (approx. 60%). By 24 Ehr more than 99% of the /sup 14/C-DTPA had been excreted in the urine and less than 0.5% remained in the plasma. After inhalation of /sup 14/C-DTPA retention in the lungs could be represented by a single component with a half time of about 75 min. As a consequence the length of time that a therapeutically useful amount of DTPA is retained in the body is approximately twice that following intravenous injection.
Studies have been carried out to determine the possible physiological effects of contact with carbon black made by the thermal process. Contact was made by ingestion, skin application and/or inhalation. Ingestion and/or skin application do not appear to lead to any changes from the normal. Inhalation exposures do not produce pulmonary function changes (antemortem or postmortem studies) but may lead to moderate to severe "perifocal" emphysema in Rhesus monkeys (not observed in guinea pigs). Inhalation studies also suggest right ventricular septal and to a degree, left ventricular hypertrophy in Rhesus monkeys as an effect. Additional studies are necessary to support these finding and consideration must be given to the variability among exposed subjects as compared to controls. PMID:136503
DBA/2J (DBA) mice are susceptible to audiogenic seizures (ASs) in an age-dependent manner. Anion transport as measured by radioiodide uptake was determined in thyroid gland, salivary gland, skeletal muscle, cerebral cortex, cerebellum, brainstem, and CSF from these mice at various ages. Anion transport was also determined in C57BL/6J(C57) mice, an AS-resistant strain. In thyroid, DBA mice had an enhanced ability to concentrate iodide at 21 days of age when they have maximal AS susceptibility, as compared with the same-aged C57 mice. This difference in thyroid function was less marked at 40 days of age, when DBA mice are less AS susceptible, and was absent at 110 days of age, when DBA mice are AS resistant. In brain, differences in iodide uptake were also noted between these two strains of mice at 21 days of age. DBA ...
Background:Tobacco smoking is the most important risk factor for chronic obstructive pulmonary disease (COPD) development. Inhaled cigarette smoke can induce tumor necrosis factor-α...Full Text Available
... HIV & AIDS (15) I Infectious Diseases (21) Injection Drug Use (7) M Mental Illness (139) Mortality (7) ... Hallucinogens (5) Hashish (2) Heroin (21) I Illegal Drugs (115) Inhalants (12) K Ketamine (1) L LSD ( ...
... HIV & AIDS (15) I Infectious Diseases (22) Injection Drug Use (7) M Mental Illness (141) Mortality (7) ... Hallucinogens (5) Hashish (2) Heroin (21) I Illegal Drugs (117) Inhalants (13) K Ketamine (1) L LSD ( ...
... HIV & AIDS (15) I Infectious Diseases (21) Injection Drug Use (7) M Mental Illness (139) Mortality (7) ... Hallucinogens (5) Hashish (2) Heroin (21) I Illegal Drugs (112) Inhalants (12) K Ketamine (1) L LSD ( ...
... HIV & AIDS (15) I Infectious Diseases (21) Injection Drug Use (7) M Mental Illness (138) Mortality (7) ... Hallucinogens (5) Hashish (2) Heroin (21) I Illegal Drugs (116) Inhalants (12) K Ketamine (1) L LSD ( ...
AIMTo compare a test version of HFA fluticasone/salmeterol (FP/SM) combination inhaler (Neolab, UK) with the reference product Seretide (GlaxoSmithKline, UK).METHODSAn...Full Text Available
Possible health risks associated with occupational inhalation of mycotoxin-containing dust remain largely unknown, partly because methods for mycotoxin detection are not sensitive enough for the small...Full Text Available
Trichloroethylene (TCE) is both acutely toxic and carcinogenic to the mouse lung following exposure by inhalation. In contrast, it is not carcinogenic in the rat lung and is markedly less toxic following...Full Text Available
The percentages of total airflows over the nasal respiratory and olfactory epithelium of female rabbits were calculated from computational fluid dynamics (CFD) simulations of steady-state inhalation....Full Text Available
Rats were exposed to aerosols of "2"3"3U and "2"3"2U nitrate in a study of the long-term biological effects. Preliminary radiation dose estimates show lung > skeleton > kidney in each dose group.
The alpha emitter plutonium-238 ("2"3"8Pu), which is produced in uranium-fueled, light-water reactors, is used as a thermoelectric power source for space applications. Inhalation of a mixed oxide form of Pu is the most likely mode of exposure of workers and the general public. Occupational exposures to "2"3"8PuO_2 have occurred in association with the fabrication of radioisotope thermoelectric generators. Organs and tissue at risk for deterministic and stochastic effects of "2"3"8Pu-alpha irradiation include the lung, liver, skeleton, and lymphatic tissue. Little has been reported about the effects of inhaled "2"3"8PuO_2 on peripheral blood cell counts in humans. The purpose of this study was to investigate hematological responses after a single inhalation exposure of Beagle dogs to alpha-emitting "2"3"8PuO_2 particles and to extrapolate results to humans.
Progressive obstructive lung disease is a characteristic component of cystic fibrosis (CF). It is the pulmonary manifestations, including obstruction and endobronchial infection, which directly contribute...Full Text Available
Rationale: Ventilator-induced lung injury (VILI) leads to an unacceptably high mortality. In this regard, the antiinflammatory properties of inhaled carbon monoxide (CO) may provide...Full Text Available
Purpose: The DBA/2J mice have been used as an animal model for human pigmentary glaucoma. However, these mice develop various degrees of disease symptoms at different ages, making it difficult to detect pathological changes of retinal degeneration at glaucoma onset. The purpose of this study is to develop a non-invasive assay to identify individual mice that develop visual deficits. Materials and Methods: We apply two behavioral tests, a swimming test of visual discrimination and a test of optomotor response, to identify glaucomatous DBA/2J mice. We then examine whether the elevation of intraocular pressure (IOP), the common risk factor for glaucoma, affects visual performances of the DBA/2J mice. We further compare the retinal ganglion cell death, one of the signature glaucoma symptoms, i...
Models of the human airways have played a major role in evaluating the health effects of inhaled radionuclides. While models such as those of Weibel (1963) provide data necessary for characterizing deposition of aerosol, they have not characterized the cells at risks in the airspaces. Given the advancements in techniques and study of cell cultures exposed to ionizing radiation there is a need to extrapolate between the simple structures of cell culture systems and the complex architecture of the human airways. The preliminary data in this paper provide a complete characterization of the size and number of cells in the airways and represents a significant advance in our study of the health consequences of exposure to inhaled radionuclides. 26 refs., 2 figs., 4 tabs.
The distribution of radiation dose commitments within the body that can result from the lung deposition of a number of transuranic radionuclides ("2"3"7Pu, "2"3"8Pu, "2"3"9Pu, "2"4"0Pu, "2"4"1Pu, "2"4"2Pu, "2"4"3Pu, "2"4"4Pu, "2"4"1Am, "2"4"2Am, "2"4"3Am, "2"4"4Am, "2"4"2Cm, "2"4"3Cm, "2"4"4Cm, and "2"4"6Cm) was calculated. The variables that influence these organ dose commitments include the mobility of the particle or its dissolution products within the body, the radiation characteristics of the inhaled radionuclides and their progeny, and the size of the particles inhaled. In the calculation of organ dose commitments for whole-body, lungs, liver, bone tissues, kidneys, and gastrointestinal tract from the inhalation of transuranium radionuclides, physical characteristics of importance are the dimensions of the particle, its aerodynamic properties, and its density. For particles within the respirable size range, a useful ...
Genetic studies of nicotine addiction in mice have utilized the oral self-administration model. However, it is unclear if strain differences in nicotine consumption are influenced by variation in bitter...Full Text Available
We previously reported that global deletion of insulin receptor substrate protein 1 (Irs1) extends lifespan and increases resistance to several age-related pathologies in female mice....Full Text Available
Sensory neurons in aging mammals undergo changes in anatomy, physiology and gene expression that correlate with reduced sensory perception. In this study we compared young and aged mice to identify...Full Text Available
BackgroundGlucocorticoids down-regulate cytokine synthesis and suppress inflammatory responses. The glucocorticoid receptor (GR) antagonist RU486 may exacerbate the inflammatory...Full Text Available
The morphogenesis of pulmonary edema and bronchiolar injury induced by the toxic furan, 4-ipomeanol, was studied by combined light and transmission electron microscopy. Weanling male CD-1 mice received...Full Text Available
The in vivo antichlamydial activities of sparfloxacin and reference drugs were examined in a experimental model of pneumonia caused by Chlamydia pneumoniae in leukopenic mice; their in vitro activities...Full Text Available
Mice and rats are important mammalian models in biomedical research. In contrast to other biomedical fields, work on sexual differentiation of brain and behavior has traditionally utilized comparative...Full Text Available
Experimental metastases in the brain of mice are infiltrated by microglia, and parabiosis experiments of green fluorescent protein (GFP+) and GFP-mice revealed that these microglia...Full Text Available
A new strain of mouse hepatitis virus (MHV) was isolated from pooled gut suspensions from an epizootic of lethal enteritis in newborn mice. Negative-contrast electron microscopy showed an abundance...Full Text Available
The influence of an immobilization stressor on lung cellular immune responses was studied. Delayed-type hypersensitivity to sheep erythrocytes was used to evaluate in vivo lung cellular immunity. Mice...Full Text Available
Type II collagen-induced arthritis (CIA) in mice is an autoimmune experimental model for rheumatoid arthritis. Susceptibility to CIA is associated with certain major histocompatibility complex class...Full Text Available
In this study, our main objective was to determine whether energy restriction (ER) affects the rate of oxygen consumption of mice transiently or lastingly and whether metabolic rate plays a role in...Full Text Available
The long-term impact of early stress on behavior and emotions is well documented in humans, and can be modeled in experimental animals. In mice, maternal separation during early postnatal development...Full Text Available
An in vitro assay for curative antibody present in plasma of mice cured of Trypanosoma musculi is described. The assay involves the addition of plasma to a sample of infected blood, followed by hourly...Full Text Available
This study investigated the impact of lifelong sedentariness on skeletal muscle mass and mitochondrial function. Thirty C57BL/6 strain mice (2 months) were randomly divided into three groups (young-Y;...Full Text Available
The outcome of various osteoprogenitor-cell transplantation protocols was assessed using Col1a1-GFP reporter transgenic mice. The model requires the recipient mice to undergo lethal total body irradiation...Full Text Available
Following the descovery of its transposition activity in mammalian culture systems, the Sleeping Beauty (SB) transposon has since been applied to achieve germline mutagenesis in mice....Full Text Available
The results of a study of the expression of embryonic hemoglobin genes in mice which show an imbalance of alpha and non-alpha chain synthesis are reported. (ACR)
The hypothesis, that a decrease in metabolic rate mediates the life span prolonging effect of caloric restriction (CR), was tested using two strains of mice, one of which, C57BL/6, exhibits...Full Text Available
Spontaneous mouse models of cancer show promise to more accurately recapitulate human disease and predict clinical efficacy. Transgenic mice or viral vectors have been required to generate spontaneous...Full Text Available
We introduce cyclophosphamide-induced alopecia (CYP-IA) in C57BL-6 mice as a clinically relevant model for studying the biology of chemotherapy-induced alopecia and for developing anti-alopecia drugs....Full Text Available
Mice harboring a null mutation in Abca4/Abcr serve as a model of autosomal recessive Stargardt disease. Consistent with the human retinal disorder, deficiency...Full Text Available
Mice homozygous for the recessive gene achondroplasia (cn) aged 16 and 17 days and some homozygotes aged 22-34 days have disruptions in the growth of the proximal tibial growth plate which are due solely...Full Text Available
The aim of the present study was to evaluate the ameliorative potential of quercetin (QC) against paracetamol (PCM)-induced oxidative stress and biochemical alterations in mice blood. A total of 36...Full Text Available
We reported previously that Fas-induced hepatic failure in normal mice was attenuated or prevented by exogenous transferrin (Tf), particularly apoTf. Here we show in C57BL6J/129 mice with genetic...Full Text Available
The sera of NZB/BL mice have been found to be active in the complement fixation test against isogeneic liver antigens to a higher titre than the sera of CBA, C57BL and DBA/2 mice. Six sera from NZB...Full Text Available
An animated test is made for mice with malignant tumors irradiated by a self-made millimetre wave radiator for medical purpose. It is observed that S-180 sarcomas in mice after irradiation has been distinctly suppressed. And remarkable effects are shown through a lot of clinical practices on peptic ulcer, skin-deep ulcer, acute and chromic soft tissue injuries etc.
Biglycan (bgn)-deficient mice (KO) have defective osteoblasts which lead to changes in the amount and quality of bone. Altered tissue strength in C57BL6/129 (B6;129) KO mice, a property which...Full Text Available
The experiment was designed to study the effects of sodium pentobarbital on behavioral thermoregulation in rats and mice. Male Sprague-Dawley rats were given intraperitoneal (i.p.) injections of sodium pentobarbital in doses of 0, 1, 5, 10 or 15 mg/kg and male CBA/J mice were giv...
It has been postulated that fetal vascular abnormalities in aryl hydrocarbon receptor null (ahr−/−) mice may alter cardiovascular homeostasis in adulthood....Full Text Available
Manganese toxicity can cause a neurodegenerative disorder affecting cortical and basal ganglia structures with a neurological presentation resembling features of Parkinson's disease. Children are more sensitive to Mn-induced neurological dysfunction than adults, and recent studies from our laboratory revealed a marked sensitivity of male juvenile mice to neuroinflammatory injury from Mn, relative to females. To determine the role of estrogen (E2) in mediating sex-dependent vulnerability to Mn-induced neurotoxicity, we exposed transgenic mice expressing an NF-kB-driven enhanced green fluorescent protein (EGFP) reporter construct (NF-kB-EGFP mice) to Mn, postulating that supplementing male mice with E2 during juvenile development would attenuate neuroinflammatory changes associated with glia...
Laboratory studies have been carried out to determine the toxicity of methiocarb pellets to wild trapped wood mice in order to provide some background data prior to any further evaluation of hazard in the field. In this study, wood mice were exposed to dry and to dampened methiocarb pellets in order to reproduce field trial application conditions. Field observations of methiocarb pellets indicate that the physical character changes under dry and wet weather conditions. This may affect their relative attractiveness and potential toxicity to wood mice. The laboratory assessment of exposed wood mice included measurement of brain esterase activities, methiocarb residues in selected mouse tissue, carcasses, and histological evaluation of kidney, liver and lungs.
This analysis is one of 10 reports that support the Environmental Radiation Model for Yucca Mountain, Nevada (ERMYN) biosphere model. The ''Biosphere Model Report'' (BSC 2004 [DIRS 169460]) describes in detail the conceptual model as well as the mathematical model and its input parameters. This report documents development of input parameters for the biosphere model that are related to atmospheric mass loading and supports the use of the model to develop biosphere dose conversion factors (BDCFs). The biosphere model is one of a series of process models supporting the total system performance assessment (TSPA) for a Yucca Mountain repository. Inhalation Exposure Input Parameters for the Biosphere Model is one of five reports that develop input parameters for the biosphere model. A graphical representation of the documentation hierarchy for the ERMYN is presented in Figure 1-1. This figure shows the interrelationships among the ...
Non-invasive methods are described for estimating local cerebal blood flows (LCBF) and local partition coefficients (Llambda) during inhalation of 30 % stable xenon gas (Xe) in oxygen during CT scanning. After the denitrogenation with pure oxygen breathing, 30 % Xe is inhaled for four minutes to minimize subanesthetic effects with a rubber facemask and the delivery system of Xe. Local time-..delta.. Hounsfield units curve during the Xe wash-in and wash-out phase is utilized in order to calculate Llambda and LCBF using a least squares curve fitting analysis. Calculated Llambda and LCBF with the new method manifested reasonable distribution between the grey and white matters, and reproducibility was excellent in our study. Several case studies of patients with cerebral infarction are presented to demonstrate the characterization of Llambda and LCBF patterns in various tissues and theoretical grounds underlying the new method of curve fitting ...
Non-invasive methods are described for estimating local cerebal blood flows (LCBF) and local partition coefficients (L#lambda#) during inhalation of 30 % stable xenon gas (Xe) in oxygen during CT scanning. After the denitrogenation with pure oxygen breathing, 30 % Xe is inhaled for four minutes to minimize subanesthetic effects with a rubber facemask and the delivery system of Xe. Local time-#DELTA# Hounsfield units curve during the Xe wash-in and wash-out phase is utilized in order to calculate L#lambda# and LCBF using a least squares curve fitting analysis. Calculated L#lambda# and LCBF with the new method manifested reasonable distribution between the grey and white matters, and reproducibility was excellent in our study. Several case studies of patients with cerebral infarction are presented to demonstrate the characterization of L#lambda# and LCBF patterns in various tissues and theoretical grounds underlying the new method of curve ...
Our understanding of prenatal behavior has been significantly advanced by techniques for direct observation and manipulation of unanesthetized, behaving rodent fetuses with intact umbilical connections to the mother. These techniques involve brief administration of an inhalant anesthesic, enabling spinal transection of the rat or mouse dam, after which procedures can continue with unanesthetized dams and fetuses. Because anesthetics administered to the mother can cross the placental barrier, it is possible that fetuses are anesthetized to varying degrees. We compared in perinatal rats the effects of prenatal maternal exposure to two inhalant anesthetics: ether and isoflurane. Fewer spontaneous fetal movements and first postpartum nipple attachments were observed following maternal exposure...
Evaporation of "9"9"mTc-pertechnetate at about 2500"0C on a carbon surface generates an ultrafine aerosol of labelled carbon clusters. Its particle size of about 2-5 nm enables the aerosol to behave similarly to a gas regarding the ability of penetration. After inhalation, the radioactive particles adhere to the walls of the respiratory bronchioli and alveoli. The high concentration of the radioactivity in the argon carrier gas makes it possible to record a scintigram after a single deep breath. We studied four healthy volunteers and 79 patients including 34 with a tentative diagnosis of pulmonary embolism, 20 with bronchus carcinoma, and 15 with various other lung diseases. Ten of these patients were infants, the youngest being nine months old. All patients also had a perfusion scintigraphy. (orig.).
Health risks associated with inhalation of mineral dusts have been identified to a great extent through epidemiology studies, but also have been assessed by conducting subchronic and chronic inhalation studies typically on rodents. However, in vivo studies are softly, time-consuming, requiring complex technologies, and may not yield information on cellular and molecular mechanisms of response. As a result, the use of in vitro cell culture systems has played an important role in studying the toxicology of mineral dusts and providing insight into action mechanisms. This article reviews selected in vitro approaches that are used to investigate the cytotoxic and inflammatory properties of mineral particles and fibers. In addition key findings as they relate to understanding the toxicology of mineral dusts are presented. 165 refs., 1 fig., 5 tab.
In many drug dispensing devices, such as syringes and inhalers, an elatomeric gasket is used to prevent the formulation from leaking from the chamber. During device actuation, the seal is subjected to friction, which in turn causes its deformation and can cause unintentional leakage, thus dose variability. Additionally, friction of seal is responsible for a host of potential problems such undue effort required for actuation and potential wear. The mechanism of friction generation in the seal conjunction is complex, arising from adhesion of rubber in contact with the moving interface, viscous action of a thin film of fluid and deformation of seal asperities. Therefore, the first step in understanding the conjunctional behaviour of rubber seals is a fundamental study of mechanisms of frictio...
Eribulin is a new anticancer agent currently in Phase III clinical trials for the treatment of metastatic breast cancer. In the current studies, we have investigated the effects of P-glycoprotein (P-gp) on the in vivo disposition of eribulin using CF-1 abcb1a-deficient mice, and the influence of eribulin on P-gp-mediated efflux of digoxin in Caco-2 cells. Eribulin was administered intravenously and orally in both CF-1 wild-type and CF-1 abcb1a-deficient mice. P-gp-mediated efflux of digoxin in Caco-2 cell monolayers was measured in the presence of eribulin. The plasma exposure to eribulin was higher in CF-1 abcb1a-deficient mice than that in CF-1 wild-type mice after intravenous (IV) and oral (PO) administrations. The oral bioavailability of eribulin was 62.3% in CF-1 abcb1a-deficient mice...
This study was undertaken to investigate the effects of neonatal asphyxia on brain development, with special reference to the kinetics of neuronal proliferation by using autoradiography. For 30 minutes, two-day-old suckling mice, Jcl:ICR strain, were put into a chamber which was constantly flushed with 100% CO_2 gas. After the exposure to asphyxia, 29% of the mice survived. Cell cycle studies were carried out at two days and at seven days on the external matrix cells, the precursor of the granule cells, at the external granular layer of the cerebellum from CO_2-exposed and control mice by "3H-thymidine autoradiography. At two days the generation time of the control mice was about 15 hours, whereas that of the asphyxiated mice was about 17 hours. The prolongation of the generation time in the asphyxiated mice was caused mainly by a delay in the G2 phase. This ...
An intact basement membrane (BM) is essential for the proper function, differentiation and morphology of many epithelial cells. The disruption or loss of this BM occurs during normal development as well as in the disease state. To examine the importance of BM during mammary gland development in vivo, we generated transgenic mice that inappropriately express autoactivating isoforms of the matrix metalloproteinase stromelysin-1. The mammary glands from these mice are both functionally and morphologically altered throughout development. We have now documented a dramatic incidence of breast tumors in several independent lines of these mice. These data suggest that overexpression of stromelysin-1 and disruption of the BM may be a key step in the multi-step process of breast cancer.
Abstract Objective: The aim of this investigation was to compare the healing of laser-irradiated and non-irradiated wounds covered by an occlusive dressing in mice. Background data: Many previous studies of the effects of laser irradiation of experimental wounds in mice and rats did not cover the wounds so that healing occurred mainly by contraction. Healing of covered wounds is slower and mimics more closely wound healing in humans. Materials and Methods: Forty-seven diabetic and twenty non-diabetic mice were used. A single wound (5?mm diameter) was created on the left flank of each animal and covered by Tegaderm HP dressing (Day 1). Wounds were irradiated (660?nm) for 20?s using a lower power (18?mW) or higher power (80?mW) laser starting immediately post-wounding for seven consecutive d...
Nano-sized silica is a promising material for disease diagnosis, cosmetics and drugs. For the successful application of nano-sized material in bioscience, evaluation of nano-sized material toxicity is important. We previously found that nano-sized silica particles with a diameter of 70nm showed acute liver failure in mice. Here, we performed histological analysis of major organs such as the liver, spleen, lung, kidney, brain and heart in mice, chronically injected with 70-nm silica particles for 4weeks. Histological analysis revealed hepatic microgranulation and splenic megakaryocyte accumulation in these 70-nm silica particles treated mice, while the kidney, lung, brain and heart remained unaffected. Thus, liver and spleen appear to be the major target organs for toxicity by the chronic a...
BackgroundCystinuria is the most common inherited cause of urinary tract stones in children. It can lead to obstructive uropathy, which is a major cause of renal...Full Text Available
When casein, a milk protein, is hydrolyzed, it renders human foods that contain it (e.g., hypoallergenic infant formula, cheeses) distasteful to many people. This rejection...Full Text Available
Methylene chloride is an organic solvent with many industrial uses. Inhalation of methylene chloride fumes can result in toxicity, caused by hepatic biotransformation of methylene chloride to carbon monoxide. A case of acute methylene chloride poisoning is presented, including successful treatment of this patient with the use of hyperbaric oxygenation. The rationale for the use of hyperbaric oxygenation in the treatment of methylene chloride poisoning is discussed. (aw)
The aims of the work described here were to provide an experimental basis for evaluating the committed effective dose equivalent per unit intake together with the ALI for four industrial oxide bearing dusts, and to assess the extent to which {sup 241}Am could be used for estimating the {sup 239}Pu content of the lung after an accidental intake of these materials. (author).
PuO_2 particles behaved similarly in the lungs of rat and hamster. The relative concentrations of PuO_2 up to 1-yr postexposure were 1.0 for lung parenchyma, 1.3 for subpleural areas, 0.5 for peribronchiolar regions and 0.2 for perivascular regions in the lungs.
Accumulation of "8"5Kr in arterial blood of sheep occurs within 10 min of inhalation exposure initiation, and disappears by 30 min after exposure termination. As reported for other species, "8"5Kr concentrations in fat were approximately 10 times those in other tissues.
This research has two main goals; (1) to quantify mechanisms for radon entry into homes of different types and to determine the fraction of indoor radon attributable to each source and (2) to model and calculate the dose (and therefore alpha particle fluence) to cells in the human and animal tracheobronchial tree that is pertinent to induction of bronchogenic carcinoma from inhaled radon daughters.
Tritium is produced in large quantities at heavy water nuclear power reactors via the neutron activation reaction "2H(n,#gamma#)"3H. At Wolsung nuclear power plant which has a CANDU reactor, the tritium concentrations in coolant and in moderator systems are 1.5 Ci/Kg-D_2O and 35 Ci/kg-D_2O, respectively, after 12 years of operation. The airborne tritium concentration in main access area is normally less than 5 MPCa except short-term peaks. The average tritium concentrations in main access controlled areas are normally less than 100 MPCa. Tritium is mainly present in the air of workplace of CANDU reactors as a tritiated water vapour. Airborne tritiated water vapour enters the workers body via inhalation and absorption through skin and can result in a significant dose. The occupational doses from tritium at Wolsung NPP have been maintained below 1 man-Sv per year so far. The tritium contribution to the total plant man-Sv changes between 30 percent and 50 percent. For ...
Hamsters breathed, nose-only, for 13 weeks, 5 days/week, 6 hr/day, either man-made vitreous fiber (MMVF)10a, MMVF33, or long amosite asbestos at approximately 300 World Health Organization (WHO) fibers/cc...Full Text Available
Eight rabbits and 24 guinea-pigs were exposed to a silica dust cloud of about 40,000 pp./ml. (0·3-3·0 μ) and killed at four-weekly intervals up to 30 weeks. The guinea-pigs showed...Full Text Available
A noninvasive, simplified method using inhalation of stable xenon (Xe{sup s}) and computed tomographic (CT) scanning to estimate regional cerebral blood flow (rCBF) and regional partition coefficient (r{lambda}) is described. Twenty-four patients with cerebrovascular occlusive disease and six volunteer controls inhaled 30% Xe{sup s} and 70% oxygen for 180 seconds and exhaled for 144 seconds during serial CT scanning without denitrogenation. The end-tidal Xe{sup s} concentration was continuously monitored with a thermoconductivity analyzer to determine the build-up range (A value) and build-up rate constant (K value) for arteries with the curve fitting method. The time-CT number (Hounsfield unit) curve for cerebral tissue during the Xe{sup s} washin and washout phases was used to calculate r{lambda} and rCBF using least squares curve fitting analysis. The resultant r{lambda} and rCBF map demonstrated a reliable distribution between the gray and ...
A noninvasive, simplified method using inhalation of stable xenon (Xe"s) and computed tomographic (CT) scanning to estimate regional cerebral blood flow (rCBF) and regional partition coefficient (r#lambda#) is described. Twenty-four patients with cerebrovascular occlusive disease and six volunteer controls inhaled 30% Xe"s and 70% oxygen for 180 seconds and exhaled for 144 seconds during serial CT scanning without denitrogenation. The end-tidal Xe"s concentration was continuously monitored with a thermoconductivity analyzer to determine the build-up range (A value) and build-up rate constant (K value) for arteries with the curve fitting method. The time-CT number (Hounsfield unit) curve for cerebral tissue during the Xe"s washin and washout phases was used to calculate r#lambda# and rCBF using least squares curve fitting analysis. The resultant r#lambda# and rCBF map demonstrated a reliable distribution between the gray and white matter, and ...
Ingestion or inhalation of botulinum neurotoxin (BoNT) results in botulism, a severe and frequently fatal disease. Current treatments rely on antitoxins, which while effective cannot reverse...Full Text Available
When the vehicle-treated, sham-operated mice underwent heat stress, the fraction survival and core temperature at +4 h of body heating were found to be 5 of 15 and 34.4°C ± 0.3°C,...Full Text Available
C57BL/6ByJ (B6) and 129P3/J (129) mice have different alleles of Tas1r3, which is thought to influence gustatory transduction of sweeteners, but studies have provided conflicting...Full Text Available
The properties of a nonviable, aqueous ether-extracted Brucela abortus preparation, Bru-Pel, are described. In addition to inducing a "virus-type" interferon response and protecting mice against challenge with otherwise lethal doses of Semliki Forest virus, Bru-Pel is demonstrated to have potent antitumor properties in mice. These antitumor effects appear to be mediated by an increase in nonspecific resistance similar to that seen with other experimental antitumor agents. PMID:728911
To study the role in AIDS pathogenesis of the human immunodeficiency virus type 1 (HIV-1) Tat protein, a transactivator of viral and cellular genes, we generated transgenic mice with a recombinant DNA...Full Text Available
We have recently shown that viable Borrelia burgdorferi organisms induce a chronic infection associated with arthritis and carditis in severe combined immunodeficiency (scid) mice but not in immunocompetent...Full Text Available
Here we report the first 1H NMR metabolomics studies on excised lungs and bronchoalveolar lavage fluid (BALF) from mice exposed to crystalline silica. High resolution 1H...Full Text Available
Earlier studies have indicated that xylitol may increase the absorption and urinary excretion of dietary oxalate. It has also been indicated that xylitol increases the absorption of calcium. Intestinal absorption of lead, a divalent contaminant in the diet, is in many respects similar to that of calcium. The purpose of this study was to evaluate the effects of xylitol on the intestinal absorption of lead using two different approaches: the in situ ligated intestinal loop technique in cockerels and gastric gavage in mice.
Following infection with the protozoan parasite Leishmania major, C57BL/6 mice develop a small lesion that heals spontaneously. Resistance to infection is associated with the development...Full Text Available
Cholestatic liver injury induced by alpha-naphthylisothiocyanate (ANIT) is provoked by injury to intrahepatic bile ducts and the progression of hepatic necrosis requires the procoagulant protein tissue factor (TF) and extrahepatic cells including neutrophils. Recent studies have shown that myeloid cell TF contributes to neutrophil activation. We tested the hypothesis that myeloid cell TF contributes to neutrophil activation in ANIT-treated mice. TF activity in liver homogenates increased significantly in TF^f^l^o^x^/^f^l^o^x mice treated with ANIT, but not in TF^f^l^o^x^/^f^l^o^x/LysMCre mice (TFD^M^y^e^l^o^i^d mice), which have reduced TF expression in monocytes/macrophages and neutrophils. Myeloid cell-specific TF deficiency did not alter expression of the chemokines KC or MIP-2 but redu...
Chemical analyses were done on the abnormal hemoglobins of the five (101 x SEC)F_1 offspring of X- irradiated adult SEC mice to determine which hemoglobin genes were expressed in each hemoglobin variant. Three offspring of irradiated SEC males did not express either of the two kinds of #alpha#-chains normally found in all SEC mice. The deficient #alpha#-chain synthesis caused these mice to exhibit an #alpha#-thalassemia similar to human #alpha#-thalassemia. Scanning electron microscopy was used to show that many erythrocytes of mice with #alpha#-thalassemia have bizarre shapes; e.g. many erythrocytes appeared flattened or had thorny projections (acanthocytes). One mutant with a tandem duplication of a segment of chromosome 7 (site of locus determining #beta#-chain structure) produced twice as much SEC as 101 #beta#-chain polypeptides. One mutant that probably arose by non-disjunction of chromosome 7's ...
2,6-Dinitrotoluene (2,6-DNT) and pentachlorophenol (PCP) are used for industrial purposes and are found in the environment as hazardous contaminants. Because concurrent exposure to both compounds can occur, it is of interest to determine if organochlorine compounds potentiate the effect of nitroaromatic chemicals. A significant increase in mutagenicity was observed in urines from mice treated with 2,6-DNT alone and in combination with PCP. By week 4, mice that received both 2,6-DNT and PCP excreted urine that was more mutagenic than that from animals which received only 2,6-DNT. At weeks 2 and 4, mice were sacrificed and intestinal enzyme activities (nitroreductase, azo reductase, {beta}-glucuronidase, dechlorinase, and dehydrochlorinase) were quantitated. The enhanced genotoxicity observed in urines from 2,6-DNT/PCP-treated mice coincided with a decrease in nitroreductase and an increase in ...
Background The objective of this study was to confirm provisional quantitative trait loci (QTL) for cocaine-induced locomotor activation, on chromosomes 1, 5, 6, 9, 12, 15, 16, 17, and 18, previously identified in the AXB/BXA recombinant inbred (RI) and AcB/BcA recombinant congenic (RC) strains of mice derived from A/J (A) and C57BL/6J (B6) progenitors. This was accomplished through a genetic analysis of cocaine-induced activity in an AxB6 F2 cross and a phenotypic survey across a panel of B6.A chromosome substitution strains (CSS) mice. Mice were tested for cocaine-induced activity, following administration of saline and cocaine (20?mg/kg), utilizing an open-field procedure. Results Among AxB6 F2 mice, differences in cocaine-induced activity were associated with loci on chromosome 1 (D1Mi...
One such agent is the widely used anesthetic, halothane. To study the toxicity of u.v. decomposed halothane, mice were exposed to anesthetic concentrations (1.3%) of non- and u.v.-irradiated halothane in oxygen for 90 min. Halothane sleeping times increased from 14.3 min to 72.5 min. Microsomal mixed function oxidase activity decreased, as shown by prolonged pentobarbital sleeping times 1 day after exposure to halothane and irradiated halothane (54.6 min and 149.1 min, respectively, as compared to a 34.6-min control). Quantitative and qualitative differences were found in the amount of (/sup 14/C)-pentobarbital metabolites excreted by u.v. irradiated halothane-exposed mice compared to either oxygen or non-irradiated halothane-exposed groups. In addition, serum glutamic-oxalacetic transaminase (SGOT) of irradiated halothane-exposed mice increased to 233% of the control values, and serum glutamic-pyruvic transaminase (SGPT) ...
Cinnabar, a naturally occurring mercuric sulfide (HgS), has long been used in combination with traditional Chinese medicine as a sedative for more than 2000 years. Up to date, its pharmacological and toxicological effects are still unclear, especially in clinical low-dose and long-term use. In this study, we attempted to elucidate the effects of cinnabar on the time course of changes in locomotor activities, pentobarbital-induced sleeping time, motor equilibrium performance and neurobiochemical activities in mice during 3- to 11-week administration at a clinical dose of 10 mg/kg/day. The results showed that cinnabar was significantly absorbed by gastrointestinal (G-I) tract and transported to brain tissues. The spontaneous locomotor activities of male mice but not female mice were preferentially suppressed. Moreover, frequencies of jump and stereotype-1 episodes were progressively decreased after 3-week oral administration ...
The dose-dependent transfer of [sup 203]Pb to milk and uptake in suckling rats and mice during a three-day nursing period was studied. On day 14 of lactation, the dams were administered a single intravenous dose of lead, labelled with [sup 203]Pb, in four or five doses from 0.0005 to 2.0 mg Pb/kg b.wt. There was a linear relationship between Pb levels in plasma and milk of both species. The Pb milk: plasma ratios at 24 hr after administration were 119 and 89 in mice and rats, respectively. At 72 hr the Pb milk: plasma ratio had decreased to 72 in mice and 35 in rats. The tissue levels of lead in the suckling rats and mice were also linearly correlated with lead concentration in milk at 72 hr, showing that milk could be used as an indicator of lead exposure to the suckling offspring. It is concluded that lead is transported into rat and mouse milk to a very high extent and the excretion into milk is more ...
Radiation protection programs for workers are based, in the United States, on a hierarchy of limitations stemming from Federal guidance approved by the President. This guidance, which consists of principles, policies, and numerical primary guides, is used by Federal agencies as the basis for developing and implementing their own regulatory standards. The primary guides are usually expressed in terms of limiting doses to workers. The protection of workers against taking radioactive materials into the body, however, is accomplished largely through the use of regulations based on derived guides expressed in terms of quantities or concentrations of radionuclides. The values of these derived guides are chosen so as to assure that workers in work environments that conform to them are unlikely to receive radiation doses that exceed the primary guides. The purpose of the present report is to set forth derived guides that are consistent with current Federal radiation protection guidance. They ...
Individual monitoring of personal exposure to inhalation of uranium oxides throughout the manufacture of fuel for pressurized water reactor (PWR) includes lung gamma-spectrometry, fecal analysis and urine analysis. Examination of the results shows the following: internal exposure is the consequence of repeated intake incidents as revealed by early peaks of urinary and particularly fecal elimination; a shift is often observed with the results of aerosol concentration measured through air collectors; the measured variations of uranium lung incorporations are relatively fast (apparent mean period 165 d). Correct evaluation of the effective dose equivalent from inhalation requires further information concerning the aerosol size distribution at work stations, the physico-chemical characteristics of the product leading to an estimate of its actual biological solubility, and the measurement of the fraction of aerosol liable to intake with an ...
Beagle dogs given a single exposure to "2"3"9PuO_2 or "2"3"8PuO_2 aerosols are being observed for life-span dose-effect relationships. The "2"3"9Pu body burden of the nine dogs that died of pulmonary fibrosis-induced respiratory insufficiency during the first 3 yr after exposure was 1 to 12 #mu#Ci. One of these dogs had a pulmonary tumor. Five additional dogs with body burdens of 0.7 to 1.8 #mu#Ci died due to pulmonary neoplasia 3 to 5 yr after exposure. None of the dogs exposed to "2"3"8Pu have died during the first 3 postexposure yr. Lymphocytopenia was the earliest observed effect after inhalation of "2"3"9PuO_2 or "2"3"8PuO_2, occurring 0.5 to 2 yr after deposition of greater than or equal to 80 nCi plutonium in the lungs.
Cerebral blood flow (CBF) was measured by the "1"3"3Xe inhalation method in patients with multi-infarct dementia (MID, N = 26), Alzheimer's dementia (AD, N = 19), and among age-matched, neurologically normal, healthy volunteers (N = 26). Cognitive performance was assessed in all subjects using the Cognitive Capacity Screening Examination (CCSE). Cerebral vasomotor responses were calculated from differences in values of mean hemispheric gray matter blood flow (Delta CBF) measured during inhalation of 100% oxygen (hyperoxia) compared with CBF measured while breathing room air. Significant correlations were found between CCSE performance and vasomotor responsiveness in patients with MID (P less than .01), but not in patients with AD or in neurologically normal volunteers. Loss of vasomotor responsiveness is an indicator of cerebrovascular disease with rigidity and/or loss of reactivity of cerebral vessels, which impairs cerebrovascular responses ...
The thin windows for the Muon Ionization Cooling Experiment (MICE) liquid Absorber will be fabricated from 6061-T6-aluminum. The absorber and vacuum vessel thin windows are 300-mm in diameter and are 180 mm thick at the center. The windows are designed for an internal burst pressure of 0.68 MPa (100 psig) when warm. The MICE experiment design calls for changeable windows on the absorber, so a bolted window design was adopted. Welded windows offer some potential advantages over bolted windows when they are on the absorber itself. This report describes the bolted window and its seal. This report also describes an alternate window that is welded directly to the absorber body. The welded window design presented permits the weld to be ground off and re-welded. This report presents a thermal FEA analysis of the window seal-weld, while the window is being welded. Finally, the results of a test of a welded-window are presented.
ObjectiveExtended periods of muscle disuse, physical inactivity, immobilization, and bedrest result in a loss of muscle mass and a decrease in muscle force, which are accompanied by an increase in oxidative stress. We investigated the effects of the intake of green tea catechins on unloading-induced muscle dysfunction in tail-suspended mice. MethodsTen-week-old male BALB/c mice were fed a purified control diet or a diet containing 0.5% tea catechins for 14 d. Thereafter, the mice were subjected to continuous tail suspension for 10 d. On the final day, muscle mass, contractile force production, antioxidant potential, and carbonylated protein levels were evaluated. ResultsHind limb unloading caused a loss of soleus muscle weight and muscle force. Intake of tea catechins significantly inhibit...
The involvement of dorsal root ganglia was studied in an in vivo model of experimental rabies virus infection using the challenge virus standard (CVS-11) strain. Dorsal root ganglia neurons infected with CVS in vitro show prolonged survival and few morphological changes, and are commonly used to study the infection. It has been established that after peripheral inoculation of mice with CVS the brain and spinal cord show relatively few neurodegenerative changes, but detailed studies of pathological changes in dorsal root ganglia have not previously been performed in this in vivo experimental model. In this study, adult ICR mice were inoculated in the right hindlimb footpad with CVS. Spinal cords and dorsal root ganglia were evaluated at serial time points for histopathological and ultrastru...
Purpose PR-104, a bioreductive prodrug in clinical trial, is a phosphate ester which is rapidly metabolized to the corresponding alcohol PR-104A. This dinitrobenzamide mustard is activated by reduction to hydroxylamine (PR-104H) and amine (PR-104M) metabolites selectively in hypoxic cells, and also independently of hypoxia by aldo-keto reductase (AKR) 1C3 in some tumors. Here, we evaluate reductive metabolism of PR-104A in mice and its significance for host toxicity. Methods The pharmacokinetics of PR-104, PR-104A and its reduced metabolites were investigated in plasma and tissues of mice (with and without SiHa or H460 tumor xenografts) and effects of potential oxidoreductase inhibitors were evaluated. Results Pharmacokinetic studies identified extensive non-tumor reduction of PR-104A to t...
The Muon Ionization Cooling Experiment (MICE) focusing solenoid magnets focus the muon beam within the MICE cooling channel on a liquid or solid absorber that is within the warm bore of solenoid. The focusing magnet has a warm bore of 470 mm. his magnet consists of two coils 210-mm long that is separated by an aluminum mandrel that is 200 mm long. Each of the coils has its own leads. The coils may be operated in either the non-flip mode (solenoid mode with both coils at the same polarity) or the lip mode (quadrupole focusing mode where both coils are at opposite polarity). This report describes the focusing solenoid magnet design that will be built by the vendor. The progress on the construction of the first of the focusing magnets will also be discussed in this report. Ultimately three of these magnets will be built. These magnets will be cooled using a pair 1.5 W (at 4.2 K) pulse tube coolers.
Abstract: The ability of melatonin as a potent antioxidant was used as a rationale for testing its antiapoptotic ability in normal cells. Recently, melatonin was shown to possess proapoptotic action by increasing reactive oxygen species in certain cancer cells. The modification of radiation-induced apoptosis by melatonin and the expression of apoptosis-associated upstream regulators were studied in normal mice splenocytes and Jurkat T leukemia cells. C57BL/6 mice were exposed to a single whole body X-ray radiation dose of 2 Gy with or without 250 mg/kg melatonin pretreatment. The Jurkat cells were divided into four groups of control, 1 mm melatonin alone, 4 Gy irradiation-only and melatonin pretreatment before irradiation. The highest level of apoptosis in the normal splenic white pulp was...
Glycyrrhizin is a triterpene glycoside, a major active constituent of licorice (Glycyrrhiza glabra) root and numerous pharmacological effects like anti-inflammatory, anti-viral, anti-tumour and hepatoprotective activities has been attributed to it. In this study we evaluated the anti-inflammatory activities of glycyrrhizin in mice model of acute inflammation, carrageenan-induced pleurisy. We report here that glycyrrhizin (given at 10mg/kg i.p. 5min prior to carrageenan) exerts potent anti-inflammatory effects in this model. Injection of carrageenan into the pleural cavity of mice elicited an acute inflammatory response characterized by fluid accumulation in the pleural cavity which contained a large number of neutrophils (PMNs) as well as an infiltration of PMNs in lung tissues and subsequ...
The effects of dietary plant and yeast cerebroside (glucosylceramide), a major sphingolipid in plants and yeast, on atopic dermatitis (AD) like symptoms were investigated in a mouse model. After 7 wk of feeding with a diet containing maize glucosylceramide, plasma IgE levels became significantly lower and in contrast, the levels of interleukin (IL)-12, which induces cellular immunity, became significantly higher in the AD mice than in the controls. However, the sphingolipid constituents of the skin fraction in the maize glucosylceramide fed group did not contain sphingoid bases of plant origin, such as 8-unsaturated sphingoid bases. The results of the present study indicated that dietary plant glucosylceramide prevented AD-like symptoms in AD model mice via regulation of Th1/Th2 balance. P...
The effect of exposure to gamma rays on LPO contents in liver, spleen and kidney of mice and the anti-lipid-peroxidation of preparations of chinonin, tannic acid and squalene were reported. All these preparations were given by intragastric perfusion. For LPO, a modified method of TBA spectrophotometry was used for determination. The results show that LPO contents in tissues increased 72 h after whole-body exposure of mice to gamma rays, that in range of 0-4 Gy, there was a linear relationship between radiation doses and LPO contents, and that all three preparations were effective in reduction of the LPO content in liver, spleen and kidney of mice, with chinonin (at dose of 0.35 mg/mouse#centre dot#day) being more effective than tannic acid (at dose of 15 mg/mouse#centre dot#day) and squalene (at dose of 0.6 mg/mouse#centre dot#day).
Please cite this paper as: Ectopic mineralization of connective tissue in Abcc6-/- mice: effects of dietary modifications and a phosphate binder - a preliminary study. Experimental Dermatology 2008; 17: 203-207. Abstract: Pseudoxanthoma elasticum (PXE), a heritable multisystem disorder, is caused by mutations in the ABCC6 gene. We have developed a murine model for PXE by targeted inactivation of the corresponding mouse gene. A feature of this mouse model is ectopic mineralization of connective tissue capsule surrounding the bulb of vibrissae. This study was designed to investigate the effect of dietary sevelamer hydrochloride (Renagel), a phosphate binder, and specific mineral modifications on ectopic mineralization of connective tissue in Abcc6-/- mice. Three groups were fed a specific di...
Fyn is a Src-family tyrosine kinase that affects long term potentiation (LTP), synapse formation, and learning and memory. Fyn is also implicated in dendritic spine formation both in vitro and in vivo. However, whether Fyn's regulation of dendritic spine formation is brain-region specific and age-dependent is unknown. In the present study, we systematically examined whether Fyn altered dendritic spine density and morphology in the cortex and hippocampus and if these effects were age-dependent. We found that Fyn knockout mice trended toward a decrease in dendritic spine density in cortical layers II/III, but not in the hippocampus, at 1month of age. Additionally, Fyn knockout mice had significantly decreased dendritic spine density in both the cortex and hippocampus at 3months and 1year, an...
Abstract Crouzon syndrome is characterized by premature fusion of sutures and synchondroses. Recently, the first mouse model of the syndrome was generated, having the mutation Cys342Tyr in Fgfr2c, equivalent to the most common human Crouzon/Pfeiffer syndrome mutation. In this study, a set of micro-computed tomography (CT) scannings of the skulls of wild-type mice and Crouzon mice were analysed with respect to the dysmorphology caused by Crouzon syndrome. A computational craniofacial atlas was built automatically from the set of wild-type mouse micro-CT volumes using (1) affine and (2) non-rigid image registration. Subsequently, the atlas was deformed to match each subject from the two groups of mice. The accuracy of these registrations was measured by a comparison of manually placed landma...
The authors have studied the distribution of H-3 labelled schistosomicidal drug in mice by autoradiography. The H-3-labelled substances were found in liver and kidney and in successfully decreasing amounts in brain, lung, heart, fat, testis, pancreas and spleen. In various cells the silver granules were present mainly in the cytoplasms but a few in the nucleus. After administration of this labelled schistosomicidal drug, the mice were killed and studied in groups successively at 4, 8, 24 hrs. No difference in the distribution of silver granules were observed. This fact indicated that, this drug was rapidly absorbed and highly concentrated with a long duration of reservation in liver. All of these favours the schistosomicidal effect of the drug. As this drug was highly concentrated in the cytoplasm of liver cells, that might provide a pathophysiologic basis for the explanation of jaundice in the clinical practice. Moreover, the appearance of ...
On September 25, 1986, an elderly Virginia couple had their home fumigated by a local pest extermination company for the control of wood-boring insects. Two hundred and fifty pounds of sulfurylfluoride (SF), a colorless, odorless fumigant gas commonly used for this purpose, was applied in the approximately 80,000-cubic-foot home that date. Within 1 week, both husband and wife were dead. Because both deaths occurred within a short period of time and the wife's illness was compatible with toxic gas inhalation, these deaths were then thought to be related to the home fumigation.
The usefulness of the mouse, rat, and Syrian golden hamster as experimental models for studies of the development of respiratory tract cancer is considered. Three different application methods for examining the effects of environmental chemicals on the respiratory tract in these species are discussed: implantation, intratracheal instillation, and inhalation. The results of various investigations are presented to demonstrate that each particular method has both advantages and disadvantages. The techniques are also considered in comparison with the human situation and in the light of obtaining the most valid data for extrapolation to man. Brief attention is paid to the relevance to respiratory tract carcinogenesis of more recently developed organ and cell culture systems.
Adult and newborn rats were exposed to "2"3"9PuO_2 aerosols of four different size distributions. Rats of both ages were killed at intervals between 1 hr and 60 days postexposure. There were marked age- and particle-related size differences in deposition, although retention was similar throughout. The differences in deposition are attributable to relatively greater deposition of larger particles in the upper respiratory tracts of newborns.
Carbonyl sulfide (COS), a colorless gas, is a side product of industrial procedures sure as coal hydrogenation and gasification. It is structurally related to and is a metabolite of carbon disulfide. COS is metabolized in the body by carbonic anhydrase to hydrogen sulfide (H{sub 2}S), which is thought to be responsible for COS toxicity. No threshold limit value for COS has been established. Results of these studies indicate COS (with an LC{sub 50} of 590 ppm) is slightly less acutely toxic than H{sub 2}S (LC{sub 50} of 440 ppm).
There is a continuing need to understand dose-response relationships for ionizing radiation in order to protect the health of the public and nuclear workers from undue exposures. However, relatively few human populations have been exposed to doses of radiation high enough to cause observable, long-term health effects from which to derive dose-response relationships. This is particularly true for internally deposited radionuclides, although much effort has been devoted to epidemiological studies of the few types of exposures available, including lung cancers in uranium miners form the inhalation of the radioactive decay products of Ra, liver cancers in patients injected with Thorotrast X-ray contrast medium containing Th, bone cancers in radium dial painters who ingested Ra, and bone cancers in patients who received therapeutic doses of Ra. These four types of exposures to internally deposited radionuclides provide a basis for understanding the health effects of ...
Transposons are promising systems for somatic gene integration because they can not only integrate exogenous genes efficiently, but also be delivered to a variety of organs using a range of transfection...Full Text Available
Virtually all biomedical research makes use of a relatively small pool of laboratory-adapted, inbred, isogenic stocks of mice. Although the advantages of these models are many, there are a number of...Full Text Available
Exercise promotes weight loss and improves insulin sensitivity. However, the molecular mechanisms mediating its beneficial effects are not fully understood. Obesity correlates with increased production...Full Text Available
Bloodstream infection by highly antibiotic-resistant bacteria, such as vancomycin-resistant Enterococcus (VRE), is a growing clinical problem that increasingly defies medical intervention....Full Text Available
BackgroundThe dynorphin-kappa opioid receptor (KOR) system regulates glial proliferation after sciatic nerve injury. Here, we investigated its role in cell proliferation following...Full Text Available
Iron overload is common in patients undergoing allogeneic hematopoietic cell transplantation (HCT), but the mechanisms leading to overload are unknown. Here, we determined iron levels and the expression...Full Text Available
BackgroundIsoproterenol-induced cardiac hypertrophy in mice has been used in a number of studies to model human cardiac disease. In this study, we compared the transcriptional response...Full Text Available
PurposeThe goal of this study was to clarify the dynamics of tumor oxygen (partial pressure of oxygen, pO2) in SCC VII murine tumors in mice after X-ray...Full Text Available
Studies in rodents have shown that male sexual function can be disrupted by fetal or neonatal administration of compounds that alter endocrine homeostasis, such as the synthetic nonsteroidal estrogen...Full Text Available
The effect of thiamin on the organ distribution of lead was evaluated in CD-1 mice exposed intragastrically or intraperitoneally to a single dose of lead acetate (100 micrograms) containing 100 microCi...Full Text Available
BackgroundAKXD recombinant inbred strains of mice have proven to be very useful in the identification of potential oncogenes and tumor suppressors involved in the development of...Full Text Available
Previous studies have revealed marked differences in the incidence of leukemia between rats and mice exposed to 1,3-butadiene that do not appear to be readily explained on the basis of pharmacokinetics...Full Text Available
The number and type of stem cells in spleen and bone marrow of mice were determined after exposure to a single dose of 150 R on day 6, to a single dose of 500 R on day 6 or day 9 or to a fractionated dose of 150 R + 350 R on day 6 and 9. The stem cells were assayed on the basis of colony forming units (CFU) in spleen and of incorporation of iododeoxyuridine in spleen and bone marrow of lethally irradiated host mice. During the first month of life, the number of stem cells in non-irradiated mice increases markedly in bone marrow and slightly in spleen. Irradiation causes a long-lasting depression in stem cells, particularly in bone marrow and affecting preferentially erythropoietic precursor cells. Following a dose of only 150 R, the number of CFU in bone marrow is still below control levels 24 days later. An exposure to 500 R fractionated between day 6 and 9 has a markedly greater effect on stem cells in the spleen than the ...
Patients with Alport syndrome progressively lose renal function as a result of defective type IV collagen in their glomerular basement membrane. In mice lacking the α3 chain of type IV collagen...Full Text Available
The technology of gene targeting through homologous recombination has been extremely useful for elucidating gene functions in mice. The application of this technology was thought impossible in the large...Full Text Available
This unit presents two basic protocols that offer rapid assessments of anosmia (the absence of a sense of smell) in mice. The buried food test is used to check for the ability to smell volatile...Full Text Available
How an individual’s sex and genetic background modify cardiac adaptation to increased workload is a topic of great interest. We systematically evaluated morphological and physiological...Full Text Available
We hypothesized that I kappa B kinase (IKK)-mediated nuclear factor kappa B and forkhead BoxO3a phosphorylation will be associated with age-related endothelial dysfunction. Endothelium-dependent dilation and aortic protein expression/phosphorylation were determined in young and old male B6D2F1 mice and old mice treated with the IKK inhibitor, salicylate. IKK activation was greater in old mice and was associated with greater nitrotyrosine and cytokines. Endothelium-dependent dilation, nitric oxide (NO), and endothelial NO synthase phosphorylation were lower in old mice. Endothelium-dependent dilation and NO bioavailability were restored by a superoxide dismutase mimetic. Nuclear factor kappa B and forkhead BoxO3a phosphorylation were greater in old and were associated with increased express...
Interleukin 12 (IL-12) activates natural killer (NK) and T cells with the secondary synthesis and release of interferon-gamma (IFN-gamma) and other cytokines. IL-12-induced organ alterations are reported...Full Text Available
IntroductionIrradiation of normal, non-malignant bone during cancer therapy can lead to atrophy and increased risk of fracture at several skeletal sites, particularly...Full Text Available
We have recently reported that progeroid Zmpste24−/−mice, which exhibit multiple defects that phenocopy Hutchinson-Gilford progeria syndrome, show a profound dysregulation...Full Text Available
In mice and humans the circadian rhythm of many biochemical reactions, physiology, and behavior is generated by a transcriptional-translation feedback loop (TTFL) made up of the so-called core clock...Full Text Available
It has been of interest whether and when the rearrangement of neuronal circuits can be induced after projection patterns are formed during development. Earlier studies using cats reported that the rearrangement...Full Text Available
RasGRF1 is a Ras-guanine nucleotide exchange factor implicated in a variety of physiological processes including learning and memory and glucose homeostasis. To determine the role of RASGRF1 in aging,...Full Text Available
Several different neuronal populations are involved in regulating energy homeostasis. Among these, agouti-related protein (AgRP) neurons are thought to promote feeding and weight gain; however, the...Full Text Available
The activity of mice in their home cage is influenced greatly by the cycle of light and dark. In addition, home-cage activity shows remarkable time-dependent changes that result in a prominent temporal...Full Text Available
BackgroundSeveral proteins are known to be markedly expressed in the brain during cerebral ischemia; however, the changes in protein profiles within the ischemic brain after an ischemic...Full Text Available
Clinical and experimental evidence has demonstrated the potential role of probiotics in the prevention or treatment of inflammatory bowel disease. Probiotic clones with direct immunomodulatory activity...Full Text Available
The objective of this study was to determine if inflammatory tolerance and enhancement of innate immune function could be induced by the gram-positive cell wall component peptidoglycan (PGN)....Full Text Available
Insulin resistance plays a central role in type 2 diabetes and obesity, which develop as a consequence of genetic and environmental factors. Dietary changes including high fat diet (HFD) feeding promotes...Full Text Available
OBJECTIVENicotinamide adenine dinucleotides (NAD+ and NADH) play a crucial role in cellular energy metabolism, and a dysregulated NAD+-to-NADH ratio is implicated...Full Text Available
Allergic asthma is characterized by airway hyperresponsiveness, inflammation, and a cellular infiltrate dominated by eosinophils. Numerous epidemiological studies have related the exacerbation of allergic...Full Text Available
Despite the health-related benefits of exercise, many people do not engage in enough activity to realize the rewards, and little is known regarding the genetic or environmental components that account...Full Text Available
Phenylketonuria (PKU) is a common genetic disorder in humans that arises from deficient activity of phenylalanine hydroxylase (PAH), which catalyzes the conversion of phenylalanine to tyrosine....Full Text Available
The ability to achieve tumor selective expression of therapeutic genes is an area that needs improvement for cancer gene therapy to be successful. One approach to address this is through the...Full Text Available
Mouse models for the study of autistic-like behaviors are increasingly needed to test hypotheses about the causes of autism, and to evaluate potential treatments. Both the automated 3-chambered...Full Text Available
Increased oxidative stress is associated with perinatal asphyxia and respiratory distress in the newborn period. Induction of nuclear factor erythroid 2 p45-related factor (Nrf2) has been shown to decrease...Full Text Available
OBJECTIVE—Identification of arterial genes and pathways altered in obesity and diabetes.RESEARCH DESIGN AND METHODS—Aortic gene expression profiles of...Full Text Available
Male transgenic mice expressing the polyomavirus middle T (PyV-MT) gene exhibited growth and developmental abnormalities in prostatic and other urogenital epithelium. Expression of PyV-MT was directed...Full Text Available
Naturally occurring, double-stranded RNA (ds-RNA)) was immunogenic when injected into mice, rats, guinea-pigs, rabbits, dogs and baboons. The response to native material administered intravenously (i.v.)...Full Text Available
A highly purified preparation of double-stranded RNA, obtained from virus-like particles in Penicillium cultures, was found to affert humoral immune responses in mice differentially depending on its...Full Text Available
The studies reported here used genetic differences in susceptibility of C57BL/6N and C3H/HeN mice and exacerbation of the disease by nitrogen dioxide (NO/sub 2/) as tools in assessing the role of early host responses in the pathogenesis of MRM. The two strains did not differ in susceptibility to infection, but C3H/HeN mice were more susceptible to and had increased severity of lung lesions 14 days after intranasal inoculation as determined by 50% biological endpoints and morphometric analysis of tissues. Exposure to NO/sub 2/ for 4 hours prior to exposure to infectious aerosols exacerbated murine respiratory mycoplasmosis (MRM) by 7 days after exposure in both mouse strains. NO/sub 2/ appeared to affect host lung defense mechanisms responsible for limiting mycoplasmal growth in the lungs. The NO/sub 2/ exposure concentration required for this effect varied with the genetic background of the host, the dose of mycoplasmas administered, and the ...
Muscular dystrophies (MDs) comprise a group of degenerative muscle disorders characterized by progressive muscle wasting and often premature death. The primary defect common to most MDs involves disruption...Full Text Available
BackgroundThe tumor microenvironment has been described as a critical milieu determining tumor growth and metastases. A pivotal role of metastasis-inducing S100A4 in the development...Full Text Available
The use of infectious pathogens has allowed the detection of the development of synergism between pathogens and ubiquitous environmental chemical contaminants. This synergism has been demonstrated to...Full Text Available
Despite the demonstrated clinical efficacy of CD20 monoclonal antibody (mAb) for lymphoma therapy, the in vivo mechanisms of tumor depletion remain controversial and variable. To identify the molecular...Full Text Available
Retinal degenerative diseases, such as retinitis pigmentosa and Leber congenital amaurosis, are a leading cause of untreatable blindness with substantive impact on the quality of life of affected individuals...Full Text Available
Hematopoietic stem and progenitor cell (HSPC) expansion is regulated by intrinsic signaling pathways activated by cytokines. The intracellular kinase JAK2 plays an essential role in cytokine signaling,...Full Text Available
Rationale: Human data suggest that the incidence of acute lung injury is reduced in patients with type II diabetes mellitus. However, the mechanisms by which diabetes confers protection...Full Text Available
1. Interactions of pyrazole and ethanol were studied in three laboratory test procedures. They included sleeping time in mice, rotor rod balance in rats and lever pressing behaviour of rats. 2....Full Text Available
The receptors for IGF-I (IGF-IR) and insulin (IR) have been implicated in physiological cardiac growth, but it is unknown whether IGF-IR or IR signaling are critically required. We generated mice with...Full Text Available
The AKR mouse strain is characterized by a high incidence of spontaneous thymic lymphoma that appears in older animals (greater than 6 months of age) and is associated with novel provirus integrations...Full Text Available
Hyperproliferation of the colonic epithelium, leading to expansion of colonic crypt progenitors, is a recognized risk factor for colorectal cancer. Overexpression of progastrin, a nonamidated and incompletely...Full Text Available
Hyperglycemia and hyperinsulinemia accelerate both aging and cancer. Antidiabetic biguanides such as metformin decrease glucose, insulin and IGF-1 level. Metformin increases lifespan and prevents cancer...Full Text Available
Francisella tularensis is a highly infectious bacterium causing the zoonotic disease tularaemia. During its infectious cycle, F. tularensis is not only exposed to the...Full Text Available
Skeletal formation is an essential and intricately regulated part of vertebrate development. Humans and mice deficient in Growth and Differentiation Factor 6 (Gdf6) have numerous...Full Text Available
Background:The cardiac sodium–calcium exchanger (NCX1) is a key sarcolemmal protein for the maintenance of calcium homeostasis in the heart. Since heart failure...Full Text Available
The tea polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been studied for chronic disease preventive effects, and is marketed as part of many dietary supplements. However, case reports have...Full Text Available
One of the major decisions that germ cells make during their development is whether to differentiate into oocytes or sperm. In mice, the germ cells’ decision to develop as male or female depends...Full Text Available
Mood and anxiety disorders and rodent phenotypic measures modeling these disorders have a strong genetic component. Various assays are used to study the neurobiological basis of fear- and anxiety-related...Full Text Available
Exercise is essential for health, yet the amount, duration, and intensity that individuals engage in are strikingly variable, even under prescription. Our focus was to identify the locations and effects...Full Text Available
Neurofibromatosis type 1 (NF1) results from mutations in the NF1 tumor suppressor gene, which encodes the protein neurofibromin. NF1 patients display diverse clinical manifestations,...Full Text Available
Keap1 regulates Nrf2 activity in response to xenobiotic and oxidative stresses. Nrf2 is an essential regulator of cytoprotective genes. Keap1-null mice are lethal by weaning age due...Full Text Available
Cigarette smoke (CS) induces recruitment of inflammatory cells in the lungs leading to the generation of reactive oxygen species (ROS), which are involved in lung inflammation and injury. Nicotinamide...Full Text Available
Studies in mammals have led to the suggestion that hyperglycemia and hyperinsulinemia are important factors both in aging and in the development of cancer. It is possible that the life-prolonging effects...Full Text Available
PurposeTo investigate the effects of laser photocoagulation (LP)-induced ocular hypertension (OHT) on the survival and retrograde axonal transport of retinal ganglion cells (RGC),...Full Text Available
The discovery that aerobic exercise increases adult hippocampal neurogenesis and can enhance cognitive performance holds promise as a model for regenerative medicine. This study adds two new...Full Text Available
Fibroblast cell population kinetics in the developing molar periodontal ligament was investigated in 10, 12, 16 and 20 days old mice by autoradiography after the administration of [3H]thymidine. Labelled...Full Text Available
Deficits in prepulse inhibition (PPI) are a biological marker for schizophrenia. To unravel the mechanisms that control PPI, we performed quantitative trait loci (QTL) analysis on 1,010 F2 mice derived...Full Text Available
The destiny of the mitotically active cells of the subventricular zone (SVZ) in adult rodents is to migrate to the olfactory bulb, where they contribute to the replacement of granular and periglomerular...Full Text Available
We developed mice with germline endogenous expression of oncogenic Hras to study effects on development and mechanisms of tumor initiation. They had high perinatal mortality, abnormal...Full Text Available
BackgroundAntigen sparing and cross-protective immunity are regarded as crucial in pandemic influenza vaccine development. Both targets can be achieved by adjuvantation strategy...Full Text Available
Both deficiency and excess of growth hormone (GH) are associated with increased mortality and morbidity. GH replacement in otherwise healthy subjects leads to complications, whereas individuals with...Full Text Available
BackgroundDespite numerous treatments available for deteriorated cutaneous wound healing such as a diabetic foot, there is still the need for more effective therapy. Adipose-derived...Full Text Available
Mice lacking acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1), an enzyme that catalyzes the terminal step in triacylglycerol synthesis, have enhanced insulin sensitivity and are protected from...Full Text Available
Chemoprevention strategies to prevent the development of lung cancer in at-risk individuals are a key component in disease management. In addition to being highly effective, an ideal chemopreventive...Full Text Available
Antivenoms are the currently available agents for treatment of snake venom intoxication in humans. The development of therapeutic strategies employing more generally available drugs could improve treatment of invenomation by reducing hypersensitive reacti...
In chronic kidney disease, fibroblast dysfunction causes renal fibrosis and renal anemia. Renal fibrosis is mediated by the accumulation of myofibroblasts, whereas renal anemia is mediated by the reduced...Full Text Available
The distribution of lead in lactating mice and suckling offspring was studied with whole body autoradiography at 4 and 24 h after a single intravenous injection of {sup 203}Pb (50 mmol Pb/kg) to the dams. In the lactating mice on day 14 of lactation, the highest uptake of radioactivity at 4 h after administration was recorded in renal cortex, skeleton and liver. A high uptake was also evident in the mannary gland. At 24 h after administration, the radioactivity had decreased in most organs except in the skeleton. In the suckling pups, exposed to lead only via dams` milk for 24 h, the highest level of radioactivity was present in the intestinal mucosa and a much lower level of radioactivity was present in the skeleton. The mammary glands from mice given three daily intravenous injections of 240 {mu}mol Pb/kg were examined with X-ray microanalysis. At 4 h after the last injection, lead was found associated with casein ...
The distribution of lead in lactating mice and suckling offspring was studied with whole body autoradiography at 4 and 24 h after a single intravenous injection of "2"0"3Pb (50 mmol Pb/kg) to the dams. In the lactating mice on day 14 of lactation, the highest uptake of radioactivity at 4 h after administration was recorded in renal cortex, skeleton and liver. A high uptake was also evident in the mannary gland. At 24 h after administration, the radioactivity had decreased in most organs except in the skeleton. In the suckling pups, exposed to lead only via dams' milk for 24 h, the highest level of radioactivity was present in the intestinal mucosa and a much lower level of radioactivity was present in the skeleton. The mammary glands from mice given three daily intravenous injections of 240 #mu#mol Pb/kg were examined with X-ray microanalysis. At 4 h after the last injection, lead was found associated with casein micelles ...
Whereas genetic factors are known to influence both susceptibility to carcinogens and the capacity to respond to specific antigenic stimuli, little is known regarding the influence of phenotype per...Full Text Available
Uncoupling protein 2 (UCP2) maps to a region on distal mouse chromosome 7 that has been linked to the phenotypes of obesity and type II diabetes. We recently reported that UCP2 expression is increased...Full Text Available
The objective of this study was to develop a specific immunological diagnostic assay for yellow disease in hyacinths, using monoclonal antibodies (MAbs). Mice were immunized with a crude cell wall preparation...Full Text Available
The utility of a two-photon optical fiber fluorescence probe (TPOFF) for sensing and quantifying tumor fluorescent signals was tested in vivo. Xenograft tumors were developed in athymic mice using MCA207...Full Text Available
The increased transmission and geographic spread of dengue fever (DF) and its more severe presentation, dengue hemorrhagic fever (DHF), make it the most important mosquito-borne viral disease of humans...Full Text Available
Circadian clock is implicated in the regulation of aging. The transcription factor CLOCK, a core component of the circadian system, operates in complex with another circadian clock protein BMAL1. Recently...Full Text Available
OBJECTIVEPhosphoinositide 3-kinase enhancer A (PIKE-A) is a proto-oncogene that promotes tumor growth and transformation by enhancing Akt activity. However, the physiological functions...Full Text Available
The pathogenic mechanisms of human autosomal dominant polycystic kidney disease (ADPKD) have been well known to include the mutational inactivation of PKD2. Although haploinsufficiency...Full Text Available
Huntington's disease (HD) is one of several neurodegenerative disorders caused by expansion of CAG repeats in a coding gene. Somatic CAG expansion rates in HD vary between organs, and the greatest instability...Full Text Available
ATP-binding cassette A3 (ABCA3) is a lipid transport protein required for synthesis and storage of pulmonary surfactant in type II cells in the alveoli. Abca3 was conditionally deleted...Full Text Available
Mice were killed 7, 11, 19, and 27 weeks after infection with strains of Schistosoma mansoni from Puerto Rico, Brazil, St Lucia, and Tanzania. The percentage recovery of adult worms...Full Text Available
Germ cell tumor development in humans has been proposed to be part of testicular dysgenesis syndrome (TDS), which manifests as undescended testes, sterility, hypospadias, and, in extreme cases,...Full Text Available
Growing evidences indicate that proteases are implicated in adipogenesis and in the onset of obesity. We previously reported that the cysteine protease cathepsin K (ctsk) is overexpressed in the white...Full Text Available
New neurons are generated in the granule cell layer of the dentate gyrus (GCL) throughout adulthood. This process is modulated by many environmental and neurochemical factors. We previously...Full Text Available
Tick-borne encephalitis (TBE) virus causes severe encephalitis with serious sequelae in humans. The disease is characterized by fever and debilitating encephalitis that can progress to chronic illness...Full Text Available
Molecular chaperones protect cells from the deleterious effects of protein misfolding and aggregation. Neurotoxicity of amyloid-beta (Aβ) aggregates and their deposition in senile plaques are...Full Text Available
CSV consists of a very complex of molecules and demonstrates significant cellular activities capable of stimulating immune functions in vivo. The purpose of this study was to analyze the effects of...Full Text Available
Cytokines produced by Th2 cells are responsible for the pathogenesis of asthma. Th1-biased immune responses caused by attenuated salmonella have the potential to relieve asthmatic symptoms. We evaluated...Full Text Available
AIM: To investigate atrial natriuretic peptide (ANP) secretion from gastric mucosa and the relationship between the ANP/natriuretic peptide receptor type A (NPR-A) pathway and diabetic gastroparesis.METHODS:...Full Text Available
Chagas disease, caused by infection with Trypanosoma cruzi, is an important cause of cardiovascular disease. It is increasingly clear that parasite-derived prostaglandins potently modulate...Full Text Available
The amyloidoses are the prototype gain of toxic function protein misfolding diseases. As such, several naturally occurring animal models and their inducible variants provided some of the first...Full Text Available
BackgroundMale infertility is a common cause of reproductive failure in humans. In mice, targeted deletions of the genes coding for FKBP6 or FKBP52, members of the FK506 binding...Full Text Available
Even in healthy individuals, aging leads to deterioration in visual acuity, contrast sensitivity, visual field, and dark adaptation. Little is known about the neural mechanisms that drive the...Full Text Available
Neurons are born throughout adulthood in the hippocampus and show enhanced plasticity compared to mature neurons. However, there are conflicting reports on whether or not young neurons contribute...Full Text Available
Cerebral malaria is the most severe complication of human infection with Plasmodium falciparum. It was shown that Plasmodium berghei ANKA-induced cerebral malaria was...Full Text Available
The abnormal megakaryocytopoiesis associated with idiopathic myelofibrosis (IM) plays a role in its pathogenesis. Because mice with defective expression of transcription factor GATA-1 (GATA-1low...Full Text Available
BackgroundObesity is one of the principal causative factors involved in the development of metabolic syndrome. AMP-activated protein kinase (AMPK) is an energy sensor that regulates...Full Text Available
Here we describe a Sleeping Beauty (SB) transposition system that utilizes a conditional SB transposase allele, which can be activated by Cre...Full Text Available
This study investigated the effect of copper as an antibacterial agent on the infectivity of Salmonella enterica serovar Typhimurium. Mice were infected orally with a standardized dose...Full Text Available
Humanin (HN), a 24-residue peptide, was identified as a novel neuroprotective factor and shows anti-cell death activity against a wide spectrum of Alzheimer's disease (AD)-related cytotoxicities, including...Full Text Available
Infant mice were used to measure the amount of fluid accumulation (enterosorption) in the intestinal tract after oral inoculation of a porcine strain of enteropathogenic Escherichia coli (K88-+, Ent-+). Significant reduction in the amount of fluid found in the intestinal tract was observed if the mice were first inoculated with a K88-possessing, non-enterotoxigenic strain of E. coli. The protection provided is thought to be due to specific competition for attachment sites on cells of the small intestine. PMID:1095492
Three N-methylcarbamates of iodonitrobenzyl alcohols (4-iodo-2-nitrobenzyl alcohol 2, 5-iodo-2-nitrobenzyl alcohol 3 and 4-iodo-2,6-dinitrobenzyl alcohol 4) bearing [[sup 125]I] have been prepared and characterized for their lipophilicity, their reduction potentials and the in vivo lability of the radioiodine in healthy mice. Based upon these results, 2 and 4 were tested in tumor-bearing mice showing limited uptake of radioactivity in tumours and a tumor-to-blood ratio of less than 1. Consequently these particular carbamates are not satisfactory as hypoxia imaging agents. (author).
Thermal neutron beam from the TNRF of JRR-3M was utilized for detection of mice lung cancer in vivo. Both the static and real-time neutron imaging were tried. Very strong thermal neutron beam is necessary to detect lung cancers because small changes are hidden by the very large attenuation of thermal neutron beam by the hydrogens in the tissues. The detection was successfully performed. Especially, the Super Eye of Hamamatsu Photonics contributed very effectively. Bone marrows and cartilages were also shown clearly. If an efficient and compact neutron source will become available in future, this method will grow up as a powerful tool for biomedical application. (author).
Full text: Lung cancer is responsible for most of the cancer related deaths and calls for new approaches to control the menace. In the present study chemopreventive efficacy of curcumin and quercetin was investigated against benzo(a)pyrene (BP) induced lung carcinogenesis. The mice were segregated into five groups which included normal control, BP treated, BP+curcumin treated, BP+quercetin treated and BP+curcumin+quercetin treated groups. The morphological and histological analyses of tumor nodules confirmed lung carcinogenesis, after 22 weeks of single i.p. injection of BP at a dose of 100 mg/Kg body weight to mice. Tumor incidence and tumor multiplicity were observed to be 88% and 1.75, respectively in the BP treated mice. A statistically significant increase in the uptake of "3H thymidine indicative of increased DNA synthesis which in turn is the marker of uncontrolled cancer cell proliferation, was observed in the lung ...
A factor produced by plerocercoids of the tapeworm Spirometra mansonoides is similar to human growth hormone (hGH) in that it stimulates body growth, binds to hGH receptors, cross-reacts with anti-hGH antibodies, and has lactogenic and insulin-like activities. The purpose of this study was to determine whether plerocercoid growth factor (PGF) is similar to hGH in expressing diabetogenic activity in the genetically obese (ob/ob) mouse. To determine an effective dose for use in the obese mice, the ability of daily injections of PGF to stimulate growth of phenotypically normal mice of the same strain was assessed in a 10-day weight gain assay. Injections of PGF stimulated a dose-dependent weight gain (r = 0.83) and 25 ng eq/day of PGF stimulated a response not significantly different from that produced by 100 micrograms of bovine growth hormone/day. Diabetogenicity was assessed using fasting blood glucose and glucose tolerance tests in obese ...
Insulitis is considered the histopathological hallmark of type I diabetes. In the non-obese diabetic (NOD) mouse, diabetes has never been observed in the absence of insulitis. The in vivo detection of insulitis could be of relevance for early prediction of diabetes. As approximately 15% of islet-infiltrating lymphocytes express interleukin 2 receptors, the authors have labelled recombinant inter-leukin 2 with "1"2"3I and used this radiopharmaceutical to detect insulitis by gamma camera imaging. The authors studied 71 prediabetic NOD and 27 normal Balb/c mice. Labelled #alpha#-lactalbumin was used as the control protein. In the first set of experiments the tissue distribution of radiolabelled interleukin 2 in isolated organs from animals sacrificed at different time points was studied. Higher radioactivity was detected in the pancreas of NOD mice injected with labelled interleukin 2, as compared to NOD mice receiving ...
By polymerase chain reaction with arbitrary primer (AP-PCR), the possibility of transmission of genome instability to somatic cells of the offspring (F_1 generation) from male parents of mice exposed to chronic low-dose #gamma#-radiation was studied. Male mice 15 days after exposure to 10-50 cGy were mated with unirradiated females. Biopsies were taken from tale tips of two month-old mice progeny for DNA separation. Primer in the AP-PCR was 20-mer oligonucleotide flanking the micro-satellite locus Atplb2 on chromosome 11 of the mouse. Comparative analysis of individual fingerprints of AP-PCR products on DNA-templates from the offspring of irradiated and unirradiated male mice revealed an increased variability of micro-satellite-associated sequences in the genome of the offspring of males exposed to 25 and 50 cGy. DNA-fingerprints of the offspring of male mice exposed to chronic ...
There are very different views on the health hazards of DU munitions. Most of the concerns of veterans and their advisors focus on the radiological effects of DU and consequently these are the focus of this editorial. Effects on the kidney and environmental consequences are, however, considered in the second of the Royal Society reports and the main conclusions of both of the reports are outlined in the summary document published in this issue of the journal. The main radiological concerns focus on the irradiation of lung tissues from inhaled DU particles and irradiation resulting from the translocation of inhaled particles to the thoracic lymph nodes.The overwhelming scientific view, presented in the two Royal Society reports and in other independent reviews, is that the main risks of exposure to DU aerosols are an increase in lung cancer and (from chemical toxicity) damage to the kidney, although these are likely to be evident only following ...
''Paraquat lung'' which is complicated with paraquat poisoning has been a lethal pulmonary pathology presenting intra-alveolar fibrosis, but an effective therapy has not been developed so far. We hypothesized that the type II alveolar cells producing surfactant were damaged by paraquat which was actively accumulated through out the blood by alveolar epithelial cells. To prove this hypothesis, we examined the effect of an intratracheal administration of an artificial lung surfactant (surfacten, Mitsubishi Tanabe Pharma Corporation, Osaka) on mortality in a model of murine paraquat poisoning. Paraquat was given intramuscularly 3 days after the intratracheal surfactant administration. The mice used were C57BL/6J strain and Balb/C strain. The lethal dose, 50% (LD50), of paraquat was about 28 mg/kg in the C57BL/6J strain and about 9 mg/kg in the Balb/C strain, respectively. Mortalities of paraquat poisoning in both strains of mice improved ...
The insulin signaling pathway, involving protein kinase B (PKB) and mitogen-activated protein kinase (MAPK), mediates the biological response to insulin and several growth factors and cytokines. To investigate the correlation between glucose transporter (Glut) biosynthesis and the insulin signaling pathway activated by novel compounds of Liriope platyphylla (LP9M80-H), alterations in Glut and key protein expression in the insulin signaling pathway were analyzed in the liver and brain of ICR mice treated with LP9M80-H. An in vitro assay showed that the highest level of insulin concentration was observed in the LP9M80-H-treated group, followed by the LP-H, LP-M, LP-E, and LP9M80-C-treated groups. Therefore, LP9M80-H was selected for use in studying the detailed mechanism of the insulin signaling pathway in animal systems. In an in vivo experiment, LP9M80-H induced a significant increase in glucose levels and a decrease of insulin concentration in the blood of ...
In this paper the measurements of radon-222 concentration in the air of Kowary Radon Inhalatorium in the vicinity of Jelenia Gora, Lower Silesia, Poland, performed by Radiation Protection and Radiobiology Department of National Institute of Hygiene in Warsaw, have been presented. For the measurements the integration method with the application of charcoal canisters have been used. The radon concentration was found within the very broad ranges from about 4 to 420 kBq m"-"3 depending of the season of the year. Basing on the radon concentration measurements during the inhalation therapy session and taking into account the equilibrium factor of 0.8 the doses to the bronchi of the patients in range from 1.2 to about 204 mSv (0.12-20.4 rem) have been assessed. The majority of patients (ca. 76%) received the doses between 115 and 204 mSv. (author)
Tert-Butanol is an important intermediate in industrial chemical synthesis, particularly of fuel oxygenates. Human exposure to tert-butanol may occur following fuel oxygenate metabolism or biodegradation. It is poorly absorbed through skin, but is rapidly absorbed upon inhalation or ingestion and distributed to tissues throughout the body. Elimination from blood is slower and the half-life increases with dose. It is largely metabolised by oxidation via 2-methyl-1,2-propanediol to 2-hydroxyisobutyrate, the dominant urinary metabolites. Conjugations also occur and acetone may be found in urine at high doses. The single-dose systemic toxicity of tert-butanol is low, but it is irritant to skin and eyes; high oral doses produce ataxia and hypoactivity and repeated exposure can induce dependence...
We have previously reported that periventricular structures are hypoperfused in attention deficit and hyperactivity disorder (ADHD). This study has expanded the number of patients, who were divided into two groups: six patients with pure ADHD, and 13 patients with ADHD in combination with other neurologic symptoms. By using xenon 133 inhalation and emission tomography, the regional cerebral blood flow distribution was determined and compared with a control group. Striatal regions were found to be hypoperfused and, by inference, hypofunctional in both groups. This hypoperfusion was statistically significant in the right striatum in ADHD, and in both striatal regions in ADHD with other neuropsychologic and neurologic symptoms. The primary sensory and sensorimotor cortical regions were highly perfused. Methylphenidate increased flow to striatal and posterior periventricular regions, and tended to decrease flow to primary sensory regions. Low striatal activity, ...
The estimation of radiation dose to man from either external or internal exposure to radionuclides requires a knowledge of the energies and intensities of the atomic and nuclear radiations emitted during the radioactive decay process. The availability of evaluated decay data for the large number of radionuclides of interest is thus of fundamental importance for radiation dosimetry. This handbook contains a compilation of decay data for approximately 500 radionuclides. These data constitute an evaluated data file constructed for use in the radiological assessment activities of the Technology Assessments Section of the Health and Safety Research Division at Oak Ridge National Laboratory. The radionuclides selected for this handbook include those occurring naturally in the environment, those of potential importance in routine or accidental releases from the nuclear fuel cycle, those of current interest in nuclear medicine and fusion reactor technology, and some of those of interest to ...
A noninvasive method is described for estimating local cerebral blood flow (LCBF) and local partition coefficients by means of computed tomographic scanning during inhalation of 30% stable xenon gas in oxygen. Time-dependent xenon concentrations in arterial blood and brain tissue during the wash-in and washout phases are used to calculate partition coefficients and LCBF values by means of a least-squares curve-fitting analysis. Control values for partition coefficient and LCBF obtained from control subjects with minor head trauma in the chronic stage were compatible with those in several past reports, and reproducibility was satisfactory. The theoretic grounds underlying this new method of curve-fitting analysis are discussed.
A noninvasive method is described for estimating local cerebral blood flow (LCBF) and local partition coefficients by means of computed tomographic scanning during inhalation of 30% stable xenon gas in oxygen. Time-dependent xenon concentrations in arterial blood and brain tissue during the wash-in and washout phases are used to calculate partition coefficients and LCBF values by means of a least-squares curve-fitting analysis. Control values for partition coefficient and LCBF obtained from control subjects with minor head trauma in the chronic stage were compatible with those in several past reports, and reproducibility was satisfactory. The theoretic grounds underlying this new method of curve-fitting analysis are discussed.
Fischer-344 rats were exposed to quartz dusts and to quartz-bearing oil shale dusts in long-term inhalation studies. Aerosol concentrations of 12 mg/m/sup 3/ and 152-176 mg/m/sup 3/ for quartz and shale dusts, respectively, were used in exposure regimens lasting up to two years. Pulmonary fibrosis was observed in most animals surviving beyond 400 days. Adenocarcinomas and epidermoid carcinomas of the lung were observed in animals from all exposure groups, including those exposed to quartz alone. The pulmonary tumors were a late effect, with the earliest lung tumor being observed after 651 days. 13 references, 10 figures, 4 tables.
Deferoxamine (DFA) (250 mg/kg), orally administered to rats, decreased Pu absorption from orally administered "2"3"8Pu(NO_3)_4 by about 1/3. The calcium salt of diethylenetriaminepentaacetic acid (Ca-DTPA), given orally 5 to 10 min after the Pu, increased absorption about four times. DFA given 10 min before the DTPA decreased the effect of the latter by a factor of two. Deferoxamine administration prior to inhalation treatment of man with DTPA may be one way to decrease possible DTPA-enhanced gut absorption of Pu.
Radon concentration measurements were performed for one year in 12 different boron, chromium and coal underground mines in Western Turkey. Lucas cells and nuclear track detectors were used for the measurements of radon and its decay products. The effects of parameters, such as type of mine, gallery depth and ventilation rate, on the radon concentration in mine air were examined. The radiation exposure doses of miners due to the inhalation of radon and radon daughters were determined. Gamma survey measurements were also realized together with radon measurements and the total effective dose equivalents in mSv y{sup -1} were estimated.
Following the United Kingdom's nuclear tests at Maralinga in Australia in the 1960's, the Australian government signed away its rights to claim compensation for decontamination costs in a 1968 agreement. Controversy now rages as the Australian government is claiming pound33 million for this purpose from the United Kingdom to compensate the Maralinga Tjarutja for the loss of access to their traditional lands. They claim that the UK clean-up operation was inadequate and that much plutonium was spread over the land, rather than contained in pits. Measurements of contamination at the site were wrong by a factor of ten according to a 1984 visit when Australian scientists were horrified to realize that an Aboriginal child living near Taranaki could inhale more than 460 millisieverts a year. As ministers from both countries meet in June 1993 the debate is likely to be heated and hotly defended. (UK).
Locomotion is a complex behavior affected by many different brain- and spinal cord systems, as well as by variations in the peripheral nervous system. Recently, we found increased gene expression for EphA4, a gene intricately involved in motor neuron development, between high-active parental strain C57BL/6J and the low-active chromosome substitution strain 1 (CSS1). CSS1 mice carry chromosome 1 from A/J mice in a C57BL/6J genetic background, allowing localization of quantitative trait loci (QTL) on chromosome 1. To find out whether differences in motor neuron anatomy, possibly related to the changes in EphA4 expression, are involved in the motor activity differences observed in these strains, motor performance in various behavioral paradigms and anatomical differences in the ventral roots ...
Tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) have been shown to stimulate bone resorption in vitro. We have now investigated whether these cytokines also cause a similar action when administered in vivo. This was made possible by the adaptation of a newly developed technique that enables the continual assessment of bone resorption in vivo in mice by measuring urinary excretion of {sup 3}H from ({sup 3}H)tetracycline-prelabeled animals. Experiments using maneuvers known to influence bone resorption, such as a change in dietary calcium or administration of parathyroid hormone or dichloromethylenebisphosphonate, indicate that the technique is reliable and sensitive in mice. Daily intravenous administration of either recombinant human or recombinant murine TNF-alpha, as well as subcutaneous administration of recombinant human IL-1 alpha, were found to stimulate bone resorption in a dose-dependent manner. The effect was maximal ...
The radiosensitivity of spermatogonial stem cells of C3H/HeHx101/H F[sub 1] hybrid mice was determined by counting undifferentiated spermatogonia at 10 days after X-irradiation. During the spermatogenic cycle, differences in radiosensitivity were found, which were correlated with the proliferative activity of the spermatogonial stem cells. In stage VIII[sub irr], during quiescence, the spermatogonial stem cells were most radiosensitive with a D[sub 0] of 1.4 Gy. In stages XI[sub irr]-V[sub irr], when the cells were proliferatively active, the D[sub 0] was about 2.6 Gy. Based on the D[sub 0] values for sensitive and resistant spermatogonia and on the D[sub 0] for the total population, a ratio of 45:55% of sensitive to resistant spermatogonial stem cells was estimated for cell killing. When the present data were compared with data on translocation induction obtained in mice of the same genotype, a close fit was obtained when the translocation ...
CBA/Ca mice were infected by either the intravenous or intraperitoneal route with Mycobacterium microti and the subsequent changes in local macrophage populations examined. Following infection, the number of macrophages increased and they showed greater expression of both MHC Class II molecules. This response was not dependent on viability of the mycobacteria, in contrast to reports with other microorganisms such as Listeria. Studies in sublethally irradiated mice indicated that persistent antigen could give rise to a response after a period of host recovery which was radiation dose dependent. This procedure also highlighted differences in the regulation of different murine class II antigens in vivo, as seen by delayed re-expression of I-E antigens. Macrophage accessory cell function, as assessed by an in vitro T cell proliferation assay, correlated with Ia expression after fixation, but not after indomethacin treatment; this highlights the ...
Experiments were carried out on mice and the subjects irradiated for cancer therapy to evaluate the protective efficacy of a Chinese medicinal herb-compound (CMHC). The lethality and the degree of leucopenia caused by radiation in mice medicated with CMHC were significantly less in comparison with control mice (p less than 0.01 and p less than 0.001, respectively). CMHC significantly improved the WBC and the thrombocytes in irradiated workers (p less than 0.01 and p less than 0.001, respectively). The WBC count of 40 patients under radiotherapy while treated with CMHC recovered from 3450 +/- 77/c.mm to 5425 +/- 264/c.mm (p less than 0.001); whereas, in the control group, without any medication, the WBC count dropped significantly (p less than 0.001). Our results revealed the applicabilities of CMHC in protection against radiation damage in spaceflight and in other fields.
Previous research utilizing the AcB/BcA recombinant congenic strains (RCS) of mice mapped provisional quantitative trait loci (QTLs) for the psychostimulant effects of nicotine to multiple regions on chromosomes 7, 11, 12, 14, 16, and 17. The current study was designed to confirm these QTLs in an A/J (A)??C57Bl/6J (B6) F2 cross and a panel of B6.A chromosome substitution strains (CSS). The panel of B6.A CSS consists of 21 strains, each carrying a different A/J chromosome on a B6 background. The A??B6 F2, CSS, A, and B6 mice were tested for sensitivity to the effects of nicotine on locomotor activity using a computerized open-field apparatus. In A??B6 F2 mice two QTLs were identified which confirm those previously observed in the AcB/BcA RCS. Significant differences in the expression of ...
Water and mud samples were collected from canals and rivers which were adjacent to outlets discharging warm water of 3 power plants in Berlin. Downstream samples from 1 bathing resort were also collected. Free living amoebae were isolated from 138 water and 69 mud samples. From these respectively 156 and 73 strains could be cultured and were administered intranasally to mice for pathogenicity tests. Two Acanthamoeba strains from water and 7 from mud could be reisolated from mouse brain and or lungs, although no pathological disorders could be observed. Five Naegleria strains were negative in mouse inoculation tests. Four Acanthamoeba strains which were positive in mice were cultured at + 45 degrees C; no cytopathogenic effects were observed in tissue cultures. Acanthamoeba infective for mice could also be isolated from samples at low water temperatures. Further investigations have to show, whether changes in virulence of ...
Introduction: We have evaluated the ability of a semi-automated, optomotor reflex method to assess drug-induced visual dysfunction, in albino and pigmented rats and mice. Methods: Male Han Wistar (HW) and Long Evans (LE) rats and mice (CD-1 and C57BL/6) were tested in a chamber formed by 4 computer monitors displaying a rotating vertical grating, to elicit head-tracking movements. The highest visible grating frequency was taken as the threshold of visual acuity, in cycles per degree (c/d). Animals received an intravenous infusion of either sodium iodate (50mg/kg) or 0.9% w/v NaCl (aq). They were tested 2h later, then re-tested daily for a further 3days. The time course of the effect was assessed in HW rats over a 6-week period, including electron microscopy, and immunohistochemical analysi...
Abstract Polycystic kidney diseases (PKD) are inherited disorders characterized by fluid-filled cysts primarily in the kidneys. We previously reported differences between the expression of Cux1, p21, and p27 in the cpk and Pkd1 null mouse models of PKD. Embryonic lethality of Pkd1 null mice limits its study to early stages of kidney development. Therefore, we examined mice with a collecting duct specific deletion in the Pkd1 gene. Cux1 was ectopically expressed in the cyst lining epithelial cells of newborn, P7 and P15 Pkd1CD mice. Cux1 expression correlated with cell proliferation in early stages of cystogenesis, however, as the disease progressed, fewer cyst lining cells showed increased cell proliferation. Rather, Cux1 expression in late stage cystogenesis was associated with increased ...
Exercise training associated with robust conditioning can be useful for the study of molecular mechanisms underlying exercise-induced cardiac hypertrophy. A swimming apparatus is described to control training regimens in terms of duration, load, and frequency of exercise. Mice were submitted to 60- vs 90-min session/day, once vs twice a day, with 2 or 4% of the weight of the mouse or no workload attached to the tail, for 4 vs 6 weeks of exercise training. Blood pressure was unchanged in all groups while resting heart rate decreased in the trained groups (8-18%). Skeletal muscle citrate synthase activity, measured spectrophotometrically, increased (45-58%) only as a result of duration and frequency-controlled exercise training, indicating that endurance conditioning was obtained. In groups which received duration and endurance conditioning, cardiac weight (14-25%) and myocyte dimension (13-20%) increased. The best conditioning protocol to promote physiological ...
Changes in contents of the two kinds of neuropeptides have been measured in the brains of postnatal G57BL/6J strain mice that received accumulative doses of 0, 0.05, 0.10 or 0.30 Gy respectively in utero from tritium #beta#-irradiation during the mother mice's pregnancy from the 12.5th day of gestation to the day of delivery. Dose response relationship for alteration in somatostatin content due to exposure to 0.10 Gy or above was observed, and it was also noted that 0.30 Gy could cause decrease in arginine vasopressin in hypothalamus. These results were consistent with findings in research on brain development and reflex behavior in the literature. 0.10 Gy exposure may represent a threshold for exposure to tritiated water within the range from day 12.5 of gestation to the day of delivery using change in content of somatostatin in hypophysis as a parameter.
We studied the dose-response effects of #gamma#-irradiation on the weight gains of the body and the brain in ICR mice exposed to various doses of "6"0Co #gamma#-irradiation ranging from 0 to 1.5 Gy on day 13 of pregnancy (E13). We found that 0.5 Gy #gamma#-irradiation caused a significant reduction in brain weight but not in body weight among 6-week-old mice. Higher doses (1.0, 1.5 Gy) seriously inhibited body and brain development, resulting in significantly low weights at 6 weeks of age. A significantly lower brain weight among fetuses exposed to 1.5 Gy was found as early as 24 hours after exposure, while significant reductions in the body weight of these same fetuses appeared 3 days after exposure. The effects of radiation on brain and body development were similar for both males and females. (author).
Neuron differentiation is a complex process involving various cell-cell interactions, and multiple signaling pathways. We showed previously that CD40 is expressed and functional on mouse and human neurons. In neurons, ligation of CD40 protects against serum withdrawal-induced injury and plays a role in survival and differentiation. CD40 deficient mice display neuron dysfunction, aberrant neuron morphologic changes, and associated gross brain abnormalities. Previous studies by Tone and colleagues suggested that five isoforms of CD40 exist with two predominant isoforms expressed in humans: signal-transducible CD40 type I and a C-terminal truncated, non-signal-transducible CD40 type II. We hypothesized that differential expression of CD40 isoform type I and type II in neurons may modulate neuron differentiation. Results show that adult wild-type, and CD40"-"/"- deficient mice predominantly express CD40 type I and II isoforms. Whereas adult ...
In Kanazawa, Japan, air pollution from a Mn treatment factory was found to affect local junior high school students, who showed reduced respiratory function relative to their exposure to Mn. The use of Mn as an antiknock ingredient in automobile fuels has recently been introduced, placing the general population at risk of chronic low-level exposure. There are few animal studies on the effects of compounds other than manganese chloride (MnCl{sub 2}). In the case of environmental pollution by Mn, the differing physiological effects of the various chemical forms of Mn must be considered. The present study therefore examined the differences in the effects of several Mn compounds on the physiology and behavior of mice by short-term oral administration.
Fgf receptor 2c (Fgfr2c) was expressed in mature adipocytes of mouse white adipose tissue (WAT). To examine the role of Fgfr2c in mature adipocytes, we generated adipocyte-specific Fgfr2 knockout (Fgfr2 CKO) mice. The hypertrophy impairment of adipocytes in the mesenteric WAT but not in the subcutaneous WAT and decreased plasma free fatty acid (FFA) levels were observed in Fgfr2 CKO mice. Although the expression of genes involved in adipocyte differentiation and lipid metabolism in the mesenteric WAT was essentially unchanged, the expression of uncoupling protein 2 potentially involved in energy dissipation was significantly increased. Among potential Fgf ligands for Fgfr2c, Fgf9 was preferentially expressed in the mesenteric WAT. The present findings indicate that Fgfr2c potentially activ...
The petroleum ether fraction (PEF) from the EtOH extract of flowers and buds of Chrysanthemum indicum was evaluated on antinociception in mice using chemical and thermal models of nociception. PEF administered orally at doses of 188 and 376mg/kg produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid, subplantar formalin or capsaicin injections and on thermal nociception in the tail-flick test and the hot plate test. In the pentobarbital sodium-induced sleep time test and the open-field test, PEF neither enhanced the pentobarbital sodium-induced sleep time nor impaired the motor performance, indicating that the observed antinociception was unrelated to sedation or motor abnormality. In a measurement of core body temperature, PEF did not affect temper...
Abstract Objectives: This investigation reviewed experimental studies of laser irradiation of wound healing in mice and rats published from 2003 to August 2008, respectively, to assess putative stimulatory effects of this treatment. Background: Animal models, including rodents, attempt to reflect human wound healing and associated problems such as dehiscence, ischemia, ulceration, infection, and scarring. They have played a key role in furthering understanding of underlying mechanisms involved in impaired wound healing, and in testing new therapeutic strategies including laser irradiation. Method: Original research papers investigating effects of laser or monochromatic light therapy on wound healing in mice and rats and published from January 2003 to August 2008 were retrieved from library...
We developed mice with germline endogenous expression of oncogenic Hras to study effects on development and mechanisms of tumor initiation. They had high perinatal mortality, abnormal cranial dimensions, defective dental ameloblasts, and nasal septal deviation, consistent with some of the features of human Costello syndrome. These mice developed papillomas and angiosarcomas, which were associated with Hras(G12V) allelic imbalance and augmented Hras signaling. Endogenous expression of Hras(G12V) was also associated with a higher mutation rate in vivo. Tumor initiation by Hras(G12V) likely requires augmentation of signal output, which in papillomas and angiosarcomas is achieved via increased Hras-gene copy number, which may be favored by a higher mutation frequency in cells expressing the oncoprotein. PMID:19416908
Abstract This study investigated the effects of Maillard reaction products (MRPs) on in vitro starch hydrolysis, and in vivo blood glucose responses in mice. Four MRPs of various dextrose equivalents were prepared by heating a mixture of hydrolyzed rice starch and glycine at 200C for 4-min. The starch hydrolysis rates of gelatinized rice starch (GRS) decreased as the browning reaction of added MRPs increased. The hydrolysis kinetic constants of the GRS with 5% MRPs were relatively lower than that of GRS without MRPs. Blood glucose responses showed similar tendencies to the in vitro starch hydrolysis results. The activity of digestive enzymes was inhibited by the MRPs. The relative crystallinity of all MRPs (29.9-60.1%) appeared to have higher values than GRS (15.1%). The samples heated to ...
The integral membrane protein synaptophysin is one of the most abundant polypeptide components of synaptic vesicles. It is not essential for neurotransmission despite its abundance but is believed to modulate the efficiency of the synaptic vesicle cycle. Detailed behavioral analyses were therefore performed on synaptophysin knockout mice to test whether synaptophysin affects higher brain functions. We find that these animals are more exploratory than their wild type counterparts examining novel objects more closely and intensely in an enriched open field arena. We also detect impairments in learning and memory, most notably reduced object novelty recognition and reduced spatial learning. These deficits are unlikely caused by impaired vision, since all electroretinographic parameters measur...
AbstractBackground: The dinitrofluorobenzene/dinitrosulfonic acid (DNFB/DNS) model was originally described as an experimental model of intestinal inflammation resembling human ulcerative colitis (UC). Due to the absence of acceptable UC experimental models for pharmacological preclinical assays, here we examine the immune response induced in this model. Methods: Balb/c mice were sensitized by skin application of DNFB on day 1, followed by an intrarectal challenge with DNS on day 5. We further expanded this model by administering a second DNS challenge on day 15. The features of colonic inflammation and immune response were evaluated. Results: The changes observed in colonic tissue corresponded, in comparison to the trinitrobenzene sulfonic acid (TNBS) colitis model, to a mild mucosal effe...
The activity of tyrosine aminotransferase (TAT) in the liver of mice subjected simultaneously to ionizing radiation and to local inflammatory process showed in the first 24 hours of the experiment statistically significant changes resulting from summation of the harmful effects of both factors. In the second 24-hour period an evident tendency was observed for return of a normal circadian rhythm of the enzyme. This points to presence of an endogenous mechanism of suppression of the manifestations of significant desynchronization of the circadian rhythm. The paper contains also a trial of mathematical analysis of changes in TAT activity in the circadian rhythm, a description and analysis or the suppression process, qualitative and quantitative determination of the phenomenon of cumulation of the effects of powerful stress factors acting on the animal organism. The obtained results were compared with the results of investigations of TAT activity changes obtained in ...
The power?time curves of mice splenic lymphocytes growth at 37??C affected by ginsenoside Rh2 were determined by microcalorimetry using a 3114/3236 TAM air bioactivity monitor with ampoule mode. Then, the minimal inhibitory concentration (MIC) of Rh2 on splenic lymphocytes growth was determined by serial dilution method. From factor analysis (FA) on six quantitative thermokinetic parameters from the power?time curves, the activity of Rh2 on splenic lymphocytes could be quickly evaluated by analyzing the changes in the two main parameters: growth rate constant k, and maximum heat-output power, P m. The results showed that Rh2 had strong inhibitory activity on splenic lymphocytes growth, and this inhibitory activity was strengthened with increasing concentration of Rh2 in the concentration r...
Combinations of exposure concentrations, durations and frequencies were tested in four-week inhalation exposures followed by two weeks of recovery to define the interactive effects of these variables on biologic responses and to select the most-sensitive biologic response parameters for the subsequent subchronic studies. Response surface modeling was used for the experimental design and statistical analysis of the data. Results of preliminary testing suggested that exposure duration and frequency did not have major effects. Subsequently, male and female Sprague-Dawley rats were exposed in separate studies to RP/BR aerosols ranging from 0.40 to 1.20 mg/1 or to filtered air for 2.25 hr/day on four days/week for four weeks. Test-atmosphere monitoring data demonstrated that aerosol concentrations were consistently within 4% of the target values and mean particle size ranged from 0.44-0.64 ..mu..m with mean sigma g's of 1.66-1.97. During the exposure period, ...
The results of a scoping study of onsite radiation exposures which could take place in each of three types of postulated reactor accidents are presented. The accident types are (1) a fuel handling accident at a Mark III BWR; an interfacing system LOCA or V sequence at a PWR; and and Anticipated Transient Without Scram (ATWS) at a Mark I BWR. Both external and internal dose pathways are considered. The results of the study indicate the prohibitively high radiation doses could be received in some plant areas if personnel were to remain there. However, times of the order of a few minutes to a few hours, depending on the type of accident, would be available before life-threatening doses would be accumulated assuming that the provided full face respiratory protection equipment were used promptly. Special attention was given radiation doses possibly received by control room personnel for several control room air in-leakage assumptions. For occupancy during severe accidents it would be ...
This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of /sub 86/Rb and 9-microns spheres labeled with /sup 141/Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, ...
This study was designed to evaluate the influence of inhalational agents on the intestinal circulation in an isolated loop preparation. Sixty dogs were studied, using three intestinal segments from each dog. Selected intestinal segments were pumped with aortic blood at a constant pressure of 100 mmHg. A mixture of _8_6Rb and 9-microns spheres labeled with "1"4"1Ce was injected into the arterial cannula supplying the intestinal loop, while mesenteric venous blood was collected for activity counting. A very strong and significant correlation was found between rubidium clearance and microsphere entrapment (r = 0.97, P less than 0.0001). Nitrous oxide anesthesia was accompanied by a higher vascular resistance (VR), lower flow (F), rubidium clearance (Cl-Rb), and microspheres entrapment (Cl-Sph) than pentobarbital anesthesia, indicating that the vascular bed in the intestinal segment was constricted and flow (total and nutritive) decreased. Halothane, enflurane, and ...
In the context of radiation protection for both workers and the population in general, natural sources of radiation, and in particular radon gas and its short-life decay products assume great importance. In particular, workers in thermal spas can easily be exposed to a level of radon radiation and its decay products comparable to those in uranium mines, though often these workers are unaware of the danger. The main source of radon in thermal baths is the thermal water itself, coming as it often does from deep springs, and this can produce high radon concentrations which are left in those areas in which therapy is carried out. Another factor which cannot be overlooked is the radioactive content of thermal mud, often matured for long periods by contact with thermal water. Thermal cures, though varying slightly from site to site, consist principally of mud cures, hydro-therapy and inhalation in various forms. Both health workers and patients are exposed to radiation, ...
The emission isolation flux chamber (EIFC) methodology was applied to Superfund investigations at the Lawrence Livermore National Laboratory Site 300 to determine if on-site workers were exposed to VOCs volatilizing from the subsurface and what, if any, health risks could be attributed to the inhalation of the VOCs volatilizing from the subsurface. During July and August of 1996, twenty, eighteen, and twenty six VOC soil vapor flux samples were collected in the Building 830, 832, and 854 areas, respectively using EIFCS. The VOC concentrations in the vapor samples were used to calculate soil flux rates which were used as input into an air dispersion model to calculate ambient air exposure-point concentrations. The exposure-point concentrations were compared to EPA Region IX Preliminary Remediation Goals (PRGs). Buildings 830 and 832 exposure-point concentrations were less then the PRGs therefore no cancer risks were calculated. The cancer risks for Building 854 ...
We tested the hypothesis that the basal release of nitric oxide (NO) from endothelial cells modulates contractile activity in the corpus cavernosum (CC) via inhibition of the RhoA/Rho-kinase signaling...Full Text Available
An assay system for the stem cell that colonizes the thymus and differentiates into T cells was developed, and by using this assay system the existence of two subpopulations of stem cells for T cell lineage was clarified. Part-body-shielded and 900-R-irradiated C57BL/6 (H-2b, Thy-1.2) recipient mice, which do not require the transfer of pluripotent stem cells for their survival, were transferred with cells from B10 X Thy-1.1 (H-2b, Thy-1.1) donor mice. The reconstitution of the recipient's thymus lymphocytes was accomplished by stem cells in the donor cells and those spared in the shielded portion of the recipient that competitively colonize the thymus. Thus, the stem cell activity of donor cells can be evaluated by determining the proportion of donor-type (Thy-1.1+) cells in the recipient's thymus. Bone marrow cells were the most potent source of stem cells. By contrast, when the stem cell activity was compared between spleen ...
West Nile virus (WNV) is a mosquito-borne flavivirus that infects the central nervous system of humans and other animals. In this study, we found that C3H/HeN (C3H) mice exhibited a higher morbidity...Full Text Available
In both type 1 and type 2 diabetes, pancreatic islet dysfunction results in part from cytokine-mediated inflammation. The ubiquitous eukaryotic translation initiation factor 5A (eIF5A), which is the...Full Text Available
In neurodegenerative conditions such as Alzheimer's and prion disease it has been shown that host genetic background can have a significant effect on susceptibility. Indeed, human genome-wide association studies (GWAS) have implicated several candidate genes. Understanding such genetic susceptibility is relevant to risks of developing variant CJD (vCJD) in populations exposed to bovine spongiform encephalopathy (BSE) and understanding mechanisms of neurodegeneration. In mice, aspects of prion disease susceptibility can be modelled by examining the incubation period following experimental inoculation. Quantitative trait linkage studies have already identified multiple candidate genes; however, it is also possible to take an individual candidate gene approach. Rarb and Stmn2 were selected as candidates based on the known association with vCJD. Because of the increasing overlap described between prion and Alzheimer's diseases we also chose Clu, Picalm and Cr1, which ...
The loss of lead in various kinds of biological materials after drying and ashing is studied by using "2"0"3Pb as tracer which is intravenously injected into mice. The experimental results show that although the oven ashing can be used for determining the lead in samples of lung, kidney, and liver, etc., the oxygen plasma and high pressure digestion are the most suitable methods for the determination of lead in biological materials. (author) 5 refs.; 2 tabs.
Pulmonary fibrosis was produced in mice treated with butylated hydroxytoluene (BHT) 400 mg/kg and immediately exposed to 80% oxygen for 3 days. This treatment regimen resulted in 47% mortality. Surviving mice exhibited significant accumulations of pulmonary collagen as evidence by increases in total lung hydroxyproline levels. The administration of indomethacin (4 mg/kg/day) on days 1-6 after BHT decreased mortality to 14% and diminished the accumulation of collagen in lung tissue. Indomethacin also enhanced survival when administered on days 1-3 after BHT/O/sub 2/ but had no effect on lung collagen levels. Treatment with indomethacin on days 4-6 after BHT had no beneficial effect. The administration of prednisolone (60 mg/kg/day) on days 1-3, 1-6, or 4-6 after BHT decreased mortality but had not effect on accumulation of lung collagen. Cis-4-hydroxyproline (400 mg/kg/day) also had no effect on pulmonary fibrosis but did enhance survival when ...
Werner syndrome (WS) is a rare disorder characterized by the premature onset of several pathologies associated with aging. The gene responsible for WS codes for a RecQ-type DNA helicase and is believed...Full Text Available
Protective immunity against infection with Bacillus anthracis is almost entirely based on a response to the protective antigen (PA), the binding moiety for the two other toxin components....Full Text Available
Lead-203 [52.1 h, 279 (80.1%) KeV] has been recognized as a potentially useful tracer for tumor specific radiopharmaceuticals due to its favorable nuclear and chemical properties. This paper reports the cyclotron production of lead-203 and the labelling of monoclonal antibody B72.3, conjugated with 2-(p-isothiocyanatobenzyl)DOTA, with lead-203 in 30% yield. In vivo biodistribution and stability studies in mice are being conducted.
With collaboration between chemistry, X-ray crystallography, and molecular modeling, we designed and synthesized a series of novel piperazine sulfonamide BACE1 inhibitors. Iterative exploration of the non-prime side and S2prime sub-pocket of the enzyme culminated in identification of an analog that potently lowers peripheral Ab40 in transgenic mice with a single subcutaneous dose.
BackgroundAmplification of 3q26 is one of the most frequent genetic alterations in many human malignancies. Recently, we isolated a novel oncogene eIF-5A2 within...Full Text Available
Neuropilin 1 (Nrp1) is a coreceptor for vascular endothelial growth factor A165 (VEGF-A165, VEGF-A164 in mice) and semaphorin 3A (SEMA3A). Nevertheless, Nrp1 null embryos display vascular...Full Text Available
Anti-TAG-72 monoclonal antibodies target the tumor-associated glycoprotein (TAG)-72 in various solid tumors. This study evaluated the use of anti-TAG-72 monoclonal antibodies, both murine CC49...Full Text Available
The CCAAT/enhancer-binding protein β (C/EBPβ) is required for adipocyte differentiation and maturation. We have studied the role of the transcription factor, C/EBPβ,...Full Text Available
Chondroitin sulfate (CS) and dermatan sulfate (DS) containing N-acetylgalactosamine 4,6-bissulfate (GalNAc(4,6-SO4)) show various physiological activities through interacting...Full Text Available
TH1 cytokine secretion was examined in response to synthetic peptides of the 85A component of the major secreted, fibronectin-binding antigen 85 complex from Mycobacterium tuberculosis in seven different...Full Text Available
Mice lacking Kv1.1 Shaker-like potassium channels encoded by the Kcna1 gene exhibit severe seizures and die prematurely. The channel is widely expressed in...Full Text Available
BackgroundhTERTC27 is a 27 kDa C-terminal polypeptide of human telomerase reverse transcriptase that has previously been shown to reduce tumorigenicity of HeLa cells and suppress...Full Text Available
BackgroundApoptosis is a major mode of hematological tumor death after radiation. Early detection of apoptosis may be beneficial for cancer adaptive treatment. 99mTc-HYNIC-annexinV...Full Text Available
The possible genetic (dominant lethal mutations (DLM) and cytogenetic changes in the regenerating liver) and somatic (hematopoietic stem cell changes, growth and nonspecific life time shortening) effects in mice maintained on tritiated water (HTO) over two generations was investigated. Results to date are summarized. (ACR)
The harmful effects of high-intensity electric fields on human beings are discussed. Formulas for determining the field strength of high voltage transmission lines and track lines and experimental data of these effects on mice are given. Protective measures from these hazards are introduced. 18 references, 7 figures, 5 tables.
The occupational chemical 4-vinylcyclohexene diepoxide (VCD) selectively destroys ovarian small pre-antral follicles in rats and mice via apoptosis. Detoxification of VCD can occur through glutathione...Full Text Available
Little is known about how diet and energy metabolism interact in determination of lifespan under ad libitum feeding. From 12 weeks of age until death, male and female wild-type (WT) and transgenic (TG)...Full Text Available
We have previously described a monoclonal antibody (FA6-152), obtained by immunizing mice with fetal human erythrocytes [Edelman, Vinci, Villeval, Vainchenker, Henri, Miglierina, Rouger, Reviron, Breton-Gorius,...Full Text Available
Although trefoil factor 1 (TFF1; previously named pS2) is abnormally expressed in about 50% of human breast tumors, its physiopathological role in this disease has been poorly studied. Moreover,...Full Text Available
In this study we show the effect of anti-sulfatide (RmAb) antibodies and inflammatory cytokines, TNF-α and IFN-γ in inducing myelin basic protein (MBP) degradation in myelin...Full Text Available
Excitotoxicity plays a major role in various neurological disorders. In this study, we explored the behavioral and neurotoxic effects of intraventricular NMDA administration in mice. After NMDA injection, acute seizures were followed by impairments in locomotor activity, motor performance on a rotarod, and climbing ability. Mice killed 1 day after NMDA administration showed increased synaptosomal reactive oxygen species ROS production and calcium concentration and decreased mitochondrial membrane potential, mitochondrial reductase activities, and neuronal membrane Na+, K+ -ATPase and mg2+ -ATPase activities. One and 3 days after excitotoxic injury, Golgi stains showed that dendritic length and spine density were significantly decreased in neurons of the hippocampal dentate gyrus. Some mice received honokiol, tea polyphenol plus memantine, and honokiol plus memantine prior to NMDA treatment; the occurrence of generalized ...
PurposeTo characterize differences in retinal ganglion cell (RGC) function in mouse strains relevant to disease models. C57BL/6J (B6) and DBA/2J (D2) are the two most common mouse...Full Text Available
Stress exposure increases the risk of addictive drug use in human and animal models of drug addiction by mechanisms that are not completely understood. Mice subjected to repeated forced swim stress...Full Text Available
This study is aimed at exploring the possible mechanism of hypnosis-enhancing effect of HgS or cinnabar (a traditional Chinese medicine containing more than 95% HgS) in mice treated with pentobarbital. We also examined whether the effect of HgS is different from that of the well-known methyl mercury (MeHg). After a short period (7 days) of oral administration to mice, a nontoxic dose (0.1 g/kg) of HgS not only significantly enhanced pentobarbital-induced hypnosis but also attenuated tolerance induction; while a higher dose (1 g/kg) of HgS or cinnabar exerted an almost irreversible enhancing effect on pentobarbital-hypnosis similar to that of MeHg (2 mg/kg) tested, which was still effective even after 10 or 35 days cessation of administration. To study comparatively the effects of different mercury forms from oral administration of MeHg and HgS on membrane ATPase activities of experimental mice, analysis of the Hg content in ...
BackgroundAberrant CD40 ligand (CD154) expression occurs on both T cells and B cells in human lupus patients, which is suggested to enhance B cell CD40 signaling and play a role...Full Text Available
Gonadotropin–releasing hormone (GnRH) neurons are the central regulators of reproduction. GABAergic transmission plays a critical role in pubertal activation of pulsatile GnRH secretion....Full Text Available
This paper aims at the study of the transfer and accumulation of "1"0"6Ru from marine foods to man through the grazing food chain and evaluation of the radiation exposure to man. As a model, accumulation and excretion of "1"0"6Ru in mice orally administered by the meat of prawn (Penaeus japonicus) which accumulated the radionuclide from the sea water, were examined and compared with those in mice administered by non-radioactive prawn meat mixed with the contaminant in inorganic chemical forms (the control diet); on the latter experiment, the previous evaluation method of the radiation exposure was based. Higher concentrations of "1"0"6Ru in tissues and organs of mice were observed in the former diet than in the latter because of the higher absorption rate of "1"0"6Ru from the gastrointestinal tract (17.4 +- 4.4%, the control diet: 0.7 +- 0.7%) and smaller excretion. As the results of this experiment, the critical organs for ...
In the present study Balb/c mice were exposed to 3,4-benzopyrene, painted on the skin every 2nd day for a total of 6 months, and simultaneously irradiated with athermal (5 mW/cm/sup 2/) or subthermal (15 mW/cm/sup 2/) doses of 2,450 MHz microwaves. The other group of animals was preirradiated with microwaves at 10 mW/cm/sup 2/ power level for 1, 2, or 3 months and then treated with benzopyrene, as above. Control mice were exposed for 6 months to benzopyrene, resulting in the development of baso- or spinocellular skin carcinoma within approximately 9 months, and sham-irradiated with microwaves. The growth of the tumour was assessed according to a self-designed 7-range macroscopic scale, supported by microscopical examinations of skin sections. All protocols of microwave irradiations resulted in a significant acceleration of the development of benzopyrene-induced skin cancer and in shortening of life span of the tumour-bearing hosts. This effect ...
Amyloid plaques are a characteristic feature in Alzheimer’s disease (AD). A novel non-toxic contrast agent is presented, Gd-DTPA-K6Aβ1–30, which is homologous to Aβ,...Full Text Available
Background and purpose:Theoretically, three α1-adrenoceptor subtypes can interact at the signalling level to alter vascular contraction or at the molecular level...Full Text Available
The US Nuclear Regulatory Commission is currently considering revision of rule 10 CFR Part 20, which covers disposal of solid wastes containing minimal radioactivity. In support of these revised rules, we have evaluated the consequences of disposing of four waste streams at four types of disposal areas located in three different geographic regions. Consequences are expressed in terms of human exposures and associated health effects. Each geographic region has its own climate and geology. Example waste streams, waste disposal methods, and geographic regions chosen for this study are clearly specified. Monetary consequences of minimal activity waste disposal are briefly discussed. The PRESTO methodology was used to evaluate radionuclide transport and health effects. This methodology was developed to assess radiological impacts to a static local population for a 1000-year period following disposal. Pathways and processes of transit from the trench to exposed populations included the ...
The purpose of this study was to investigate the feasibility of a simple deformable phantom as a QA tool for testing and validation of deformable image registration algorithms. A diagnostic thoracic imaging phantom with a deformable foam insert was used in this study. Small plastic markers were distributed through the foam to create a lattice with a measurable deformation as the ground truth data for all comparisons. The foam was compressed in the superior-inferior direction using a one-dimensional drive stage pushing a flat 'diaphragm' to create deformations similar to those from inhale and exhale states. Images were acquired at different compressions of the foam and the location of every marker was manually identified on each image volume to establish a known deformation field with a known accuracy. The markers were removed digitally from corresponding images prior to registration. Different image registration algorithms were tested using this method. Repeat ...
Active oxygens produced by low-dose irradiation can induce the synthesis of proteins involved in the active oxygen reduction path and can activate the chemical self-defense mechanisms in vivo, which can alleviate the injuries caused by active oxygens themselves. The following findings suggests that it is not only by low-dose irradiation that can induce the responses described above but also by any physical and/or chemical stresses which can produce small amount of active oxygens in vivo. 1. X-irradiation with 0.5 Gy and/or water immersion and restraint induced heat shock protein (HSP)70 in rat stomach cells. HSP70 was also induced in adrenal cells by paraquat administration. 2. The SOD activity in pancreas of rat significantly increased by #gamma#-irradiation with 0.5 Gy. 0.5 Gy irradiation preceeding the alloxan administration significantly suppressed the increase in pancreatic lipid peroxides and in blood glucose levels, degranulation in #beta# cells, and decrease in blood insulin ...
Inhalation of radon and its daughter products makes the major contribution to the total exposure of the population to natural radiations. In implementing a complex ecological survey, concentrations of radon and its daughter products were measured in different regions of Russia, namely, in the St. Petersburg Region, the Central Territories and the Altay Territory. Two suitable low price versions of the dosemeters for measuring environmental radon concentrations based on track-etch and activated-charcoal detectors were used. The radon daughter product activity and the effective dose equivalents were calculated with an equilibrium factor of 0.5 and a recommended effective dose equivalent factor of 0.061 mSv (Bq m{sup -3}){sup -1}. Indoor measurements were taken in more than 1000 dwellings and public and industrial buildings of 21 towns and villages. The track chambers were exposed for about 2-3 months and the charcoal detectors for 6-10 days, mainly during the summer. ...
Inhalation of radon and its daughter products makes the major contribution to the total exposure of the population to natural radiations. In implementing a complex ecological survey, concentrations of radon and its daughter products were measured in different regions of Russia, namely, in the St. Petersburg Region, the Central Territories and the Altay Territory. Two suitable low price versions of the dosemeters for measuring environmental radon concentrations based on track-etch and activated-charcoal detectors were used. The radon daughter product activity and the effective dose equivalents were calculated with an equilibrium factor of 0.5 and a recommended effective dose equivalent factor of 0.061 mSv (Bq m"-"3)"-"1. Indoor measurements were taken in more than 1000 dwellings and public and industrial buildings of 21 towns and villages. The track chambers were exposed for about 2-3 months and the charcoal detectors for 6-10 days, mainly during the summer. The ...
The measurement of physiological parameters in man is possible with the help of positron emission tomography (PET) and radiopharmaceuticals labeled with short lived positron emitters as C 11, N 13, O 15 and F 18. With the use of this substances it is possible to make a tomographic map defining regional metabolic parameters in normal and diseased brain. This technique has therefore also be named 'in vivo autoradiography'. The possibility of applying C 11 or F 18 labeled deoxyglucose with PET for detecting regional and local changes in cerebral metabolic rate of glucose in brain development in children of 5 days to 1 year of age is discussed. Beyond this a relationship between cerebral metabolic rate of glucose, cerebral blood flow and cerebral metabolic rate of oxygen by use of this technique after inhalation of O 15 and C 11-labeled CO_2 is shown. Attention is drawn to the application of C 11-methyl-spiperone and PET to visualize dopamine receptor density in the ...
Qualitative and quantitative methods have been developed to relate phosphate/UO{sub 2} interactions and U dissolution, in vitro, in a medium containing 0 or 10 mM phosphate concentrations at pH 5. This was performed by Energy Dispersive X ray Spectrometry (EDS) at 200 kV on entire particles and by fluorimetric measurement. The U dissolution rate was larger in a medium without phosphate than in a medium containing 10 mM phosphate. During the first day, the initial U dissolution involved 80.55% and 91.13% of the powder in media with and without phosphate respectively. From 5 to 15 d after beginning the assay, the dissolution half-times were longer than 92 d and 22 d for media with and without phosphate. EDS analyses have shown a constant P/U X ray intensity ratio for reference U{sub 2}O(PO{sub 4}){sub 2} for the same range of particle diameter. A gradual increase of this ratio was measured for UO{sub 2} incubated in a 10 mM phosphate medium throughout the experiment. (author)
A new miniature high-frequency (HF) plasma source intended for bio-medical applications is studied using nitrogen/oxygen mixture at atmospheric pressure. This plasma source can be used as an element of a plasma source array for applications in dermatology and surgery. Nitric oxide and ozone which are produced in this plasma source are well-known agents for proliferation of the cells, inhalation therapy for newborn infants, disinfection of wounds and blood ozonation. Using optical emission spectroscopy, microphotography and numerical simulation, the gas temperature in the active plasma region and plasma parameters (electron density and electron distribution function) are determined for varied nitrogen/oxygen flows. The influence of the gas flows on the plasma conditions is studied. Ozone and nitric oxide concentrations in the effluent of the plasma source are measured using absorption spectroscopy and electro-chemical NO-detector at variable gas flows. Correlations ...
The purpose of this document is to provide a framework for developing protective strategies in the longer term following an accidental release of radionuclides to the offsite environment. This advice covers all forms and scales of accidental release, including releases from nuclear sites and reactors, weapons accidents, and damaged industrial or medical sealed sources. The countermeasures considered are those intended to protect the public from external irradiation from radionuclides deposited in the environment, from the inhalation of resuspended radionuclides, and from inadvertent ingestion of radionuclides resulting from contact with contaminated surfaces. The Board terms these recovery countermeasures. They can be broadly grouped as either decontamination measures (ie measures that deal directly with the radionuclides, whether by removing them, shielding them or physically or chemically bonding them) or as restricted access measures (ie measures that reduce ...
This paper addresses the quantification of human exposure to volatile organic compounds (VOC's) as a result of mass transfer from tap water to indoor air. A three-compartment model is developed and used to simulate the 24-h concentration profile within the shower, bathroom, and remaining household volumes of a dwelling. Mass transfers from water to air are derived from measured data for radon and adjusted to account for the difference in mass-transfer properties for VOC's. A preliminary data base for household parameters is used to calculate a range of concentrations and human exposures in U.S. dwellings. The model is used to estimate exposure factors for seven compounds-chloroform, ethylene dibromide, dibromo-chloropropane, methylchloroform, perchloroethylene, trichloroethylene, and carbon tetrachloride. The calculated ratio of indoor-air exposure to tap water concentration is compared to measured values for one of the compounds, chloroform. A sensitivity analysis is used to identify ...
The release rate of a nuclide from a reactor or a radioactive waste disposal plant at the accident is not steady, but varies with time. The various parameters of a nuclide migration into environment vary also day after day, or with the seasons. In such cases, dynamic behavior of the nuclide in the environment must be taken into consideration. It is difficult for a mathematical model to involve all of mechanisms for the nuclide migration. The environment for evaluation of doses are usually divided into some of compartments in which a nuclide concentration is uniform. Time variations of the nuclide concentration in the compartment are described in simultaneous differential equations. The nuclide concentration can be solved as a time function, and the radiation doses, therefore, can be estimated as a time function. Generic analysis code for dynamic compartment model (GACOM) is developed for the nuclide migration and the evaluation of doses in terrestrial biosphere. The code contains many ...
Tritium, a beta emitting gas at room temperature causes a biological hazard in the locations where it is present beyond acceptable limits. The hazard can be due to inhalation, and absorption by skin. Hence is the necessity of Tritium monitoring instruments/systems for ensuring safety in the PHWRs and the nuclear research plants and laboratories. It is desirable that the instruments address satisfactorily to certain factors like the following: (i) Wide range of Tritium concentrations - 1 to 104 DAC ( Derived Air Concentration) (ii) On-line monitoring features (iii) Small response time (On-spot instantaneous measurements) (iv) Portability (v) Mitigation of memory effects. This paper presents an overview of the Online Tritium in Air Monitoring Systems manufactured by ECIL for Pressurised Heavy Water Reactors at Tarapur, Kaiga, and Rawatbhata. Significant aspects of design, function, testing, limitations of the detectors and electronics and the further development work ...
Desorption behavior of pyrene, phenanthrene and naphthalene from fullerene, single-walled carbon nanotubes (SWCNTs) and multi-walled carbon nanotubes (MWCNTs) was examined. Available adsorption space of carbon nanotubes (CNTs) was found to be the cylindrical external surface, neither the inner cavities nor inter-wall spaces due to impurities in the CNTs and restricted spaces (0.335 nm) of the MWCNTs, respectively. Desorption hysteresis was observed for fullerene but not for CNTs. Deformation-rearrangement was proposed to explain the hysteresis of polycyclic aromatic hydrocarbons (PAHs) for fullerene, due to the formation of closed interstitial spaces in spherical fullerene aggregates. However, long, cylindrical carbon nanotubes could not form such closed interstitial spaces in their aggregates due to their length, thus showing no significant hysteresis. High adsorption capacity and reversible adsorption of PAHs on CNTs imply the potential release of PAHs if PAH-adsorbed CNTs are ...
Farmers' lung disease (FLD) is a pulmonary disease that results from repeated inhalation of antigens from mouldy hay or straw. The objective of this prospective study was to assess the reliability of four serological techniques in FLD diagnosis. Sera from 15 consecutive patients with FLD, 15 healthy control farmers and 30 urban controls were analysed using four serological techniques [electrosyneresis (ES), Ouchterlony double diffusion (DD), ELISA and Western blot (WB)] with four antigens (Absidia corymbifera, Eurotium amstelodami, Wallemia sebi and Saccharopolyspora rectivirgula). In the authors' region, ES on cellulose acetate with A. corymbifera antigen was the most relevant diagnostic tool for discriminating FLD patients from healthy exposed farmers (sensitivity 87 %, specificity 100 %). DD tests were in accordance with ES, but their discriminatory power was lower. No threshold indicating both good sensitivity and specificity could be established with ELISA. WB ...
AIDE (Activity and Internal Dose Estimates) is a software for calculating activities in compartments and committed doses due to occupational exposures, and for performing intake and dose estimates using bioassay data. It has been continuously developed and tested for more than 20 years. Its calculation core has been applied in several situations, like performing all dose estimates due to (137)Cs intakes, which occurred during the Goiania accident in 1987; performing quality assurance of the ICRP Task Group on Dose Calculations regarding calculations of activities in compartments and generation of dose coefficients for adults due to intakes by inhalation, ingestion and injection of several radionuclides; and producing the tables of activities in compartments and dose coefficients using the NCRP Wound Model for the NCRP report. It provides several capabilities like performing calculations using modified Human Respiratory Tract Model parameters for the mechanical ...
Noninvasive and simplified methods for estimating regional cerebral blood flow (CBF) and regional partition coefficient ({lambda}) using the inhalation of stable xenon (Xe{sup s}) and computed tomographic (CT) scanning are described. Thirty percent Xe{sup s} in 70% oxygen was inhaled for 240 seconds and exhaled for 160 seconds during serial CT scanning without denitrogenation in 26 patients with cerebrovascular diseases and four volunteer controls. During the investigation, the end-tidal Xe{sup s} concentration was continuously monitored with a thermoconductivity analyzer to determine the build-up range (A value) and build-up rate constant (K value) of the artery by the curve fitting method. Calculated A and K values were corrected by the following formulae reported previously: for patients aged 0-20 years, A{sub e} = 0.75A{sub a} + 2.15, K{sub e} = 0.67K{sub a} + 0.69; 21-40 years, A{sub e} = 0.56A{sub a} + 3.24, K{sub e} = 0.38K{sub a} + ...
Noninvasive and simplified methods for estimating regional cerebral blood flow (CBF) and regional partition coefficient (#lambda#) using the inhalation of stable xenon (Xe"s) and computed tomographic (CT) scanning are described. Thirty percent Xe"s in 70% oxygen was inhaled for 240 seconds and exhaled for 160 seconds during serial CT scanning without denitrogenation in 26 patients with cerebrovascular diseases and four volunteer controls. During the investigation, the end-tidal Xe"s concentration was continuously monitored with a thermoconductivity analyzer to determine the build-up range (A value) and build-up rate constant (K value) of the artery by the curve fitting method. Calculated A and K values were corrected by the following formulae reported previously: for patients aged 0-20 years, A_e = 0.75A_a + 2.15, K_e = 0.67K_a + 0.69; 21-40 years, A_e = 0.56A_a + 3.24, K_e = 0.38K_a + 1.12; 41-60 years, A_e = 0.91A_a + 1.95, K_e = 0.38K_a + ...
The elucidation on the metabolic products of the {sup 99}mTc-antibody conjugates may provide insights and approaches that would reduce the undesirable deposition of radioactive species in normal tissue. In this investigation, the radiolabeled species in blood, urine, bile and extracts of liver and kidney obtained at different times after the injection of a model antibody, {sup 99}mTc, into mice were analyzed with various chromatographic methods. Ninety-nine to 100% of the radioactivity in serum was associated with intact Mab 170. The radioactivity in liver homogenate extract was strictly protein-bound to either intact Mab or low molecular weight species (LMW). In kidney extracts, the majority of the radioactivity was protein bound {sup 99}mTc, with less than 8% of the activity being non- protein bound . Multiple {sup 99}mTc -containing protein and non-protein species were found in urine and bile. Evidence supporting the presence of {sup 99}mTc-cysteine and {sup ...
The ability of Yersinia pestis to forestall the mammalian innate immune response is a fundamental aspect of plague pathogenesis. In this study, we examined the effect of Ail, a 17-kDa outer membrane protein that protects Y. pestis against complement-mediated lysis, on bubonic plague pathogenesis in mice and rats. The Y. pestis ail mutant was attenuated for virulence in both rodent models. The attenuation was greater in rats than in mice, which correlates with the ability of normal rat serum, but not mouse serum, to kill ail-negative Y. pestis in vitro. Intradermal infection with the ail mutant resulted in an atypical, subacute form of bubonic plague associated with extensive recruitment of polymorphonuclear leukocytes (PMN or neutrophils) to the site of infection in the draining lymph node and the formation of large purulent abscesses that contained the bacteria. Systemic spread and mortality were greatly attenuated, however, and a productive ...
Neuron-restrictive silencer factor (NRSF) binds its consensus element to repress the transcription of various genes. The dominant-negative form (dnNRSF) has a hypertrophic effect on cardiogenesis through an unidentified mechanism. We examined the involvement of transient receptor potential (TRP) channel proteins, using transgenic mice overexpressing dnNRSF (dnNRSF mice). Electrophoretic mobility-shift assays revealed an interaction between NRSF and a neuron-restrictive silencer element-like sequence in intron 4 of TRPC1 genomic DNA. According to RT-PCR and Western analyses, TRPC1 was up-regulated in dnNRSF mouse heart. Transient overexpression of TRPC1 in HEK 293T cells increased the activity of the nuclear factor in activated T cells (NFAT) promoter and stimulated store-operated Ca"2"+ channel (SOCC)-mediated Ca"2"+ entry. Transfection of TRPC1 into primary cardiomyocytes increased NFAT activity, indicating a major role for TRPC1 in NFAT ...
We evaluated the use of a novel gene porter (Den123-a nontoxic self-assembled dendritic spheroidal nanoparticle made of biodegradable monomers), aiming to enhance and improve the desired immune response in protection from allergy. Footpad DNA immunization in Balb/c mice was done three times using the Bet v 1a gene with or without Den123 with 2-week intervals followed by sensitization with rBetv1 (5mg) in alum twice in a weekly interval. Different doses of pCMV-Betv1 were used (10mg and 100mg). The protective role of different formulations was evaluated by measuring the IgG1, IgG2a and IgE antibody production, cytokine release of isolated splenocytes and b-hexosaminidase release from the RBL cells. Higher and increasing ratios of IgG2a/IgG1 were seen in mice which received plasmids in combi...
As reported previously (Namba et al., 1985), normal human fibroblasts were transformed by 60Co gamma-ray irradiation into immortal cells with abnormal karyotypes. These transformed cells (KMST-6), however, showed a low cloning efficiency in soft agar and no transplantability. However, upon treatment with Harvey murine sarcoma virus (Ha-MSV), the cells acquired elevated clonability in soft agar and transplantability in nude mice. Ha-MSV alone, however, did not convert normal human fibroblasts into either immortal or tumorigenic cells. The Ha-MSV-transformed KMST-6 cells showed an enhanced expression of the ras oncogene, but normal and 60Co gamma-ray-transformed cells did not. Our current data suggest that gamma rays worked against normal human cells as an initiator, giving rise to chromosome aberrations and immortality, and that Ha-MSV, probably through its ras oncogene, played a role in the progression of the malignant cell population to a more malignant one ...
Although it has been established that lead is transferred in milk from mother to suckling offspring, the physiological processes and parameters involved are not well understood. Single i.v. doses (0.2 mg/kg) or p.o. doses (2 mg/kg) of radiolabeled lead were administered to lactating and nonlactating female mice, and lead concentrations in blood, plasma, and milk were determined during a 21-day period. Large differences in lead elimination were observed between lactating and nonlactation mice. A significant fraction (25%) of the initial maternal dose (absorbed dose) was transferred to the suckling pups. The ratio of lead concentration in milk to lead concentration in plasma was found to be nearly constant over time. However, the milk-to-blood concentration ratios decreased during the same period. Furthermore, the concentration of lead in milk exceeded the plasma concentration by a factor of approximately 25, indicating that there is a ...
This report concerns investigations in the title conducted by 8 groups of National Institute of Radiological Sciences (NIRS) during the period of 1998-2000. The groups are for investigation of: Effects of p53 tumor suppressor gene in radiation-induced leukemia, Role of atm-gene in dose rate effect of ionizing radiation, Function of DNA-dependent protein kinase catalytic subunit (DNA-PK{sub cs}), Functional complementation of radiation-sensitive mutant M10 cell line by human XRCC4 cDNA expression, Role of radiation-induced apoptosis in digital defects in embryonic mice, Functional analysis of S-phase specific novel nuclear protein NP95 by gene targeting, Role of chemokine in T cell development and lymphomagenesis, and establishment of production techniques of gene-modified mice using embryonic stem cells for genetic analysis of radiation-sensitive genes. The groups describe summaries of their studies and published original articles are also ...
The aim of this study was to evaluate the radioprotective effect of turmeric extract (40 mg/kg body weight) and vitamin E (#alpha# - tocopherol acetate, 400 IU/kg body weight) supplementation on lipid peroxidation, reduced glutathione and antioxidant defense enzymes in various organs like liver, kidney and salivary glands at 24 h in adult Swiss mice. "1"3"1Iodine exposure significantly increased lipid peroxidation in kidney and salivary glands in comparison to control animals. Pre supplementation with turmeric extract for 15 days showed significant lowering of lipid peroxidation in kidney. On the other hand vitamin E pre supplementation showed marked reduction in lipid peroxidation in salivary glands. Reduced glutathione levels decreased significantly in liver after radiation exposure. However, pre supplementation with turmeric extract and vitamin E did not improve glutathione levels in liver. In conclusion we have observed differential radioprotective effect of ...
A suspension of bone marrow cells from femurs of female (CBA . C57B1)F1 mice was exposed to 2450 MHz CW microwaves in a specially designed waveguide exposure system. The temperature of the suspension rose, during exposure to microwaves, from 20/sup 0/C to 45/sup 0/C, and at an interval within 20/sup 0/C to 45/sup 0/C the number of haemopoietic stem cells (CFUs) was determined by the spleen exocolony method. The time of exposure of bone marrow cells to each temperature studied was 20 s. Control suspensions of bone marrow cells were exposed to a water bath temperature. There were no significant effects of the CFUs with the water bath temperature, while after exposure to microwaves the number of spleen colonies was elevated with a nadir at the temperature of 37/sup 0/C. With a microwave-induced increase of the temperature above 41/sup 0/C the number of CFUs in the bone marrow suspension decreased. The increase in the number of colonies was related to the rise in the ...
Single doses of lead (trace to 445 mg/kg) were administered per os to suckling and adult mice. Both groups exhibited dose-independent lead retention when doses of 4 to 445 mg/kg were administered. However, developmental differences in the fraction of initial dose (FID) retained were evident for all doses administered. A much larger FID was retained in both age groups following administration of carrier-free /sup 203/Pb. The results are consistent with a mechanism of gastrointestinal lead absorption comprising two or more processes. Developmental differences were also observed in organ lead concentration relative to whole body concentration for kidneys, skull and brain 6 days following lead administration. Lead retentions (relative to whole body retention) in brain and in bone were linearly related to dose of lead administered in both suckling and adult age groups. Though uptake of lead into brain and into femur was observed to be directly related to dose over a ...
In searching modulators of immunity and hematopoiesis among natural products, being used as foods, six herbs exhibited lymphocyte proliferation in vitro, and six exhibited augmentation of hematopoietic cell growth. The combined treatments showed synergistic effects of lymphocyte proliferation and of hematopoietic cell growth. On the other hand, we found four effective oriental medicinal prescriptions, used as energy tonic or blood-building decoctions, for survival and regeneration of hematopoietic cells and for protection of stem cells of intestinal crypt in irradiated mice. On the basis of these results, extracts from combinations of herbs were made in expectation of higher effects in the three respects. In immuno modulation activity by the two combinations of herbs was confirmed in mice. In culture of bone narrow cells, growth improvement of non-adherent precursor and induction of cytokine expression by herb mixture extracts were observed. In ...
Sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) has worse outcome because of multiresistance to a large group of antibiotics, which may lead to death from septic shock. In the present study, we firstly found that artesunate in combination with oxacillin was capable of protecting mice challenged with live MRSA WHO-2 (WHO-2) and the protection was related to the reduced TNF-a and IL-6 levels and decreased bacterial load. Based on above results, artesunate was further investigated from two aspects in vitro, anti-inflammation effect and antibacterial enhancement effect on antibiotics. Artesunate not only inhibited TNF-a and IL-6 release but also inhibited mRNA and protein expressions of TLR2 and Nod2, two important receptors, in murine peritoneal macrophages stimulated wit...
The aqueous fraction (AF) of an ethanolic extract from Chrysanthemum indicum was evaluated for analgesic activity in mice using chemical and thermal models of nociception. Given orally, AF at doses of 300 and 600 mg/kg produced significant inhibitions on chemical nociception induced by intraperitoneal acetic acid, subplantar formalin/capsaicin injections and on thermal nociception in the tail-flick test and in the hot plate test. In the pentobarbital sodium-induced sleeping time test and the open-field test, AF neither significantly enhanced the pentobarbital sodium-induced sleeping time nor impaired the motor performance, indicating that the observed analgesic activity was unlikely due to sedation or motor abnormality. In a measurement of core body temperature, AF did not affect temperature within 80 min. Moreover, the effective dose (600 mg/kg) also showed no toxicity within 7 days. These results suggested further that AF produced analgesic activity possibly ...
The identification of genes influencing sensitivity to stimulants and opioids is important for determining their mechanism of action and may provide fundamental insights into the genetics of drug abuse. We used a panel of C57BL/6J (B6; recipient)x A/J (donor) chromosome substitution strains (CSSs) to identify quantitative trait loci (QTL) for both open field activity and sensitivity to the locomotor stimulant response to methamphetamine (MA). Mice were injected with saline (days 1 and 2) and MA (day 3; 2 mg/kg i.p.). We analyzed the total distance traveled in the open field for 30 min following each injection. CSS-8, -11 and -16 showed reduced MA-induced locomotor activity relative to B6, whereas CSS-10 and -12 showed increased MA-induced locomotor activity. Further analysis focused on CSS...
Six kinds of diamino-dithiol compounds are labelled with "9"9Tc"m by ligands exchange reaction. Their ligands exchange percentage is over 95%. The biodistribution of one of these compounds in mice shows 0.88% brain uptake after two minutes and 0.28% after 15 minutes respectively. Although the brain uptake is lower for this compound, it has longer retention in brain. So, the experiment results are valuable to the design of new brain imaging agent in the future.
Water-soluble, ethanol-insoluble extracts prepared from several medicinal herbs of the Araliaceae and other families were tested for their radioprotective activity by either measuring 30 days survival rates (a commonly applied method) or counting the thrombocytes 14 days after irradiation (an improved method) in mice. The extracts were i.p. injected once within 4 min after the whole body X-ray irradiation. Of 12 materials examined, Aralia elata, Angelica acutiloba and Morus bombysis seemed to be good starting materials for preparing radioprotective substance(s) because of their relatively high specific activity and high yields of the extracts. (author).
During spring and autumn, the total number of amoebae and the number of acanthamoeba species able to grow at 37 degrees C were determined in six thermally polluted factory discharges and the surrounding surface waters. The isolated Acanthamoeba strains were studied for growth in axenic medium, cytopathic effect in Vito cell cultures, and virulence in mice. Although more amoebae were isolated in autumn, the number of Acanthamoeba species was lower than in spring, when the percent of pathogenic strains among the isolates was highest. Higher concentrations of amoebae were found in warm discharges, and more virulent strains occurred in thermal discharges than in surface waters.
A short-chain neurotoxin Pseudechis australis a (toxin Pa a) was isolated from the venom of an Australian elapid snake Pseudechis australis (king brown snake) by sequential chromatography on CM-cellulose, Sephadex G-50 and CM-cellulose columns. Toxin Pa a has an LD50 (intravenous) value of 76 micrograms/kg body wt. in mice and consists of 62 amino acid residues. The amino acid sequence of Pa a shows considerable homology with those of short-chain neurotoxins of elapid snakes, especially of true sea snakes. PMID:4091794
A series of pyrrolo[2,3-d]pyrimidine-2,4-diones and intermediates was tested for anticonvulsant activity in mice. Eleven of the 15 compounds possessed anticonvulsant activity against pentylenetetrazol-induced convulsions. One compound afforded more anticonvulsant protection against pentylenetetrazol than did trimethadione (67 and 50%, respectively). A suspension of this compound was found to be as effective as a solution in producing anticonvulsant activity. The results suggest that the nitrile analogs were more potent compared to the carbamyl analog due to higher lipid solubility. PMID:7373552
The radiation properties of the #alpha# emitter "2"1"1At are in favor of its application malignant tumor therapy. As a basis for further investigations the biokinetics of At"-, At x H_2O, At I_2"-, and [At(thio)_2]"+ were determined after i.v. injection into healthy and tumor-bearing mice. The estimation of the ion mobility of the carrier-free compounds allowed the use of uniquely characterized initial compounds. The organ distribution of all species examined was similar to the distribution of astatide. Accumulation was found in the thyroid and other inner organs. (author).
The rate of hepatic cytochrome P450 Cypla1 and Cyp1a2 induction was investigated in C57BL male mice during induction with o-aminoazotoluene (OAT), benzo[a]pyrene (BP) and 1,4-dihydroxyanthraquinone (AQ). The Cypla1 mPNA level determined by quantitative RT-competitive PCR increased more than three orders of magnitude during induction with OAT and BP compared with untreated animals and remained unchanged during induction with AQ. The Cypla2 mRNA level was only 8.5, 18.7 and 1.9 times higher during induction with OAT, BP and AQ respectively than in untreated mice. At the same time 7-Ethoxyresorufin-O-deethylase (EROD) and 7-Methoxyresorufin-O-demethylase (MROD) activities of Cypla were also investigated in liver. The increase of Cypla1 mRNA level correlated with the increase of EROD activity. This suggests involvement of the transcriptional mechanism of the inducibility of this enzyme. In the case of Cypla2 there was insignificant increase of its ...
Changes of /sup 67/Ga uptake in the lungs and changes of components of the so-called ground substance of the lung connective tissues of mice were followed for 7 weeks after the start of bleomycin (BLM) administration (20 mg/kg body weight IP, twice weekly for 5 weeks; this treatment induced fibrosis of the lung). /sup 67/Ga uptake of the lung was elevated at 1 week, and reached a maximum at 5 weeks (3.00+-0.11% dose/g lung), and then decreased slightly at 7 weeks. The uronic acid content in the 1.2 M NaCl-soluble fraction, which contained predominantly heparan sulfate (HS), was increased at 1 week, peaked at 3 weeks, and then remained unchanged up to 7 weeks. This pattern was similar to that of /sup 67/Ca acumulation in the lungs. The uronic acid content of the 0.4 M NaCl-fraction, which contained predominantly hyaluronic acid (HA), was decreased at 1 week, but increased to a maximum at 3 weeks, then decreased to about the initial level at 5 weeks and decreased ...
Sida rhomboidea. Roxb leaf extract (SRLE) is being used by the populace of North-East India to alleviate symptoms of diabetes and obesity. We have previously reported its hypolipidemic and anti-diabetic properties. In this study, we report the effect of SRLE on (i) in vivo modulation of genes controlling high fat diet (HFD) induced obesity and (ii) in vitro 3T3L1 pre-adipocyte differentiation and leptin release. Supplementation with SRLE significantly prevented HFD induced increment in bodyweight, plasma lipids and leptin, visceral adiposity and adipocyte hypertrophy. Also, SRLE supplementation reduced food intake, down regulated PPAR?2, SREBP1c, FAS and LEP expressions and up-regulated CPT-1 in epididymal adipose tissue compared to obese mice. In vitro adipogenesis of 3T3L1 pre-adipocytes was significantly retarded in the presence of SRLE extract. Also decreased triglyceride accumulation, leptin release and glyceraldehyde-3-Phosphate dehydrogenase activity along ...
{sup 188}Re is a {beta}{sup -} (Emax=2.12 MeV) and {gamma} (155 keV) emitter. Since its chemistry is similar to that of the largely employed tracer, {sup 99m}Tc, molecules of hyaluronic acid (HA) have been labelled with {sup 188}Re to produce a target specific radiopharmaceutical. The radiolabeled compound, i.v. injected in healthy mice, is able to accumulate into the liver after a few minutes. To study the effect of metabolic radiotherapy in mice, we have built a small gamma camera based on a matrix of YAP:Ce crystals, with 0.6x0.6x10 mm{sup 3} pixels, read out by a R2486 Hamamatsu PSPMT. A high-sensitivity 20 mm thick lead parallel-hole collimator, with hole diameter 1.5 mm and septa of 0.18 mm, is placed in front of the YAP matrix. Preliminary results obtained with various phantoms containing a solution of {sup 188}Re and with C57 black mice injected with the {sup 188}Re-HA solution are presented. To increase the space ...
Streptococcus pneumoniae colonizes the mucosal surface of the human upper respiratory tract. A colonization event is gradually cleared through phagocytosis by monocytes/macrophages that are recruited to the airway lumen. Here, we sought to define the bacterial and host factors that promote monocyte/macrophage influx and S. pneumoniae clearance using intranasal bacterial challenge in mice. We found that the recruitment of monocytes/macrophages required their expression of the chemokine receptor CCR2 and correlated with expression of the CCR2 ligand CCL2. Production of CCL2 and monocyte/macrophage recruitment were deficient in mice lacking digestion of peptidoglycan by lysozyme (LysM) and cytosolic sensing of the products of digestion by Nod2. Ex vivo macrophages produced CCL2 following bacterial uptake, digestion by LysM, and sensing of peptidoglycan by Nod2. Sensing of digested peptidoglycan by Nod2 also required the pore-forming toxin ...
Two plasmids which express either nearly intact or truncated filamentous hemagglutinin (FHA) from Bordetella pertussis and which are marked with a tetracycline resistance (Tcr) gene were transformed into Salmonella dublin SL1438, an aroA deletion mutant intended for use as an attenuated oral vaccine against salmonellosis. These S. dublin recombinants, when fed to mice, induced serum immunoglobulin, immunoglobulin M (IgM), and sometimes IgA antibody responses to FHA and S. dublin. In addition, IgA antibodies against FHA were found in gut wash fluids. S. dublin carrying pDB2300, a multicopy plasmid encoding truncated FHA protein, induced a better antibody response than did S. dublin carrying pDB2000, a low-copy-number plasmid encoding full-sized FHA. Administration of tetracycline to mice enhanced the stability of recombinant plasmids, and tetracycline-treated mice developed higher anti-FHA titers. Although neither strain ...
Intercrosses of heterozygous pro-opiomelanocortin (POMC) mice result in homozygous null progeny at lower frequencies than expected. Genotyping offspring at pre-, peri-, and postnatal stages revealed that over half of homozygous null mutants die in the early postnatal stages. To investigate the reasons for this early postnatal lethality, we analyzed in detail different parameters in the initial hours after birth. POMC null mutants born to heterozygous dams presented at birth with corticosterone levels no different from wildtype littermates, were euglycemic, and had normal liver glycogen stores. However, already 30 min after birth corticosterone levels dropped by 80% and were undetectable thereafter, while corticosterone levels in wildtype animals increased during postnatal hours. Circulating adrenaline was almost below detection 1h after birth. Blood glucose levels fell sharply in all genotypes within 30 min after birth; however, wildtype and heterozygous pups ...
Purpose: Previous data suggest that the PKC? catalytic V5 (PKC?-V5) heptapeptide (HEPT) (FEQFLDI) binds HSP27 and blocks HSP27-mediated radio- or chemoresistance. Here we investigated further the in vivo function of the PKC?-V5 HEPT. Methods and Materials: Labeling of HEPT with Cy5.5 or fluorescein isothiocyanate was performed to evaluate in vitro or in vivo distribution of HEPT. A clonogenic survival assay, flow cytometry, and Western blotting of cleaved caspase-3 were performed to determine in vitro sensitization effects of HEPT plus ionizing radiation (IR) versus IR alone or those of HEPT plus cisplatin(Cis) versus Cis alone. A nude mouse xenografting system was also applied to detect in vivo sensitizing effects of HEPT. Results: HEPT efficiently bound to HSP27 and showed sensitization after combined treatment with IR versus treatment with Cis alone in NCI-H1299 lung carcinoma cells, with higher HSP27 expression, which was similar to that of combined treatment with IR or with Cis ...
In mice, coat pigmentation requires a stem cell (SC) system in which the survival, proliferation, and differentiation of melanocytes (MCs) are regulated by microenvironments in hair follicles (HFs). In vitro systems are required to analyze the behavior of single melanocyte stem cells (MCSCs) and their potential to form SC systems in vivo. We describe here an experimental system for the isolation, self-renewal, and differentiation of MCSCs, as well as an in vivo reconstitution assay for assessing their potential. Using Dct(tm1(Cre)Bee)/CAG-CAT-GFP mice, we show that, in the presence of stem cell factor and basic fibroblast growth factor and the XB2 feeder cell line, purified MCSCs can undergo clonogenic proliferation, resulting in c-Kit(low) side scatter(low) cells. In culture, these cells maintain their capacity to differentiate and reconstitute an MCSC system in HFs. As these cells are present in the upper part of the HF near the bulge region, ...
HEMATOLOGICAL MALIGNANCIES IN HUMANS TYPICALLY INVOLVE TWO TYPES OF GENETIC CHANGES: those that promote hematopoietic cell proliferation and survival (often the result of activation of tyrosine kinases) and those that impair hematopoietic cell differentiation (often the result of changes in transcription factors). The multi-stage erythroleukemia induced in mice by Friend spleen focus-forming virus (SFFV) is an excellent animal model for studying the molecular basis for both of these changes. Significant progress has been made in understanding the molecular basis for the multi-stage erythroleukemia induced by Friend SFFV. In the first stage of leukemia, the envelope protein encoded by SFFV interacts with and activates the erythropoietin (Epo) receptor and the receptor tyrosine kinase sf-Stk in erythroid cells, causing their Epo-independent proliferation, differentiation and survival. In the second stage, SFFV integration into the Sfpi1 locus activates the myeloid ...
The present study was designed to assess the radioprotective effects of amifostine on ovarian follicles. Three week-old female mice with or without pretreatment of amifostine were irradiated with 6.42 Gy of #gamma# -ray. Ovaries were collected 0 and 6h after irradiation. DNA fragmentation pattern and expression of genes and activity of proteins related with apoptosis were investigated by means of RT-PCR and Western blot. Proliferation of granulosa cells was reduced and incidence rate of follicular atresia was increased in ovarian follicles in #gamma# -ray irradiated mice compared to those in control or amifostine-treated group. DNA fragmentation was increased in time-dependent manner in granulosa cells of all irradiated groups. However, no difference between amifostine pre-treated group and irradiated groups was found and the expression of p53 as tumor suppressor gene and Bax as one of pro-apoptotic Bcl-2 family was increased in irradiated ...
Colorectal carcinoma is a highly prevalent and common cause of cancer in Taiwan. There is still no available cure for this malignant disease. To address this issue, we applied the multimodality of molecular imaging to explore the efficacy of diagnostic and therapeutic nanoradiopharmaceuticals in an animal model of human colorectal adenocarcinoma [colorectal cancer (CRC)] that stably expresses luciferase (luc) as a reporter. In this study, an in vivo therapeutic efficacy evaluation of dual-nanoliposome (100 nm in diameter) encaged vinorelbine (VNB) and "1"1"1In-oxine on HT-29/luc mouse xenografts was carried out. HT-29/luc tumor cells were transplanted subcutaneously into male SCID mice. Multimodality of molecular imaging approaches including bioluminescence imaging (BLI), gamma scintigraphy, whole-body autoradiography (WBAR) and in vivo tumor growth tracing, histopathology and biochemistry/hematology analyses were applied on xenografted SCID ...
In order to gain an overall picture of the genetic effects of an increased level of background radiation it is necessary to study the results of protracted exposures to embryonic and immature germ-cell stages as well as to stages found in the mature organism. For this purpose, litters produced by female mice, kept in a 10 or 20 rad/day /sup 60/Co ..gamma..-irradiation field, were kept in the same fields from conception until about 60 days later, having absorbed doses of 526 and 1078 rad respectively. Tests on exposed female offspring showed them to be sterile. Eight weeks after removal from the gamma field, mean testis masses of males in the 20 rad/day series were only half normal but those receiving 10 rad/day were little affected. Frequencies of translocations in spermatocytes at diakinesis/metaphase I were only slightly increased in the exposed series, differences not being significant. Estimated rates of translocation induction were around 5 x 10sup(-6) per ...
Hepatocellular carcinoma (HCC) is the most common primary liver cancer and has very limited therapeutic options. Recently, it has been found that hyaluronic acid (HA) shows selective binding to CD44 receptors expressed in most cancer histotypes. Since the trend in cancer treatment is the use of targeted radionuclide therapy, the aim of this research was to label HA with rhenium-188 and to evaluate its potential use as a hepatocarcinoma therapeutic radiopharmaceutical. Methods: {sup 188}Re-HA was prepared by a direct labelling method to produce a ReO(O-COO){sub 2}-type coordination complex. {sup 188}Re-HA protein binding and its stability in saline, phosphate buffer, human serum and cysteine solutions were determined. Biokinetic and dosimetric data were estimated in healthy mice (n=60) using the Medical Internal Radiation Dose methodology and mouse model beta-absorbed fractions. To evaluate liver toxicity, alanine aminotranferase (AST) and aspartate aminotranferase ...
The aim of this paper was to develop potential technetium 99m-labeled diagnostic imaging agents specific for the detection of A#beta# plaques. Based on previously obtained A#beta# plaque-specific biphenyls containing a benzimidazol group, "9"9Tc"m and Re-benzimidazol derivatives, ["9"9Tc"m(CO)_3]"+-EPBI and Re(CO)_3 Cl (EPBI), were prepared. The latter showed binding affinities towards A#beta#_(_1_#approx#_4_0_) aggregates in vitro (K_d=13.3 #mu#mol/L) by fluorophotometry. 2-(1-Ethylbenzimidazol-2-yl) pyridine (EPBI) and Re(CO)_3 Cl (EPBI) were synthesized. Binding affinity of Re(CO)_3 Cl (EPBI) for A#beta#_(_1_#approx#__4_0_) aggregates was determined. ["9"9Tc"m(CO)_3]"+-EPBI was prepared and analyzed by HPLC and paper eletrophoresis. Its biodistribution in mice was obtained. The K_d value of Re (CO)_3 Cl (EPBI) is 13.3 #mu#mol/L. Biodistribution of ["9"9Tc"m(CO)_3]"+-EPBI in mice shows brain penetration (0.63 #+-# 0.17) %ID/g (n=3) at 2 min ...
Purpose: The purpose of this study was to evaluate the efficacy and toxicity of replication-competent adenovirus-mediated double suicide gene therapy in an adjuvant setting with external beam radiation therapy (EBRT) in an experimental prostate cancer model in preparation for a Phase I clinical study in humans. Methods: For efficacy studies, i.m. DU145 and intraprostatic LNCaP C4-2 tumors were established in immune-deficient mice. Tumors were injected with the lytic, replication-competent Ad5-CD/TKrep adenovirus containing a cytosine deaminase (CD)/herpes simplex virus thymidine kinase (HSV-1 TK) fusion gene. Two days later, mice were administered 1 week of 5-fluorocytosine + ganciclovir (GCV) prodrug therapy and fractionated doses of EBRT (trimodal therapy). Tumor control rate of trimodal therapy was compared to that of EBRT alone. For toxicology studies, immune-competent male mice received a single intraprostatic ...
Elevation of zinc protoporphyrin (ZPP) levels in the blood has served as an indicator of lead poisoning and iron deficiency anemia for many years. We have discovered that sublethal doses of whole body irradiation with x-rays also elevates ZPP 2-3-fold over normal levels. The ZPP level does not begin to increase until days 12-14 postirradiation and peaks between days 18 and 20 before returning to normal levels between days 28 and 35. Increasing the radiation dose delays the onset of the rise in ZPP, but does not affect the magnitude of the elevation. At lethal doses, ZPP elevation is not observed. Neither of the two previously described mechanisms that cause elevations of ZPP, namely iron deficiency and inhibition of ferrochelatase, are responsible for the radiation-induced elevation of ZPP. The elevation of ZPP appears to be correlated with the recovery of the hematopoietic system from radiation injury.
In the present study, chloroform, aqueous, (polyethylene glycol/propylene carbonate) PEG/PC extracts were made from coconut, onion, garlic, fig, date tree, chicory, ananas, and cistrose. These extracts were tested in vivo and in vitro on their anthelmintic activity against cestodes (Hymenolepis diminuta, H. microstoma, Taenia taeniaeformis) and trematodes (Fasciola hepatica, Echinostoma caproni). In all in vitro tests, the target parasites died. It turned out that the treatment of mice and rats with a combination of onion and coconut extracts (with PEG/PC) eliminated all cestodes from their final hosts. In addition, the same composition was effective against the intestinal fluke E. caproni, but not against the liver fluke F. hepatica in the final host, while both worms were killed in vitro...
A hypofunctionality of Gi proteins has been found in migraine patients. The fixed combination of indomethacin, prochlorperazine and caffeine (Indoprocaf) is a drug of well-established use in the acute treatment of migraine and tension-type headache. The aim of this study was to investigate if Indoprocaf was able to exert its central antinociceptive action when Gi proteins activity is abolished by pertussis toxin (PTX), compared to its single active ingredients and to sumatriptan. The mice model of abdominal constriction test induced by an i.p. injection of a 0.6% solution of acetic acid was used. The study showed that Indoprocaf (a fixed combination of indomethacin 1?mg/kg, prochlorperazine 1?mg/kg and caffeine 3?mg/kg, s.c.) and sumatriptan (20?mg/kg, s.c.) exert their central antinocicep...
Introduction.Microfluidic technology allows fast reactions in a simple experimental setup, while using very low volumes and amounts of starting material. Consequently, microfluidic technology is an ideal tool for radiolabeling reactions involving short-lived positron emitters. Optimization of the complex array of different reaction conditions requires knowledge of the different reaction parameters linked to the microfluidic system as well as their influence on the radiochemical yields. 1-(5-Deoxy-5-fluoro-?-d-arabinofuranosyl)-2-nitroimidazole ([18F]FAZA) is a frequently used radiotracer for PET imaging of tumor hypoxia. The present study describes the radiosynthesis of [18F]FAZA by means of microfluidic technology and subsequent small animal PET imaging in EMT-6 tumor-bearing mice.Methods...
Mono- and disubstituted novel derivatives of the heptaene nystatin analog 28,29-didehydronystatin A1 (S44HP, 1) were obtained by chemical modification of the exocyclic C-16 carboxyl and/or an amino group of mycosamine moiety. The strategy of preparation of mono- and double-modified polyene macrolides was based on the use of intermediate hydrophobic N-Fmoc (9-fluorenylmethoxycarbonyl) derivatives that facilitated the procedures of isolation and purification of new compounds. The antifungal activity of the new derivatives was first tested in vitro against yeasts and filamentous fungi, allowing the selection of the most active compounds that were subsequently tested for acute toxicity in mice. 2-(N,N-dimethylamino)ethylamide of 1 (2) and 2-(N,N-dimethylamino)ethylamide of N-fructopyranosyl-28...
The dimercaptosuccinic acid metronidazole ester (DMSAMe) was synthesized and radiolabeled with 99mTc to form the 99mTc-DMSAMe complex in high yield. The radiochemical purity of the 99mTc-DMSAMe complex was over 90%, as measured by TLC and by HPLC, without any notable decomposition at room temperature over a period of 6?h. Its partition coefficient indicated that it was a lipophilic complex. The tumor cell experiment and the biodistribution in mice bearing S 180 tumor showed that the 99mTc-DMSAMe complex had a certain hypoxic selectivity and accumulated in the tumor with high uptake and good retention. The tumor/blood and tumor/muscle ratios increased with time, suggesting it would be a possible tumor hypoxia imaging agent.
Bisphenol-A (BPA) is one of the most common environmental endocrine disrupters and has a wide range of effects on central nervous system. Adolescence is another important developmental period besides the early critical prenatal and neonatal periods. In the present study, we exposed mice to BPA (40, 400 mg/kg/d) between adolescence and young adulthood for 8 weeks and investigated its effects on the non-reproductive behaviors. In open field tests, rearing and grooming sex differences were abolished by BPA exposure. In the elevated plus maze test, the number of open arm entries, the time spent in open arms, and the number of unprotected head dips in the center area were reduced in males but increased in females by BPA at 40 or 400 mg/kg/d, thus eliminating or reversing sex differences in thes...
The laboratory environment existing outside the test situation itself can have a substantial influence on results of some behavioral tests with mice, and the extent of these influences sometimes depends on genotype. For alcohol research, the principal issue is whether genotype-related ethanol effects will themselves be altered by common variations in the lab environment or instead will be essentially the same across a wide range of lab environments. Data from 20 inbred strains were used to reduce an original battery of seven tests of alcohol intoxication to a compact battery of four tests: the balance beam and grip strength with a 1.25g/kg ethanol dose and the accelerating rotarod and open-field activation tests with 1.75g/kg. The abbreviated battery was then used to study eight inbred str...
In developing new brain imaging agents for single photon emission computed tomography (SPECT), we synthesized eleven radioiodinated phenoxyacetic acid derivatives and investigated the relationship between the chemical structure and in vivo characteristics. Biodistribution studies in mice revealed high initial brain uptake for all the compounds. Blood radioactivity level depended markedly upon the chemical stability of the compound. The alpha,alpha-dimethylester derivative, amide derivatives and diamine derivatives, which were stable to hydrolysis, showed low blood activity levels following intravenous administration. Disappearance of the ester and amide compounds from the brain was rapid. However, the diamine derivatives displayed improved retention in the brain. Compounds 3a and 4 possessed the best combination of high brain uptake and sufficient retention to be useful as potential brain imaging radiopharmaceuticals with SPECT devices.
Olfactory memory dysfunctions were investigated in the triple-transgenic murine model of Alzheimer's disease (3x Tg-AD). In the social transmission of food preference test, 3x Tg-AD mice presented severe deficits in odor-based memory, without gross changes in general odor-ability. Ab and tau immunoreactivity was not observed in the primary processing regions for odor, the olfactory bulbs (OBs), whereas marked immunostaining was present in the piriform, entorhinal, and orbitofrontal cortex, as well as in the hippocampus. Our results suggest that the impairment in olfactory-based information processing might arise from degenerative mechanisms mostly affecting higher cortical regions and limbic areas, such as the hippocampus.
Lipophilic tertiary amines attached to cylcopentadienyl technetium-99m tricarbonyl (cytectrene) have been prepared with high radiochemical yield and purity. Biodistribution studies in mice showed that [{sup 99m}Tc]-cytectrenes, containing in their structure an N-methylpiperidine, were accumulated in the brain up to 2.8% of injected dose with high brain-to-blood ratios at 15 min p.i. They therefore indicate some potential as brain imaging agents. It has to be pointed out that the N-methylpiperidine ester showed similar biological behaviour as the keto derivatives. This indicates that the conversion to polar metabolite(s) via hydrolysis of the ester group - as described for [{sup 99m}Tc]-ECD -is not essential for brain retention. (Author).
Lipophilic tertiary amines attached to cylcopentadienyl technetium-99m tricarbonyl (cytectrene) have been prepared with high radiochemical yield and purity. Biodistribution studies in mice showed that ["9"9"mTc]-cytectrenes, containing in their structure an N-methylpiperidine, were accumulated in the brain up to 2.8% of injected dose with high brain-to-blood ratios at 15 min p.i. They therefore indicate some potential as brain imaging agents. It has to be pointed out that the N-methylpiperidine ester showed similar biological behaviour as the keto derivatives. This indicates that the conversion to polar metabolite(s) via hydrolysis of the ester group - as described for ["9"9"mTc]-ECD -is not essential for brain retention. (Author).
Radiolabeled lipiodol has been used for targeting liver cancer. We developed a lipiodol solution of {sup 188}Re-TDD (2,2,9,9-tetramethyl-4,7-diaza-1,10-decanedithiol) and investigated its feasibility for the treatment of liver cancer. The lipiodol solution of {sup 188}Re-TDD was well-retained in the lipiodol phase in vitro. After injection through the tail veins of mice, high lung-uptake was investigated which is evidence of embolizing activity. We also found high accumulation in hepatoma after injection through the hepatic arteries of hepatoma-bearing rats. In conclusion, the lipiodol solution of {sup 188}Re-TDD is a promising agent for liver cancer therapy.
Fibroblast growth factor (FGF) signaling has been shown to regulate lung epithelial development but its influence on mesenchymal differentiation has been poorly investigated. To study the role of mesenchymal FGF signaling in the differentiation of the mesenchyme and its impact on epithelial morphogenesis, we took advantage of Fgfr2c+/? mice, which due to a splicing switch express Fgfr2b in mesenchymal tissues and manifest Apert syndrome-like phenotypes. Using a set of in vivo and in vitro studies, we show that an autocrine FGF10?FGFR2b signaling loop is established in the mutant lung mesenchyme, which has several consequences. It prevents the entry of the smooth muscle progenitors into the smooth muscle cell (SMC) lineage and results in reduced fibronectin and elastin deposition. Levels of...
Vaccine-mediated prevention of primary HIV-1 infection at the heterosexual mucosal portal of entry may be facilitated by highly optimised formulations or drug delivery devices for intravaginal (i.vag) immunization. Previously we described hydroxyethylcellulose (HEC)-based rheologically structured gel vehicles (RSVs) for vaginal immunization of an HIV-1 vaccine candidate, a soluble recombinant trimeric HIV-1 clade-C envelope glycoprotein designated CN54gp140. Here we investigated the efficacy of lyophilized solid dosage formulations (LSDFs) for prolonging antigen stability and as i.vag delivery modalities. LSDFs were designed and developed that upon i.vag administration they would reconstitute with the imbibing of vaginal fluid to mucoadhesive, site-retentive semi-solids. Mice were immunize...
BACKGROUND AND PURPOSE Controlling vascular tone involves K+ efflux through endothelial cell small- and intermediate-conductance calcium-activated potassium channels (KCa2.3 and KCa3.1, respectively). We investigated the expression of these channels in astrocytes and the possibility that, by a similar mechanism, they might contribute to neurovascular coupling. EXPERIMENTAL APPROACH Transgenic mice expressing enhanced green fluorescent protein (eGFP) in astrocytes were used to assess KCa2.3 and KCa3.1 expression by immunohistochemistry and RT-PCR. KCa currents in eGFP-positive astrocytes were determined in situ using whole-cell patch clamp electrophysiology. The contribution of KCa3.1 to neurovascular coupling was investigated in pharmacological experiments using electrical field stimulatio...
Sulfur mustard (HD) is an alkylating and cytotoxic chemical warfare agent, which inflicts severe skin toxicity and an inflammatory response. Effective medical countermeasures against HD-caused skin toxicity are lacking due to limited knowledge of related mechanisms, which is mainly attributed to the requirement of more applicable and efficient animal skin toxicity models. Using a less toxic analog of HD, chloroethyl ethyl sulfide (CEES), we identified quantifiable inflammatory biomarkers of CEES-induced skin injury in dose- (0.05-2 mg) and time- (3-168 h) response experiments, and developed a CEES-induced skin toxicity SKH-1 hairless mouse model. Topical CEES treatment at high doses caused a significant dose-dependent increase in skin bi-fold thickness indicating edema. Histopathological e...
One of the research challenges in oncology is to develop new biochemical methods for noninvasive tumor therapy evaluation to determine whether the chemotherapeutics is effective. Vascular endothelial growth factor (VEGF) was labeled with radioiodine and evaluated in vitro as well as in vivo, using A2058, a melanoma cell line overexpressing VEGFR-1 and -2. Saturation binding analysis with [{sup 125}I]-VEGF resulted in a K {sub d} of 0.1 nM. Internalization assays indicate the preserved ligand induced internalization and metabolization of the tracer. Biodistribution studies with [{sup 123}I]-VEGF in wild type and A2058 tumor-bearing athymic mice showed low background activity and a tumor to reference tissue ratio of maximum 6.12. These results suggest that [{sup 123}I]-VEGF is a potentially suitable tracer for tumor therapy evaluation.
Astrocytes have important immune functions in CNS, and astrocytes stimulated by interferon-g were showed to have direct antimicrobial function. However whether astrocytes without the stimulation of cytokines have antibacterial function, and how this function is regulated are still largely unknown. In this study, we found that primary cultured astrocytes inhibited the growth of both gram-negative and gram-positive bacteria. Further more, we showed that interleukin-1b (IL-1b) enhanced the antibacterial effect in a dose-dependent manner, and the antibacterial effect of astrocytes from IL-1b receptor-deficient mice failed to be enhanced by IL-1b. IL-1b stimulated IkBa degradation, NF-kB nuclear translocation, and transactivation in astrocytes. NF-kB inhibitors blocked NF-kB activation and the ...
Previous studies suggest that the radiosensitivity and origin of tissue macrophage precursors differ from those of hemopoietic macrophage colony-forming units (CFU-Ms) committed to macrophage-lineage cells. We assessed the origins of tissue macrophage colony-forming cells (M-CFCs) in mice by comparing their kinetics and radiosensitivities in the normal steady state and under the conditions of bone marrow depletion by [sup 89]Sr-administration and/or splenectomy. The results indicate that the radiosensitive peritoneal M-CFCs elicited by thioglycollate are derived from bone marrow macrophage precursors; where as alveolar M-CFCs, which are radioresistant, are self-sustained locally and independent of hemopoietic macrophage precursors. In contrast, highly radiosensitive liver M-CFCs are probably derived from CFU-Ms that appear to be propagated in the spleen in association with hemopoietic responses. (author).
Obesity is associated with increased susceptibility to dyslipidemia, insulin resistance, and hypertension, a combination of traits that comprise the traditional definition of the metabolic syndrome. Recent evidence suggests that obesity is also associated with the development of nonalcoholic fatty liver disease (NAFLD). Despite the high prevalence of obesity and its related conditions, their etiologies and pathophysiology remains unknown. Both genetic and environmental factors contribute to the development of obesity and NAFLD. Previous genetic analysis of high-fat, diet-induced obesity in C57BL/6J (B6) and A/J male mice using a panel of B6-ChrA/J/NaJ chromosome substitution strains (CSSs) demonstrated that 17 CSSs conferred resistance to high-fat, diet-induced obesity. One of these CSS st...
Research on hematological disorders relies on suitable animal models. We retrospectively evaluated the use of the hematological parameters hematocrit (HCT), hemoglobin (HGB), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), mean corpuscular volume (MCV), red blood cell count (RBC), white blood cell count (WBC), and platelet count (PLT) in the phenotype-driven Munich N-ethyl-N-nitrosourea (ENU) mouse mutagenesis project as parameters for the generation of novel animal models for human diseases. The analysis was carried out on more than 16,000 G1 and G3 offspring of chemically mutagenized inbred C3H mice to detect dominant and recessive mutations leading to deviations in the levels of the chosen parameters. Identification of animals exhibiting altered valu...
Keratinocyte growth factor receptor (KGFR) and fibroblast growth factor receptor (FGFR) 2c share identical amino acid sequences, except for a 46-amino acid domain in the extracellular region. Monoclonal antibodies (MAbs) specific to KGFR have not been reported nor are commercially available. In this study, we generated murine MAbs specific to KGFR in non-obese diabetic (NOD) mice using a modified Repeated Immunizations at Multiple Sites (RIMMS) technology. Stable cell lines expressing the full-length human KGFR or FGFR2c were produced to facilitate the identification of KGFR-specific MAbs. Following the initial screening of hybridoma clones with a fluorescence-based, confocal cell detection method and ELISA, KGFR-specific MAbs were selected and confirmed by flow cytometry and Western blot ...
Aim of study: Clitoria ternatea L. (Family: Fabaceae) is being used in traditional medicine for the treatment of severe bronchitis and asthma. So the aim of study was to evaluate antiasthmatic activity of ethanol extract of Clitoria ternatea roots. Materials and methods: In the present study ethanol extract of Clitoria ternatea root (ECTR) was evaluated for preliminary phytochemical screening, acute toxicity studies and antiasthmatic activity using milk induced leucocytosis and eosinophilia in mice, egg albumin induced mast cell degranulations in rats and passive cutaneous anaphylaxis in rats at doses (100-150mg/kg ip). Results: The results of present investigation showed that the LD50 of ECTR is more than 1300mg/kg. ECTR significantly decreases milk induced leucocytosis and eosinophilia, ...
Purpose Evaluation of the all-trans retinoic acid (t-RA) effects on in vitro maturation (IVM) and in vitro fertilization (IVF) of immature mouse oocytes in the presence and absence of granulosa cell monolayer. Methods Denuded oocytes isolated from mice ovaries and matured in IVM medium alone (Control I), IVM medium in the presence of granulosa cells (Control II), IVM medium with t-RA (Experimental I) and IVM medium simultaneously with t-RA and granulosa cells (Experimental II). After 24?h, matured oocytes were fertilized in T6 medium and their development was followed until the blastocyst stage. Metaphase II oocytes ploidy were evaluated by chromosome counting. Results The t-RA group compared to the control groups showed no obvious abnormalities. Additionally maturation and embryo developm...
Aims A depressed cGMP-dependent protein kinase (PKG) activity is implicated in nitrate tolerance. The present study determines whether the leucine zipper-positive (LZ+) isoform of myosin phosphatase target subunit 1 (MYPT1), a key target protein for PKG actions, is involved in the development of nitrate tolerance. Methods and results Nitrate tolerance in in vitro preparations was obtained by a 24 h incubation with nitroglycerin (NTG). Nitrate tolerance in in vivo preparations was obtained by subcutaneous injection of mice with NTG, and the aortas were used. Protein levels of total MYPT1, MYPT1 (LZ+), PP1Cd, myosin light chain (MLC), and phosphorylated MLC were determined by Western blot analysis. Isometric vessel tension was determined by an organ chamber technique. Protein levels of MYPT1...
Abstract NorUDCA (24 norursodeoxycholic acid), the C23 homolog of ursodeoxycholic acid (UDCA), showed remarkable therapeutic effects in cholestatic Mdr2 (Abcb4) (multidrug resistance protein 2/ATP binding cassette b4) knockout mice with sclerosing/fibrosing cholangitis. In contrast to UDCA, norUDCA is inefficiently conjugated in human and rodent liver, and conjugation has been discussed as a key step for the anticholestatic action of UDCA in cholestasis. We compared the choleretic, anticholestatic, and antiapoptotic properties of unconjugated and taurine conjugated UDCA (C24) and norUDCA (C23) in isolated perfused rat liver (IPRL) and in natrium/taurocholate cotransporting polypeptide (Ntcp) transfected human hepatoma (HepG2) cells. Taurolithocholic acid (TLCA) was used to induce a predomi...
Excessive physical activity plays an important role in the progression of anorexia nervosa (AN) by accelerating weight loss during dietary restriction. To search for mechanisms underlying this trait, a panel of mouse chromosome substitution strains derived from C57BL/6J and A/J strains was exposed to a scheduled feeding paradigm and to voluntary running wheel (RW) access. Here, we showed that A/J chromosomes 4, 12 and 13 contribute to the development of a disrupted RW activity in response to daily restricted feeding. This pattern is characterized by intense RW activity during the habitual rest phase and leads to accelerated body weight loss. Regions on mouse chromosomes 4, 12 and 13 display homology with regions on human chromosomes linked with anxiety and obsessionality in AN cohorts. The...
Two lines of mouse tumor cells were shown to be capable of aggregating mouse and rabbit platelets in vitro. This process required higher Mg/sup 2 +/ concentrations than were needed by other commonly used platelet-aggregating agents. Platelet-aggregating activity was also found in tumor cell membrane fragments. This membrane-bound platelet-aggregating material contained protein, lipid, and carbohydrate moieties. The presence of all three appeared to be essential for stimulating platelet aggregation. Destruction of any component abolished its activity. Platelet aggregation induced by tumor cell membrane fragments was associated with a secretory release reaction. In this process, growth-promoting activity for tumor cells was also released from platelets. These results underline the importance of platelets in establishing tumor metastases.
Glioblastoma multiforme is the most aggressive form of human brain tumor, which has no effective cure. Previously, we have demonstrated that overexpression of the C-terminal fragment of the human telomerase reverse transcriptase (hTERTC27) inhibits the growth and tumorigenicity of human cervical cancer HeLa cells. In this study, the therapeutic effect and molecular mechanisms of hTERTC27-mediated cancer gene therapy were further explored in vivo in established human glioblastoma xenografts in nude mice. We showed that intratumoral injection of adeno-associated virus carrying hTERTC27 (rAAV-hTERTC27) is highly effective in reducing the growth of the subcutaneously transplanted glioblastoma tumors. Histological analyses showed that rAAV-hTERTC27 treatment leads to profound necrosis, apoptosi...
We hypothesize that the mushroom-derived active compound may be a potential strategy for increasing survival in response to influenza virus (H1N1) infection through the stimulation of host innate immune response. The validity of the hypothesis can be tested by immune response to influenza infection as seen through survival percentage, virus clearance, weight loss, natural killer cell cytotoxicity, Tumor Necrosis Factor-? (TNF-?) and Interferon-gamma (IFN-?) levels, lytic efficiency in the spleens of mice and inducible nitric oxide synthase mRNA expressions in RAW 264.7 murine macrophage cells. The hypothesis may improve people's quality of life, reduce the medical cost of our healthcare system and eliminate people's fears of influenza outbreak. PMID:21660092
This human investigation of lead absorption from the lungs utilized two forms of lead, lead chloride and lead hydroxide; the former was used in picogram amounts and the latter at microgram levels. These two species of lead were selected in an attempt to simulate the range of physicochemical properties found in atmospheric lead (urban air). Aerosols labeled with lead-203 were made of comparable aerodynamic size (MMAD 0.25 ..mu..m +- 0.1) by using sodium chloride as the deposition-determining aerosol. After brief, mouthpiece exposures, 17 subjects were followed by serial counting with a thoracic array of 12 2-in. scintillation detectors and two 2-in. leg counters, all coupled to single channel analyzers. Serial blood samples were also taken. The two exposure groups showed similar total deposition values (23 vs 26%) and the same biological retention halftimes, viz., 22.6 h. When the retention data were corrected for blood-borne /sup 203/Pb, the biological halftimes for lung lead retention ...
Manganese is an essential metal of toxicologic concern primarily because of exposure via inhalation. Environmental forms of Mn exist mainly as insoluble oxides, yet much of the research information available relates to the soluble salts. In the present study, adult male Sprague-Dawley rats were intratracheally instilled with either soluble MnCl/sub 2/ or insoluble Mn/sub 3/O/sub 4/ labeled with /sup 54/Mn. Lungs and other major organs were sampled over a span of 3 mo after dosing with the respective chemicals, which were equivalent to 8 ..mu..Ci and 1 ..mu..mol of manganese in 0.2 ml of buffer. There was rapid clearance of Mn from the lungs in the case of both chemicals; the chloride cleared at an initial rate of nearly four times that of the oxide. Despite this early difference, the amount of /sup 54/Mn remaining in the lungs after 2 wk was similar for both compounds. The level of /sup 54/Mn in the liver, kidney, spleen, and testes peaked at the 3-d sampling point ...
To predict the response of blood lead to airborne and dietary lead requires knowledge of the rate of uptake of lead into the body from lung and gut, its subsequent partitioning between compartments, the stay time in those compartments, and its redistribution or excretion. Tracer studies with volunteers have shown no differences in systemic distribution of inorganic lead between tissues whether it is taken by inhalation, ingestion or injection. Lead is rapidly transferred from plasma to red cells, and there is slower movement thence into liver and other soft tissues, to bone, and to excreta. Work at Harwell and elsewhere with /sup 203/Pb has shown that the initial rapid distribution leaves rather over half the assimilated lead attached to red cells. The result is remarkably consistent, and applies also to dogs and baboons. The renal clearance (Vu) (ratio of U to CB, or daily urinary output expressed as mass of blood having the same lead content), and also the ...
Polycyclic aromatic hydrocarbons (PAHs) are combustion products of organic materials, mixtures of which contain multiple known and probable human carcinogens. PAHs occur in indoor and outdoor air, as well as in char-broiled meats and fish. Human exposure to PAHs occurs by inhalation, ingestion and topical absorption, and subsequently formed metabolites are either rendered hydrophilic and excreted, or bioactivated and bound to cellular macromolecules. The formation of PAH-DNA adducts (DNA binding products), considered a necessary step in PAH-initiated carcinogenesis, has been widely studied in experimental models and has been documented in human tissues. This review describes immunohistochemistry (IHC) studies, which reveal localization of PAH-DNA adducts in human tissues, and semi-quantify PAH-DNA adduct levels using the Automated Cellular Imaging System (ACIS). These studies have shown that PAH-DNA adducts concentrate in: basal and supra-basal epithelium of the ...
Samples of Parmelia sulcata and Xanthoria parietina from different biotopes have been analysed for elements of the series of uranium 238 and thorium 232. These species have been used as bio-monitors in different cases : urban areas, coal fired power plant, tip for uranium-mining residues. The concentration of most of these elements in lichens is decreasing as follows: radium waste-disposal site > area with uranium-rich soil > urban area > rural area. Road traffic was not found to increase notably the presence of radioactive lead in the environment. The two foliose lichens seem to have a comparable concentration ability, but Parmelia sulcata appeared to be more reliable. Some of the elements under investigation could be particularly problematic from a sanitary point of view: the intake limits in case of inhalation are very low and the atmospheric deposition is not negligible; this is particularly so for lead 210 and thorium 228. These elements should not ...
Incorporation of tritium into body constituent molecules from tritiated water and its in vivo behaviors were studies using rats. In single administration of HTO, "3H behaviors were studied in lipids that are rich in hydrogen. Incorporation of "3H into the lipid fraction from HTO and its release differed by each organ and by the type of lipid components. Of routes of administration, the oral and parenteral routes showed same results, and no prominent difference was noted by inhalation. By consecutive administration, the urine "3H concentration showed no difference according to the route, but increased as the concentration of administered HTO increased. When administration was discontinued after the urine "3H concentration reached a plateau, the biological half-life was about 4.5 days, almost in agreement with the value by single administration. In relation to water intake, increase in the urine volume and accompanying promotion of urine "3H excretion in approximate ...
This paper summarizes results of preliminary experiments to develop cytological and biochemical indicators for estimating damage to respiratory cells in test animals exposed by inhalation to toxic agents associated with nonnuclear energy production, the specific goal being the application of advanced multiparameter flow-systems technologies to the detection of early atypical cellular changes in lung epithelium. Normal Syrian hamster lung cell samples composed of histiocytes, leukocytes, macrophages, ciliated columnar cells, and epithelial cells were stained with fluorescent dyes specific for different biochemical parameters and were analyzed in liquid suspension as they flowed through a chamber intersecting a laser beam of exciting light. Multiple sensors measured the total or two-color fluorescence and light scatter on a cell-by-cell basis. Cellular parameters proportional to optical measurements (i.e., cell size, DNA content, total protein, nonspecific esterase ...
Isocapnic hyperventilation with cold air (IHCA) is a reliable technique for assessing indirect bronchial hyperresponsiveness in patients with asthma. Impedance measurement of the respiratory system by the forced pseudorandom noise oscillation technique is a sensitive technique to assess changes in bronchial tone after IHCA. The aim of this study was to evaluate the effect of 6 weeks of treatment with beclomethasone dipropionate, 1,000 microg x day-1, on IHCA in asthmatic patients, measured with both forced oscillation technique and flow-volume recordings. Forty patients with mild asthma were included in this double-blind, placebo-controlled parallel-group study. Stratification on the basis of sex was performed to overcome differences in airway diameter. At entry and every 2 weeks during the treatment period, IHCA was performed and patient diaries were evaluated. Characteristic changes in forced oscillation parameters after IHCA were observed in all patients. After 6 weeks of treatment, ...
In June 1997, the US Navy plans to close its Naval Air Facility on Sand Island and transfer the atoll to the US Fish and Wildlife Service for use as a National Wildlife Refuge. Midway provides breeding and feeding habitat for migratory seabirds, terrestrial and marine mammals, sea turtles and other reptiles, and a variety of reef fishes and invertebrates. As part of the base closure and transfer process, 36 sites of potential environmental concern were identified on Sand and Eastern islands. These sites include landfills and uncontrolled disposal areas, hazardous materials storage areas, abandoned transformers, sewer outfalls, and other potential hazardous waste sites. Potential contaminants include pesticides, PAHs, PCBs, and heavy metals. A screening ecological risk assessment was performed at each site with a goal of determining whether contaminants could pose any current or future risks to protected migratory bird or marine mammal wildlife species. Specific exposure pathways ...
The purpose of the paper is to investigate whether high-resolution CT (HRCT) can detect the subjects with massive emphysematous destruction in a group of patients with severe chronic obstructive pulmonary disease (COPD) and therefor be of help in selecting the candidates to surgical lung volume reduction. Have been examined 40 former smokers with severe COPD (FEV_1#<=#40% of the predicted value, with no major improvement after inhalation of bronchodilators). The emphysema extent score was significantly correlated with the hematocrit value and Tiffeneau index (p<2) in all the 40 patients. The severity of bronchial obstruction was the same in bronchitis and dyspnoeic patients. The subject with chronic bronchitis had milder emphysema (mean extent 35% versus 47% in the dyspnoeic subjects) and a higher frequency of bronchial involvement. A decrease in FEV_1 was significantly correlated with emphysema extent (p<1) in dyspnoeic, but not in bronchitis, patients. ...
This monograph provides basic notions and principles in dosimetry and radiation protection in compliance with two fundamental works: IAEA Safety Series No.115 - International Basic Safety Standards for Protection against Ionizing Radiation and for the Safety of Radiation Sources - and Publication no. 60 of International Commission on Radiological Protection. After the review of quantities and units necessary in radiation protection, the book presents the new values of dose limits as well as the values of 'radiation weighting factor', 'tissue weighting factor' and 'conversion factor intake-dose' (committed effective dose per unit intake) by ingestion and inhalation for 30 most important radionuclides. The new values of dose limits, lower than the old values, are a challenge for the radiation protection, especially of the 'public' where the dose limit diminished by a factor of five relative to the earlier edition. The new value of dose limit for public, 1 mSv per ...
Respiratory allergy affects all age groups but the children are the worst affected by the respiratory allergy. Bioparticles from different biological sources are the main cause of allergy. Pollen grains, fungal spores, insect and other materials of biological origin form the most important allergen load in the air. For the efficient diagnosis of the allergy and its effective treatment it is very important to know about the prevalence, seasonal and annual variations of aeroallergens of the area. India being the climatically diversed country, there is diversity in the flora and fauna of different parts of the country. Atmospheric surveys carried out in different parts of India reveal that, Alanus nitida, Amarantus spinosus, Argemone mexicana Cocos nucifera, Betula utilis, Borasus flabellifer, Caraica papaya, Cedrus deodara, Cassia fistula, Parthenium, Chenopodium album, Dodonaea viscosa, Malotus phillipensis, Plantago ovata, Prosopis juliflora, Ricinus communis, Holoptelea intergifolia ...
The release of {sup 14}C as {sup 14}CO{sub 2} from partly failed spent fuel containers has been analyzed by the flow of gases into and out of the containers. This flow of gases is driven by pressure differences, which are in turn caused by heating by the spent fuel. In this analysis, the timing and size of holes in the containers are assumed to be given. A better means of predicting the time distribution and sizes of penetrations in nuclear waste containers is needed. For the purposes of far-field transport calculations, we have adopted release rates that are shown to be bonding for the large range of hole sizes studied. The transport of released {sup 14}CO{sub 2} has been analyzed by transport in equivalent porous medium. The peak {sup 14}CO{sub 2} concentration in pore gas at 350 m above the repository does not depend on the time of hole occurrence, although the time of penetration obviously affects the arrival and duration of exposure to {sup 14}C. Nor does water saturation have ...
Bone is a complex, highly structured, mechanically active, three-dimensional (3-D) tissue composed of cellular and matrix elements. We previously published a report on in situ collagen gelation using a rotary 3-D culture system (CG-RC system) for the construction of large tissue specimens. The objective of the current study was to evaluate the feasibility of bone tissue engineering using our CG-RC system. Osteoblasts from the calvaria of newborn Wistar rats were cultured in the CG-RC system for up to 3 wk. The engineered 3-D tissues were implanted into the backs of nude mice and calvarial round bone defects in Wistar rats. Cell metabolic activity, mineralization, and bone-related proteins were measured in vitro in the engineered 3-D tissues. Also, the in vivo histological features of the transplanted, engineered 3-D tissues were evaluated in the animal models. We found that metabolic activity increased in the engineered 3-D tissues during cultivation, and that ...
The purpose of this study is to evaluate the therapeutic efficacy of the liposome encaged with vinorelbine (VNB) and "1"1"1In-oxine on human colorectal adenocarcinoma (HT-29) using HT-29/luc mouse xenografts. HT-29 cells stably transfected with plasmid vectors containing luciferase gene (luc) were transplanted subcutaneously into the male NOD/SCID mice. Biodistribution of the drug was performed when tumor size reached 500-600 mm"3. The uptakes of "1"1"1In-VNB-liposome in tumor and normal tissues/organs at various time points postinjection were assayed. Multimodalities, including gamma scintigraphy, bioluminescence imaging (BLI) and whole-body autoradiography (WBAR), were applied for evaluating the therapeutic efficacy when tumor size was about 100 mm"3. The tumor/blood ratios of "1"1"1In-VNB-liposome were 0.044, 0.058, 2.690, 20.628 and 24.327, respectively, at 1, 4, 24, 48 and 72 h postinjection. Gamma scinitigraphy showed that the tumor/muscle ratios were 2.04, ...
The synthesis and brain uptake in mice of the radioidinated derivatives of N,N-dimethyl-N'-(idodimethoxyphenyl)-1,3-propanediamine, as well as the N-substituted derivatives of (iodoalkylphenyl)isopropyl, iodoalkylphenylethylamine and 3,4-(methylenedioxy)phenyl-amphetamine (MDA) are described. These compounds contain structural features of both IMP and HIPDM, the cerebral perfusion agents currently in clinical use. The radiolabeled analogs were obtained via the [{sup 125}I]I exchange method, or by [{sup 125}I]NaI treatment of the iodo-free precursor in the presence of an oxidant. Following intravenous injection in mice, all compounds showed important radioactivity concentrations in the lungs and kidneys. The N-substituted (iodoalkylphenyl)isopropyl and iodoalkylphenyl-ethylamine derivatives displayed a high initial brain uptake (>10%IDg{sup -1}) followed by a rapid clearance phase, resulting in lower brain-to-blood ratios as ...
The synthesis and brain uptake in mice of the radioidinated derivatives of N,N-dimethyl-N'-(idodimethoxyphenyl)-1,3-propanediamine, as well as the N-substituted derivatives of (iodoalkylphenyl)isopropyl, iodoalkylphenylethylamine and 3,4-(methylenedioxy)phenyl-amphetamine (MDA) are described. These compounds contain structural features of both IMP and HIPDM, the cerebral perfusion agents currently in clinical use. The radiolabeled analogs were obtained via the ["1"2"5I]I exchange method, or by ["1"2"5I]NaI treatment of the iodo-free precursor in the presence of an oxidant. Following intravenous injection in mice, all compounds showed important radioactivity concentrations in the lungs and kidneys. The N-substituted (iodoalkylphenyl)isopropyl and iodoalkylphenyl-ethylamine derivatives displayed a high initial brain uptake (>10%IDg"-"1) followed by a rapid clearance phase, resulting in lower brain-to-blood ratios as those reported for IMP and ...
Purpose: Photodynamic therapy (PDT) is based on the interaction of a photosensitizing (PS) agent, light, and oxygen. Few new PS agents are being developed to the in vivo stage, partly because of the difficulty in finding the right treatment conditions. Response surface methodology, an empirical modeling approach based on data resulting from a set of designed experiments, was suggested as a rational solution with which to select in vivo PDT conditions by using a new peptide-conjugated PS targeting agent, neuropilin-1. Methods and Materials: A Doehlert experimental design was selected to model effects and interactions of the PS dose, fluence, and fluence rate on the growth of U87 human malignant glioma cell xenografts in nude mice, using a fixed drug-light interval. All experimental results were computed by Nemrod-W software and Matlab. Results: Intrinsic diameter growth rate, a tumor growth parameter independent of the initial volume of the tumor, was selected as ...
In the use of doxorubicin and radiation for treatment of human malignant tumors in vivo, the relationship between treatment-induced apoptosis and Ki-67 labeling index was investigated. Four human tumor xenografts (ependymoblastoma, NNE; primitive neuroectodermal tumor, YKP; small cell lung carcinoma, GLS; glioblastoma, KYG) were transplanted under the skin of thigh of the nude mice (BALB/cA JcL-nu). The mice were given a single radiation dose of 1 Gy, or doxorubicin alone intraperitoneally at a dose of 8 mg/kg. After treatment, sections of tumor specimens were prepared from paraffin-embedded tissues. Hematoxylin and eosin staining, TUNEL staining, and immunohistochemical analysis of Ki-67 were performed. In NNE, apoptotic cells appeared most frequently after treatment compared with all other tumors, and the incidence of apoptosis in the radiation-treated group was much higher than in the doxorubicintreated group. As the incidence of apoptosis ...
The distribution of i.v. administered lead (/sup 203/Pb-acetate; 50 nmol/kg b.w.) was studied by means of autoradiography and impulse counting in pregnant C57BL mice (day 18) treated orally with dithiocarbamates. Diethyldithiocarbamate (DEDTC), disulfuram or thiram (2 X 1) mmol/kg b.w.) or vehicle (gelatine) alone, was given by gavage 2 h before and immediately after the injection of lead. All three dithiocarbamates, especially thiram, changed the distribution pattern of lead. Thiram and DEDTC had the greatest effect at 4 h after lead administration, disulfiram at 24 h. In the mother, most notably the brain concentration increased (70-fold for thiram at 4 h) while that of erythrocytes and skeleton decreased (50- and 4-fold, respectively). The total fetal concentration unexpectedly showed only a moderate increase (proportional 2-fold for thiram), which may be due partly to the low maternal plasma lead concentration. The partition within the fetal tissues was, ...
The distribution of i.v. administered lead ("2"0"3Pb-acetate; 50 nmol/kg b.w.) was studied by means of autoradiography and impulse counting in pregnant C57BL mice (day 18) treated orally with dithiocarbamates. Diethyldithiocarbamate (DEDTC), disulfuram or thiram (2 X 1) mmol/kg b.w.) or vehicle (gelatine) alone, was given by gavage 2 h before and immediately after the injection of lead. All three dithiocarbamates, especially thiram, changed the distribution pattern of lead. Thiram and DEDTC had the greatest effect at 4 h after lead administration, disulfiram at 24 h. In the mother, most notably the brain concentration increased (70-fold for thiram at 4 h) while that of erythrocytes and skeleton decreased (50- and 4-fold, respectively). The total fetal concentration unexpectedly showed only a moderate increase (proportional 2-fold for thiram), which may be due partly to the low maternal plasma lead concentration. The partition within the fetal tissues was, however, ...
Purpose: The predictive potential of tumor cell kinetic parameters may be improved when they are studied in relation to other microenvironmental parameters. The purpose of this investigation was to quantitatively categorize human tumor samples according to proliferation patterns. Second, it was examined whether these characteristics are retained after xenotransplantation. Methods and Materials: Fifty tumor samples from head-and-neck cancer patients were immunohistochemically stained for Ki-67 and vessels. Also, parts of the samples were transplanted into nude mice. Tumors were categorized according to previously described patterns of proliferation. Vascular and proliferation patterns were analyzed using an image processing system. Results: The 50 tumors were categorized into four patterns of proliferation by visual assessment: marginal (6), intermediate (10), random (21), and mixed (12). One tumor could not be classified. These patterns were quantified by ...
The human olfactomedin 4 gene (OLFM4) encodes an olfactomedin-related glycoprotein. OLFM4 is normally expressed in a limited number of tissues, including the prostate, but its biological functions in prostate are largely unknown. In this study, we found that OLFM4 messenger RNA was reduced or undetectable in prostate cancer tissues and prostate cancer cell lines. To study the effects of OLFM4 on prostate cancer progression, we transfected PC-3 prostate cancer cells with OLFM4 to establish OLFM4-expressing PC-3 cell clones. The OLFM4-expressing PC-3 cell clones were found to have decreased proliferation and invasiveness compared with vector-transfected control PC-3 cells in vitro. In addition, nude mice injected with OLFM4-expressing PC-3 cells demonstrated reduced tumor growth and bone invasion and metastasis compared with mice injected with vector-transfected control cells. Mechanistic studies revealed that OLFM4 may exhibit its anticancer ...
Consensus principles from radiation biology were used to describe a generic set of nonlinear, first-order differential equations for modeling of toxicity-induced compensatory cell kinetics in terms of sublethal injury, repair, direct killing, killing of cells with unrepaired sublethal injury, and repopulation. This cellular model was linked to a probit model of hematopoietic mortality that describes death from infection and/or hemorrhage between {approximately} 5 and 30 days. Mortality data from 27 experiments with 851 doseresponse groups, in which doses were protracted by rate and/or fractionation, were used to simultaneously estimate all rate constants by maximum-likelihood methods. Data used represented 18,940 test animals distributed according to: (mice, 12,827); (rats, 2,925); (sheep, 1,676); (swine, 829); (dogs, 479); and (burros, 204). Although a long-term, repopulating hematopoietic stem cell is ancestral to all lineages needed to restore normal ...
Objectives: We have previously shown that chronic exposure to ambient fine particulate matter (less than 2.5 ?m in aerodynamic diameter, PM(2.5)) pollution in conjunction with high-fat diet induces insulin resistance through alterations in inflammatory pathways. In this study we evaluated the effects of PM(2.5) exposure over a substantive duration of a rodent's lifespan and focused on the impact of long-term exposure on adipose structure and function.Methods and Results: C57BL/6 mice were exposed to PM(2.5) or filtered air (FA) (6 hours/day, 5 days/week) for duration of 10 months in Columbus, OH. At the end of the exposure, PM(2.5)-exposed mice demonstrated insulin resistance (IR) and a decrease in glucose tolerance compared with the FA-exposed group. Although there were no significant differences in circulating cytokines between PM(2.5)- and FA-exposed groups, circulating adiponectin and leptin were significantly decreased in PM(2.5)-exposed ...
A comparative test in mice for pulmonary toxicity between butylated hydroxytoluene (2,6-di-tert.-butyl-4-methylphenol, BHT) and 2,6-di-tert.-butyl-4-(alpha, alpha, alpha-2H3)methylphenol (BHT-d3) showed a significantly lower toxic potency of the latter. The rate of in vitro BHT metabolism to 2,6-di-tert.-butyl-4-methylene-2,5-cyclohexadienone (BHT-QM) was slowed by deuterating BHT in the 4-methyl group. On the other hand, the rate of in vitro metabolism to 2,6-di-tert.-butyl-4-hydroxy-4-methyl-2,5-cyclohexadienone (BHT-OH) was increased with the deuteration. A similar isotope effect of the deuterium substitution on the in vivo metabolic rates of BHT was observed. These observations support the concept that the lung damage caused by BHT is mediated by BHT-QM. The pulmonary toxicity of 2-tert.-butyl-4-ethylphenol (4-EP) and their deuterated analogs was also compared. 2-tert.-Butyl-4-(1,1-2H2)ethylphenol (4-EP-d2) showed a significantly lower toxic potency than 4-EP, ...
Objectives: To minimize movement artifacts during tracer imaging studies, the animals are generally sedated. Although many reports describe the effect of barbiturates on brain function, less is published about the general impact on the extracerebral metabolism and tracer biodistribution. This report describes the influence of pentobarbital on tumor uptake of ["1"2"3I]-2-iodo-L-phenylalanine (["1"2"3I]-2I-L-PA) using dissection and nuclear imaging. Methods: R1M tumor-bearing athymic mice were divided into two populations: untreated and pentobarbital-treated. Each group was subjected to dynamic and static planar imaging and organ dissection after ["1"2"3I]-2I-L-PA injection. Two-compartment blood modeling was performed. Analysis of variance (ANOVA), t test and clustered boxplot analyses were used to compare the results between the treatment groups and between the data acquisition methods. Results: Two-compartment blood modeling demonstrated that pentobarbital ...
A human cholangiocarcinoma, Ch-1, serially transplanted to nude mice was used for experimental chemotherapy, radiotherapy, and conbination chemoradiotherapy. In the group of chemotherapy with single drug, Mitomycin C (MMC) revealed greater effectiveness than Adriamycin in terms of tumor regression, histological findings, and minor side effects. MMC and radiotherapy by Linac X-ray showed exponential linear dose response curve against tumor weight. Their effects were equivalent at doses of MMC 1 mg/kg and radiation 1,000 rads/mouse in the changes of tumor weight and of histological findings which were similar to each other. Combination chemoradiotherapy showed the synergistic action when the radiation (500 rads/mouse) was performed before MMC (0.5 mg/kg) administration, whereas only the additive effect was observed when the sequence was reversed. The cell kinetic analysis was performed by the impulse cytophotometry, "3H-thymidine uptake labeling index (L.I.), and ...
Several short-lived, high-energy beta emitters are being proposed as the radionuclide components for molecular-targeted potential cancer therapeutic agents. The laboratory mice used to determine the efficacy of these new agents have organs that are relatively small compared to the ranges of these high-energy particles. The dosimetry model developed by Hui et al. was extended to provide realistic beta-dose estimates for organs in mice that received therapeutic radiopharmaceuticals containing 90Y, 188Re, 166Ho, 149Pm, 64Cu, and 177 Lu. Major organs in this model included the liver, spleen, kidneys, lungs, heart, stomach, small and large bowel, thyroid, pancreas, bone, marrow, carcass, and a 0.025-g tumor. The study as reported in this paper verifies their results for 90Y and extends them by using their organ geometry factors combined with newly calculated organ self-absorbed fractions from PEREGRINE and MCNP. PEREGRINE and MCNP agree to within 8% ...
Radiation chimeras in the early phase after bone marrow transplantation are a good model to study the efficiency of the body's nonspecific defense system represented by macrophages (M phi), polymorphonuclear cells (PMN), and NK cells. These cell types are present in large numbers in spleen and liver at that time, whereas the specific immune system represented by T and B cells is functionally deficient. We previously reported enhanced activities in vitro of M phi (and PMN) from recipient animals in an early phase after allogeneic bone marrow transfer. We here demonstrate that these activities result in enhanced spontaneous resistance against Listeria monocytogenes in vivo: CFU of L. monocytogenes in spleen and liver 48 h after infection were about 1 or 2 to 4 log steps less than in untreated control mice of donor or host haplotype. This enhanced resistance decreased over the 4-mo period after marrow transfer. Preactivated M phi were identified as the most important ...
Whole-body retention and excretion following a single oral dose of radiolabeled lead (/sup 203/Pb) in chronically lead-exposed pregnant BK:W mice were examined over 10-13 days. This was compared with values in similarly treated nonpregnant females and in ip injected females. Whole-body and bone retention were greater in injected than in orally dosed nonpregnant females; gastrointestinal absorption was estimated from this difference. Whole-body retention in the pups was measured at birth and at the end of the experiment. Whole-body retentions in pregnant females and in their pups at birth were significantly raised after treatment at Gestational Day 17, but not after treatment at Gestational Day 11, 14, 20, 23, or 26. Pup body burdens at birth were significantly and positively correlated with maternal retention. Measurement of radioactivity in bone, kidney, brain, heart, and liver of adults at the end of the experiments showed significantly increased levels in bone ...
Whole-body retention and excretion following a single oral dose of radiolabeled lead ("2"0"3Pb) in chronically lead-exposed pregnant BK:W mice were examined over 10-13 days. This was compared with values in similarly treated nonpregnant females and in ip injected females. Whole-body and bone retention were greater in injected than in orally dosed nonpregnant females; gastrointestinal absorption was estimated from this difference. Whole-body retention in the pups was measured at birth and at the end of the experiment. Whole-body retentions in pregnant females and in their pups at birth were significantly raised after treatment at Gestational Day 17, but not after treatment at Gestational Day 11, 14, 20, 23, or 26. Pup body burdens at birth were significantly and positively correlated with maternal retention. Measurement of radioactivity in bone, kidney, brain, heart, and liver of adults at the end of the experiments showed significantly increased levels in bone and ...
Single doses of lead (trace to 445 mg/kg) were administered per os to suckling and adult mice. Both groups exhibited dose-independent lead retention when doses of 4 to 445 mg/kg were administered. However, developmental differences in the fraction of initial dose (FID) retained were evident for all doses administered. A much larger FID was retained in both age groups following administration of carrier-free "2"0"3Pb. The results are consistent with a mechanism of gastrointestinal lead absorption comprising two or more processes. Developmental differences were also observed in organ lead concentration relative to whole body concentration for kidneys, skull and brain 6 days following lead administration. Lead retentions (relative to whole body retention) in brain and in bone were linearly related to dose of lead administered in both suckling and adult age groups. Though uptake of lead into brain and into femur was observed to be directly related to dose over a wide ...
Investigations of radionuclide metabolism and effects in various mammalian species revealed important similarities between animals and humans and between some animal species. These include skeletal deposition of radium and radiostrontium in bone volume; deposition on bone surfaces of plutonium and other actinides; liver deposition of actinides; induction of skeletal or liver malignancies by these radionuclides; induction of tooth and jaw abnormalities; mammary cancer induction by radium in humans and in the beagle; depression of circulating cells in blood; and induction of bone fractures. There are also inter-species differences that may not have been noted if multiple species (including humans) had not been studied. Some of these are more rapid excretion of radium in humans compared with most other mammals; induction by radium of eye melanomas in animals but not humans; rapid loss of deposited plutonium from liver in many species of mice and rats but not in humans ...
A quantitative comparison of tissue distribution and excretion of an orally administered sublethal dose of [3H]diacetoxyscirpenol (anguidine) was made in rats and mice 90 min, 24 hr, and 7 days after treatment. Total recoveries of 95-100% were obtained. Approximately 90% of the dose was excreted in urine and feces during the first 24 hr with a feces:urine ratio of about 1:4.5 in both species. Carcass and tissue radioactivity dropped rapidly during the first 24 hr but remained relatively constant at low, but detectable, levels over the course of the experiment. Few substantive interspecies differences were noted in tissue distribution. At 90 min the highest percentage of dose was in tissues involved in sequestering diacetoxyscirpenol because of high body water/lipid content or the absorption, metabolism, or excretion of the toxin. The rank order of these tissues was generally stable over the course of the experiment. When data were expressed as specific ...
Magnolia bark and ginger rhizome is a drug pair in many prescriptions for treatment of mental disorders in traditional Chinese medicine (TCM). However, compatibility and synergism mechanism of two herbs on antidepressant actions have not been reported. The aim of this study was to approach the rationale of the drug pair in TCM. We evaluated antidepressant-like effects of mixture of honokiol and magnolol (HMM), polysaccharides (PMB) from magnolia bark, essential oil (OGR) and polysaccharides (PGR) from ginger rhizome alone, and the possibility of synergistic interactions in their combinations in the mouse forced swimming test (FST) and tail suspension test (TST). Serotonin (5-HT) and noradrenaline (NE) levels in prefrontal cortex, hippocampus and striatum were also examined. 30 mg/kg HMM decreased immobility in the FST and TST in mice after one- and two-week treatment. OGR (19.5 or 39 mg/kg) alone was ineffective. The combination of an ineffective dose of 39 mg/kg ...
Purpose: Antitumor activity of the dichloroplatinum(II)-histamine complexes labeled with I-125 or I-131 was investigated in a transplantable murine adenocarcinoma (MA) model. Methods: The tumor model was obtained in C3H/W female mice after subcutaneous inoculation of the tumor cells derived from the mice bearing a mammary tumor of spontaneous origin. Antitumor activities of the platinum-histamine complexes were investigated in three independent experiments, which differed in applied doses of preparations (PtCl{sub 2}Hist, PtCl{sub 2}[{sup 125}I]Hist, PtCl{sub 2}[{sup 131}I]Hist, PtCl{sub 2}Hist/PtCl{sub 2}[{sup 125}I]Hist and PtCl{sub 2}Hist/PtCl{sub 2}[{sup 131}I]Hist), treatment schedules as well as stages of the disease progress in the animals used. Experiment 1 included long-term, multidose treatment with low single doses (treatment duration 31-32 days; 8-10 doses of ca. 0.25{center_dot}MTD{sub Pt} each). Experiment 2 included short-term, ...
After the reactor accident at Chernobyl on April 26, 1986 radioactive fallout was carried by air currents to most parts of Europe. The radioactive air currents reached Finland on April 27. Immediately after the arrival of such air in Finland, contamination of people by radioactive nuclides began via inhalation of this air. The ingestion route become important later, when radionuclides were transported via different foodchains to man. To determine the level of radionuclides in the body and to estimate the internal radiation doses caused by the Chernobyl accident, whole-body counting measurements were performed. The results of whole-body counting of six different groups of Finnish people measured during 1986 after the accident at Chernobyl are reported. Three were reference groups measured routinely once or twice annually, two groups were comprised of workers at nuclear power stations and one group consisted of 262 persons not belonging to any other group. The total ...
Operations at the Savannah River Site (SRS) result in releases of small amounts of radioactive materials to the atmosphere and to the Savannah River. For regulatory compliance purposes, potential offsite radiological doses are estimated annually using computer models that follow U.S. Nuclear Regulatory Commission (NRC) Regulatory Guides. Within the regulatory guides, default values are provided for many of the dose model parameters but the use of site-specific values by the applicant is encouraged. A detailed survey of land and water use parameters was conducted in 1991 and is being updated here. These parameters include local characteristics of meat, milk and vegetable production; river recreational activities; and meat, milk and vegetable consumption rates as well as other human usage parameters required in the SRS dosimetry models. In addition, the preferred elemental bioaccumulation factors and transfer factors to be used in human health exposure calculations at SRS are documented. ...
In this study, radon-222 in indoor air was surveyed in 62 rooms located in four governmental schools, for girls, in Tarqumia town that lies in the north western part of Hebron city in Palestine. The annual effective dose equivalents resulting from the inhalation of radon and its daughters by 2318 pupils and 102 staff members occupying the surveyed rooms were also measured. TASTRAK, a solid state nuclear track detector, has been used to measure the indoor radon concentrations at those schools thus, 124 radon detectors were distributed in the four school buildings. The radon detectors stayed for 70 days between February 2006 and April 2006. The results showed that the radon concentration and the annual effective dose equivalent in these schools were varied from 12 to 232.5 Bq/m"3 with an average of 34.1 Bq/m"3 and 0.62 to 12.0 mSv/y with an average of 1.76 mSv/y, respectively. The mean values of radon concentrations in Tarqumia secondary girls school, Al-aqsa ...
Non-traumatic osteonecrosis of the femoral head (ONF) is considered to be a disease that occurs primarily due to ischemia of the femoral head, while its etiology and pathology are not fully understood. It is therefore necessary to identify the characteristics of the hemodynamics of the femoral head. In this study, the hemodynamics in the ilium and proximal regions of the femur, including the femoral head, was investigated using positron emission tomography (PET). The subjects of this study consisted of 8 hip joints of four healthy male adults and 3 hip joints on the contralateral side of a femoral neck fracture, avulsion fracture of the greater trochanter and coxarthrosis (1 case each, all females) for a total of 11 hip joints of 7 subjects. The ages of the subjects ranged from 25 to 87 years (average age: 54 years). Blood flow was measured by means of the H_2"1"5O dynamic study method and blood volume was measured by means of the "1"5O-labeled carbon monoxide bolus ...
The U.S. Department of Energy's (DOE) Savannah River Site (SRS) is decommissioning many of its excess facilities through removal of the facility structures leaving only the concrete-slab foundations in place. Site-specific, risk-based derived concentration guideline levels (DCGLs) for radionuclides have been determined for a future industrial worker potentially exposed to residual contamination on these concrete slabs as described in Jannik. These risk-based DCGLs were estimated for an exposure area of 100 m2. During deactivation and decommissioning (D and D) operations at SRS, the need for area factors for larger and smaller contaminated areas arose. This paper compares the area factors determined for an industrial worker exposed to a concrete slab end-state for several radionuclides of concern at SRS with 1) the illustrative area factors provided in MARSSIM, 2) the area correction factors provided in the U.S. Environmental Protection Agency's (EPA) Soil Screening Guidance, and 3) the ...
We investigated activity patterns of 17 elementary school students aged 10-12, and 19 high school students aged 13-17, in suburban Los Angeles during the oxidant pollution season. Individuals' relationships between ventilation rate (VR) and heart rate (HR) were calibrated' in supervised outdoor walking/jogging. Log VR was consistently proportional to HR; although calibrations' were limited by a restricted range of exercise, and possibly by artifact due to mouthpiece breathing, which may cause overestimation of VR at rest. Each subject then recorded activities in diaries, and recorded HR once per minute by wearing Heart Watches, over 3 days (Saturday-Monday). For each activity the subject estimated a breathing rate--slow (slow walking), medium (fast walking), or fast (running). VR ranges for each breathing rate and activity type were estimated from HR recordings. High-school students' diaries showed their aggregate distribution of waking hours as 68% ...
The aim of this study was to assess the utility of a radioimmunoconjugate containing a lead radionuclide for therapy and scintigraphy applications. The radioimmunoconjugate evaluated consisted of a bifunctional DOTA ligand and monoclonal antibody (MAb) B72.3 using athymic mice bearing LS-174T tumors, human colon carcinoma xenografts. In the studies reported here, the lead-203-DOTA complex itself was first demonstrated to have in vivo stability. MAb B72.3 was then conjugated with the DOTA ligand and labeled with "2"0"3Pb, and the immunoreactivity of B72.3 was maintained. The localization of the radioimmunoconjugate to tumor tissue and other select organs paralleled that of DOTA-"1"2"5I-B72.3, suggesting a similar metabolic pattern of the two radioimmunoconjugates. Thus, the DOTA-metal complex does not alter the behavior of the radioimmunoconjugate. Tumor localization of the "2"0"3Pb-DOTA-B72.3 conjugate was demonstrated with biodistribution studies as well as ...
Reference is made to Cheng and Leblond (Amer. J. Anat.; 141:537 (1974)) who used tritiated thymidine to kill cells synthesising DNA in the crypts of the small intestine. Amongst their findings was that very low doses caused measurable cell killing and that the killing was not random throughout the crypt but occurred selectively at the crypt base where stem cells are presumably located. It is here reported that the presence of hypersensitive cells at the base of the crypts can be demonstrated after whole-body X- or gamma-irradiation, and the time sequence for the production and loss of the killed cells is described together with their dose-response relationship. The studies were conducted on mice. The data were expressed as surviving rather than killed cells, and it was established that the crypt are amongst the most sensitive of mammalian cells. The mechanism by which these sensitive cells are killed is not known, but DNA damage can be detected. The vital stem ...